Publications by authors named "Xiaoying Zhang"

494 Publications

Global analysis of DNA methylation in hepatocellular carcinoma via a whole-genome bisulfite sequencing approach.

Genomics 2021 Aug 27;113(6):3618-3634. Epub 2021 Aug 27.

Department of Oncology, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address:

Alterations in DNA methylation patterns are considered early events in hepatocellular carcinoma (HCC). However, their mechanism and significance remain to be elucidated. We studied the genome-wide DNA methylation landscape of HCC by applying whole-genome bisulfite sequencing (WGBS) techonlogy. Overall, HCC exhibits a genome-wide hypomethylation pattern. After further annotation, we obtained 590 differentially hypermethylated genes (hyper-DMGs) and 977 differentially hypomethylated genes (hypo-DMGs) from three groups. Hyper-DMGs were mainly involved in ascorbate and alternate metabolism pathways, while hypo-DMGs were mainly involved in focal adhesion. By integrating the DMGs with HCC-related differentially expressed genes (DEGs) and DMGs from the TCGA database, we constructed prognostic model based on thirteen aberrantly methylated DEGs, and verified our prognostic model in GSE14520 dataset. This study compares the patterns of global epigenomic DNA methylation during the development of HCC, focusing on the role of DNA methylation in the early occurrence and development of HCC, providing a direction for future research on its epigenetic mechanism.
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http://dx.doi.org/10.1016/j.ygeno.2021.08.024DOI Listing
August 2021

Predicting mortality from intracranial hemorrhage in allogeneic hematopoietic stem cell transplantation patients.

Blood Adv 2021 Aug 27. Epub 2021 Aug 27.

Peking University People's Hospital, Peking University Institute of Hematology; National Clinical Research Center for Hematologic Disease; Beijing Key Laboratory of Hematopoietic Stem Cell Transplan, Beijing, China.

Intracranial hemorrhage (ICH) is a rare but fatal central nervous system complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, factors that are predictive of early mortality in patients who develop ICH after undergoing allo-HSCT have not been systemically investigated. From January 2008 to June 2020, 70 allo-HSCT patients with ICH diagnosis formed the derivation cohort. Forty-one allo-HSCT patients with ICH diagnosis were collected from 12 other medical centers during the same period, and they comprised the external validation cohort. We used these 2 cohorts to develop and validate a grading scale that enables the prediction of 30-day mortality from ICH in all-HSCT patients. Four predictors, lactate dehydrogenase level, albumin level, white blood cell count and disease status, were retained in the multivariable logistic regression model, and a simplified grading scale, termed the LAWS score, was developed. The LAWS score was adequately calibrated (Hosmer-Lemeshow test, p>0.05) in both cohorts. It had good discrimination power in both the derivation cohort (C-statistic of 0.859, 95% CI 0.776-0.945) and the external validation cohort (C-statistic of 0.795, 95% CI 0.645-0.945). The LAWS score is the first scoring system capable of predicting the 30-day mortality from ICH in allo-HSCT patients. It showed good performance in identifying allo-HSCT patients at increased risk of early mortality after ICH diagnosis. We anticipate that it would help risk-stratify allo-HSCT patients with ICH and facilitate future studies on developing individualized and novel interventions for patients within different LAWS risk groups.
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http://dx.doi.org/10.1182/bloodadvances.2021004349DOI Listing
August 2021

Synergistically promoting plant health by harnessing synthetic microbial communities and prebiotics.

iScience 2021 Aug 30;24(8):102918. Epub 2021 Jul 30.

State Key Laboratory of Crop Biology, Shandong Provincial Key Laboratory for Biology of Vegetable Diseases and Insect Pests, College of Plant Protection, Shandong Agricultural University, Taian, Shandong 271018, P. R. China.

