Publications by authors named "Xiaoya Li"

72 Publications

Peroxiredomin-4 ameliorates lipotoxicity-induced oxidative stress and apoptosis in diabetic cardiomyopathy.

Biomed Pharmacother 2021 Jun 12;141:111780. Epub 2021 Jun 12.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. Electronic address:

Diabetic cardiomyopathy (DCM), one severe complication in the diabetes, leads to high mortality in the diabetic patients. However, the understanding of molecular mechanisms underlying DCM is far from completion. Herein, we investigated the disease-related differences in the proteomes of DCM based on db/db mice and verified the protective roles of peroxiredoxin-4 (Prdx4) in H9c2 cardiomyocytes treated by palmitic acid (PA). Fasting blood glucose (FBG) and cardiac function was detected in the 6-month-old control and diabetic mice. The hearts were then collected and analyzed by a coupled label-free and mass spectrometry approach. In vivo investigation indicated that body weight and FBG of db/db mice markedly increased, and diabetic heart exhibited obvious cardiac hypertrophy and lipid droplet accumulation, and cardiac dysfunction as is indicated by the increases of left ventricle posterior wall thickness in systole (LVPWd) and diastole (LVPWs), and reduction of fractional shortening (FS). We used proteomic analysis and then detected a grand total of 2636 proteins. 175 differentially expressed proteins (DEPs) were markedly detected in the diabetic heart. Thereinto, Prdx4 was markedly down-regulated in the diabetic heart. In vitro experiments revealed that 250 μM PA significantly inhibited viability of H9c2 cell. PA induced much accumulation of lipid droplet in cardiomyocytes and resulted in an increase of mRNA expressions of lipogenic genes (FASN and SCD1) and cardiac hypertrophic genes. Additionally, protein level of Prdx4 evidently reduced in the PA-treated H9c2 cell. It was further found that shRNA-mediated Prdx4 knockdown exacerbated PA-induced oxidative stress and cardiomyocyte apoptosis, whereas overexpressing Prdx4 in the H9c2 cells noteworthily limited PA-induced ROS generation and cardiomyocytes apoptosis. These data collectively reveal the essential role of abnormal Prdx4 in pathological alteration of DCM, and provide potentially therapeutic target for the prevention of DCM.
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http://dx.doi.org/10.1016/j.biopha.2021.111780DOI Listing
June 2021

Isorhamnetin Promotes Estrogen Biosynthesis and Proliferation in Porcine Granulosa Cells via the PI3K/Akt Signaling Pathway.

J Agric Food Chem 2021 Jun 7;69(23):6535-6542. Epub 2021 Jun 7.

College of Animal Science and Technology, Northwest A&F University, Yangling 712100, P. R. China.

Isorhamnetin is a natural flavonoid widely distributed in fruits and vegetables. However, the roles of isorhamnetin involved in steroidogenesis, proliferation, and apoptosis in ovarian granulosa cells (GCs) are poorly understood. We found that isorhamnetin promoted the secretion of estrogen and inhibited the secretion of progesterone and testosterone by modulating steroidogenesis-associated proteins and mRNA such as , , and in ovarian GCs. Mechanistically, isorhamnetin stimulated the expression of the proliferating cell nuclear antigen and C-myc and promoted the proliferation of GCs via the PI3K/Akt signaling pathway. Furthermore, isorhamnetin increased the protein expression of CyclinB, CyclinD, CyclinE, and CyclinA, thereby raising the ratio of S-phase cells in response to GC proliferation. Changes in the expression of apoptosis-associated proteins (Bcl2, Bax, and cytochrome ) and intracellular reactive oxygen species levels showed that isorhamnetin inhibited GC apoptosis. Collectively, these findings indicate that isorhamnetin regulates steroidogenesis through the activation of PI3K/Akt, which promotes proliferation, inhibits apoptosis, and alleviates oxidative stress.
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http://dx.doi.org/10.1021/acs.jafc.1c01543DOI Listing
June 2021

Macrophage LAMTOR1 Deficiency Prevents Dietary Obesity and Insulin Resistance Through Inflammation-Induced Energy Expenditure.

Front Cell Dev Biol 2021 20;9:672032. Epub 2021 May 20.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.

Here, we studied the metabolic function of LAMTOR1 from macrophages using LAMTOR1 macrophage-specific knockout (MKO) mice. LAMTOR1 MKO mice showed resistance to high-fat diet (HFD)-induced obesity, lipid steatosis, and glucose metabolic disorders, with elevated levels of pro-inflammatory cytokines. The energy expenditure, oxygen consumption, and CO production increased significantly in HFD-fed MKO vs. wild-type (WT) mice. HE and immunohistochemistry staining showed a remarkable CD68 Kupffer cell accumulation in the liver. Additionally, flow cytometry revealed that the proportion of macrophages and monocytes increased significantly in the liver of MKO mice. Of note, these macrophages were probably derived from the bone marrow since the proportion of CD11b cells as well as the proliferative activity was also increased in the context of femoral bone marrow cells. In addition, the Kupffer cells of both WT and KO mice were double-positive for the M1 (CD86) and M2 (CD206) markers. However, the expression of both M1 and M2 macrophage-related genes was increased in the liver of HFD-fed KO mice. Murine primary hepatocytes and Kupffer cells were further isolated and incubated with oleic acid for 24 h. The glucose output of primary hepatocytes from MKO mice was not affected. However, decreased lipid tolerance was observed in LAMTOR1-deficient Kupffer cells. Overall, our results suggest that LAMTOR1 deficiency in macrophages prevents obesity and metabolic disorders via the accumulation of Kupffer cells in the liver and the consequent hyper-inflammation and increased energy expenditure. Therefore, our results provide a new perspective for macrophage-derived LAMTOR1 in the context of systemic metabolism.
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http://dx.doi.org/10.3389/fcell.2021.672032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173123PMC
May 2021

Evaluation of the photocatalytic performance of molecularly imprinted S-TiO by paper microzones.

Environ Res 2021 08 23;199:111258. Epub 2021 May 23.

