Publications by authors named "Xiaoying Lin"

59 Publications

Gut microbiota mediated the therapeutic efficacies and the side effects of prednisone in the treatment of MRL/lpr mice.

Arthritis Res Ther 2021 Sep 14;23(1):240. Epub 2021 Sep 14.

Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.

Background: Growing evidences indicate that the alterations in gut microbiota are associated with the efficacy of glucocorticoids (GCs) in the treatment of systemic lupus erythematosus (SLE). However, there is no evidence to prove whether gut microbiota directly mediates the effects of GCs.

Methods: Using the MRL/lpr mice, this study firstly addressed the effects of three doses of prednisone on gut microbiota. Then, this study used fecal microbiota transplantation (FMT) to transfer the gut microbiota of prednisone-treated MRL/lpr mice into the blank MRL/lpr mice to reveal whether the gut microbiota regulated by prednisone had similar therapeutic efficiency and side effects as prednisone.

Results: The effects of prednisone on gut microbiota were dose-dependent in the treatment of MRL/lpr mice. After transplantation into MRL/lpr mice, prednisone-regulated gut microbiota could alleviate lupus, which might be due to decreasing Ruminococcus and Alistipes and retaining the abundance of Lactobacillus. However, prednisone-regulated gut microbiota did not exhibit side effects as prednisone. The reason might be that the pathogens upregulated by prednisone could not survive in the MRL/lpr mice as exogenous microbiota, such as Parasutterella, Parabacteroides, and Escherichia-Shigella.

Conclusions: These data demonstrated that the transplantation of gut microbiota may be an effective method to obtain the therapeutic effects of GCs and avoid the side effects of GCs.
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http://dx.doi.org/10.1186/s13075-021-02620-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439074PMC
September 2021

Integrin CD11b Negatively Regulates B Cell Receptor Signaling to Shape Humoral Response during Immunization and Autoimmunity.

J Immunol 2021 Sep 1. Epub 2021 Sep 1.

Division of Immunotherapy, The Hiram C. Polk, Jr. Department of Surgery, Immuno-Oncology Program, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY;

Our previous work has revealed the ability of CD11b to regulate BCR signaling and control autoimmune disease in mice. However, how CD11b regulates the immune response under normal conditions remains unknown. Through the use of a CD11b knockout model on a nonautoimmune background, we demonstrated that CD11b-deficient mice have an elevated Ag-specific humoral response on immunization. Deletion of CD11b resulted in elevated low-affinity and high-affinity IgG Ab and increases in Ag-specific germinal center B cells and plasma cells (PCs). Examination of BCR signaling in CD11b-deficient mice revealed defects in association of negative regulators pLyn and CD22 with the BCR, but increases in colocalizations between positive regulator pSyk and BCR after stimulation. Using a CD11b-reporter mouse model, we identified multiple novel CD11b-expressing B cell subsets that are dynamically altered during immunization. Subsequent experiments using a cell-specific CD11b deletion model revealed this effect to be B cell intrinsic and not altered by myeloid cell CD11b expression. Importantly, CD11b expression on PCs also impacts on BCR repertoire selection and diversity in autoimmunity. These studies describe a novel role for CD11b in regulation of the healthy humoral response and autoimmunity, and reveal previously unknown populations of CD11b-expressing B cell subsets, suggesting a complex function for CD11b in B cells during development and activation.
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http://dx.doi.org/10.4049/jimmunol.2100070DOI Listing
September 2021

MRI study of changes in knee bone marrow edema-like signal in asymptomatic amateur marathon runners before and after half-marathon running.

Clin Imaging 2021 May 18;80:150-157. Epub 2021 May 18.

Department of Radiology, The Affiliated Hospital of Hangzhou Normal University, No. 126, Wenzhou Road, Gongshu District, Hangzhou 310000, Zhejiang, China.

Objective: To evaluate the incidence of knee bone marrow edema-like signal and its changes before and after running a half marathon running in asymptomatic amateur marathon runners to explore the impact of the half marathon on knee bone marrow edema-like signal.

Methods: 50 asymptomatic amateur marathon runners (30 males, 20 females) were recruited. T1-weighted imaging (T1WI), fat-suppressed protein density weighted imaging (fs-PDWI) and three-dimensional double-echo steady-state (3D-DESS) sequence on the right knee were performed before and within 3 h after a half-marathon running. 20 healthy volunteers were recruited as control. According to the whole-organ magnetic resonance imaging score (WORMS) system, the involvement of bone marrow edema-like signal in 15 regions of knee was graded from 0 to 3. The results were classified and Mann Whitney U test was used for comparison between groups.

Results: The total incidence of bone marrow edema-like signal in amateur marathon group was 62%. Among them, the incidence of grade 1-3 was 48% (24/50), 12% (6/50), 2% (1/50), respectively, which was statistically significant compared with the controls (P = 0.007). There was no significant difference between gender before running (P = 0.172) and after running (P = 0.162). There was no significant difference before and after running (P > 0.05). However, 3 subjects showed new lesions, 8 subjects showed progression and 4 subjects showed decreased signal.

Conclusion: The occurrence of knee bone marrow edema-like signal in amateur marathon runners is more common. The lesions of bone marrow edema-like signal will show aggravation or improvement in a certain extent after the half marathon.
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http://dx.doi.org/10.1016/j.clinimag.2021.05.005DOI Listing
May 2021

Huoxin pill attenuates myocardial infarction-induced apoptosis and fibrosis via suppression of p53 and TGF-β1/Smad2/3 pathways.

Biomed Pharmacother 2020 Oct 18;130:110618. Epub 2020 Aug 18.

Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. Electronic address:

Huoxin Pill (HXP), a Traditional Chinese Medicine, is used widely to treat patients with coronary heart disease and angina pectoris in China. However, the underlying protective mechanism of HXP on cardiac apoptosis and fibrosis has never been evaluated. Therefore, the aim of this study was to investigate the role of HXP in a myocardial infarction (MI) mouse model. The mice were randomly divided into 3 groups and subjected to surgical ligation of the left anterior descending (LAD) coronary artery or sham surgery (n = 6 for each group) and treated with HXP (50 mg/kg/day) or saline by gavage for 2 weeks. At 2 weeks post MI, we found that HXP significantly enhanced myocardial function and attenuated the increase of heart weight index (HWI) and pathological changes in MI mice. RNA-sequencing and KEGG pathway analyses identified 660 differentially expressed genes and multiple enriched signaling pathways including p53 and TGF-β. In support of these findings, HXP attenuated cardiac apoptosis and decreased p53 and Bax protein expression, while increasing Bcl-2 protein expression in cardiac tissues of MI mice. Furthermore, HXP treatment inhibited cardiac fibrosis and significantly down-regulated TGF-β1 protein expression and Smad2/3 phosphorylation in cardiac tissues. In summary, HXP can improve cardiac function in mice after MI by attenuating cardiac apoptosis and fibrosis partly via supression of the p53/Bax/Bcl-2 and TGF-β1/Smad2/3 pathways.
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http://dx.doi.org/10.1016/j.biopha.2020.110618DOI Listing
October 2020

HMGB1 Translocation is Associated with Tumor-Associated Myeloid Cells and Involved in the Progression of Fibroblastic Sarcoma.