Soil-borne diseases cause serious economic losses in agriculture. Managing diseases with microbial preparations is an excellent approach to soil-borne disease prevention. However, microbial preparations often exhibit unstable effects, limiting their large-scale application. This review introduces and summarizes disease-suppressive soils, the relationship between carbon sources and the microbial community, and the application of human microbial preparation concepts to plant microbial preparations. We also propose an innovative synthetic microbial community assembly strategy with synergistic prebiotics to promote healthy plant growth and resistance to disease. In this review, a new approach is proposed to improve traditional microbial preparations; provide a better understanding of the relationships among carbon sources, beneficial microorganisms, and plants; and lay a theoretical foundation for developing new microbial preparations.
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http://dx.doi.org/10.1016/j.isci.2021.102918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365361PMC
August 2021

An R2R3-MYB Transcription Factor Responds to Chilling Stress of and Conferred Cold Tolerance of .

Front Plant Sci 2021 27;12:696919. Epub 2021 Jul 27.

College of Horticulture and Landscape Architecture, Northeast Agricultural University, Harbin, China.

A sudden cooling in the early spring or late autumn negatively impacts the plant growth and development. Although a number of studies have characterized the role of the transcription factors (TFs) of plant R2R3-myeloblastosis (R2R3-MYB) in response to biotic and abiotic stress, plant growth, and primary and specific metabolisms, much less is known about their role in under chilling stress. In the present study, , which encodes a nuclear-localized R2R3-MYB TF with a self-activation activity, was identified based on the earlier published RNA-seq data of plants exposed to short-term low-temperature stress and also on the results of prediction of the gene function referring . The gene was induced by stress due to chilling, salt, and drought and was expressed in higher levels in the roots than in the leaves. The heterologous expression of in significantly enhanced the tolerance of transgenic plants to freezing, water deficit, and high salinity, enabling higher survival and growth rates, earlier flowering and silique formation, and better seed quantity and quality compared with the wild-type (WT) plants. When exposed to a continuous low-temperature stress at 4°C, transgenic lines-overexpressing showed higher activities of superoxide dismutase and peroxidase, lower relative conductivity, and lower malondialdehyde content than the WT. Moreover, the initial fluorescence ( ) and maximum photosynthetic efficiency of photosystem II ( / ) changed more dramatically in the WT than in transgenic plants. Furthermore, the expression levels of cold-related genes involved in the cascade were higher in the overexpression lines than in the WT. These results suggest that was positively involved in the tolerance responses when was exposed to challenges against cold, freeze, salt, or drought and improved the cold tolerance of transgenic by reducing plant damage and promoting plant growth.
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http://dx.doi.org/10.3389/fpls.2021.696919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353178PMC
July 2021

Intraoperative Vitamin C Reduces the Dosage of Propofol in Patients Undergoing Total Knee Replacement.

J Pain Res 2021 19;14:2201-2208. Epub 2021 Jul 19.

Department of Pain Medicine, First Medical Center, Chinese PLA General Hospital, Beijing, People's Republic of China.

Purpose: Propofol is commonly used as an intravenous anesthetic in surgical patients. However, its usage is associated with adverse effects. Auxiliary medication can reduce the dose of intravenous anesthetics. Hence, we investigated whether vitamin C could lower propofol dosage in elderly patients undergoing total knee replacement surgery.

Patients And Methods: The trial was carried out in PLA General Hospital in Beijing, China. We enrolled patients aged ≥50 years who were undergoing unilateral total knee arthroplasty with total intravenous anesthesia combined with lumbar sciatic nerve block. The patients were randomly assigned to either the vitamin C (Vc) group (0.067 g/kg) or the control group (an equivalent dose of normal saline). Nerve block was done for all the patients before the general anesthesia. The same depth of anesthesia was maintained during the operation. We compared the propofol dosage and adverse events (eg hypotension) during anesthesia between the two groups. This study was registered with the Chinese Clinical Trial Registry, www.chictr.org.cn, number ChiCTR-TRC-16010112.