School of Urban Construction, Wuhan University of Science and Technology, Wuhan, 430065, China. Electronic address:

The paper microzones method (PMZs) is a green chemical method that uses the principle of the three primary colors of red, green and blue (RGB) to detect the water quality of the droplets on white paper. However, this method is rarely used in the performance evaluation of photocatalysts. The paper details the first use of paper microzones utilized in the evaluation of photocatalyst performance. A sol-gel method was used to prepare molecularly imprinted modified TiO photocatalysts for the treatment of different wastewaters, and characterized the catalysts using XRD and several other methods. The reliability of PMZs on the evaluation of photocatalytic activity and selectivity was also analyzed. The following results were obtained: EP-TiO catalysts (EP, ethyl paraben, the imprinting molecule) with different S doping levels were synthesized using a one-step sol-gel method, and the best S doping ratio was found to be n(Ti):n(S) 3:1. S-EP-TiO was found to be 100% anatase and showed excellent photocatalytic performance, while the PMZs method accurately determined changes in RGB levels for the photocatalytic degradation process of pollutants using S-EP-TiO as the photocatalyst. A photocatalytic kinetic analysis showed the PMZs method was quite suitable for the evaluation of photocatalyst activity, but the evaluation of selectivity needs improvement. This method is a promising green chemistry way to evaluate photocatalyst performance and the rapid detection of outdoor sewage water quality.
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http://dx.doi.org/10.1016/j.envres.2021.111258DOI Listing
August 2021

Enhancing the Capacity and Stability by CoFeO Modified g-CN Composite for Lithium-Oxygen Batteries.

Nanomaterials (Basel) 2021 Apr 22;11(5). Epub 2021 Apr 22.

Department of Materials of Science and Engineering, University of Science and Technology, Hefei 230026, China.

As society progresses, the task of developing new green energy brooks no delay. Li-O batteries have high theoretical capacity, but are difficult to put into practical use due to problems such as high overvoltage, low charge-discharge efficiency, poor rate, and cycle performance. The development of high-efficiency catalysts to effectively solve the shortcomings of Li-O batteries is of great significance to finding a solution for energy problems. Herein, we design CoFeO/g-CN composites, and combine the advantages of the g-CN material with the spinel-type metal oxide material. The flaky structure of g-CN accelerates the transportation of oxygen and lithium ions and inhibits the accumulation of CoFeO particles. The CoFeO materials accelerate the decomposition of LiO and reduce electrode polarization in the charge-discharge reaction. When CoFeO/g-CN composites are used as catalysts in Li-O batteries, the battery has a better discharge specific capacity of 9550 mA h g (catalyst mass), and the cycle stability of the battery has been improved, which is stable for 85 cycles.
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http://dx.doi.org/10.3390/nano11051088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146125PMC
April 2021

Synthesis, Enzymatic Degradation, and Polymer-Miscibility Evaluation of Nonionic Antimicrobial Hyperbranched Polyesters with Indole or Isatin Functionalities.

Biomacromolecules 2021 05 26;22(5):2256-2271. Epub 2021 Apr 26.

Centre for Analysis and Synthesis, Department of Chemistry, Lund University, P.O. Box 124, SE-22100 Lund, Sweden.

Most macromolecular antimicrobials are ionic and thus lack miscibility/compatibility with nonionic substrate materials. In this context, nonionic hyperbranched polyesters (HBPs) with indole or isatin functionality were rationally designed, synthesized, and characterized. Antimicrobial disk diffusion assay indicated that these HBPs showed significant antibacterial activity against 8 human pathogenic bacteria compared to small molecules with indole or isatin groups. According to DSC measurements, up to 20% indole-based HBP is miscible with biodegradable polyesters (polyhydroxybutyrate or polycaprolactone), which can be attributed to the favorable hydrogen bonding between the N-H moiety of indole and the C═O of polyesters. HBPs with isatin or methylindole were completely immiscible with the same matrices. None of the HBPs leaked out from plastic matrix after being immersed in water for 5 days. The incorporation of indole into HBPs as well as small molecules facilitated their enzymatic degradation with PETase from , while isatin had a complex impact. Molecular docking simulations of monomeric molecules with PETase revealed different orientations of the molecules at the active site due to the presence of indole or isatin groups, which could be related to the observed different enzymatic degradation behavior. Finally, biocompatibility analysis with a mammalian cell line showed the negligible cytotoxic effect of the fabricated HBPs.
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http://dx.doi.org/10.1021/acs.biomac.1c00343DOI Listing
May 2021

An overview of traditional Chinese medicine therapy for Helicobacter pylori-related gastritis.

Helicobacter 2021 Jun 25;26(3):e12799. Epub 2021 Mar 25.

College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China.

Background: Helicobacter pylori-associated gastritis (HPAG) is a common digestive system disease that its therapeutic goal is to eradicate Helicobacter pylori. However, due to the widespread use of antibiotics, problems for example, antibiotic resistance, reinfection, and gastrointestinal side effects have emerged. The solution of above problems provides a broad space for traditional Chinese medicine (TCM) to exert its remarkable advantages on the treatment of HPAG.

Methods: Extensive database retrieval using platforms not limited to but including Web of Science, SpringerLink, ScienceDirect, Google Scholar, China National Knowledge Infrastructure, Wanfang, and VIP database was performed using keywords such as "Helicobacter pylori-associated gastritis" or "HPAG" or "Helicobacter pylori" or "H. pylori" or "gastritis" and "traditional Chinese medicine" or "TCM" or "herbs" or "Chinese herbal medicine". In addition, related books, PhD, and master's dissertations were also researched to provide a comprehensive review.

Results: This review mainly introduces the clinical efficacy of TCM formulas for HPAG, as well as active ingredient and pharmacological mechanisms of herbs. What's more, this review puts forward potential prospects for future research.

Conclusion: These research works have shown the therapeutic benefits of TCM in the treatment of HPAG. The development of TCM with more specific functions and practical data will not only become a significant trend in the world market but also have an irreplaceable role in the future treatment of HPAG. More continued researches should be undertaken in the future.
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http://dx.doi.org/10.1111/hel.12799DOI Listing
June 2021

Transcriptional regulation of telomeric repeat-containing RNA by acridine derivatives.

RNA Biol 2021 Mar 22:1-17. Epub 2021 Mar 22.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, Guangzhou and P.R. China.

Telomere is a specialized DNA-protein complex that plays an important role in maintaining chromosomal integrity. Shelterin is a protein complex formed by six different proteins, with telomeric repeat factors 1 (TRF1) and 2 (TRF2) binding to double-strand telomeric DNA. Telomeric DNA consists of complementary G-rich and C-rich repeats, which could form G-quadruplex and intercalated motif (i-motif), respectively, during cell cycle. Its G-rich transcription product, telomeric repeat-containing RNA (TERRA), is essential for telomere stability and heterochromatin formation. After extensive screening, we found that acridine derivative and acridine dimer could selectively interact with TRF1 and telomeric i-motif, respectively. Compound blocked the binding of TRF1 with telomeric duplex DNA, resulting in up-regulation of TERRA. Accumulated TERRA could bind with TRF1 at its allosteric site and further destabilize its binding with telomeric DNA. In contrast, could destabilize telomeric i-motif, resulting in down-regulation of TERRA. Both compounds exhibited anti-tumour activity for A549 cells, but induced different DNA damage pathways. Compound significantly suppressed tumour growth in A549 xenograft mouse model. The function of telomeric i-motif structure was first studied with a selective binding ligand, which could play an important role in regulating TERRA transcription. Our results showed that appropriate level of TERRA transcript could be important for stability of telomere, and acridine derivatives could be further developed as anti-cancer agents targeting telomere. This research increased understanding for biological roles of telomeric i-motif, TRF1 and TERRA, as potential anti-cancer drug targets.
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http://dx.doi.org/10.1080/15476286.2021.1899652DOI Listing
March 2021

Subgroup analysis of the relationship between polycyclic aromatic hydrocarbons and rheumatoid arthritis: Data from the National Health and Nutrition Examination Survey, 2003-2014.