Pathol Oncol Res 2021 31;27:608582. Epub 2021 Mar 31.

Department of Pathology, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.

The morphological variability and genetic complexity of fibroblastic sarcoma makes its diagnosis and treatment a challenge. High-mobility group box 1 protein (HMGB1), which functions as a DNA chaperone and a prototypical damage-associated molecular pattern, plays a paradoxical role in cancer. However, the expression pattern and role of HMGB1 in fibroblastic sarcomas is ill defined. By immunostaining of 95 tissue microarray cores of fibroblastic sarcomas, HMGB1 was found to be expressed in most tumor tissues. Nuclear HMGB1 translocation to cytoplasm was observed both in tumor cells and vascular endothelial cells. A visible number of tumor-associated myeloid cells including CD68 and CD163 macrophages and CD33 myeloid cells were also detected in most tumor tissues. HMGB1 translocation was not only associated with CD68, CD163, and CD33 density, but also with disease progression. These results imply that HMGB1, an important regulator of the tumor microenvironment, is associated with tumor-associated myeloid cells and involved in the progression of fibroblastic sarcomas; HMGB1 may serve as a promising prognostic biomarker and a potential therapeutic target for fibroblastic sarcoma.
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http://dx.doi.org/10.3389/pore.2021.608582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262203PMC
March 2021

Correlation between Thyroid Homeostasis and Obesity in Subclinical Hypothyroidism: Community-Based Cross-Sectional Research.

Int J Endocrinol 2021 29;2021:6663553. Epub 2021 May 29.

Department of Endocrinology and Metabolism, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, China.

Objective: It remains unknown whether obesity has an effect on the pituitary-thyroid feedback control axis in subclinical hypothyroidism (SCH). We aimed to investigate the association of thyroid homeostasis with obesity in a SCH population.

Methods: Our study consisted of a community-based and cross-sectional study from the Epidemiological Survey of Thyroid Diseases in Fujian Province, China. A total of 193 subjects with SCH (90 males and 103 females) without a history of treatment of thyroid disease, such as surgery, radiation, and thyroid hormone or antithyroid medication, were included in the present study. Indices of obesity, including body mass index (BMI), waist circumference (WC), and waist-height ratio (WHtR) were measured.

Results: Our results showed that the secretory capacity of the thyroid gland (SPINA-GT) and Jostel's thyrotropin index (TSHI) were negatively correlated with BMI, WC, and WHtR, whereas the reciprocal of the thyrotroph thyroid hormone resistance index (TTSI-1) was positively correlated with BMI (all < 0.05). After adjustment for age, sex, smoking, iodine status, and glucolipid metabolism, the associations between TSHI, TTSI (reciprocal transformation), and BMI still persisted (all < 0.05).

Conclusions: These results suggest that low levels of thyroid homeostasis indexes may be associated with overall obesity in SCH, rather than central adiposity.
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http://dx.doi.org/10.1155/2021/6663553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179776PMC
May 2021

Prognostic and immunological roles of Fc fragment of IgG binding protein in colorectal cancer.

Oncol Lett 2021 Jul 13;22(1):526. Epub 2021 May 13.

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.

Valuable diagnostic and prognostic biomarkers are urgently needed for colorectal cancer (CRC), which is one of the leading causes of mortality worldwide. Previous studies have reported altered expression of a mucin-like protein Fc fragment of IgG binding protein (FCGBP) in various types of cancer, but its potential diagnostic, prognostic and immunological roles in CRC remain to be determined. Therefore, the aim of current study was to investigate the potential roles of FCGBP in CRC. The present study investigated FCGBP mutations and changes in its expression levels using a combination of microarray and public dataset analyses, as well as immunohistochemistry. The results demonstrated a 10.5% mutation frequency in the coding sequence in CRC tissues, and identified decreased FCGBP mRNA or protein expression levels in colorectal adenoma and CRC (compared with those in normal colorectal tissues from healthy control subjects), including pathologically advanced CRC (stage III+IV vs. I+II). Survival analysis using the GEPIA and Kaplan-Meier Plotter databases revealed that low FCGBP expression levels were associated with short overall, disease-free, relapse-free and event-free survival times in patients with CRC. Notably, analysis using the online Tumor IMmune Estimation Resource database revealed a positive correlation between expression levels and the extent of infiltrating immune cells, such as B cells and dendritic cells. Consistently, the expression levels of most markers (51/57) for various types of immune cells were significantly correlated with expression levels in CRC tissues. These findings suggested that FCGBP may serve as a diagnostic and prognostic biomarker, and that FCGBP may be associated with immune infiltration in CRC.
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http://dx.doi.org/10.3892/ol.2021.12787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138899PMC
July 2021

Lifestyle is associated with thyroid function in subclinical hypothyroidism: a cross-sectional study.

BMC Endocr Disord 2021 May 28;21(1):112. Epub 2021 May 28.

Department of Endocrinology and Metabolism, Fujian Medical University Union Hospital, 29 Xinquan Road, Fujian, 350001, Fuzhou, China.

Background: Few studies have focused on the association between lifestyle and subclinical hypothyroidism (SCH). The purpose of this study was to investigate the association between lifestyle and thyroid function in SCH.

Methods: This study was a part of a community-based and cross-sectional study, the Epidemiological Survey of Thyroid Diseases in Fujian Province, China. A total of 159 participants with SCH (81 males and 78 females) and 159 euthyroid (87 males and 72 females) participants without any missing data were included in the analysis. General information and lifestyle information including sleep, exercise, diet and smoking habits of the participants was collected by questionnaire and Pittsburgh sleep quality index scale (PSQI) was collected. Thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroid globulin antibody (TgAb) and urine iodine concentration (UIC) were tested. Thyroid homeostasis parameter thyroid' s secretory capacity (SPINA-GT), Jostel's TSH index (TSHI), thyrotroph T4 sensitivity index (TTSI) were calculated. Logistic regression and multiple linear regression were performed to assess associations.

Results: Compared with euthyroid subjects, patients with SCH were more likely to have poor overall sleep quality (15.1 vs.25.8 %, P = 0.018) and l less likely to stay up late on weekdays (54.7 vs. 23.9 % P < 0.001). In SCH group, exercise was the influencing factor of TSH (β= -0.224, P = 0.004), thyroid secretory capacity (β = 0.244, P = 0.006) and thyrotropin resistance (β = 0.206, P = 0.009). Iodine excess was the influencing factor of thyroid secretory capacity (β = 0.209, P = 0.001) and pituitary thyroid stimulating function (β = 0.167, P = 0.034). Smoking was the influencing factor of pituitary thyroid stimulating function (β = 0.161, P = 0.040). Staying up late on weekends was the influencing factor of thyroid secretory capacity (β = 0.151, P = 0.047). After adjusting for possible confounders, logistic regression showed that those with poor overall sleep quality assessed by PSQI and iodine excess had an increased risk of SCH (OR 2.159, 95 %CI 1.186-3.928, P = 0.012 and OR 2.119, 95 %CI 1.008-4.456, P = 0.048, respectively).