Results: There were significant differences in the total infusion dose (Vc group: 704.3 ± 188.6 mg; control group: 888.6 ± 232.7 mg; = 0.016) and the average maintenance dose of propofol (Vc group: 5.8 ± 1.0 mg/kg/h; control group: 6.9 ± 1.6 mg/kg/h; = 0.013). But there were no significant differences in the induction dose of propofol (control group: 90 mg, range 80-115 mg; Vc group: 100 mg, range 90-110 mg, = 0.379) between the Vc and control groups. Furthermore, there were no significant differences in the hemodynamics and the incidence of intraoperative hypotension.

Conclusion: Vitamin C can reduce the dosage of propofol in patients undergoing total knee replacement.
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http://dx.doi.org/10.2147/JPR.S319172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302814PMC
July 2021

IF1 inactivation attenuates experimental colitis through downregulation of neutrophil infiltration in colon mucosa.

Int Immunopharmacol 2021 Oct 20;99:107980. Epub 2021 Jul 20.

Metabolic Disease Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China; Center for Advanced Medicine, College of Medicine, Zhengzhou University, Zhengzhou 450007, China. Electronic address:

IF1 is a mitochondrial protein involved in the regulation of ATP synthase activity. The role of IF1 remains to be established in inflammatory bowel diseases (IBD). In this study, we report that IF1 gene inactivation generated protection against IBD in the dextran sodium sulfate (DSS) model. IF1 gene knockout (IF1-KO) mice developed less severe colitis than the wild type (WT) mice as judged by parameters including disease activity index (DAI), body weight loss, inflammatory cytokines, leukocyte infiltration and bacterial invasion in the colon tissue. The intestinal barrier integrity was protected in the colon tissue of IF1-KO mice through a reduction in apoptosis and inflammasomal activity. The protection was abolished in the KO mice after substitution of the immune cells with the wild type cells following bone marrow transplantation. Depletion of neutrophils with anti-Gr-1 antibody abolished the protection from colitis in IF1-KO mice. Neutrophil number was decreased in the peripheral blood of IF1-KO mice, which was associated with a reduction in LC3A/B proteins in the KO neutrophils in Rapamycin-induced autophagy response. Inhibition of autophagy with the lysosome inhibitor Chloroquine (CQ) decreased the absolute number of neutrophils in WT mice and protected the mice from colitis. Taken together, these findings suggest that IF1 may contribute to the pathogenesis of IBD through acceleration of neutrophil autophagy. The activity is attenuated in the IF1-KO mice through reduction of autophagy in neutrophils leading to resistance to IBD.
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http://dx.doi.org/10.1016/j.intimp.2021.107980DOI Listing
October 2021

Hepatoprotective Effects of Against Carbon Tetrachloride-Induced Acute Liver Injury in Rats.

Dose Response 2021 Jul-Sep;19(3):15593258211029510. Epub 2021 Jul 12.

Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China.

Purpose: To determine the hepatoprotective mechanisms of in rats with acute liver injury induced by carbon tetrachloride (CCl).

Methods: Rats were intragastrically administered twice a day for 14 consecutive days and were intraperitoneally challenged with CCl. Alanine aminotransferase and aspartate aminotransferase were measured to indicate liver injury. Malondialdehyde antioxidant enzyme activity and tumor necrosis factor-alpha and interleukin 6 secretion were measured as liver injury indicators. Histopathological tests were conducted to determine whether ameliorated liver injury.

Results: CCl-induced liver injury led to significant increases in liver injury biochemical indicators transaminase and malondialdehyde activities. pretreatments inhibited these increases. Pathological sections in pretreated samples exhibited reduced vacuole formation, neutrophil infiltration, and necrosis.

Conclusion: increases the antioxidant capacity of the liver and maintains hepatocyte function in the face of CCl-induced injury.
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http://dx.doi.org/10.1177/15593258211029510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278464PMC
July 2021

Insights into molecular structure, genome evolution and phylogenetic implication through mitochondrial genome sequence of Gleditsia sinensis.

