Publications by authors named "Yating Li"

81 Publications

M1 macrophage-derived exosomes impair beta cell insulin secretion via miR-212-5p by targeting SIRT2 and inhibiting Akt/GSK-3β/β-catenin pathway in mice.

Diabetologia 2021 Jun 11. Epub 2021 Jun 11.

Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.

Aims/hypothesis: Macrophage levels are elevated in pancreatic islets, and the resulting inflammatory response is a major contributor to beta cell failure during obesity and type 2 diabetes mellitus. Previous studies by us and others have reported that exosomes released by macrophages play important roles in mediating cell-to-cell communication, and represent a class of inflammatory factors involved in the inflammatory process associated with type 2 diabetes mellitus. However, to date, no reports have demonstrated the effect of macrophage-derived exosomes on beta cells, and little is known regarding their underlying mechanisms in beta cell injury. Thus, we aimed to study the impact of macrophage-derived exosomes on islet beta cell injury in vitro and in vivo.

Methods: The phenotypic profiles of islet-resident macrophages were analysed in C57BL/6J mice fed a high-fat diet (HFD). Exosomes were collected from the medium of cultured bone marrow-derived macrophages (BMDMs) and from isolated islet-resident macrophages of HFD-fed mice (HFD-Exos). The role of exosomes secreted by inflammatory M1 phenotype BMDMs (M1-Exos) and HFD-Exos on beta cell function was assessed. An miRNA microarray and quantitative real-time PCR (qPCR) were conducted to test the level of M1-Exos-derived miR-212-5p in beta cells. Then, miR-212-5p was overexpressed or inhibited in M1-Exos or beta cells to determine its molecular and functional impact.

Results: M1-polarised macrophages were enriched in the islets of obese mice. M1 macrophages and islet-resident macrophages of HFD-fed mice impaired beta cell insulin secretion in an exosome-dependent manner. miR-212-5p was notably upregulated in M1-Exos and HFD-Exos. Enhancing the expression of miR-212-5p impaired beta cell insulin secretion. Blocking miR-212-5p elicited a significant improvement in M1-Exos-mediated beta cell insulin secretion during injury. Mechanistically, M1-Exos mediated an intercellular transfer of the miR-212-5p, targeting the sirtuin 2 gene and regulating the Akt/GSK-3β/β-catenin pathway in recipient beta cells to restrict insulin secretion.

Conclusions/interpretation: A novel exosome-modulated mechanism was delineated for macrophage-beta cell crosstalk that drove beta cell dysfunction and should be explored for its therapeutic utility.
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http://dx.doi.org/10.1007/s00125-021-05489-1DOI Listing
June 2021

Effects of Notch2 on proliferation, apoptosis and steroidogenesis in bovine luteinized granulosa cells.

Theriogenology 2021 Sep 13;171:55-63. Epub 2021 May 13.

College of Animal Science, Shanxi Agricultural University, Taigu, 030801, Shanxi, China. Electronic address:

Notch signaling pathway plays an important regulatory role in the development of mammalian follicles. This study aimed to explore the effect of Notch2 on the function of bovine follicles luteinized granulosa cells (LGCs). We detected that the coding sequence (CDS) of bovine Notch2 gene is 7416 bp, encoding 2471 amino acids (AA). The homology of Notch2 AA sequence between bovine and other species is 86.04%-98.75%, indicating high conservatism. Immunohistochemistry found that Notch2 receptor and its ligand Jagged2 localize in granulosa cells (GCs) and theca cells in bovine antral follicles. And immunofluorescence found that positive signals of Notch2 and Jagged2 overlap in bovine LGCs, speculating that Notch2 receptor may react with Jagged2 ligand to activate Notch signaling pathway and play an important role in bovine LGCs. To further investigate the function of Notch2, Notch2 gene was silenced by short hairpin RNA (shRNA) and CCK-8 analysis showed that the proliferation rate of LGCs was downregulated significantly (P < 0.01). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that the mRNA expression of apoptosis related gene Bcl-2/Bax decreased (P < 0.01) and Caspase3 increased (P < 0.05), cell cycle related gene CyclinD2/CDK4 complex decreased (P < 0.01) and P21 increased (P < 0.05), steroidogenesis gene STAR and 3β-HSD decreased (P < 0.01) while CYP19A1 and CYP11A1 had no significant difference (P > 0.05). In addition, Enzyme-linked immunosorbent assay (ELISA) showed that there was no difference in estradiol (E) secretion (P > 0.05) while the progesterone (P) secretion decreased (P < 0.01). In conclusion, Notch2 plays an important role in regulating bovine LGCs development.
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http://dx.doi.org/10.1016/j.theriogenology.2021.05.009DOI Listing
September 2021

Comparative Proteomic Analysis of Different Parts of .

Front Vet Sci 2021 26;8:626579. Epub 2021 Apr 26.

College of Life Science and Technology, Xinjiang University, Urumqi, China.

, a globally distributed parasite, is a canine tapeworm and causes huge economic losses in the food industry. Using LC-MS/MS, the proteomes of cyst scolex, designated as CS, and the cyst without the scolex, designated as CWS, were profiled and a total of 764 different proteins were identified, 664 of which were identified in CS, 412 identified in CWS, and 312 in both. Comparative analysis revealed that CS had more abundant proteins associated with growth and development, while CWS had more abundant proteins constituting a scaffolding and protective extracellular matrix. Consistent with the sequencing data, the abundance of the five selected proteins was validated to be higher in CWS than CS by Western blotting. The current data will provide a clue for further pinpointing a role of these proteins in the biology of .
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http://dx.doi.org/10.3389/fvets.2021.626579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107385PMC
April 2021

Effects of Pediococcus pentosaceus LI05 on immunity and metabolism in germ-free rats.

Food Funct 2021 Jun 7;12(11):5077-5086. Epub 2021 May 7.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Many Pediococcus spp. have health-promoting benefits, and Pediococcus pentosaceus LI05 is one such species that was proved to be beneficial in previous studies. Our research aimed to determine the immune and metabolic effects of P. pentosaceus LI05 on germ-free rats. Germ-free rats were gavaged with P. pentosaceus LI05 suspensions (1 × 10 CFU) for 2 weeks, and 3 weeks later, blood, spleen, intestine and liver samples were gathered for metabolome, intestine morphology, immunity, and transcriptomics analyses. Oral gavage of P. pentosaceus LI05 reduced the bodyweight of rats, which manifested as increased fecal carbohydrate concentrations, decreased intestinal fat intake and the hepatic fat synthesis gene expression, and accelerated fat-to-glycogen conversion. In addition, P. pentosaceus LI05 exhibited an anti-inflammatory ability, reducing serum proinflammatory cytokine levels and increasing intestinal subepidermal CD4 cell levels. Furthermore, administration of P. pentosaceus LI05 increased the antimicrobial ability and enhanced the liver detoxification function. These results indicate that as a probiotic, P. pentosaceus LI05 ameliorates the hampered immune response of GF animals and improves the metabolism of fat and toxic substances.
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http://dx.doi.org/10.1039/d0fo02530eDOI Listing
June 2021

Glyphosate exposure attenuates testosterone synthesis via NR1D1 inhibition of StAR expression in mouse Leydig cells.