Conclusions: Lifestyle including sleep, smoking, diet and exercise was closely related to thyroid function especially thyroid homeostasis in SCH.
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http://dx.doi.org/10.1186/s12902-021-00772-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161919PMC
May 2021

The high expression of miR-564 in patients with systemic lupus erythematosus promotes differentiation and maturation of DC cells by negatively regulating TP53 expression in vitro.

Lupus 2021 Aug 27;30(9):1469-1480. Epub 2021 May 27.

Department of Dermatology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.

Background: miRNA is involved in the occurrence and progression of systemic lupus erythematosus (SLE), but the regulatory effect of miRNA on dendritic cells in SLE patients is still unclear.

Material And Methods: Bioinformatics methods were used to analyze the differentially expressed miRNA and its target genes in SLE patients. In vitro experiments were conducted to explore the effects and mechanisms of differentially expressed miRNAs in SLE patients on the differentiation and maturation of monocyte-derived dendritic cells.

Results: Bioinformatics analysis showed that miR-564 was up-regulated in SLE patients, and TP53 was the core target gene of miR-564. The expression level of miR-564 showed a rising trend during the differentiation and maturation of monocytes into Mo-DC cells. The differentiation, maturation and proliferation of Mo-DC cells were significantly inhibited by transfection with miR-564 antagomir. The expression of TP53 is negatively regulated by miR-564. In rescue experiments, the proliferation and migration of DC cells were significantly restored by co-transfection of miR-564 antagomir and TP53 si-RNA.

Conclusion: Highly expressed miR-564 promotes the maturation, proliferation of Mo-DC cells by negatively regulating the expression of TP53.
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http://dx.doi.org/10.1177/09612033211020367DOI Listing
August 2021

Induced Autophagy of Macrophages and the Regulation of Inflammatory Effects by Perovskite Nanomaterial LaNiO.

Front Immunol 2021 22;12:676773. Epub 2021 Apr 22.

CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety & CAS-HKU Joint Laboratory of Metallomics on Health and Environment, and Beijing Metallomics Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.

Perovskite nanomaterials (NMs) possess excellent physicochemical properties and have promising applications in light-emitting diodes (LEDs), lasers, photodetectors, and artificial synapse electronics. Potential exposure to these NMs happens in the manufacture and application of the perovskite-based products, however, the biological safety of these NMs is still unknown. Here, we used the LaNiO NM (LNO), a typical kind of perovskite nanostructures to study the interaction with macrophages (J774A.1) and to explore its biological effects at the cellular level. Firstly, we characterized the properties of LNO including the size, shape, and crystal structure using Transmission electronic microscope (TEM), Dynamic lighting scattering (DLS), and X-ray diffraction (XRD). Secondly, to gain a better understanding of the biological effect, we evaluated the effect of LNO on cell viability and found that LNO induced cell autophagy at a concentration of 5 μg/ml and influenced the inflammatory response based on RT-PCR result. Finally, we demonstrated the mechanism that LNO causes cell autophagy and immune response is probably due to the metal ions released from LNO in acidic lysosomes, which triggered ROS and increased lysosomal membrane permeation. This study indicates the safety aspect of perovskite NMs and may guide the rational design of perovskite NMs with more biocompatibility during their manufacture and application.
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http://dx.doi.org/10.3389/fimmu.2021.676773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100511PMC
April 2021

Mobilization of endothelial progenitor cells promotes angiogenesis after full thickness excision by AMD3100 combined with G-CSF in diabetic mice by SDF-1/CXCR4 axis.

Diab Vasc Dis Res 2021 Mar-Apr;18(2):14791641211002473

Department of Dermatology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.

Aim: The aim of the present study was to investigate the effect of the mobilization of EPCs by AMD3100 combined with G-CSF on wound healing in diabetic mice.

Methods: The full-thickness excisional wounds model of diabetic mice (db/db) was examined by hematoxylin and eosin staining, immunohistochemical staining, and western blotting to compare the wound healing and neovascularization among the combination, AMD3100 alone, G-CSF alone, and control groups.

Results: The wounds reached the complete closure in the combination, AMD3100 alone, G-CSF alone, and control groups on days 17, 20, 21, 21 after surgery, respectively. In addition, the combination group promoted the inflammatory cell recruitment and glandular formation. On day 10 from injury, the protein expression of CD31 in the combination group was significantly higher compared with the other three groups ( < 0.001). The level of SDF-1 protein remained high in the combined group until on day 10 after surgery ( < 0.001).

Conclusion: The mobilization of endogenous EPCs by AMD3100 combine with G-CSF is able to enhance the complete healing of full-thickness wounds and neovascularization in db/db mice may by SDF-1/CXCR4 axis. These findings provided a novel method and indication of duration of mobilization on diabetic wound healing and tissue regeneration.
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http://dx.doi.org/10.1177/14791641211002473DOI Listing
September 2021

Clinical Analysis of Cervical Lymph Node Metastasis Risk Factors and the Feasibility of Prophylactic Central Lymph Node Dissection in Papillary Thyroid Carcinoma.

Int J Endocrinol 2021 31;2021:6635686. Epub 2021 Jan 31.

Department of General Surgery, South Branch of Fujian Provincial Hospital, Fuzhou 350000, Fujian, China.

Objective: To identify the risk factors for cervical lymph node metastasis (CLNM) and the feasibility of prophylactic central lymph node dissection.

Methods: The characteristics of 1107 patients were extracted and analyzed. Univariate and multivariate analyses were used to identify risk factors associated with lymph node metastasis. The relationship between the central lymph node dissection (CLND) and lateral lymph node metastasis (LLNM) was analyzed using the correlation analysis.

Results: The probability of CLNM was closely related to the male gender, age <55, and the increase of tumor size. Those patients with an increase in tumor size and CLNM were extremely prone to LLNM. Also, LLNM was more likely to happen in those with the more positive central lymph nodes. Routine prophylactic central lymph node dissection (P-CLND) did not increase the risk of complications.

Conclusion: P-CLND should be considered as a reasonable surgical treatment for PTC.
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http://dx.doi.org/10.1155/2021/6635686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868159PMC
January 2021

Specific TLR4 Blocking Effect of a Novel 3,4-Dihydropyrimidinone Derivative.

Front Pharmacol 2020 1;11:624059. Epub 2021 Feb 1.