Sci Rep 2021 Jul 21;11(1):14850. Epub 2021 Jul 21.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.

Gleditsia sinensis is an endemic species widely distributed in China with high economic and medicinal value. To explore the genomic evolution and phylogenetic relationships of G. sinensis, the complete mitochondrial (mt) genome of G. sinensis was sequenced and assembled, which was firstly reported in Gleditsia. The mt genome was circular and 594,121 bp in length, including 37 protein-coding genes (PCGs), 19 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. The overall base composition of the G. sinensis mt genome was 27.4% for A, 27.4% for T, 22.6% for G, 22.7% for C. The comparative analysis of PCGs in Fabaceae species showed that most of the ribosomal protein genes and succinate dehydrogenase genes were lost. In addition, we found that the rps4 gene was only lost in G. sinensis, whereas it was retained in other Fabaceae species. The phylogenetic analysis based on shared PCGs of 24 species (22 Fabaceae and 2 Solanaceae) showed that G. sinensis is evolutionarily closer to Senna species. In general, this research will provide valuable information for the evolution of G. sinensis and provide insight into the phylogenetic relationships within the family Fabaceae.
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http://dx.doi.org/10.1038/s41598-021-93480-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295344PMC
July 2021

A scalable and reproducible preparation for the antitumor protein TLC, a human-derived telomerase inhibitor.

Protein Expr Purif 2021 Nov 17;187:105942. Epub 2021 Jul 17.

Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University, Huzhou, 313000, China; School of Medicine, Huzhou University, Huzhou, 313000, China. Electronic address:

Telomerase, which is overexpressed in approximately 90% of liver cancer cells, is an ideal target for anti-liver cancer therapy. LPTS, a putative liver tumor suppressor, is the only human-derived protein that can bind telomerase directly and inhibit the extension of telomere activity. Our previous studies demonstrated that TAT-LPTS-LC (TLC), a recombinant protein fused by the C-terminal 133-328 fragment of LPTS and TAT peptides, could be delivered into cells to inhibit telomerase-positive hepatoma cell growth in vitro and in vivo with very low toxicity. In the present study, E. coli strains which expressed TLC in abundance were screened and cultured in a laboratory bioreactor. A reproducible protein separation process was built, and this process was suitable for industrial amplification. The yields of TLC protein were up to 184 mg in one batch with a purity of approximately 95%. The purified TLC protein had a similar inhibitory effect on telomerase activity in vitro compared with those purified by Ni-affinity chromatography. Furthermore, TLC protein could be delivered into the cell nucleus to increase the doubling time of the cell and suppress cell growth in telomerase-positive liver cancer cell lines. Cell growth inhibition was negatively correlated with telomere length, suggesting that TLC is a highly targeted telomerase-telomere anticancer agent. These results will contribute to future preclinical studies of the TLC protein.
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http://dx.doi.org/10.1016/j.pep.2021.105942DOI Listing
November 2021

Acidic Microenvironment Aggravates the Severity of Hepatic Ischemia/Reperfusion Injury by Modulating M1-Polarization Through Regulating PPAR-γ Signal.

Front Immunol 2021 21;12:697362. Epub 2021 Jun 21.

Hepatopancreatobiliary Surgery Department, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, China.