Sci Total Environ 2021 Sep 25;785:147323. Epub 2021 Apr 25.

Northwest A&F University, Yangling 712100, Shaanxi, China; Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:

Glyphosate is a broad-spectrum herbicide that impairs testosterone synthesis in mammals. Leydig cells (LCs), the primary producers of testosterone, demonstrate rhythmic expression of circadian clock genes both in vivo and in vitro. The nuclear receptor NR1D1 is an important clock component that constitutes the subsidiary transcriptional/translational loop in the circadian clock system. Nr1d1 deficiency resulted in diminished fertility in both male and female mice. However, whether NR1D1 is involved in the glyphosate-mediated inhibition of testosterone synthesis in LCs remains unclear. Here, the involvement of NR1D1 in glyphosate-mediated inhibition of testosterone synthesis was investigated both in vitro and in vivo. Glyphosate exposure of TM3 cells significantly increased Nr1d1 mRNA levels, but decreased Bmal1, Per2, StAR, Cyp11a1, and Cyp17a1 mRNA levels. Western blotting confirmed elevated NR1D1 and reduced StAR protein levels following glyphosate exposure. Glyphosate exposure also reduced testosterone production in TM3 cells. In primary LCs, glyphosate exposure also upregulated Nr1d1 mRNA levels and downregulated the mRNA levels of other clock genes (Bmal1 and Per2) and steroidogenic genes (StAR, Cyp17a1, Cyp11a1, and Hsd3b2), and inhibited testosterone synthesis. Moreover, glyphosate exposure significantly reduced the amplitude and shortened the period of PER2::LUCIFERASE oscillations in primary LCs isolated from mPer2 knock-in mice. Four weeks of oral glyphosate upregulated NR1D1 at both the mRNA and protein levels in mouse testes, and this was accompanied by a reduction in StAR expression. Notably, serum testosterone levels were also drastically reduced in mice treated with glyphosate. Moreover, dual-luciferase reporter and EMSA assays revealed that in TM3 cells NR1D1 inhibits the expression of StAR by binding to a canonical RORE element present within its promoter. Together, these data demonstrate that glyphosate perturbs testosterone synthesis via NR1D1 mediated inhibition of StAR expression in mouse LCs. These findings extend our understanding of how glyphosate impairs male fertility.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147323DOI Listing
September 2021

Modulatory Effects of emu-let-7-5p on the Immunological Functions of RAW264.7 Macrophages.

Front Vet Sci 2021 15;8:663497. Epub 2021 Apr 15.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China.

is a zoonotic tapeworm with great medical significance. In -infected mice, parasite-derived let-7-5p (emu-let-7-5p) is present in the sera, but its role remains unclear. Using qPCR, ELISA and flow cytometry, the immunomodulatory effects of emu-let-7-5p were investigated using RAW264.7 macrophages. Compared with the control, emu-let-7-5p significantly downregulated IL-1α ( < 0.05), but anti-inflammatory cytokine genes remained to be stably expressed in the treated macrophages. Moreover, significantly decreased expression of and , key components in the LPS/TLR4 signaling pathway, was also observed in the emu-let-7-5p-transfected cells ( < 0.05). Furthermore, CD40 was upregulated in these transfected cells ( < 0.05), while CD86, CD54 and CD80 remained unchanged compared that in the control. These results demonstrate a property of emu-let-7-5p in regulation of immune functions of macrophages, making it be possibly involved in the pathogen-host interplay during infection.
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http://dx.doi.org/10.3389/fvets.2021.663497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081858PMC
April 2021

Pregnant women's psychological state and influence factors: anxiety, and depression during COVID-19 outbreak.

J Perinat Med 2021 Apr 16. Epub 2021 Apr 16.

Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, WuhanHubei, P. R. China.

Objectives: The outbreak of COVID-19 affects both physical and mental health of pregnant women. This study focuses on their psychological status, and analyzes the main factors affecting their emotions of pregnant women so as to provide guidance for psychological counseling and social intervention during epidemics.

Methods: Multiple researchers distributed a questionnaire online via the Internet. Pregnant women volunteered, and the questionnaire was automatically collected in the background.

Results: The 298 valid questionnaires recovered showed that 82 cases of pregnant women were in states of anxiety, accounting for 27.51%, of which 78.05% were mild (82 cases), 19.51% were moderate (16 cases), and 2.44% were severe (2 cases). Moreover, 31.21% of pregnant women were in states of depression (93 cases), of which 52.69% were mild (49 cases), 40.86% were moderate (38 cases), and 6.45% were severe (6 cases). The risk factors for states of anxiety or depression were fear of fetal malformation or genetic disease, history of adverse pregnancy, can't do routine prenatal examination, and insufficient support and care from husbands and families. Besides, 16 cases had sought psychological help during the epidemic, among whom 62.50% (10 cases) experienced anxiety, 68.75% (11 cases) had depression.

Conclusions: During the outbreak of COVID-19, obstetricians may take use of the Internet, based on the advantages in epidemic prevention, controlling health education, and popularizing science. In addition, husbands and family members should provide greater care for pregnant women, to protect their mental health during public health incidents.
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http://dx.doi.org/10.1515/jpm-2020-0541DOI Listing
April 2021

Pure erythroid leukemia subsequent to acute myelomonocytic leukemia: A case report.

Medicine (Baltimore) 2021 Apr;100(15):e25528

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Hematology of Nanjing Medical University.

Rationale: Pure erythroid leukemia is a rare subcategory of acute myeloid leukemia characterized by predominant immature erythroid population. Its occurrence subsequent to acute myelomonocytic leukemia has not been reported before. We reported this rare case to call attention because it may pose a diagnostic challenge.

Patients Concerns: A 54-year-old female patient presented to our hospital in March 2018 with symptoms of easy fatigability.