College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

Toll-like receptor 4 (TLR4) initiates both innate and adaptive immune responses, which plays an important protective role in self-defense mechanisms. Excessive or inappropriate TLR4 activation causes the development of many autoimmune diseases. Dihydropyrimidinone derivatives are medicinally important molecules with diverse pharmacological activities, including anti-inflammatory activity. The present study focused on novel synthesized 3,4-dihydropyrimidinone derivatives and evaluated their inhibitory effects on TLR4. A series of 3,4-dihydropyrimidinone derivatives were recently synthesized and evaluated for their TLR4 inhibition activities and cytotoxic on HEK-Blue hTLR4 cells with the help of QUANTI-Blue assay and MTS assay. Selected compound 3 was analyzed for its molecular docking with TLR4 by using Autodock vina 1.1.2. Its effect on the TLR4 pathway related cytokines was also evaluated in THP-1 cells and human peripheral blood mononuclear cells by using real-time PCR, ELISA and western blot. Five compounds were synthesized and characterized for effectiveness based on 3,4-dihydropyrimidinone. Compound 3 was found to be the potent hybrid among the synthesized compounds, with high TLR4 inhibition activities and low cytotoxic activities against HEK-Blue hTLR4 cells. Molecular docking analysis showed that two hydrogen bonds between compound 3 and residues Asp209(TLR4) and Asp99(MD-2) mainly contribute to the TLR4 inhibition. In addition, compound 3 suppressed LPS-induced of the mRNA expression of TLR4, IP-10, TNF-α, IL-6, IL-12A, and IL-12B, the protein expression of pIRF3 and pNFκB and the secretion of IP-10, TNF-α in THP-1 cell line. Compound 3 also inhibited LPS-induced expression of TNF-α, IL-6, and IL-1β but increased IP-10 at mRNA levels in human peripheral blood mononuclear cells. Our study reveals compound 3, a novel 3,4-dihydropyrimidinone derivative, is a potential TLR4 antagonist, which opens up new research avenues for the development of promising therapeutic agents for inflammatory and autoimmune diseases.
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http://dx.doi.org/10.3389/fphar.2020.624059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882735PMC
February 2021

Towards screening the neurotoxicity of chemicals through feces after exposure to methylmercury or inorganic mercury in rats: A combined study using gut microbiome, metabolomics and metallomics.

J Hazard Mater 2021 05 30;409:124923. Epub 2020 Dec 30.

CAS-HKU Joint Laboratory of Metallomics on Health and Environment, & CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & Beijing Metallomics Facility, & National Consortium for Excellence in Metallomics, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Mercury (Hg) is one of the chemicals that bring serious adverse effects to the environment and human beings. Methylmercury (MeHg) is a neurotoxin while inorganic Hg (IHg) is not. Early screening of the neurotoxicity of chemicals may help reduce the occurrence of neurological disorders by minimizing chemical exposure. This work proposed the combined application of gut microbiome, metabolomics and metallomics to differentiate the neurotoxicity between MeHg and IHg in rats. It was found that MeHg caused down-regulated Bacteroides, Firmicutes and Proteobacteria, and up-regulated Actinobacteria and Verrucomicrobia at phylum level, while MeHg caused up-regulated Verrucomicrobiaceae, Desulfovibrionaceae, Helicobacteraceae, Lachnospiraceae and down-regulated Rikenellaceae, Erysipelotrichaceae, Sutterellaceae, Anaeroplasmataceae and Coriobacteriaceae in feces than IHg did at family level; Besides, MeHg brought metabolites change in activation of gut-brain axis pathway than IHg did, such as Glutamate, γ-aminobutyric acid (GABA), Dopamine (DA) and Tryptophan. These differences between MeHg and IHg were further confirmed by the distribution of Hg in the intestine, as well as the level of brain-derived neurotrophic factor (BDNF) in the intestine, brain and serum. Therefore, the difference of toxicity between MeHg and IHg can be well distinguished through feces after exposure for only 24 h, which may be used for the screening of neurotoxicity of other chemicals.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124923DOI Listing
May 2021

Effect of thrombolysis in a mobile stroke unit versus in hospital for patients with ischemic stroke: A protocol for systematic review and meta-analysis of randomized controlled trials.

Medicine (Baltimore) 2021 Jan;100(1):e23676

Department of Neurology, Chongqing Armed Corps Police Hospital, Chongqing, China.

Introduction: Ischemic stroke caused by arterial occlusion is the cause of most strokes. The focus of treatment is rapid reperfusion through intravenous thrombolysis and intravascular thrombectomy. Two acute stroke management including prehospital thrombolysis and in hospital have been widely used clinically to treat ischemic stroke with satisfied efficacy. However, there is no systematic review comparing the effectiveness of these 2 therapies. The aim of this study is to compare the effect of prehospital thrombolysis versus in hospital for patients with ischemic stroke.

Methods And Analysis: The following electronic databases will be searched: Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), Wanfang Database, and Chinese Scientific Journal Database.The randomized controlled trials of prehospital thrombolysis versus in hospital for ischemic stroke will be searched in the databases from their inception to December 2020 by 2 researchers independently. Onset to therapy (OTT) duration and National Institute Health Stroke Scale (NIHSS) scores will be assessed as the primary outcomes; safety assessment including intracerebral hemorrhage (ICH) and mortality will be assessed as the secondary outcomes. The Review Manager 5.3 will be used for meta-analysis and the evidence level will be assessed by using the method for Grading of Recommendations Assessment, Development and evaluation Continuous outcomes will be presented as the weighted mean difference or standardized mean difference with 95% confidence interval (CI), whereas dichotomous data will be expressed as relative risk with 95% CI. If heterogeneity existed (P < .05), the random effect model was used. Otherwise, we will use the fixed effect model for calculation.

Ethics And Dissemination: Ethical approval is not required because no primary data are collected. This review will be published in a peer-reviewed journal.

Prospero Registration Number: CRD42020200708.
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http://dx.doi.org/10.1097/MD.0000000000023676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793433PMC
January 2021

Qingda granule attenuates angiotensin II-induced cardiac hypertrophy and apoptosis and modulates the PI3K/AKT pathway.

Biomed Pharmacother 2021 Jan 1;133:111022. Epub 2020 Dec 1.

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China. Electronic address:

Qingda granule (QDG), simplified from Qingxuan Jiangya Decoction, is a well-known traditional Chinese medicine formula that has been used for decades to treat hypertension. However, the cardioprotective effects of QDG on Ang II-induced hypertension remain unknown. This study aimed to investigate the effects of QDG on hypertension-induced cardiac hypertrophy and apoptosis, as well as explore its underlying mechanisms. Mice were infused with Ang II (500 ng/kg/min) or saline solution as control, then administered oral QDG (1.145 g/kg/day) or saline for two weeks. QDG treatment attenuated the elevation in blood pressure caused by Ang II, as well as the decreased left ventricle ejection fractions and fractional shortening. Moreover, QDG treatment significantly alleviated the Ang II-induced elevation of the ratio of heart weight to tibia length, as well as cardiac injury, hypertrophy, and apoptosis. In cultured H9C2 cells stimulated with Ang II, QDG partially reversed the increase in cell surface area and number of apoptotic cells, up-regulation of hypertrophy markers ANP and BNP, and activation of caspases-9 and -3. QDG also partially reversed Ang II-induced accumulation of reactive oxygen species (ROS), depolarization of the mitochondrial membrane, release of cytochrome C, up-regulation of Bax, and decrease in levels of p-PI3K, p-AKT, and Bcl-2. These results suggest that QDG can significantly attenuate Ang II-induced hypertension, cardiac hypertrophy and apoptosis, and it may exert these effects in part by suppressing ROS production and activating the PI3K/AKT signaling pathway.
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http://dx.doi.org/10.1016/j.biopha.2020.111022DOI Listing
January 2021

The application of topical vancomycin powder for the prevention of surgical site infections in primary total hip and knee arthroplasty: A meta-analysis.