Hepatic injury induced by ischemia and reperfusion (HIRI) is a major clinical problem after liver resection or transplantation. The polarization of macrophages plays an important role in regulating the severity of hepatic ischemia/reperfusion injury. Recent evidence had indicated that the ischemia induces an acidic microenvironment by causing increased anaerobic glycolysis and accumulation of lactic acid. We hypothesize that the acidic microenvironment might cause the imbalance of intrahepatic immunity which aggravated HIRI. The hepatic ischemia/reperfusion injury model was established to investigate the effect of the acidic microenvironment to liver injury. Liposomes were used to deplete macrophages . Macrophages were cultured under low pH conditions to analyze the polarization of macrophages . Activation of the PPAR-γ signal was determined by Western blot. PPAR-γ agonist GW1929 was administrated to functionally test the role of PPAR-γ in regulating macrophage-mediated effects in the acidic microenvironment during HIRI. We demonstrate that acidic microenvironment aggravated HIRI while NaHCO reduced liver injury through neutralizing the acid, besides, liposome abolished the protective ability of NaHCO through depleting the macrophages. In vivo and vitro experiment showed that acidic microenvironment markedly promoted M1 polarization but inhibited M2 polarization of macrophage. Furthermore, the mechanistic study proved that the PPAR-γ signal was suppressed during the polarization of macrophages under pH = 6.5 culture media. The addition of PPAR-γ agonist GW1929 inhibited M1 polarization under acidic environment and reduced HIRI. Our results indicate that acidic microenvironment is a key regulator in HIRI which promoted M1 polarization of macrophages through regulating PPAR-γ. Conversely, PPAR-γ activation reduced liver injury, which provides a novel therapeutic concept to prevent HIRI.
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http://dx.doi.org/10.3389/fimmu.2021.697362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255974PMC
June 2021

Mitochondrial protein IF1 is a potential regulator of glucagon-like peptide (GLP-1) secretion function of the mouse intestine.

Acta Pharm Sin B 2021 Jun 8;11(6):1568-1577. Epub 2021 Feb 8.

Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 201306, China.

IF1 (ATPIF1) is a nuclear DNA-encoded mitochondrial protein whose activity is inhibition of the FF-ATP synthase to control ATP production. IF1 activity remains unknown in the regulation of GLP-1 activity. In this study, IF1 was examined in the diet-induced obese mice using the gene knockout (-KO) mice. The mice gained more body weight on a high fat diet without a change in food intake. Insulin tolerance was impaired, but the oral glucose tolerance was improved through an increase in GLP-1 secretion. The KO mice exhibited an improved intestine structure, mitochondrial superstructure, enhanced mitophagy, reduced apoptosis and decreased adenine nucleotide translocase 2 (ANT2) protein in the intestinal epithelial cells together with preserved gut microbiota. The data suggest that GLP-1 secretion was enhanced in the obese KO mice to preserve glucose tolerance through a signaling pathway of ANT2/mitochondria/L-cells/GLP-1/insulin. IF1 is a potential mitochondrial target for induction of GLP-1 secretion in L-cells.
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http://dx.doi.org/10.1016/j.apsb.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245909PMC
June 2021

Leveraging 16S rRNA Microbiome Sequencing Data to Identify Bacterial Signatures for Irritable Bowel Syndrome.

Front Cell Infect Microbiol 2021 11;11:645951. Epub 2021 Jun 11.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain or discomfort. Previous studies have illustrated that the gut microbiota might play a critical role in IBS, but the conclusions of these studies, based on various methods, were almost impossible to compare, and reproducible microorganism signatures were still in question. To cope with this problem, previously published 16S rRNA gene sequencing data from 439 fecal samples, including 253 IBS samples and 186 control samples, were collected and processed with a uniform bioinformatic pipeline. Although we found no significant differences in community structures between IBS and healthy controls at the amplicon sequence variants (ASV) level, machine learning (ML) approaches enabled us to discriminate IBS from healthy controls at genus level. Linear discriminant analysis effect size (LEfSe) analysis was subsequently used to seek out 97 biomarkers across all studies. Then, we quantified the standardized mean difference (SMDs) for all significant genera identified by LEfSe and ML approaches. Pooled results showed that the SMDs of nine genera had statistical significance, in which the abundance of , and in IBS were higher, while the dominant abundance genera of healthy controls were Ruminococcaceae , , , and . In summary, based on six published studies, this study identified nine new microbiome biomarkers of IBS, which might be a basis for understanding the key gut microbes associated with IBS, and could be used as potential targets for microbiome-based diagnostics and therapeutics.
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http://dx.doi.org/10.3389/fcimb.2021.645951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231010PMC
July 2021

Bawei Chenxiang Wan Ameliorates Cardiac Hypertrophy by Activating AMPK/PPAR-α Signaling Pathway Improving Energy Metabolism.