Diagnosis: Bone marrow aspiration was hypercellular showing 67.2% blasts mainly including moderate myeloblasts and monoblasts. There was mild dysplasia with some cells having round, oval, or bizarre nuclei which containing 1 to 3 nucleolus. Erythroid lineage was hypoplasia and mature erythrocytes were generally normal. Conventional cytogenetics of bone marrow cells revealed complex karyotype (44, XX, del (5) (q14q34) del (5) (q14q34), del (14) t (11;14) (q10; q10), -16, del (17), -18[10]).

Interventions: The patient was treated with second line chemotherapy but did not respond.

Qutcomes: She died of cardiopulmonary failure 19days after starting of therapy.

Lessons: This unexpected and relatively uncommon occurrence was associated with a universally rapid and fatal clinical course with survival measured in <2 months despite intensive chemotherapy. We call attention to this rare phenomenon because it may pose a diagnostic challenge.
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http://dx.doi.org/10.1097/MD.0000000000025528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052012PMC
April 2021

Evolution and diffusion of information literacy topics.

Scientometrics 2021 Mar 12:1-30. Epub 2021 Mar 12.

National Engineering Laboratory for Educational Big Data, Central China Normal University, Wuhan, China.

Investigation of the topic of information literacy and its changes can be informative for researchers and provide a better understanding of the corresponding domains. This study conducted a topic model dynamic analysis of the articles on information literacy studies in the Web of Science core collection database that were published from 2005 to 2019. The global topics and their popularities, topical similarities and correlations, along with the evolution of temporal local topics and the diffusion of subject local topics were analyzed and presented. Nine global topics differed in terms of their temporal and subject characteristics, and this study focused on ability, technology, field, people, place and application of information literacy. For the temporal local topics, crossing was the main evolutionary mechanism; hence, the core topic words were relatively stable, but few new research directions have been explored in recent years. For the subject local topics, absorbing with division and absorbing were the main mechanisms, which supported the diffusion progress of information literacy studies among subjects. However, it is necessary to promote the development of future research through the innovative development of multidisciplinary integration. Researchers and practitioners should focus on the impact of information technology, increase the breadth and depth of the research field, and develop innovative evaluation methods that are based on data to promote the comprehensive, sustainable and effective improvement in information literacy.
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http://dx.doi.org/10.1007/s11192-021-03925-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970783PMC
March 2021

High Power Factor Ag/AgSe Composite Films for Flexible Thermoelectric Generators.

ACS Appl Mater Interfaces 2021 Mar 19;13(12):14327-14333. Epub 2021 Mar 19.

SUSTech Core Research Facilities and Department of Physics, Southern University of Science and Technology, Shenzhen 518055, China.

Herein, we fabricated an Ag/AgSe composite film on a flexible nylon membrane with a high power factor and excellent flexibility. First, Ag nanoparticles and multiscale AgSe nanostructure composite powders were prepared by wet chemical synthesis using Se nanowires, silver nitrate, and l-ascorbic acid as raw materials, followed by vacuum-assisted filtration of the composite powders on a porous nylon membrane and then hot pressing. The optimized composite film shows a very high power factor of 1860.6 μW m K (with a corresponding electrical conductivity of 3958 S cm) at room temperature. The composite film retains 93.3% of the original electrical conductivity after 1000 bending cycles around a rod with a diameter of 8 mm. At a temperature difference of 27 K, an 8-leg thermoelectric prototype device assembled with the optimized composite film generates a maximum power of 7.14 μW with a corresponding power density of 8.74 W m. This work provides a new strategy to synthesize flexible thermoelectric films with both a high power factor and high electrical conductivity.
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http://dx.doi.org/10.1021/acsami.1c02194DOI Listing
March 2021

Identification of Different Extracellular Vesicles in the Hydatid Fluid of and Immunomodulatory Effects of 110 K EVs on Sheep PBMCs.

Front Immunol 2021 23;12:602717. Epub 2021 Feb 23.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.

Echinococcosis, mainly caused by , is one of the 17 neglected tropical diseases. Extracellular vesicles (EVs) play an essential role in the host-parasite interplay. However, the EVs in the hydatid fluid (HF) of are not fully characterized. Herein, three different types of HF EVs, designated as 2 K, 10 K, and 110 K EVs based on the centrifugal force used, were morphologically identified. A total of 97, 80, and 581 proteins were identified in 2 K, 10 K, and 110 K EVs, respectively, 39 of which were commonly shared. Moreover, 11, 8, and 25 miRNAs were detected, respectively, and all of the 7 selected miRNAs were validated by qPCR to be significantly lower abundant than that in protoscoleces. It was further deemed that 110 K EVs were internalized by sheep peripheral blood mononuclear cells (PBMCs) in a time-dependent manner and thus induced interleukin (IL)-10, tumor necrosis factor-α (TNF-α), and IRF5 were significantly upregulated and IL-1β, IL-17, and CD14 were significantly downregulated ( < 0.05). These data demonstrate the physical discrepancy of three HF EVs and an immunomodulatory effect of 110 K EVs on sheep PMBCs, suggesting a role in immune responses during infection.
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http://dx.doi.org/10.3389/fimmu.2021.602717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940240PMC
February 2021

Gut bacteria formation and influencing factors.

FEMS Microbiol Ecol 2021 03;97(4)

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, CAAS, 1 Xujiaping, Chengguan District, Lanzhou 730046, China.

The gut microbiota plays an important role in human health. In modern life, with the improvement of living conditions, the intake of high-sugar and high-fat diets as well as the large-scale use of antibacterial drugs have an extensive impact on the gut microbiota, even leading to gut microbiota-orchestrating disorders. This review discusses the effects of various factors, including geographic location, age, diet, antibacterial drugs, psychological situation and exercise on gut bacteria, which helps us profoundly to understand the significance of gut bacteria to human health and to find effective solutions to prevent or treat related diseases.
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http://dx.doi.org/10.1093/femsec/fiab043DOI Listing
March 2021

Dynamic functional connectome predicts individual working memory performance across diagnostic categories.