Orthop Traumatol Surg Res 2021 06 27;107(4):102741. Epub 2020 Nov 27.

Department of Orthopedic Surgery, The 1st People's Hospital of Yunnan Province, The Key Laboratory of Digital Orthopaedics of Yunnan Provincial, 157, Jinbi Road, Kunming, Yunnan, 650032, China. Electronic address:

Background: Surgical site infections (SSIs), particularly periprosthetic joint infections (PJI), following a primary total joint arthroplasty (TJA) impose a major burden by increasing morbidity, mortality, disability rate, and health expenditure. Surgeons are increasingly using topical vancomycin powder as a preventative measure, but the effectiveness of this method has been debated in TJA. Thus, we designed a meta-analysis to compare the outcomes after primary TJA between a group treated with topical vancomycin powder and an untreated control group aiming to answer: (1) whether the application of topical vancomycin powder can reduce the infection rate after primary total joint replacement; (2) are the main types of pathogens causing SSIs after the application of topical vancomycin powder different from those of patients not using topical vancomycin?

Materials And Methods: A meta-analysis was conducted in accordance with the PRISMA guidelines. We included retrospective cohort studies and prospective randomized controlled trials of patients who underwent primary total joint arthroplasty with and without vancomycin powder application before wound closure and reported the SSI rates. The English literature in the PubMed (MEDLINE), EMBASE, Web of Science, and the Cochrane Library databases was comprehensively searched. Literature search, data extraction, and quality assessment were conducted by 2 authors. The main outcomes were SSI and PJI rates, and the secondary outcome was the bacterial spectrum. Statistical analyses were performed with the Review Manager (RevMan) Version 5.3.

Results: Six retrospective cohort studies and 3 prospective cohort studies with 4512 participants were included (2354 in vancomycin group and 2158 in the control group). In the TJA group, the vancomycin powder-treatment resulted in a significantly lower proportion of patients with SSIs (relative risk [RR]=0.40, 95% confidence interval [CI]=0.27-0.61 [p<0.001]) or PJI (RR=0.37, 95% CI=0.23-0.60 (p<0.001)). In the total hip arthroplasty group, the vancomycin powder treatment decreased the rate of SSIs and PJI by 66% (RR=0.34, 95% CI=0.15-0.78 [p=0.01]) and 74% (RR=0.26, 95% CI=0.10-0.67 (p=0.005)), respectively. In the total knee arthroplasty group, the vancomycin powder decreased the rate of SSIs and PJI by 67% (RR=0.43, 95% CI=0.26-0.70 [p<0.001]) and 66% (RR=0.44, 95% CI=0.25-0.77 [p=0.004]) respectively. Staphylococcus aureus (or methicillin-sensitiveStaphylococcus aureus) (6 in vancomycin group versus 11 in control group) was the most common pathogenic bacteria, followed by Staphylococcus epidermidis (1 in vancomycin group versus 2 in control group) and methicillin-resistant Staphylococcus aureus (2 in vancomycin group versus 4 in control group). Pseudomonas aeruginosa was the main gram-negative pathogen, with 3 cases in the control group and 1 case in the vancomycin powder-treatment group.

Discussion: The local application of vancomycin powder could significantly decrease the rate of SSIs and PJI in primary TJA without modifying the spectrum of bacteria involved. We recommend topical administration of the vancomycin powder before wound closure after a full evaluation of the patients.

Level Of Evidence: III; meta-analysis.
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http://dx.doi.org/10.1016/j.otsr.2020.09.006DOI Listing
June 2021

Combined effects of MSU crystals injection and high fat-diet feeding on the establishment of a gout model in C57BL/6 mice.

Adv Rheumatol 2020 11 4;60(1):52. Epub 2020 Nov 4.

Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.

Objective: Gout is characterized by inflammatory arthritis with hyperuricaemia and deposition of monosodium urate (MSU) crystals in the joints. Several animal models have been proposed based on MSU crystals injection or high-fat diet feeding; however, neither hyperuricaemia model nor acute gout model can effectively reflect clinical features of gout. This study aimed to assess the effectiveness of a compound gout model induced by the combination of MSU crystals injection and high-fat diet feeding.

Methods: The compound gout model was induced by high-fat diet feeding per day and the intraplantar injection of MSU crystals (1 mg) into the footpad of each mouse every 10 days. Serum uric acid, foot swelling and pain analyses were performed at days 22, 32 and 42. Gout inflammation, serum proinflammatory cytokines and gut microbiota analyses were performed only at day 42.

Results: Compared to hyperuricaemia model or acute gout model, the compound gout model showed little advantages of elevating serum uric acid, causing foot swelling and gout inflammation, while it caused more severe serum inflammation and gut microbiota dysbiosis. Severe serum inflammation in the compound gout model could be reflected by the increased levels of IL-1α, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IFN-γ, KC, MCP-1 and MIP-1β. In addition, the compound gout model induced more alterations in the gut microbiota, including increasing levels of Desulfovibrio and Parasutterella.

Conclusion: The injection of MSU and feed of high-fat diet have a combined effect on elevating serum inflammation and causing gut microbiota disorders in the process of establishing a gout model.
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http://dx.doi.org/10.1186/s42358-020-00155-3DOI Listing
November 2020

Serum interleukin-6 level is correlated with the disease activity of systemic lupus erythematosus: a meta-analysis.

Clinics (Sao Paulo) 2020 19;75:e1801. Epub 2020 Oct 19.

Department of Endocrinology and Rheumatology, Affiliated Southeast Hospital of Xiamen University/909th Hospital of People's Liberation Army, 269 Zhanghua Middle Road, Zhangzhou, 363000, Fujian Province, China.