Sci Total Environ 2021 Jun 14;775:145841. Epub 2021 Feb 14.

Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China; Department of Emergency, China Japan Friendship Hospital, Beijing 100029, China. Electronic address:

The present study examined potential effect modifiers between polycyclic aromatic hydrocarbon (PAH) exposure and the development of rheumatoid arthritis (RA) and elucidated the relationship between PAHs and RA in subgroups using data from the National Health and Nutrition Examination Survey (NHANES) (2003-2014). The relatedness between eight PAH metabolites and RA in the whole population and different subgroups was tested using multivariable logistic regression analyses. This study included 6297 participants, including 400 RA patients and 5897 non-RA control participants, with full data. Compared to the lowest quartiles, risk of RA was increased in population with the highest quartiles of 1-hydroxynaphthalene (1-NAP), 2-NAP, 2-hydroxyfluorene (2-FLU), and 3-FLU in a bias factor corrected model. The associations between urinary PAH metabolites and RA were prominent in female, young and middle-aged, obese, smoking and alcohol-consuming populations in the subgroup analysis. Our results demonstrated that PAH exposure was related to RA, and the relationship between urinary PAH metabolites and RA differed between subgroups and depended on specific PAH metabolites.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145841DOI Listing
June 2021

Development and characterization of in vitro self-assembled recombinant human follicle stimulating hormone originated from goat mammary epithelial cells.

Mol Cell Endocrinol 2021 04 11;526:111211. Epub 2021 Feb 11.

College of Animal Science and Technology, Northwest Agriculture and Forestry University, Yangling, 712100, China. Electronic address:

Follicle stimulating hormone (FSH), composed of FSHα and FSHβ subunits, is essential for female follicle development and male spermatogenesis. The recombinant human FSH (rhFSH) products on the market are mainly generated from mammalian cells and are expensive. Large animal mammary gland bioreactors are urgently needed to produce large amounts of rhFSH. However, there are currently no effective methods to prepare rhFSH by large animals mainly due to the fact that excessive accumulation of FSH might cause many adverse effects in animals. We herein report the development and characterization of functional self-assembled rhFSH produced in goat mammary epithelial cells (GMECs). FSHα and FSHβ stably expressed in Chinese hamster ovary (CHO) cell lines were secreted into culture medium and well glycosylated. Importantly, FSHα and FSHβ expressed apart were able to assemble into functional FSH. We next inserted human FSHα or FSHβ gene separately into goat β-Lactoglobulin locus in GMECs by CRISPR/Cas9. Inactive FSHα and FSHβ subunits expressed from GMECs assembled into rhFSH as analyzed by His-tag pull down assay. Functional assessment of rhFSH by cAMP induction assay, mouse ovulation induction and rat ovarian weight gain experiments showed that the bioactivity of self-assembled rhFSH expressed by GMECs was comparable to that of Gonal-F both in vitro and in vivo. Our study demonstrated that FSHα and FSHβ can be separately expressed and assembled into functional rhFSH, and provided the basis for future preparing FSH by goat mammary gland bioreactor with less health problems on the producing animals.
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http://dx.doi.org/10.1016/j.mce.2021.111211DOI Listing
April 2021

17β-estradiol improves the developmental ability, inhibits reactive oxygen species levels and apoptosis of porcine oocytes by regulating autophagy events.

J Steroid Biochem Mol Biol 2021 May 10;209:105826. Epub 2021 Feb 10.

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. Electronic address:

Objectives: Estrogen plays a critical role in the development and apoptosis of oocytes. Autophagy is an evolutionarily conserved and exquisitely regulated self-eating cellular process with important biological functions including the regulation of reproduction. This study aimed to determine the effect of autophagy regulated by the biologically active form of estrogen (17β-estradiol) in porcine oocyte maturation in vitro.

Materials And Methods: We measured the effects of oocyte developmental competencies and autophagic activity in the porcine oocyte regulated by 17β-estradiol using autophagic inhibitor (Autophinib). In addition, we studied the role of autophagy in reactive oxygen species (ROS) levels, mitochondrial distribution, Ca production, mitochondrial membrane potential (ΔΨm), and early apoptosis by caspase-3, -8 activity in the mature oocytes.

Results: The results showed that the oocyte meiotic progression and early embryonic development were gradually decreased with Autophinib treatment, which was improved by 17β-estradiol. Immunofluorescence experiments revealed that 17β-estradiol primarily could promote the autophagy in the mature oocytes, and block the reduced-autophagic events by Autophinib. Moreover, 17β-estradiol improved the Autophinib induced high ROS levels, abnormal mitochondrial distribution and low Ca production in mature oocytes. Analyses of early apoptosis and ΔΨm showed that autophagy inhibition was accompanied by increased cellular apoptosis, and 17β-estradiol reduced apoptosis rates of mature oocytes. Importantly, autophagy was downregulated by treatment with Autophinib, an activation of caspase-8 and cleaved caspase-3 increased. Those effects were abolished by 17β-estradiol, which could upregulate autophagy.

Conclusions: Our study have showed important implications that 17β-estradiol could promote efficacy of the development of porcine oocytes, enhance the autophagy, reduce ROS levels and apoptosis activity in vitro maturation.
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http://dx.doi.org/10.1016/j.jsbmb.2021.105826DOI Listing
May 2021

Compound-Specific Chlorine Isotope Analysis of Organochlorine Pesticides by Gas Chromatography-Negative Chemical Ionization Mass Spectrometry.

J Anal Methods Chem 2021 28;2021:8874679. Epub 2021 Jan 28.

Key Laboratory of Groundwater Sciences and Engineering, Ministry of Natural Resources, Institute of Hydrogeology and Environmental Geology, CAGS, Shijiazhuang 050061, China.