Neuroimage Clin 2021 23;30:102593. Epub 2021 Feb 23.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. Electronic address:

Working memory impairment is a common feature of psychiatric disorders. Although its neural mechanisms have been extensively examined in healthy subjects or individuals with a certain clinical condition, studies investigating neural predictors of working memory in a transdiagnostic sample are scarce. The objective of this study was to create a transdiagnostic predictive working memory model from whole-brain functional connectivity using connectome-based predictive modeling (CPM), a recently developed machine learning approach. Resting-state functional MRI data from 242 subjects across 4 diagnostic categories (healthy controls and individuals with schizophrenia, bipolar disorder, and attention deficit/hyperactivity) were used to construct dynamic and static functional connectomes. Spatial working memory was assessed by the spatial capacity task. CPM was conducted to predict individual working memory from dynamic and static functional connectivity patterns. Results showed that dynamic connectivity-based CPM models successfully predicted overall working memory capacity and accuracy as well as mean reaction time, yet their static counterparts fell short in the prediction. At the neural level, we found that dynamic connectivity of the frontoparietal and somato-motor networks were negatively correlated with working memory capacity and accuracy, and those of the default mode and visual networks were positively associated with mean reaction time. Moreover, different feature selection thresholds, parcellation strategies and model validation methods as well as diagnostic categories did not significantly influence the prediction results. Our findings not only are coherent with prior reports that dynamic functional connectivity encodes more behavioral information than static connectivity, but also help advance the translation of cognitive "connectome fingerprinting" into real-world application.
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http://dx.doi.org/10.1016/j.nicl.2021.102593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930367PMC
February 2021

Modulation of the immune response and metabolism in germ-free rats colonized by the probiotic Lactobacillus salivarius LI01.

Appl Microbiol Biotechnol 2021 Feb 19;105(4):1629-1645. Epub 2021 Jan 19.

State Key Laboratory for Diagnosis, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

The gut microbiota plays an important role in multifaceted physiological functions in the host. Previous studies have assessed the probiotic effects of Lactobacillus salivarius LI01. In this study, we aimed to investigate the potential effects and putative mechanism of L. salivarius LI01 in immune modulation and metabolic regulation through the monocolonization of germ-free (GF) Sprague-Dawley (SD) rats with L. salivarius LI01. The GF rats were separated into two groups and administered a gavage of L. salivarius LI01 or an equal amount of phosphate-buffered saline. The levels of serum biomarkers, such as interleukin (IL)-1α, IL-5, and IL-10, were restored by L. salivarius LI01, which indicated the activation of Th0 cell differentiation toward immune homeostasis. L. salivarius LI01 also stimulated the immune response and metabolic process by altering transcriptional expression in the ileum and liver. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed significant enrichment of the 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which indicated that L. salivarius LI01 exerts an effect on energy accumulation. The LI01 group showed alterations in fecal carbohydrates accompanied by an increased body weight gain. In addition, L. salivarius LI01 produced indole-3-lactic acid (ILA) and enhanced arginine metabolism by rebalancing the interconversion between arginine and proline. These findings provide evidence showing that L. salivarius LI01 can directly impact the host by modulating immunity and metabolism. KEY POINTS : • Lactobacillus salivarius LI01 conventionalizes the cytokine profile and activates the immune response. • LI01 modulates carbohydrate metabolism and arginine transaction. • LI01 generates tryptophan-derived indole-3-lactic acid. • The cytochrome P450 family contributes to the response to altered metabolites.
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http://dx.doi.org/10.1007/s00253-021-11099-zDOI Listing
February 2021

Western Diet Aggravated Carbon Tetrachloride-Induced Chronic Liver Injury by Disturbing Gut Microbiota and Bile Acid Metabolism.

Mol Nutr Food Res 2021 04 24;65(7):e2000811. Epub 2021 Feb 24.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, P. R. China.

Scope: The high-fat, high-sucrose, and low-fiber Western diet (WD) is popular in many countries and affects the onset and progression of many diseases. This study is aimed to explore the influence of the WD on chronic liver disease (CLD) and its possible mechanism.

Methods And Results: C57BL/6 mice are given a control diet (CD) or WD and CLD is induced by intraperitoneally injecting carbon tetrachloride (CCL ) twice a week for 8 weeks. The WD aggravated CCL -induced chronic liver injury, as evidenced by increased serum transaminase levels, worsened hepatic inflammatory response, and fibrosis. Gut microbiota is disturbed in mice treated with CCL +WD (WC group), manifested as the accumulation of Fusobacteria, Streptococcaceae, Streptococcus, Fusobacterium, and Prevotella and the depletion of Firmicutes, Lachnospiraceae, and Roseburia. Additionally, increased hepatic taurocholic acid in the WC group activated sphingosine-1-phosphate receptor 2, which is positively correlated with hepatic fibrosis and inflammation parameters. Mice in the WC group have higher fecal primary bile acid (BA) levels and lower fecal secondary/primary BA ratios. Serum FGF15 levels are also elevated in the WC group, which is positively correlated with hepatic inflammation.

Conclusion: WD accelerates the progression of CLD which is associated with changes in the gut microbiota and BA metabolism.
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http://dx.doi.org/10.1002/mnfr.202000811DOI Listing
April 2021

Circular RNA hsa_Circ_0005795 mediates cell proliferation of cutaneous basal cell carcinoma via sponging miR-1231.

Arch Dermatol Res 2021 Jan 12. Epub 2021 Jan 12.

Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Yong'an Road, Beijing, 100050, China.

Growing evidence has revealed that circular RNAs (circRNA) play critical roles in cancer progression. Here, we examined the function of a novel circRNA, Circ_0005795, in basal cell carcinoma (BCC) and explored the possible molecular mechanism. Nodular BCC and adjacent non-tumor tissues derived from 30 patients and 2 BCC cell lines were applied to analyze gene expression. Circ_0005795 loss- and gain-of-function were constructed to investigate BCC progression. Nuclear and cytoplasmic fractionation and luciferase assay were carried out to determine cellular localization and molecular interaction of Circ_0005795. Circ_0005795 expression was significantly elevated in BCC tissues and cells. Knockdown of Circ_0005795 dramatically reduced cell viability, colony formation, and anti-apoptotic protein levels, while increased caspase-3 activity. Circ_0005795 located in cytoplasm, which exerted its tumor-promoting effect through targeting and sponging miR-1231 in BCC cells. In summary, Circ_0005795 works as an oncogene in BCC, which might be used as a promising biomarker and a potential therapeutic target for BCC diagnosis and treatment.
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http://dx.doi.org/10.1007/s00403-020-02174-yDOI Listing
January 2021

Integrated Multichip Analysis Identifies Potential Key Genes in the Pathogenesis of Nonalcoholic Steatohepatitis.

Front Endocrinol (Lausanne) 2020 26;11:601745. Epub 2020 Nov 26.

Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Nonalcoholic steatohepatitis (NASH) is rapidly becoming a major chronic liver disease worldwide. However, little is known concerning the pathogenesis and progression mechanism of NASH. Our aim here is to identify key genes and elucidate their biological function in the progression from hepatic steatosis to NASH.

Methods: Gene expression datasets containing NASH patients, hepatic steatosis patients, and healthy subjects were downloaded from the Gene Expression Omnibus database, using the R packages biobase and GEOquery. Differentially expressed genes (DEGs) were identified using the R limma package. Functional annotation and enrichment analysis of DEGs were undertaken using the R package ClusterProfile. Protein-protein interaction (PPI) networks were constructed using the STRING database.

Results: Three microarray datasets GSE48452, GSE63067 and GSE89632 were selected. They included 45 NASH patients, 31 hepatic steatosis patients, and 43 healthy subjects. Two up-regulated and 24 down-regulated DEGs were found in both NASH patients vs. healthy controls and in steatosis subjects vs. healthy controls. The most significantly differentially expressed genes were ( = 3.43×10), followed by ( = 2.87×10), and ( = 6.26×10). Proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific ( = 1.30×10) was the most significantly enriched functional term in the gene ontology analysis. KEGG pathway enrichment analysis indicated that the MAPK signaling pathway ( = 3.11×10) was significantly enriched.

Conclusion: This study characterized hub genes of the liver transcriptome, which may contribute functionally to NASH progression from hepatic steatosis.
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http://dx.doi.org/10.3389/fendo.2020.601745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726207PMC
May 2021

Comparative analysis of different extracellular vesicles secreted by Echinococcus granulosus protoscoleces.

Acta Trop 2021 Jan 13;213:105756. Epub 2020 Nov 13.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, CAAS, Lanzhou 730046, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. Electronic address:

Extracellular vesicles (EVs) are heterogeneous populations of different membrane-wrapped vesicles in size and encapsulated cargo and have recently emerged as a crucial carrier with the functions in intercellular communication, being involved in host-parasite interactions. However, Echinococcus granulosus EVs are not fully described. To separate EVs with a different size, the culture supernatant of E. granulosus protoscoleces (PSCs) was sequentially centrifuged at 2,000g, 10,000g and 110,000g, and the resulting precipitates were accordingly named as 2K, 10K and 110K EVs, respectively. The size and morphology of three different EVs were identified using ZETASIZER NANO and transmission electron microscopy (TEM), respectively. Then mass spectrometry was applied to define protein cargo of EVs and EV internalization was assessed using fluorescent microscopy and flow cytometry. The results showed that 2K EVs mainly ranged from 450 to 950 nm in diameter, 10K EVs ranged from 220 to 390 nm and 110K EVs from 60 to 150 nm. A total of 901 EV proteins were identified, 328 of which were commonly found in the three types of EVs. GO analysis revealed that these proteins were mainly involved in binding (44%) and catalytic activity (44%). Three types of EVs were different in biomarkers (Enolase and 14-3-3) and in reactivity with anti-echinococcosis positive serum. Moreover, 110K EVs were more easily internalized by hepatic cells than 10K EVs as well as 2K EVs (p < 0.0001). These results reveal the physical and biological discrepancy among 2K, 10K and 110K EVs, suggesting a distinct role in host-parasite interactions.
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http://dx.doi.org/10.1016/j.actatropica.2020.105756DOI Listing
January 2021

Effects of FOXO1 on the proliferation and cell cycle-, apoptosis- and steroidogenesis-related genes expression in sheep granulosa cells.

Anim Reprod Sci 2020 Oct 15;221:106604. Epub 2020 Sep 15.

College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, China. Electronic address:

Forkhead boxO (FOXO) transcription factors regulate diverse biological processes, including cellular metabolism, cell apoptosis, and the cell cycle. Results from several studies indicate FOXO1 regulates different granulosa cell (GC) pathways involved in proliferation, survival and differentiation. Functions and mechanisms of FOXO1 regulation of sheep GCs remain unclear. This study was conducted to analyze the function of FOXO1 in regulation of sheep GCs. In this study, the 1827 bp sheep FOXO1 coding sequence was cloned from sheep GCs. Multiple sequence alignment and phylogenetic analysis indicated that the FOXO1 protein sequence is highly homologous to FOXO1 protein sequences from other species. The results obtained from using CCK-8 assays indicated sheep GC proliferation increased when there was suppression of FOXO1 gene expression. When there was induced expression of the FOXO1 gene in sheep GCs, there was a resulting increased abundance of P21 and P27 mRNA transcript, whereas suppression of the FOXO1 gene expression had the opposite effect. Furthermore, the relative abundance in vitro of apoptosis-related protein mRNA transcripts (caspase3, caspase8, caspase9, Bax/Bcl-2) was markedly increased or decreased when there was induction or suppression of FOXO1 gene expression, respectively,(P < 0.05). Induction of FOXO1 gene expression resulted in an increase in abundance of steroidogenic protein mRNA transcripts (CYP11A1, 3β-HSD), while suppression of FOXO1 gene expresion resulted in a decrease abundance of the CYP11A1, STAR mRNA transcripts. Results from the present study indicated that FOXO1 inhibited the proliferation of sheep GCs and affected mRNA transcript abundance for proteins involved in regulation of apoptosis, the cell cycle and steroidogenesis.
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http://dx.doi.org/10.1016/j.anireprosci.2020.106604DOI Listing
October 2020

A Predictive Nomogram for Predicting Improved Clinical Outcome Probability in Patients with COVID-19 in Zhejiang Province, China.

Engineering (Beijing) 2020 Jun 6. Epub 2020 Jun 6.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019 (COVID-19). Data on 104 patients admitted to hospital with laboratory-confirmed COVID-19 infection from 10 January 2020 to 26 February 2020 were collected. Clinical information and laboratory findings were collected and compared between the outcomes of improved patients and non-improved patients. The least absolute shrinkage and selection operator (LASSO) logistics regression model and two-way stepwise strategy in the multivariate logistics regression model were used to select prognostic factors for predicting clinical outcomes in COVID-19 patients. The concordance index (C-index) was used to assess the discrimination of the model, and internal validation was performed through bootstrap resampling. A novel predictive nomogram was constructed by incorporating these features. Of the 104 patients included in the study (median age 55 years), 75 (72.1%) had improved short-term outcomes, while 29 (27.9%) showed no signs of improvement. There were numerous differences in clinical characteristics and laboratory findings between patients with improved outcomes and patients without improved outcomes. After a multi-step screening process, prognostic factors were selected and incorporated into the nomogram construction, including immunoglobulin A (IgA), C-reactive protein (CRP), creatine kinase (CK), Acute Physiology and Chronic Health Evaluation II (APACHE II), and interaction between CK and APACHE II. The C-index of our model was 0.962 (95% confidence interval (CI), 0.931-0.993) and still reached a high value of 0.948 through bootstrapping validation. A predictive nomogram we further established showed close performance compared with the ideal model on the calibration plot and was clinically practical according to the decision curve and clinical impact curve. The nomogram we constructed is useful for clinicians to predict improved clinical outcome probability for each COVID-19 patient, which may facilitate personalized counselling and treatment.
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http://dx.doi.org/10.1016/j.eng.2020.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274972PMC
June 2020

Gut Microbiome and Metabolome Were Altered and Strongly Associated With Platelet Count in Adult Patients With Primary Immune Thrombocytopenia.