Interleukin-6 (IL-6) plays a crucial role in systemic autoimmunity and pathologic inflammation. Numerous studies have explored serum IL-6 levels in systemic lupus erythematosus (SLE) and their correlation with disease activity. Here, we performed a meta-analysis to quantitatively assess the correlation between the serum IL-6 levels and SLE activity. The PubMed and EMBASE databases were thoroughly searched for relevant studies up to September 2019. Standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were used to describe the differences between serum IL-6 levels in SLE patients and healthy controls and between those in active SLE patients and inactive SLE patients. The correlation between the serum IL-6 levels and disease activity was evaluated using Fisher's z values. A total of 24 studies involving 1817 SLE patients and 874 healthy controls were included in this meta-analysis. Serum IL-6 levels were significantly higher in SLE patients than in the healthy controls (pooled SMD: 2.12, 95% CI: 1.21-3.03, Active SLE patients had higher serum IL-6 levels than inactive SLE patients (pooled SMD: 2.12, 95% CI: 1.21-3.03). Furthermore, the pooled Fisher's z values (pooled Fisher's z=0.36, 95% CI: 0.26-0.46, p<0.01) showed that there was a positive correlation between the serum IL-6 levels and SLE activity. This study suggested that serum IL-6 levels were higher in patients with SLE than in healthy controls, and they were positively correlated with disease activity when Systemic Lupus Erythematosus Disease Activity Index>4 was defined as active SLE. More homogeneous studies with large sample sizes are warranted to confirm our findings due to several limitations in our meta-analysis.
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http://dx.doi.org/10.6061/clinics/2020/e1801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536892PMC
April 2021

Polymeric Ligand-Mediated Regioselective Bonding of Plasmonic Nanoplates and Nanospheres.

J Am Chem Soc 2020 Oct 2;142(41):17282-17286. Epub 2020 Oct 2.

Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States.

Nanoparticle (NP) clusters are attractive for many applications, but controllable and regioselective assembly of clusters remains challenging. This communication reports a strategy to precisely assemble Ag nanoplates (NP-s) and Au nanospheres (NP-s) grafted with copolymer ligands into defined clusters with controlled coordination number () and orientation of the NPs. The directional bonding of shaped NPs relies on the stoichiometric reaction of complementary reactive groups on copolymer ligands. The value of NP clusters can be tuned from 1 to 4 by varying the number ratio of reactive groups on single NP-s to NP-s. The regioselective bonding of nanospheres to the edge or face of a central nanoplate is governed by the steric hindrance of copolymeric ligands on the nanoplate. The clusters exhibit distinctive plasmonic properties that are dependent on the bonding modes of NPs. This study paves a route to fabricating nanostructures with high precision and complexity for applications in plasmonics, catalysis, and sensing.
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http://dx.doi.org/10.1021/jacs.0c08135DOI Listing
October 2020

Multi-model ensemble simulated non-point source pollution based on Bayesian model averaging method and model uncertainty analysis.

Environ Sci Pollut Res Int 2020 Dec 8;27(35):44482-44493. Epub 2020 Aug 8.

College of Water Conservancy Engineering, Zhengzhou University, Zhengzhou, 450001, Henan, People's Republic of China.

Watershed models are cost-effective and powerful tools for evaluating and controlling non-point source pollution (NPSP), while the reliability of watershed models in a management context depends largely on inherent uncertainties in model predictions. The objective of this study is to present the use of multi-model ensemble applied to streamflow, total nitrogen (TN), and total phosphorus (TP) simulation and quantify the uncertainty resulting from model structure. In this study, three watershed models, which have different structures in simulating NPSP, were selected to conduct watershed monthly streamflow, TN load, and TP load ensemble simulation and 90% credible intervals based on Bayesian model averaging (BMA) method. The result using the observed data of the Yixunhe watershed revealed that the coefficient of determination and Nash-Sutcliffe coefficient of the BMA model simulate streamflow, TN load, and TP load were better than that of the single model. The higher the efficiency of a single model is, the greater the weight during the BMA ensemble simulation is. The 90% credible interval of BMA has a high coverage of measured values in this study. This indicates that the BMA method can not only provide simulation with better precision through ensemble simulation but also provide quantitative evaluation of the model structure through interval, which could offer rich information of the NPSP simulation and management.
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http://dx.doi.org/10.1007/s11356-020-10336-8DOI Listing
December 2020

Transcription Factor EBF1 Over-Expression Suppresses Tumor Growth and via Modulation of the PNO1/p53 Pathway in Colorectal Cancer.

Front Oncol 2020 26;10:1035. Epub 2020 Jun 26.

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China.

Early B cell factor 1 (EBF1) has been identified as an upstream transcription factor of the potential oncogene PNO1 and is involved in the growth of colorectal cancer (CRC) cells. However, its expression, biological function, and underlying mechanism of action in most solid tumors remain largely unknown. We postulated that EBF1 has a role in the pathophysiology of CRC. Analysis of EBF1 mRNA expression in CRC tumor samples from several public databases and directly from banked tissues revealed that EBF1 mRNA expression is lower in CRC tissue compared to non-cancerous colorectal tissue. Survival analysis of multiple datasets revealed that low EBF1 expression was correlated with shorter overall survival, relapse-free survival, and event-free survival in CRC patients. Transduction of lentivirus encoding full length EBF1 followed by and assays demonstrated that EBF1 over-expression in CRC cell lines suppresses cell growth by inhibiting cell viability, cell survival, and induces cell cycle arrest and apoptosis. Mechanistic investigation indicated that EBF1 over-expression down-regulates PNO1 mRNA and protein expression, as well as transcriptional activity while up-regulating the expression of p53 and p21 proteins. These findings suggest that EBF1 is a novel potential tumor suppressor in CRC with prognostic value for the identification of patients at high-risk of relapse.
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http://dx.doi.org/10.3389/fonc.2020.01035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333669PMC
June 2020

Simiao Decoction Alleviates Gouty Arthritis by Modulating Proinflammatory Cytokines and the Gut Ecosystem.

Front Pharmacol 2020 24;11:955. Epub 2020 Jun 24.

College of Basic Medical Science, Institute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.

Simiao decoction, a classical traditional Chinese medicine (TCM) formula, has been widely used for thousands of years due to its safety and efficiency in treating gouty arthritis. Utilizing serum proinflammatory cytokines and gut ecosystems, this study elucidated the mechanisms of alleviating gouty arthritis by Simiao decoction. Simiao decoction (4.0, 8.0, and 16.0 g/kg) was orally administered to gouty arthritis mice and febuxostat was given as a positive control. The spleen, kidney, and liver indexes indicated that Simiao decoction was safe for the treatment of gouty arthritis in C57BL/6 mice. Besides, our study demonstrated that Simiao decoction was effective for reducing the level of serum uric acid and decreasing MPO, XOD, and ADA activity, as well as alleviating gouty-related symptoms, such as foot swelling and pain. Moreover, Simiao decoction could also reduce some specific serum proinflammatory cytokines including IL-1β, IL-9, IFN-γ, MIP-1α and MIP-1β. We then surveyed the effects of Simiao decoction on the gut ecosystems in a systematic manner by combining network pharmacology, ELISA, western blot, and illumina sequencing. In the murine of model of gouty arthritis, Simiao decoction could suppress NLRP3 inflammasomes expression, reduce gut apoptosis through modulating TNF-α, Caspase 8, and AIFM1 protein expressions, affect lipid metabolism by regulating APOB, LPL, PPARα protein expressions and restore gut microbiota reducing potential pathogens. Overall, these findings suggested that Simiao decoction was an effective therapeutic drug for gouty arthritis and the gut ecosystem might act as a potential anti-inflammatory target of Simiao decoction.
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http://dx.doi.org/10.3389/fphar.2020.00955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327538PMC
June 2020

Qingda granules attenuate hypertensive cardiac remodeling and inflammation in spontaneously hypertensive rats.