Compound-specific stable chlorine isotope analysis (CSIA-Cl) is an important method for identifying sources of organochlorine contaminants and helping assess their quantification of transformation processes. However, the present CSIA-Cl is challenged by either redundant conversion pretreatment or complicated mathematical correction. To overcome the mentioned problems, a novel method has been developed for the CSIA-Cl of eight organochlorine pesticides using gas chromatography-negative chemical ionization mass spectrometry (GC-NCI-qMS) in this study. The instrument parameters, acquisition mode, and required injection amounts were optimized in terms of the precision of GC-NCI-qMS. An ionization energy of 90 eV and emission current of 90 A were selected, and the precisions for eight organochlorine pesticides were in the range of 0.37‰-2.15‰ in single ion monitoring (SIM) mode when the injected amount was 0.50 mg L (. 0.5 ng on column). Furthermore, when standards from Supelco and O2si were calibrated using standards from AccuStandard regarded as external isotope standard, chlorine isotope composition of -hexachlorocyclohexane (-HCH) and 2, 2-dichloro-1, 1-bis (4-chlorophenyl) ethylene (, -DDE) in Supelco and O2si was confidently differentiated. The provenance identification method was validated by three organochlorine contaminated groundwater samples and showed a prospect in identifying the source of organochlorine pesticides.
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http://dx.doi.org/10.1155/2021/8874679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861914PMC
January 2021

Syntheses and evaluation of acridone-naphthalimide derivatives for regulating oncogene PDGFR-β expression.

Bioorg Med Chem 2021 Mar 2;34:116042. Epub 2021 Feb 2.

School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou 510006, PR China. Electronic address:

Upregulation of platelet-derived growth factor receptor β (PDGFR-β) has been found to be associated with development of various types of cancers, which has become an attractive target for anti-tumor treatment. Previously, we have synthesized and studied an acridone derivative B19, which can selectively bind to and stabilize oncogene c-myc promoter i-motif, resulting in down-regulation of c-myc transcription and translation, however its effect on tumor cells apoptosis requires improvement. In the present study, we synthesized a variety of B19 derivatives containing a known anti-cancer fluorescent chromophore naphthalimide for the purpose of enhancing anti-cancer activity. After screening, we found that acridone-naphthalimide derivative WZZ02 could selectively stabilize PDGFR-β promoter G-quadruplex and destabilize its corresponding i-motif structure, without significant interaction to other oncogenes promoter G-quadruplex and i-motif. WZZ02 down-regulated PDGFR-β gene transcription and translation in a dose-dependent manner, possibly due to above interactions. WZZ02 could significantly inhibit cancer cell proliferation, and induce cell apoptosis and cycle arrest. WZZ02 exhibited tumor growth inhibition activity in MCF-7 xenograft tumor model, which could be due to its binding interactions with PDGFR-β promoter G-quadruplex and i-motif. Our results suggested that WZZ02 as a dual G-quadruplex/i-motif binder could be effective on both oncogene replication and transcription, which could become a promising lead compound for further development with improved potency and selectivity. The wide properties for the derivatives of 1,8-naphthalimide could facilitate further in-depth mechanistic studies of WZZ02 through various fluorescent physical and chemical methods, which could help to further understand the function of PDGFR-β gene promoter G-quadruplex and i-motif.
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http://dx.doi.org/10.1016/j.bmc.2021.116042DOI Listing
March 2021

Effect of Gegenqinlian decoction on intestinal mucosal flora in mice with diarrhea induced by high temperature and humidity treatment.

3 Biotech 2021 Feb 19;11(2):83. Epub 2021 Jan 19.

Hunan University of Chinese Medicine, Xueshi Road 300, Yuelu District, Changsha, 410208 Hunan Province China.

The objective of this study is to investigate the regulation effects of the active ingredients in Gegenqinlian Decoction (GD) on the intestinal mucosal flora of mice with diarrhea induced by high temperature and humidity based on systems pharmacology approach. Fifteen mice were randomly assigned to three equal groups of five mice, namely control (ctcm) group, model (ctmm) group and treatment (cttm) group. Mice in the cttm group were given 20 mL/kg of GD and sterile water was used as a placebo control twice a day for four consecutive days. We used the third-generation molecular high-throughput sequencing technology to measure the intestinal mucosal flora changes in mice. Combined with network pharmacology to predict the medicinal substances and action targets of GD against diarrhea. Results showed that Operational Taxonomic Unit (OTU) number and Alpha diversity in the intestinal mucosal flora of cttm group recovered and higher than that of the ctcm group. There were differences in the community structure between the ctmm and cttm groups in the Principal Coordinates Analysis (PCoA). The relative abundance results indicated dominant bacteria species (such as , , ) in the intestinal mucosa of the three groups. Moreover, we screened out 146 active ingredients in GD corresponding to 252 component targets, and 328 disease targets in diarrhea to obtain 31 drug-disease common targets. Protein-protein interaction (PPI) networks mainly involved the core proteins such as Tumor necrosis factor (TNF) and Interleukin-6 (IL-6). Enrichment analyses showed that GD played a role in the treatment of diarrhea by regulating the hypoxia inducible factor-1 (HIF-1), vascular endothelial growth factor (VEGF) and adipocytokine signaling pathways and so on. In brief, the active ingredients of GD could intervene from oxidative stress and inflammatory response through multiple targets and multiple channels to adjust the balance of intestinal mucosa flora, thereby playing a role in the treatment of diarrhea.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-020-02628-0.
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http://dx.doi.org/10.1007/s13205-020-02628-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815854PMC
February 2021

Bacterial diversity in intestinal mucosa of mice fed with and high-fat diet.

3 Biotech 2021 Jan 3;11(1):22. Epub 2021 Jan 3.

Hunan University of Chinese Medicine, Changsha, 410208 Hunan Province China.

This study aimed to explore the effect of (DO) on the diversity of intestinal mucosal flora in high-fat diet mice and provided an experimental basis for the development and research of DO and its series products. Twenty-four mice were randomly assigned to four equal groups of six mice, namely the control (bcm) group, model (bmm) group, (bdm) group, and positive control (bjm) group. Mice in the bdm group were administrated at the dose of 2.37 g·kg·days, and those in bjm group were given the Lipid-lowering decoction at the concentration of 1.19 g·kg·days, and sterile water was used as a placebo control twice a day for 40 consecutive days. We measured the dynamic weight changes and intestinal mucosal flora changes in mice. The analysis showed that DO had a regulatory effect on weight change induced by a high-fat diet in mice. DO could also regulate the changes in the diversity of the intestinal mucosa of mice, which was specifically reflected in the changes of Chao 1, ACE, Shannon and Simpson index. The sample information of the bdm group was relatively concentrated, but the distance from the bmm group was relatively scattered. The relative abundance results showed dominant bacteria phylum (such as Bacteroidetes, Actinobacteria, Verrucomicrobia) and bacterial genus (such as , ) in the intestinal mucosa of the four groups. And significant differences in the major microbiota between the bdm and bjm groups. In addition, DO changed the carbohydrate, energy, and amino acid metabolism of intestinal mucosal flora. To sum up, DO has a regulatory effect on weight change induced by high-fat diet in mice and can improve the diversity of intestinal mucosal flora, promote the abundance of , inhibit the abundance of and , and influence the intestinal flora to positively affect high-fat diet-induced negative effects in mice.
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http://dx.doi.org/10.1007/s13205-020-02558-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779387PMC
January 2021

Regional Differences in the Gut Microbiota and Gut-Associated Immunologic Factors in the Ileum and Cecum of Rats With Collagen-Induced Arthritis.