Front Pharmacol 2021 3;12:653901. Epub 2021 Jun 3.

School of Medical Science, Jinan University, Guangzhou, China.

Bawei Chenxiang Wan (BCW), a well-known traditional Chinese Tibetan medicine formula, is effective for the treatment of acute and chronic cardiovascular diseases. In the present study, we investigated the effect of BCW in cardiac hypertrophy and underlying mechanisms. The dose of 0.2, 0.4, and 0.8 g/kg BCW treated cardiac hypertrophy in SD rat model induced by isoprenaline (ISO). Our results showed that BCW (0.4 g/kg) could repress cardiac hypertrophy, indicated by macro morphology, heart weight to body weight ratio (HW/BW), left ventricle heart weight to body weight ratio (LVW/BW), hypertrophy markers, heart function, pathological structure, cross-sectional area (CSA) of myocardial cells, and the myocardial enzymes. Furthermore, we declared the mechanism of BCW anti-hypertrophy effect was associated with activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-α (PPAR-α) signals, which regulate carnitine palmitoyltransferase1β (CPT-1β) and glucose transport-4 (GLUT-4) to ameliorate glycolipid metabolism. Moreover, BCW also elevated mitochondrial DNA-encoded genes of NADH dehydrogenase subunit 1), cytochrome b (), and mitochondrially encoded cytochrome coxidase I () expression, which was associated with mitochondria function and oxidative phosphorylation. Subsequently, knocking down AMPK by siRNA significantly can reverse the anti-hypertrophy effect of BCW indicated by hypertrophy markers and cell surface of cardiomyocytes. In conclusion, BCW prevents ISO-induced cardiomyocyte hypertrophy by activating AMPK/PPAR-α to alleviate the disturbance in energy metabolism. Therefore, BCW can be used as an alternative drug for the treatment of cardiac hypertrophy.
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http://dx.doi.org/10.3389/fphar.2021.653901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209424PMC
June 2021

Therapeutic potential of targeting Tfr/Tfh cell balance by low-dose-IL-2 in active SLE: a post hoc analysis from a double-blind RCT study.

Arthritis Res Ther 2021 06 11;23(1):167. Epub 2021 Jun 11.

Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing, 100044, China.

Objective: To investigate the regulation of T follicular regulatory (Tfr) and T follicular (Tfh) cell subtypes by low-dose IL-2 in systemic lupus erythematosus (SLE) in a randomized, double-blind, placebo-controlled clinical trial.

Methods: A post hoc analysis was performed in a randomized cohort of SLE patients (n=60) receiving low-dose IL-2 therapy (n=30) or placebo (n=30), along with the standard of care treatment. The primary endpoint was the attainment of SLE responder index-4 (SRI-4) at week 12 in the trial. Twenty-three healthy controls were enrolled for T cell subset detection at the same time as the trial. The t-stochastic neighbor embedding (tSNE) analysis of CD4 T subsets based on immune cells flow cytometry markers was performed to distinguish Tfh, Tfh1, Tfh2, Tfh17, and Tfr cell subsets.

Results: Compared with HC, the frequency of Tfr (CXCR5PD-1 Treg and CXCR5PD-1 Treg) cells was significantly reduced, while the pro-inflammatory Tfh cells were increased in patients with SLE. The imbalanced Tfh cell was associated with several pathogenic factors (anti-dsDNA antibodies (r=0.309, P=0.027) and serum IL-17 (r=0.328, P=0.021)) and SLE Disease Activity Index (SLEDAI) score (r=0.273, P=0.052). Decreased CXCR5PD-1 Treg/Tfh and CXCR5PD-1 Treg/Tfh17 were both associated with increased immunoglobulin M (IgM) (r=-0.448, P=0.002 and r=-0.336, P=0.024, respectively). Efficacy of low-dose IL-2 therapy was associated with a restored Tfr/Tfh cell balance.