Front Microbiol 2020 8;11:1550. Epub 2020 Jul 8.

Institute of Hematology, Zhejiang University, Hangzhou, China.

Gut microbiota has been implicated in the pathogenesis of many autoimmune diseases. This is still an area of active research given that the role of gut microbiota on the primary immune thrombocytopenia (ITP) remains unclear. In this study, fecal samples of 30 untreated adult primary ITP patients and 29 healthy controls (HCs) were used to investigate the gut microbial community and metabolite profiles. Our results show that fecal bacteria such as , , and are enriched, whereas bacteria such as are depleted in ITP patients. Notably, fecal metabolites such as fatty acyls and glycerophospholipids are enriched and strongly correlate with discrepant gut microbiota. Furthermore, combinations of and , or Cer (t18:0/16:0), Cer (d18:1/17:0), and 13-hydroxyoctadecanoic acid could provide good diagnostic markers for ITP. Moreover, a strong negative correlation was found between platelet count and altered gut microbiota such as and gut metabolites such as Cer (t18:0/16:0) in ITP. In conclusion, dysbiosis of both gut microbiota and metabolome develops in ITP patients compared to HCs. Several ITP-altered gut bacteria and metabolites can be diagnostic biomarkers for ITP, and are highly correlated with platelet count, suggesting that they may also play a role in ITP pathogenesis.
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http://dx.doi.org/10.3389/fmicb.2020.01550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360729PMC
July 2020

Lactobacillus salivarius LI01 encapsulated in alginate-pectin microgels ameliorates D-galactosamine-induced acute liver injury in rats.

Appl Microbiol Biotechnol 2020 Sep 14;104(17):7437-7455. Epub 2020 Jul 14.

State Key Laboratory for Diagnosis, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Acute liver failure is a clinical emergency associated with high mortality. Accumulating evidence indicates that gut microbiota participates in the progression of liver injury, and preventive therapies based on altering gut microbiota are of great interest. Previous studies demonstrated that Lactobacillus salivarius LI01 attenuates hepatic injury, though efficiency in curtailed in the harsh environment in the gastrointestinal tract. In this study, a system to encapsulate LI01 in alginate-pectin (AP) microgels was investigated. Encapsulation significantly enhances probiotic viability for long-term storage and heat treatment, and in simulated gastrointestinal fluids (SGF or SIF) and bile salt solutions. Acute liver injury was induced in Sprague-Dawley (SD) rats by D-galactosamine (D-GaIN) injection following pretreatment with probiotics. Liver and gut barrier function, cytokines, liver and gut histology, bacterial translocation, and gut microbiota were assessed. Administration of encapsulated LI01 more effectively upregulates hepatic anti-inflammatory cytokine IL-10 and TLR-3, restores expressions of gut barrier biomarkers Claudin-1 and MUC2 and attenuates destruction of mucosal ultrastructure compared with unencapsulated probiotics pretreatment. Pretreatment with AP-LI01 microgels altered the microbial community, decreasing the abundance of pathogenic taxa Ruminiclostridium, Dorea and Ruminococcaceae_UCG-004 and enriching beneficial taxa Ruminococcaceae_UCG-014, Eubacterium, and Prevotella_1 that produce short-chain fatty acids. These results suggest that AP encapsulation of LI01 boosts viability and attenuates liver injury by reducing inflammation and restoring intestinal barrier function. These beneficial effects are probably due to alternation of gut flora. These findings provide new insight into encapsulation technology and prevention of liver failure. KEY POINTS: • Alginate-pectin encapsulation enhances the viability of Lactobacillus salivarius LI01 under simulated commercial conditions and simulated gastrointestinal environment. • AP-LI01 microgel attenuates hepatic and intestinal inflammation and restores gut barrier function. • AP-LI01 microgel alters gut microbial community with increased SCFAs producers and decreased pathogenic microbes. • Beneficial improvements after administration of probiotics are highly associated with alternation of gut microbial community.
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http://dx.doi.org/10.1007/s00253-020-10749-yDOI Listing
September 2020

Protective effect of Lactobacillus salivarius Li01 on thioacetamide-induced acute liver injury and hyperammonaemia.

Microb Biotechnol 2020 11 11;13(6):1860-1876. Epub 2020 Jul 11.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

The gut microbiota plays pivotal roles in liver disease onset and progression. The protective effects of Lactobacillus salivarius Li01 on liver diseases have been reported. In this study, we aimed to detect the protective effect of L. salivarius Li01 on thioacetamide (TAA)-induced acute liver injury and hyperammonaemia. C57BL/6 mice were separated into three groups and given a gavage of L. salivarius Li01 or phosphate-buffered saline for 7 days. Acute liver injury and hyperammonaemia were induced with an intraperitoneal TAA injection. L. salivarius Li01 decreased mortality and serum transaminase levels and improved histological liver damage caused by TAA. Serum inflammatory cytokine and chemokine and lipopolysaccharide-binding protein (LBP) concentrations, nuclear factor κB (NFκB) pathway activation and macrophage and neutrophil infiltration into the liver were significantly alleviated by L. salivarius Li01. L. salivarius Li01 also reinforced gut barrier and reshaped the perturbed gut microbiota by upregulating Bacteroidetes and Akkermansia richness and downregulating Proteobacteria, Ruminococcaceae_UCG_014 and Helicobacter richness. Plasma and faecal ammonia levels declined noticeably in the Li01 group, accompanied by improvements in cognitive function, neuro-inflammation and relative brain-derived neurotrophic factor (BDNF) gene expression. Our results indicated that L. salivarius Li01 could be considered a potential probiotic in acute liver injury and hepatic encephalopathy (HE).
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http://dx.doi.org/10.1111/1751-7915.13629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533332PMC
November 2020

Clinical Characteristics and Factors Associated With Long-Term Viral Excretion in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Single-Center 28-Day Study.