Front Pharmacol 2020 24;11:587534. Epub 2020 Nov 24.

Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China.

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation and a multifactorial etiology. We previously showed that gut microbiota dysbiosis in the rat ileum is involved in the development of collagen-induced arthritis (CIA). The gut microbiota in the distinct gastrointestinal tract (GIT) plays region-specific roles, but information on the different roles of the microbiota in distinct GIT compartments of CIA rats is limited. This study aimed to evaluate the region-specific differences in the gut microbial communities and certain gut-associated immunologic factors in the ileum and cecum of CIA rats. Ileal and cecal digesta were collected from CIA and control rats for microbiome analysis. We determined the microbial richness, diversity and taxa as well as the expression of interleukin (IL)-1β and IL-17A in the epithelium and lamina propria of the ileum and cecum mucosal layers. The CIA-induced microbiota alterations in the ileum differed from those in the cecum. The ileal microbiota were more markedly influenced in CIA, as revealed by sharp reductions in the abundances of the families Enterococcaceae, Lactobacillaceae and Streptococcaceae and the genera and Moreover, significant increases in IL-1β, and IL-17A mRNA expression were detected in only the ileal epithelium and lamina propria of the mucosal layer. Therefore, the microbial characteristics in the ileum were consistent with the immune-mediated inflammatory features of CIA, suggesting that the ileal microbiota might better represent the CIA-induced inflammatory responses than the cecal microbiota and that these responses might partially impact the progression of RA by regulating intestinal mucosal immunity.
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http://dx.doi.org/10.3389/fphar.2020.587534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797777PMC
November 2020

A Network Pharmacology Approach to Explore the Potential Mechanisms of Yifei Sanjie Formula in Treating Pulmonary Fibrosis.

Evid Based Complement Alternat Med 2020 30;2020:8887017. Epub 2020 Nov 30.

Provincial Innovation Team of Yunnan University of Chinese Medicine for Traditional Chinese Medicine to Regulate Human Microecology, Kunming, Yunnan, China.

Objective: Yifei Sanjie Formula (YFSJF) is an effective formula on pulmonary fibrosis (PF), which has been used in clinic for more than 30 years. In order to investigate the molecular mechanism of YFSJF in treating PF, network pharmacology was used to predict the cooperative ingredients and associated pathways.

Methods: Firstly, we collected potential active ingredients of YFSJF by TCMSP databases. Secondly, we obtained PF-associated targets through OMIM and Genecards database. Finally, metascape was applied for the analysis of GO terms and KEGG pathways.

Results: We screened out 76 potential active ingredients and 98 associated proteins. A total of 5715 items were obtained by GO enrichment analysis ( < 0.05), including 4632 biological processes, 444 cellular components, and 639 molecular functions. A total of 143 related KEGG pathways were enriched ( < 0.05), including IL-17 signaling pathway, T cell receptor signaling pathway, TNF signaling pathway, calcium signaling pathway, TH17 cell differentiation, HIF-1 signaling pathway, and PI3K-Akt signaling pathway.

Conclusion: YFSJF can interfere with immune and inflammatory response through multiple targets and pathways, which has a certain role in the treatment of PF. This study lays a foundation for future experimental research.
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http://dx.doi.org/10.1155/2020/8887017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722457PMC
November 2020

Characteristic of Clinical Studies on Baduanjin during 2000-2019: A Comprehensive Review.

Evid Based Complement Alternat Med 2020 16;2020:4783915. Epub 2020 Oct 16.

Department of Tuina and Rehabilitation Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, China.

To date, a growing number of clinical studies have demonstrated the safety and health benefits from Baduanjin intervention. Based on this, our objective is to systematically retrieve and summarize the clinical studies on Baduanjin, with a view to providing more evidence-based evidence in support of the application of Baduanjin for healthcare, and to identify the shortcomings of existing research and provide feasibility suggest for further clinical research. Both four English language and four Chinese language electronic databases were used to search articles related to Baduanjin during 2000-2019. SPSS 22.0 software was used to analyze the data, and the risk of bias tool in the RevMan 5.3.5 software was used to evaluate the methodological quality of randomized controlled trials. A total of 810 publications were identified, including 43 (5.3%) systematic reviews, 614 (75.8%) randomized controlled trials, 66 (8.1%) nonrandomized controlled clinical studies, 84 (10.4%) case series, and 3 (0.4%) case reports. The top 10 diseases/conditions included diabetes, chronic obstructive pulmonary disease, hypertension, low back pain, neck pain, stroke, coronary heart disease, cognitive impairment, insomnia, and osteoporosis or osteopenia. The style of State General Administration of Sport of China in 2003 was the most commonly used version of Baduanjin, and Baduanjin was practiced with an average of 35 minutes, 1 or 2 times a day, 3-5 days per week, and a 18-week average duration. It is also worth noting that there were no serious adverse events related to Baduanjin intervention. Most studies were small sample size research, and the methodological quality of randomized controlled trials is generally low. The clinical studies of Baduanjin have a substantial quantity and evidence base. However, there are significant differences among different studies in the specific intervention measures such as style, intensity, duration, learning, and practice methods, which need to be further standardized and unified. Further high-quality designed and reporting studies are recommended to further validate the clinical benefits of Baduanjin.
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http://dx.doi.org/10.1155/2020/4783915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603575PMC
October 2020

SNHG5 inhibits the progression of EMT through the ubiquitin-degradation of MTA2 in oesophageal cancer.

Carcinogenesis 2021 02;42(2):315-326

Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.