Conclusion: These data support the hypothesis that promotion of Tfr is associated with decreased disease activities and that low-dose IL-2 therapy can recover Tfr/Tfh immune balance.

Trial Registration Number: ClinicalTrials.gov Registries ( NCT02465580 ).
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http://dx.doi.org/10.1186/s13075-021-02535-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194162PMC
June 2021

Cytotoxic and antimicrobial activities of secondary metabolites isolated from the deep-sea-derived 12A22.

3 Biotech 2021 Jun 21;11(6):283. Epub 2021 May 21.

Institute of Applied Ecology, Chinese Academy of Sciences, South Building Rm 308, 72 Wenhua Road, Shenhe District, Shenyang, 110016 China.

A new deep-sea-derived actinomycete 12A22 was isolated from the sediment of the South China Sea which showed potential cytotoxic and antimicrobial activities. The actinomycete was identified as by investigating morphological characteristics and phylogenetic analyses based on its 16S rRNA gene sequence. Two compounds, cyclo-(-Pro--Pro--Tyr--Tyr) () and 2-hydroxyethyl-3-methyl-1,4-naphthoquinone (), were isolated and characterized from the fermentation broth of the strain 12A22. Compound exhibited significant inhibitory activities against a variety of phytopathogenic fungi ( f. sp. , , and ) and Gram-positive bacterium (). In particular, this compound showed better antifungal activity against than positive control amphotericin B. Besides, compound showed moderate cytotoxic activity against human breast cancer MDA-MB-435 cells with IC 10.59 µM, weaker than the positive control diaminedichloroplatinum with 5.91 μM. Our results suggested that this naphthoquinone could be used as a potential antimicrobial and antitumor agent.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-02846-0.
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http://dx.doi.org/10.1007/s13205-021-02846-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140039PMC
June 2021

Transdermal Delivery of Lidocaine-Loaded Elastic Nano-Liposomes with Microneedle Array Pretreatment.

Biomedicines 2021 May 23;9(6). Epub 2021 May 23.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.

This study aimed to improve the transdermal delivery of lidocaine hydrochloride (LidH) using elastic nano-liposomes (ENLs) and microneedle (MN) array pretreatment. LidH-containing ENLs were prepared using soybean phosphatidylcholine and cholesterol, with Span 80 or Tween 80, using a reverse-phase evaporation method. The ENL particle size, stability, and encapsulation efficiency (EE) were characterized and optimized based on the component ratio, pH, and type of surfactant used. In vitro transdermal diffusion study was performed on MN-pretreated mouse skin using Franz diffusion cells. The anesthetic effects of LidH in various formulations after dermal application were evaluated in vivo in rats by measuring the tail withdrawal latency after photothermic stimulation. Stable LidH-loaded Tween 80 or Span 80 ENLs were obtained with particle sizes of 115.8 and 146.6 nm and EEs of 27% and 20%, respectively. The formulations did not exert any cytotoxicity in HaCaT cells. Tween 80 and Span 80 ENL formulations showed enhanced LidH delivery on pretreated mice skin in vitro and prolonged the anesthetic effect in vivo compared to that by LidH application alone. LidH-loaded ENLs applied to MN-pretreated skin can shorten the onset time and prolong the anesthetic effect safely, which merits their further optimization and practical application.
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http://dx.doi.org/10.3390/biomedicines9060592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224805PMC
May 2021

Quantification of sorafenib, lenvatinib, and apatinib in human plasma for therapeutic drug monitoring by UPLC-MS/MS.