J Infect Dis 2020 08;222(6):910-918

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Background: Despite the ongoing spread of coronavirus disease 2019 (COVID-19), knowledge about factors affecting prolonged viral excretion is limited.

Methods: In this study, we retrospectively collected data from 99 hospitalized patients with coronavirus disease 2019 (COVID-19) between 19 January and 17 February 2020 in Zhejiang Province, China. We classified them into 2 groups based on whether the virus test results eventually became negative. Cox proportional hazards regression was used to evaluate factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding.

Results: Among 99 patients, 61 patients had SARS-CoV-2 clearance (virus-negative group), but 38 patients had sustained positive results (virus-positive group). The median duration of SARS-CoV-2 excretion was 15 (interquartile range, 12-19) days among the virus-negative patients. The shedding time was significantly increased if the fecal SARS-CoV-2 RNA test result was positive. Male sex (hazard ratio [HR], 0.58 [95% confidence interval {CI}, .35-.98]), immunoglobulin use (HR, 0.42 [95% CI, .24-.76]), APACHE II score (HR, 0.89 [95% CI, .84-.96]), and lymphocyte count (HR, 1.81 [95% CI, 1.05-3.1]) were independent factors associated with a prolonged duration of SARS-CoV-2 shedding. Antiviral therapy and corticosteroid treatment were not independent factors.

Conclusions: SARS-CoV-2 RNA clearance time was associated with sex, disease severity, and lymphocyte function. The current antiviral protocol and low-to-moderate dosage of corticosteroid had little effect on the duration of viral excretion.
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http://dx.doi.org/10.1093/infdis/jiaa388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337834PMC
August 2020

The fiber metabolite butyrate reduces gp130 by targeting TRAF5 in colorectal cancer cells.

Cancer Cell Int 2020 3;20:212. Epub 2020 Jun 3.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 China.

Background: Dietary fiber is effective for colorectal cancer (CRC) treatment. Interleukin-6 (IL-6) and its adaptors are potential targets for CRC therapy. Butyrate, a metabolite of dietary fiber, is a new, highly safe type of targeted drug.

Methods: In this study, Cell Counting Kit-8 cell viability and wound healing assays, western blot analysis, immunofluorescence staining, and xenograft tumor mouse models were used to evaluate the anticancer effect of butyrate and its possible mechanism in vivo and in vitro.

Results: Dietary fiber and sodium butyrate (NaB) decreased CRC burden by decreasing IL-6 receptor gp130 and blocking IL-6/JAK2/STAT3 axis activation in vitro and in vivo. Furthermore, NaB reduced the gp130 protein level by regulating its degradation rate via targeting TRAF5.

Conclusions: The fiber metabolite butyrate inhibits CRC development by reducing gp130 via TRAF5.
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http://dx.doi.org/10.1186/s12935-020-01305-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271451PMC
June 2020

Administration of Bifidobacterium bifidum CGMCC 15068 modulates gut microbiota and metabolome in azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis-associated colon cancer (CAC) in mice.

Appl Microbiol Biotechnol 2020 Jul 4;104(13):5915-5928. Epub 2020 May 4.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.

The gut microbiota plays an important role in colorectal cancer (CRC), and the use of probiotics might be a promising intervention method. The aim of our study was to investigate the beneficial effect of Bifidobacterium bifidum CGMCC 15068 on an azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis-associated CRC (CAC) mouse model. CAC was induced by an intra-peritoneal injection of AOM (10 mg/kg) and three 7-day cycles of 2% DSS in drinking water with a 14-day recovery period between two consecutive DSS administrations. B. bifidum CGMCC 15068 (3 × 10 CFU/mL) was gavaged once daily during the recovery period. Then, the faecal microbial composition and metabolome were profiled using the 16S rRNA sequencing technology and gas chromatography-mass spectrometry (GC-MS), respectively. The administration of B. bifidum CGMCC 15068 attenuated tumourigenesis in the CAC mouse model. In addition, B. bifidum CGMCC 15068 pre-treatment increased the relative abundance of Akkermansia, Desulfovibrionaceae, Romboutsia, Turicibacter, Verrucomicrobiaceae, Ruminococcaceae_UCG_013, Lachnospiraceae_UCG_004, and Lactobacillus. Meanwhile, B. bifidum CGMCC 15068 altered metabolites involved in the citrate cycle (TCA cycle), glycolysis, butyrate metabolism, fatty acid biosynthesis, and galactose metabolism. Several significant correlations were identified between the differentially abundant microbes and metabolites. These findings supported the beneficial role of B. bifidum CGMCC 15068 in intestinal health by modulating dysbiosis and the gut metabolic profile. The manipulation of the gut microbial composition using probiotics might be a promising prevention strategy for CRC. Long-term and large-scale clinical trials are warranted for the potential clinical applications of this strategy in the future.
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http://dx.doi.org/10.1007/s00253-020-10621-zDOI Listing
July 2020

Pediococcus pentosaceus LI05 alleviates DSS-induced colitis by modulating immunological profiles, the gut microbiota and short-chain fatty acid levels in a mouse model.

Microb Biotechnol 2020 07 3;13(4):1228-1244. Epub 2020 May 3.

State Key Laboratory for Diagnosis and Treatment of Infectious Disease, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.

The gut microbiota is considered a key factor in pathogenesis and progression of inflammatory bowel disease (IBD). The bacterium Pediococcus pentosaceus LI05 alleviated host inflammation by maintaining the gut epithelial integrity, modulating the host immunity, gut microbiota and metabolism, but its effect on IBD remains unclear. The present study aimed to investigate the role and mechanisms of P. pentosaceus LI05. Mice were administered P. pentosaceus LI05 or phosphate-buffered saline once daily by oral gavage for 14 days, and colitis was induced by providing mice 2% DSS-containing drinking water for 7 days. P. pentosaceus LI05 ameliorated colitis in mice and reduced the body weight loss, disease activity index (DAI) scores, colon length shortening, intestinal permeability and the proinflammatory cytokine levels. Furthermore, a significantly altered gut microbiota composition with increased diversity and short-chain fatty acid (SCFA) production was observed in mice treated with P. pentosaceus LI05. Several genera, including Akkermansia and Faecalibacterium, were differentially enriched in the P. pentosaceus LI05-treated mice and were negatively correlated with colitis indices and positively correlated with gut barrier markers and SCFA levels. The P. pentosaceus LI05 treatment alleviated intestinal inflammation by maintaining the intestinal epithelial integrity and modulating the immunological profiles, gut microbiome and metabolite composition. Based on our findings, P. pentosaceus LI05 might be applied as potential preparation to ameliorate colitis.
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http://dx.doi.org/10.1111/1751-7915.13583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264873PMC
July 2020

Multi-omic profiling reveals associations between the gut mucosal microbiome, the metabolome, and host DNA methylation associated gene expression in patients with colorectal cancer.