A substantial fraction of transcripts are known as long noncoding RNAs (lncRNAs), and these transcripts play pivotal roles in the development of cancer. However, little information has been published regarding the functions of lncRNAs in oesophageal squamous cell carcinoma (ESCC) and the underlying mechanisms. In our previous studies, we demonstrated that small nucleolar RNA host gene 5 (SNHG5), a known lncRNA, is dysregulated in gastric cancer (GC). In this study, we explored the expression and function of SNHG5 in development of ESCC. SNHG5 was found to be downregulated in human ESCC tissues and cell lines, and this downregulation was associated with cancer progression, clinical outcomes and survival rates of ESCC patients. Furthermore, we also found that overexpression of SNHG5 significantly inhibited the proliferation, migration and invasion of ESCC cells in vivo and in vitro. Notably, we found that metastasis-associated protein 2 (MTA2) was pulled down by SNHG5 in ESCC cells using RNA pulldown assay. We also found that SNHG5 reversed the epithelial-mesenchymal transition by interacting with MTA2. In addition, overexpression of SNHG5 downregulated the transcription of MTA2 and caused its ubiquitin-mediated degradation. Thus, overexpression of MTA2 partially abrogated the effect of SNHG5 in ESCC cell lines. Furthermore, we found that MTA2 mRNA expression was significantly elevated in ESCC specimens, and a negative correlation between SNHG5 and MTA2 expression was detected. Overall, this study demonstrated, for the first time, that SNHG5-regulated MTA2 functions as an important player in the progression of ESCC and provide a new potential therapeutic strategy for ESCC.
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http://dx.doi.org/10.1093/carcin/bgaa110DOI Listing
February 2021

[Treatment of distal tibial tumor with vascularized fibula reconstruction].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Oct;34(10):1221-1225

Department of Orthopaedics, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou Zhejiang, 310009, P.R.China.

Objective: To evaluate the effectiveness of vascularized fibula reconstruction in treatment of distal tibial malignant and invasive tumors.

Methods: Between March 2012 and January 2018, 11 patients with distal tibial malignant and invasive tumors were treated with vascularized fibula reconstruction. There were 7 males and 4 females with an average age of 20 years (range, 16-39 years). There were 8 cases of osteosarcoma, 2 cases of invasive giant cell tumor of bone, and 1 case of hemangioendothelioma. The tumors were rated as benign stage 3 in 2 cases and malignant stageⅠA in 1 case, stageⅡA in 4 cases, and stage ⅡB in 4 cases according to the Enneking staging. The disease duration was 1-6 months (mean, 2.7 months). The limb function was evaluated by Musculoskeletal Tumor Society (MSTS) score, and the distal and proximal union of the transplanted fibula and the diameter of the fibula were examined by imaging.

Results: All incisions healed by first intention. All patients were followed up 16-85 months (mean, 41 months). No tumor recurrence or metastasis occurred during the follow-up. The proximal and distal grafts in the 10 cases showed osseous healing, and the healing time was 7-12 months (mean, 10.1 months) at proximal end and 7-12 months (mean, 9.3 months) at distal end. In 1 case, the proximal end did not heal at 19 months, while the distal end healed at 13 months; proximal bone grafting was performed, and the proximal end healed. Among the 4 patients with distal screw fixation, 2 had peri-internal fixation fractures after graft healing, but no skin necrosis or infection occurred. All the 7 patients with distal steel plate fixation had no peri-internal fixation fracture, but 1 patient developed anterior tibial skin necrosis. At 12 months after operation, the diameter of fibula increased 1-5 mm (mean, 2.4 mm) by compared with that before operation. The MSTS score was 17-27 (mean, 22.8).

Conclusion: Reconstruction of ankle joint with vascularized fibula can achieve satisfactory functional results, which is one of the feasible and worthy methods for the distal tibial malignant and invasive tumors.
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http://dx.doi.org/10.7507/1002-1892.202003088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171869PMC
October 2020

Role of Endoplasmic Reticulum Stress in Atherosclerosis and Its Potential as a Therapeutic Target.

Oxid Med Cell Longev 2020 9;2020:9270107. Epub 2020 Sep 9.

Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Endoplasmic reticulum (ER) stress is closely associated with atherosclerosis and related cardiovascular diseases (CVDs). It occurs due to various pathological factors that interfere with ER homeostasis, resulting in the accumulation of unfolded or misfolded proteins in the ER lumen, thereby causing ER dysfunction. Here, we discuss the role of ER stress in different types of cells in atherosclerotic lesions. This discussion includes the activation of apoptotic and inflammatory pathways induced by prolonged ER stress, especially in advanced lesional macrophages and endothelial cells (ECs), as well as common atherosclerosis-related ER stressors in different lesional cells, which all contribute to the clinical progression of atherosclerosis. In view of the important role of ER stress and the unfolded protein response (UPR) signaling pathways in atherosclerosis and CVDs, targeting these processes to reduce ER stress may be a novel therapeutic strategy.
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http://dx.doi.org/10.1155/2020/9270107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499294PMC
May 2021

The distinct microbial community in Aurelia coerulea polyps versus medusae and its dynamics after exposure to Co-γ radiation.

Environ Res 2020 09 26;188:109843. Epub 2020 Jun 26.

Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai, 200433, China. Electronic address:

Radiation (e.g., nuclear leakage) is a common harmful factor in the ocean that potentially affects the microbial community in nearby benthic hosts such as jellyfish polyps, which is essential for the maintenance of jellyfish populations and high-quality medusae. After comparison with the microbial community of medusae, the effect of Co-γ on the microbial community in Aurelia coerulea polyps was dynamically tested using 16S rRNA gene sequencing. Our results suggested that Proteobacteria (76.19 ± 3.24%), Tenericutes (12.93 ± 3.20%) and Firmicutes (8.33 ± 1.06%) are most abundant in medusae, while Proteobacteria (29.49 ± 2.29%), Firmicutes (46.25 ± 5.59%), and Bacteroidetes (20.16 ± 2.65%) are the top three phyla in polyps. After Co-γ radiation, the proportion of Proteobacteria increased from 29.49 ± 2.29% to 59.40 ± 3.09% over 5 days, while that of Firmicutes decreased from 46.25 ± 5.59% to 13.58 ± 3.74%. At the class level, Gammaproteobacteria continually increased during the 5 days after radiation exposure, whereas Bacilli declined, followed by partial recovery, and Alphaproteobacteria and Flavobacteriia remained almost unchanged. Intriguingly, Staphylococcus from Firmicutes and three other genera, Rhodobacter, Vibrio, and Methylophaga, from Proteobacteria greatly overlapped according to their KEGG functions. It is concluded that the microbial community in A. coerulea polyps is distinct from that in the medusae and is greatly affected by Co-γ exposure, with a growth (0-3 d) period and a redistribution (3-5 d) period. The dynamic change in the microbial community is probably an important self-defense process in response to external interference that is regulated by the host's physiological characteristics and the intense interspecific competition among symbiotic microbes with similar functions and functional redundancies.
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http://dx.doi.org/10.1016/j.envres.2020.109843DOI Listing
September 2020

Corrigendum to: Extracellular vesicles-derived OncomiRs mediate communication between cancer cells and cancerassociated hepatic stellate cells in hepatocellular carcinoma microenvironment.