Biomed Pharmacother 2020 Sep 16;129:110367. Epub 2020 Jun 16.

Academy of Integrative Medicine, Fuzhou, Fujian, China; Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China; Chen Keji Academic Thought Inheritance Studio, Fuzhou, Fujian, China. Electronic address:

Qingda granules (QDG) are derived from QingXuanJiangYa Decoction (QXJYD) a traditional Chinese medication that has been used to treat hypertension for more than 60 years. QXJYD has been shown to be effective in rat models of hypertension. However, the effects of QDG on hypertension remain largely unknown. In the current study, baicalin was identified as one of the main components of QDG using Ultra Performance Liquid Chromatography (UPLC) analysis. We investigated the effects of QDG on blood pressure, cardiac remodeling, and cardiac inflammation. QDG (0.8 g/kg/day) treatment attenuated the elevated blood pressure in spontaneously hypertensive rats (SHRs). Moreover, QDG treatment reduced the degree of myocardial fiber disarray, degeneration and necrosis of myocardial cells, expression of ANP and BNP, as well as collagen content of SHRs. Moreover, we further assessed the effect of QDG treatment on cardiac inflammation and found that QDG treatment reduced CD68 protein expression, decreased levels of IL-6 and TNF-α in both serum and cardiac tissues, as well as suppressed activation of NF-κB pathway in cardiac tissues of SHRs. Differential expressed metabolites (DEMs) analysis identified 41 increased and 51 decreased metabolites in the cardiac tissues of SHRs after QDG treatment. In summary, QDG treatment of SHRs attenuated the elevated blood pressure and ameliorated cardiac remodeling and inflammation, in part, through suppression of NF-κB pathway and DEMs, which provide a basis for other therapeutic uses of this TCM.
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http://dx.doi.org/10.1016/j.biopha.2020.110367DOI Listing
September 2020

A steroidal saponin isolated from Allium chinense simultaneously induces apoptosis and autophagy by modulating the PI3K/Akt/mTOR signaling pathway in human gastric adenocarcinoma.

Steroids 2020 09 30;161:108672. Epub 2020 May 30.

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou 510006, China. Electronic address:

Allium chinense, as a side dish on Asian table, is often used in folk medicine for its health benefits. (25R)-5α-spirostan-3β-yl-3-O-acetyl-O-β-d-glucopyranosyl-(1 → 2)-O-[β-d-glucopyranosyl-(1 → 3)]-O-β-d-glucopyranosyl-(1 → 4)-β-d-galactopyranoside (A-24) is a bioactive steroidal saponin isolated from Allium chinense. Previously, we have shown that A-24 has cytotoxic effects on cancer cells, but not on normal cells. To further explore the underlying mechanisms, in this study, we investigated the anticancer activity of A-24 in human gastric cancer cell lines in terms of cell proliferation, colony formation, cell cycle, induction of apoptosis/autophagy, and PI3K/Akt/mTOR pathway. A-24 showed dose-dependent cytotoxicity in SGC-7901 and AGS cell lines, it induced intrinsic mitochondrial pathway of apoptosis as well as autophagy, G2/M phase arrest and modulation of cyclinB1, p-cdc2, p-wee1 and p-Histone H3 expression. Furthermore, A-24 downregulated the phosphorylation of Akt at Ser473 and mTOR at Ser2448 in PI3K/Akt/mTOR pathway, and its downstream substrates p-p70S6K and p-4EBP1 in a dose-dependent manner. In addition, the pre-treatment of tumor cells with 3-methyladenine (3-MA) and LY294002 increased A-24-induced apoptosis. Collectively, these findings highlight the significance of downregulation of PI3K/Akt/mTOR pathway in A-24-induced apoptosis and autophagy, and the potential application of A-24 as a novel candidate in the treatment of human gastric adenocarcinoma.
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http://dx.doi.org/10.1016/j.steroids.2020.108672DOI Listing
September 2020

Meta-analysis on the efficacy and safety of immunoadsorption for systemic lupus erythematosus among Chinese population.

Clin Rheumatol 2020 Dec 28;39(12):3581-3592. Epub 2020 May 28.

Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110000, Liaoning, China.

To systematically evaluate the efficacy and safety of immunoadsorption (IAS) versus non-IAS for systemic lupus erythematosus (SLE) among Chinese population. A meta-analysis was performed by all the literatures germane to estimate the SLE patients treated with IAS and non-IAS from published randomized controlled trials (RCTs) from 1990 to February 2020. Mean differences (MDs), relative ratios (RRs), and 95% confidence intervals (CIs) were calculated, and the meta-analysis was conducted with Stata 12.0 software. A total of 18 RCTs involving 457 patients were included. The results of meta-analysis demonstrated that the IgG, Scr, Bun, ANA, 24-h urine protein, leptin, and TNF-α of IAS combined with a drug therapy group were lower than that of non-IAS, and the levels of C3 and C4 were higher than that of non-IAS after treatment in terms of laboratory parameters. In terms of adverse reactions, the incidence of fever or chills, low blood pressure, or bleeding risk was higher in the treatment group. However, there was no difference in the incidence of puncture point bleeding, thrombocytopenia, mild rash, death due to severe infection, tightness, palpitation, or chest tightness between the two groups. However, most of the adverse effects could be considered as tolerable after timely treatment. Our results indicate that IAS may be superior to non-IAS in treating SLE patients. However, due to the lower quality of included studies, high quality of multicenter, large sample size, randomized, and double-blind controlled trials are needed to validate the results.
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http://dx.doi.org/10.1007/s10067-020-05156-7DOI Listing
December 2020

Spatial distribution of pollution characteristics and human health risk assessment of exposure to heavy elements in road dust from different functional areas of Zhengzhou, China.

Environ Sci Pollut Res Int 2020 Jul 6;27(21):26650-26667. Epub 2020 May 6.

College of Water Conservancy Engineering, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.

Road dust from different sources directly contacts the human body and has potential effects on public health. In this study, a total number of 87 road dust samples were collected at 29 sampling sites from five different functional areas (commercial area (CA), residential area (RA), educational area (EA), industrial area (IA), and park area (PA)) in Zhengzhou to study the contamination status, distribution, source identification, ecological risk assessment, and spatial distribution of human health risks due to eight heavy elements. The geo-accumulation index (I) and pollution index (PI) revealed that there was very high contamination with Cd and Hg caused by atmospheric deposition, which should be paid special attention. Additionally, the source identification indicated that Cr, Ni, Cu, Zn, Cd, and Pb originate from anthropogenic activities related to traffic, and Hg can originate from medical equipment and agricultural chemicals, while the extremely low level of pollution with As could be explained by geographic sources. Moreover, the calculated ecological risk index values were increased in the order of CA > RA > EA > IA > PA in different functional areas. According to the human health risks of the whole city, children exposed to Pb have the highest health risk, especially for CA and IA, as calculated by the noncarcinogenic hazard index (HI). For adults and children, health risks caused by Cu, Zn, and Pb were higher in the CA, RA, and PA of the downtown area, whereas Cr and Ni had the highest noncarcinogenic exposure risk in northwestern Zhengzhou due to point source pollution. Calculations of the carcinogenic risk (CR) values for Cr, Ni, As, and Cd indicate that the value of Cr is highest (1.17 × 10), especially inside the industrial area (8.55 × 10), which is close to the lower limit of the threshold values (10 to 10). These results can provide a theoretical basis and data support for air treatment, pollution control, and the implementation of public prevention in different functional areas of Zhengzhou.
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http://dx.doi.org/10.1007/s11356-020-08942-7DOI Listing
July 2020

The AMPK-MFN2 axis regulates MAM dynamics and autophagy induced by energy stresses.