BMC Microbiol 2020 04 23;20(Suppl 1):83. Epub 2020 Apr 23.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: The human gut microbiome plays a critical role in the carcinogenesis of colorectal cancer (CRC). However, a comprehensive analysis of the interaction between the host and microbiome is still lacking.

Results: We found correlations between the change in abundance of microbial taxa, butyrate-related colonic metabolites, and methylation-associated host gene expression in colonic tumour mucosa tissues compared with the adjacent normal mucosa tissues. The increase of genus Fusobacterium abundance was correlated with a decrease in the level of 4-hydroxybutyric acid (4-HB) and expression of immune-related peptidase inhibitor 16 (PI16), Fc Receptor Like A (FCRLA) and Lymphocyte Specific Protein 1 (LSP1). The decrease in the abundance of another potentially 4-HB-associated genus, Prevotella 2, was also found to be correlated with the down-regulated expression of metallothionein 1 M (MT1M). Additionally, the increase of glutamic acid-related family Halomonadaceae was correlated with the decreased expression of reelin (RELN). The decreased abundance of genus Paeniclostridium and genus Enterococcus were correlated with increased lactic acid level, and were also linked to the expression change of Phospholipase C Beta 1 (PLCB1) and Immunoglobulin Superfamily Member 9 (IGSF9) respectively. Interestingly, 4-HB, glutamic acid and lactic acid are all butyrate precursors, which may modify gene expression by epigenetic regulation such as DNA methylation.

Conclusions: Our study identified associations between previously reported CRC-related microbial taxa, butyrate-related metabolites and DNA methylation-associated gene expression in tumour and normal colonic mucosa tissues from CRC patients, which uncovered a possible mechanism of the role of microbiome in the carcinogenesis of CRC. In addition, these findings offer insight into potential new biomarkers, therapeutic and/or prevention strategies for CRC.
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http://dx.doi.org/10.1186/s12866-020-01762-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178946PMC
April 2020

Multi-omic profiling reveals associations between the gut mucosal microbiome, the metabolome, and host DNA methylation associated gene expression in patients with colorectal cancer.

BMC Microbiol 2020 04 23;20(Suppl 1):83. Epub 2020 Apr 23.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: The human gut microbiome plays a critical role in the carcinogenesis of colorectal cancer (CRC). However, a comprehensive analysis of the interaction between the host and microbiome is still lacking.

Results: We found correlations between the change in abundance of microbial taxa, butyrate-related colonic metabolites, and methylation-associated host gene expression in colonic tumour mucosa tissues compared with the adjacent normal mucosa tissues. The increase of genus Fusobacterium abundance was correlated with a decrease in the level of 4-hydroxybutyric acid (4-HB) and expression of immune-related peptidase inhibitor 16 (PI16), Fc Receptor Like A (FCRLA) and Lymphocyte Specific Protein 1 (LSP1). The decrease in the abundance of another potentially 4-HB-associated genus, Prevotella 2, was also found to be correlated with the down-regulated expression of metallothionein 1 M (MT1M). Additionally, the increase of glutamic acid-related family Halomonadaceae was correlated with the decreased expression of reelin (RELN). The decreased abundance of genus Paeniclostridium and genus Enterococcus were correlated with increased lactic acid level, and were also linked to the expression change of Phospholipase C Beta 1 (PLCB1) and Immunoglobulin Superfamily Member 9 (IGSF9) respectively. Interestingly, 4-HB, glutamic acid and lactic acid are all butyrate precursors, which may modify gene expression by epigenetic regulation such as DNA methylation.

Conclusions: Our study identified associations between previously reported CRC-related microbial taxa, butyrate-related metabolites and DNA methylation-associated gene expression in tumour and normal colonic mucosa tissues from CRC patients, which uncovered a possible mechanism of the role of microbiome in the carcinogenesis of CRC. In addition, these findings offer insight into potential new biomarkers, therapeutic and/or prevention strategies for CRC.
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http://dx.doi.org/10.1186/s12866-020-01762-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178946PMC
April 2020

Bifidobacterium longum R0175 Protects Rats against d-Galactosamine-Induced Acute Liver Failure.

mSphere 2020 Jan 29;5(1). Epub 2020 Jan 29.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

Acute liver failure is a severe liver disorder that poses considerable global challenges. Previous studies on R0175 have mainly focused on its psychotropic functions. The current research focused on the protective efficacy of R0175 against acute liver failure caused by d-galactosamine (d-GalN) in rats and further tested the hypothesis that R0175 exerted liver-protective effects by affecting the intestinal microbiota and fecal metabolites and by inhibiting inflammation. We found that oral gavage of R0175 markedly reduced the severity of liver injury in d-GalN-treated rats, as evidenced by decreased serum levels of aspartate aminotransferase (AST) and total bile acids (TBAs) ( < 0.05). Moreover, the plasma concentrations of proinflammatory cytokines (interleukin 1β [IL-1β] and tumor necrosis factor-α [TNF-α]) and chemokines (granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage chemoattractant protein 1 [MCP-1], chemokine [C-X-C motif] ligand 1 [CXCL1], chemokine [C-C motif] ligand 5 [CCL5], and macrophage inflammatory protein-1α [MIP-1α]) were also markedly reduced ( < 0.05). Pretreatment with R0175 partially reversed the gut microbiota dysbiosis in rats with liver injury by increasing the relative abundances of potentially beneficial bacteria, such as spp., and decreasing the relative abundances of potentially harmful bacteria, such as , spp., and spp. Furthermore, R0175 administration partially improved the metabolic function of the intestinal microbes, as indicated by the decreased level of lithocholic acid found in the feces. Our research investigated the protective and preventive roles of R0175 in a rat model of acute liver failure. The results illustrated that this probiotic strain exhibited protective effects in rats with acute liver failure. Thus, R0175 showed clinical application prospects that required further exploration.
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http://dx.doi.org/10.1128/mSphere.00791-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992372PMC
January 2020