Carcinogenesis 2020 09;41(9):1306-1307

Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital and National Center for Liver Cancer, Second Military Medical University, Shanghai, China.

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http://dx.doi.org/10.1093/carcin/bgz145DOI Listing
September 2020

Syntheses and Evaluation of New Bisacridine Derivatives for Dual Binding of G-Quadruplex and i-Motif in Regulating Oncogene Expression.

J Med Chem 2020 09 26;63(17):9136-9153. Epub 2020 Aug 26.

School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou 510006, P. R. China.

The oncogene is an important regulator for cell growth and differentiation, and its aberrant overexpression is closely related to the occurrence and development of various cancers. Thus, the suppression of transcription and expression has been investigated for cancer treatment. In this study, various new bisacridine derivatives were synthesized and evaluated for their binding with promoter G-quadruplex and i-motif. We found that could bind to and stabilize both G-quadruplex and i-motif, resulting in the downregulation of gene transcription. could inhibit cancer cell proliferation and induce SiHa cell apoptosis and cycle arrest. exhibited tumor growth inhibition activity in a SiHa xenograft tumor model, which might be related to its binding with promoter G-quadruplex and i-motif. Our results suggested that as a dual G-quadruplex/i-motif binder could be effective in both oncogene replication and transcription and become a promising lead compound for further development with improved potency and selectivity.
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http://dx.doi.org/10.1021/acs.jmedchem.9b01917DOI Listing
September 2020

Upregulation of BCL-2 by acridone derivative through gene promoter i-motif for alleviating liver damage of NAFLD/NASH.

Nucleic Acids Res 2020 09;48(15):8255-8268

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Wai huan East Road, Guangzhou 510006, P. R. China.

Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) are global epidemic public health problems with pathogenesis incompletely understood. Hepatocyte excessive apoptosis is a significant symbol for NAFLD/NASH patients, and therefore anti-apoptosis therapy could be used for NAFLD/NASH treatment. Up-regulation of BCL-2 has been found to be closely related with anti-apoptosis. BCL-2 gene promoter region has a C-rich sequence, which can form i-motif structure and play important role in regulating gene transcription. In this study, after extensive screening and evaluation, we found that acridone derivative A22 could up-regulate BCL-2 transcription and translation in vitro and in cells through selective binding to and stabilizing BCL-2 gene promoter i-motif. Our further experiments showed that A22 could reduce hepatocyte apoptosis in NAFLD/NASH model possibly through up-regulating BCL-2 expression. A22 could reduce inflammation, endoplasmic reticulum stress and cirrhosis in high-fat diet-fed mice liver model. Our findings provide a potentially new approach of anti-apoptosis for NAFLD/NASH treatment, and A22 could be further developed as a lead compound for NAFLD/NASH therapy. Our present study first demonstrated that gene promoter i-motif could be targeted for gene up-regulation for extended treatment of other important diseases besides cancer.
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http://dx.doi.org/10.1093/nar/gkaa615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470982PMC
September 2020

Polydatin for treating atherosclerotic diseases: A functional and mechanistic overview.

Biomed Pharmacother 2020 Aug 29;128:110308. Epub 2020 May 29.

Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address:

With the advancement of science and technology, the living standards of human beings have continuously improved, but the incidence and mortality from atherosclerosis worldwide have also increased by year. Although interventional surgery and the continuous development of new drugs have significant therapeutic effects, their side effects cannot be ignored. Polydatin, an active ingredient isolated from the natural medicine Polygonum cuspidatum, has been shown to have a prominent role in the treatment of cardiovascular diseases. Polydatin treats atherosclerosis mainly from three aspects: anti-inflammatory, regulating lipid metabolism and anti-oxidative stress. This article will review the pharmacological mechanism of polydatin in anti-atherosclerosis, the biological characteristics of Polygonum cuspidatum, the toxicology and pharmacokinetics of polydatin and will provide ideas for further research.
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http://dx.doi.org/10.1016/j.biopha.2020.110308DOI Listing
August 2020

A combined analysis of transcriptomics and proteomics of a novel Antarctic Salpa sp. and its potential toxin screenings.

Int J Biol Macromol 2020 Oct 28;160:1101-1113. Epub 2020 May 28.

Faculty of Naval Medicine, Second Military Medical University (Naval Medical University), Shanghai 200433, China. Electronic address:

Background: We successfully captured a kind of gelatinous organism DA-6 from Antarctic water, extracted its total RNAs and proteins, and performed species identification through a combination of transcriptomics and proteomics in this study.

Methods: The gelatinous organism DA-6 was captured 200 m underwater in Antarctica. Total RNA was extracted to construct the transcriptome and the proteins were identified by LC-MS/MS.

Results: DA-6 was identified as an Antarctic Salpa sp. through morphological examination and MT-CO1 phylogenetic analysis. A total of 47,183 unigenes were harvested through transcriptome. We also successfully annotated 11,954 (25.34%), 10,006 (22.21%), 4469 (9.47%) and 4901 (9.71%) unigenes with NR, SwissProt, GO and KEGG databases, respectively. In the proteomic analysis, a total of 4680 peptides and 1280 proteins were harvested using the transcriptome as the reference database. A number of both 549 (31.98%) proteins reannotated against the GO and KEGG databases. Moreover, a number of 5 toxic proteins matched from the 89 toxin-related unigenes were successfully screened, including 2 metalloproteinases, 1 serine protease, 1 serine protease inhibitor and 1 aflatoxin.

Conclusion: Our study is the first to identify an Antarctic Salpa sp. according to the combination of de novo transcriptomics and proteomics, which can further be served as a public database for the identification of potential polar Salpa-derived lead compounds. In addition to morphology and CO1, the combined analysis of transcriptome and proteome can also be used as a value method for new species identify e.g. Salpa sp.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.05.144DOI Listing
October 2020

Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota the Aryl Hydrocarbon Receptor.

Front Cell Dev Biol 2020 13;8:131. Epub 2020 Mar 13.

Department of Emergency, China-Japan Friendship Hospital, Beijing, China.

Background: Rheumatoid arthritis (RA) is an autoimmune disease that may be associated with gut microbiota the aryl hydrocarbon receptor (AhR). Human umbilical mesenchymal stem cells (HUMSCs) have therapeutic potential against RA, but the underlying mechanism has not been fully elucidated. The purpose of this study was to explore the mechanism of action of HUMSCs in rats with collagen-induced arthritis (CIA).