Autophagy 2021 05 19;17(5):1142-1156. Epub 2020 Apr 19.

Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, School of Basic Medical Sciences, Guangzhou Medical University, 511436, Guangzhou, China.

Energy deprivation activates the cellular energy sensor AMP-activated protein kinase (AMPK), which in turn induces macroautophagy/autophagy. The mitochondrial-associated ER membrane (MAM) plays a key role in mitochondrial division and autophagy, and the mitochondrial fusion protein MFN2 (mitofusin 2) tethers the MAM, but the mechanism by which AMPK and MFN2 regulate autophagy in response to energy stress remains unclear. Here, we found that energy stress not only triggers mitochondrial fission and autophagy, but more importantly increases the number of MAMs, a process that requires AMPK. Interestingly, under energy stress, considerable amounts of AMPK translocate from cytosol to the MAM and the mitochondrion as mitochondrial fission occurs. Unexpectedly, AMPK interacts directly with MFN2. The autophagic ability of mouse embryonic fibroblasts (MEFs) lacking MFN2 () is significantly attenuated in response to energy stress as compared to wild-type MEFs (WT MEFs), while re-expression of MFN2 in cells rescues the autophagy defects of these cells. The abundance of MAMs is also greatly reduced in MFN2-deficient cells. Functional experiments show that the oxygen consumption rate and the glycolytic function of cells lacking MFN2 but not MFN1 are obviously attenuated, and MFN2 is important for cell survival under energy stress. In conclusion, our study establishes the molecular link between the energy sensor AMPK and the MAM tether MFN2, and reveals the important role of AMPK and MFN2 in energy stress-induced autophagy and MAM dynamics. ACTB, actin beta; AMPK, AMP-activated protein kinase; BECN1, beclin 1; CANX, calnexin; ER, endoplasmic reticulum; HRP, horseradish peroxidase; EM, electron microscopy; FL, full-length; KD, kinase dead, KO, knockout; MAb, monoclonal antibody; MAMs, mitochondria-associated membranes; MAP1LC3/LC3B, microtubule associated protein 1 light chain 3; MFN2, mitofusin 2; OPA1, OPA1 mitochondrial dynamin like GTPase; PAb, polyclonal antibody; PtdIns3K, class III phosphatidylinositol 3-kinase; PtdIns3P, phosphatidylinositol 3-phosphate; SD, standard deviation; TEM, transmission electron microscopy; TOMM20, translocase of outer mitochondrial membrane 20; ULK1, unc-51 like autophagy activating kinase 1; MEF, mouse embryonic fibroblast; WT, wildtype.
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http://dx.doi.org/10.1080/15548627.2020.1749490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143230PMC
May 2021

Acute oral methylmercury exposure perturbs the gut microbiome and alters gut-brain axis related metabolites in rats.

Ecotoxicol Environ Saf 2020 Mar 7;190:110130. Epub 2020 Jan 7.

CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences, Beijing, 100049, China; CAS-HKU Joint Laboratory of Metallomics on Health and Environment, Chinese Academy of Sciences, Beijing, 100049, China; State Environmental Protection Engineering Centre for Mercury Pollution Prevention and Control, Chinese Academy of Sciences, Beijing, 100049, China; Beijing Metallomics Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Environmental pollutants like methylmercury (MeHg) can bring devastating neurotoxicity to animals and human beings. Gut microbiota has been found to demethylate MeHg and promote the excretion of Hg through feces. However, the impacts of MeHg on gut microbiota and metabolites related to gut-brain interactions were less studied in mammals. The object of this study was to investigate the impacts of acute MeHg exposure on gut microbiome and metabolites together with its impact on gut integrity and related biological responses in rats. Rats were exposed to MeHg through oral administration and were sacrificed after 24 h 16 S rRNA gene sequencing was used to study the perturbance to gut microbiome and liquid chromatography mass spectrometry (LC-MS) was used for metabolomics profiling. It was found that gut was one of the target tissues of MeHg. MeHg induce the changes of intestinal microbial community structure and induce the regulating neuron activity change of intestinal neurotransmitters and metabolites on intestinal neurotransmitters and metabolites regulating the neuron activity. This was supported by the increased BDNF level. These findings may suggest a potential new mechanism regarding the neurotoxicity of MeHg. The protocols used in this study may also be applied to understand the neurotoxicity of other environmental neurotoxins like Pb, Mn, polychlorinated biphenyls, and pesticides, etc and to screen the neurotoxicity of emerging environmental contaminants.
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http://dx.doi.org/10.1016/j.ecoenv.2019.110130DOI Listing
March 2020

Anthocyanin-loaded double Pickering emulsion stabilized by octenylsuccinate quinoa starch: Preparation, stability and in vitro gastrointestinal digestion.

Int J Biol Macromol 2020 Jun 22;152:1233-1241. Epub 2019 Nov 22.

School of Food Science and Engineering, Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou 510640, China; Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health (111 Center), Guangzhou 510640, China. Electronic address:

In this study, anthocyanin-loaded water-in-oil-in-water (W/O/W) double Pickering emulsions stabilized by octenylsuccinate quinoa starch (OSQS) were optimized, and their storage stability and in vitro gastrointestinal digestion were evaluated. Novel starch-based double emulsions as anthocyanin cargos were achieved at 2% (w/v of oil) of polyglycerol polyricinoleate concentration, the W/O volume proportion of 3:7, 6% (w/v of total volume) of OSQS concentration, and the volume proportion of (W/O): W = 6:4 and 5:5. CLSM results evidenced the formation of double Pickering emulsions, and the significant decreases in the encapsulation stability of anthocyanins were closely related to the increases in the droplet size induced by osmotic pressure. Less than 15% of anthocyanins in the double Pickering emulsions was released after incubated for 60 min under simulated stomach conditions; controlled-release of anthocyanins was observed during the 120 min of simulated intestinal digestion, consistent with starch hydrolysis data. These findings will be useful for designing starch-based double Pickering emulsion with intestinal-targeted delivery as a novel carrier of sensitive hydrophilic bioactive compounds.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.10.220DOI Listing
June 2020
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