Method: HUMSCs (1 × 10) were transplanted into each rat with CIA. The tissue localization of HUMSCs and the therapeutic effects in the ankles were assessed. The immune status and expression of immune-related genes and proteins in related lymphoid tissues were subsequently tested. Furthermore, the levels of immune-related factors in serum and the changes in gut microbiota in the ileum were detected, and the levels of indole and their derivatives in plasma and the levels of AhR in the ileum were evaluated.

Results: HUMSCs homed to the popliteal lymph node (PLN), mesenteric lymph node (MLN), ankle cartilage, and ileum mucosa in rats with CIA. The transplantation of HUMSCs reduced the pathology scores and the degree of bone damage in the ankles. The immune status of T regulatory cells (Tregs) and T helper (Th)17 cells and the gene expression levels of interleukin (IL)-10, transforming growth factor (TGF)-β, and IL-17A were altered in the PLN, which is the lymph tissue closest to the nidus, and the MLN, which is one of the gut-associated lymphoid tissues (GALTs). The proportion and function of B cells, Tregs, and Th17 cells were regulated in other GALTs, namely, Peyer's patches and the lamina propria. The gene expression of TGF-β and IL-17A and protein expression of IL-10, TGF-β, IL-17A, IL-22, and immunoglobulin A (IgA) were modulated in the ileum, and the serum levels of IL-10, TGF-β1, IL-17A, IL-1β, and tumor necrosis factor (TNF)-α were regulated in the rats with CIA. The relative abundances of the genera and were increased in the HUMSCs-treated rat with CIA; in addition, the levels of indole, indoleacetic acid, and indole-3-lactic acid were consistently upregulated, and this upregulation was accompanied by increases in AhR gene and protein expression.

Conclusion: Our study demonstrates that HUMSCs play a therapeutic role in rats with CIA by regulating the interactions between host immunity and gut microbiota the AhR.
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http://dx.doi.org/10.3389/fcell.2020.00131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082776PMC
March 2020

Synergistic Effects of Erzhi Pill Combined With Methotrexate on Osteoblasts Mediated the Wnt1/LRP5/-Catenin Signaling Pathway in Collagen-Induced Arthritis Rats.

Front Pharmacol 2020 11;11:228. Epub 2020 Mar 11.

Department of Emergency, China-Japan Friendship Hospital, Beijing, China.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by chronic synovitis, bone erosion, and bone loss. Erzhi Pill (EZP), a classic Chinese patent medicine, is often used to treat osteoporosis and shows a capacity for bone metabolism regulation. Methotrexate (MTX), an essential drug for RA treatment, has been reported to inhibit generalized bone loss in RA patients. However, the combined therapeutic effects and mechanism of EZP and MTX in RA have not been fully elucidated. The aim of this study was to investigate the synergistic effect of EZP and MTX on RA and to explore the underlying mechanism through network pharmacological prediction and experimental verification. Chemical compounds of EZP, human target proteins of EZP and MTX, and RA-related human genes were identified in the Encyclopedia of Traditional Chinese Medicine database, PubChem database, and NCBI database, respectively. The molecular network of EZP and MTX in RA was generated and analyzed with Ingenuity Pathway Analysis software according to the datasets. Then, MTX monotherapy, EZP monotherapy, and combined MTX and EZP therapy were administered to collagen-induced arthritis rats, followed by assessment of pathological score, bone damage, bone alkaline phosphatases (BALP), and tartrate-resistant acid phosphatase (TRACP), and of gene levels related to the Wnt1/LRP5/-catenin pathway according to network pharmacological analysis. Finally, serum samples from MTX-, EZP- and MTX+EZP-treated rats were used to treat the rat osteoblast (OB)-like UMR-106 cell line to evaluate gene levels related to Wnt1/LRP5/-catenin. Network pharmacological analysis showed that the Wnt/-catenin signaling pathway was the top signaling pathway shared among MTX, EZP, and RA. The results from experiments indicated that EZP combined with MTX reduced arthritis severity, alleviated ankle bone damage, increased BALP and decreased TRACP serum levels, and regulated the mRNA expression of Wnt1, LRP5, -catenin, Runx2, BALP, and BGP in the ankles. experiments showed that EZP combined with MTX could also improve the expression of genes related to the Wnt1/LRP5/-catenin pathway. This study demonstrated that EZP in combination with MTX played a synergistic role in regulating OBs in RA, which was connected to the modulatory effect of EZP and MTX on the Wnt1/LRP5/-catenin signaling pathway.
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http://dx.doi.org/10.3389/fphar.2020.00228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079734PMC
March 2020

Associations of urinary polycyclic aromatic hydrocarbons with albuminuria in U.S. adults, NHANES 2003-2014.

Ecotoxicol Environ Saf 2020 Jun 20;195:110445. Epub 2020 Mar 20.

Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China; Department of Emergency, China-Japan Friendship Hospital, Beijing, 100029, China. Electronic address:

Background: Polycyclic aromatic hydrocarbons (PAHs) exposure has been shown to be a risk factor for many diseases. However, studies on the association between PAHs exposure and kidney disease are limited. The aim of this study was to explore the association between urinary PAHs and albuminuria based on a national representative sample from the general U.S.

Population:

Method: The data utilized were extracted from the 2003-2014 National Health and Nutrition Examination Survey (NHANES). Eight urinary PAHs were detected as PAH metabolites (OH-PAHs). Multivariable logistic regression analyses were applied to examine the association between urinary OH-PAHs and urinary albumin-creatinine ratio (ACR). All models were adjusted for confounding demographic, anthropometric and lifestyle factors.

Result: A total of 8149 NHANES (2003-2014) participants with complete data were eligible. Compared with the lowest quartile, an increased prevalence of high ACR level (>3 mg/mmol) was observed in the participants with the highest quartile of 2-hydroxynaphthalene [OR (95% CI), 1.56 (1.28-1.90), P < 0.001], 3-hydroxyfluorene [OR (95% CI), 1.29 (1.06-1.58), P = 0.011] and 2-hydroxyfluorene [OR (95% CI), 1.47 (1.20-1.80), P < 0.001] levels after adjusting for confounding factors. In subgroup analysis, significantly high OH-PAHs leveland a strong relationship between OH-PAHs and ACR were observed in current smokers in the adjusted model.

Conclusion: High levels of urinary OH-PAHs were positively associated with high levels of ACR in the U.S.

Population: Our finding provided evidence that PAHs exposure might potentially be related to albuminuria and therefore might have implications for environmental governance and prevention/treatment of this condition.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110445DOI Listing
June 2020
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