J Pharm Biomed Anal 2021 Aug 21;202:114161. Epub 2021 May 21.

Clinical Research Center for Phase I, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China. Electronic address:

Sorafenib, lenvatinib, and apatinib, as multi-targeted tyrosine kinase inhibitors with anti-proliferative and anti-angiogenic effects, are widely used for systemic therapy in advanced hepatocellular carcinoma patients. Nevertheless, insufficient efficacy or adverse effects often appear due to the significant inter-individual variability of plasma concentration for these drugs. In order to carry out therapeutic drug monitoring of these drugs and then ensure the effectiveness and safety of the medical treatment, the first method allowing to quantify sorafenib, lenvatinib, and apatinib simultaneously in human plasma was developed in this study. The analysis was performed by UPLC-MS/MS system and the chromatographic separation was achieved on a C18 column using a gradient elution of water-acetonitrile in 3.5 min. This method presented satisfactory results in terms of specificity, precision (coefficient of variation of intra-day and inter-day:1.4-6.6 %), accuracy (92.6-105.4 %), matrix effects (96.9-107.2 %), extraction recovery (90.5-99.4 %), as well as stability in human plasma and even whole blood under certain conditions. This sensitive, rapid and simple method was successfully applied to the analysis of sorafenib, lenvatinib and apatinib for therapeutic drug monitoring in hepatocellular carcinoma patients, and it was expected to be applied to further study about clarifying the concentration- efficacy and concentration-toxic relationship of sorafenib, lenvatinib, and apatinib in hepatocellular carcinoma patients.
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http://dx.doi.org/10.1016/j.jpba.2021.114161DOI Listing
August 2021

High doses of butyrate induce a reversible body temperature drop through transient proton leak in mitochondria of brain neurons.

Life Sci 2021 Aug 19;278:119614. Epub 2021 May 19.

Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; Central Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address:

Aims: Sodium butyrate (SB) is a major product of gut microbiota with signaling activity in the human body. It has become a dietary supplement in the treatment of intestinal disorders. However, the toxic effect of overdosed SB and treatment strategy remain unknown. The two issues are addressed in current study.

Materials And Methods: SB (0.3-2.5 g/kg) was administrated through a single peritoneal injection in mice. The core body temperature and mitochondrial function in the brown adipose tissue and brain were monitored. Pharmacodynamics, targeted metabolomics, electron microscope, oxygen consumption rate and gene knockdown were employed to dissect the mechanism for the toxic effect.

Key Findings: The temperature was reduced by SB (1.2-2.5 g/kg) in a dose-dependent manner in mice for 2-4 h. In the brain, the effect was associated with SB elevation and neurotransmitter reduction. Metabolites changes were seen in the glycolysis, TCA cycle and pentose phosphate pathways. Adenine nucleotide translocase (ANT) was activated by butyrate for proton transportation leading to a transient potential collapse through proton leak. The SB activity was attenuated by ANT inhibition from gene knockdown or pharmacological blocker. ROS was elevated by SB for the increased ANT activity in proton leak in Neuro-2a.

Significance: Excessive SB generated an immediate and reversible toxic effect for inhibition of body temperature through transient mitochondrial dysfunction in the brain. The mechanism was quick activation of ANT proteins for potential collapse in mitochondria. ROS may be a factor in the ANT activation by SB.
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http://dx.doi.org/10.1016/j.lfs.2021.119614DOI Listing
August 2021

Calcium modified basalt fiber bio-carrier for wastewater treatment: Investigation on bacterial community and nitrogen removal enhancement of bio-nest.

Bioresour Technol 2021 Sep 7;335:125259. Epub 2021 May 7.

School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China; Institute of Environmental Health and Ecological Security, Jiangsu University, Zhenjiang, Jiangsu 212013, China. Electronic address:

Modified basalt fiber (MBF) is a sustainable material studied as novel wastewater treatment bio-carrier recently. This work studied the effects of calcium modification on the bacterial affinity of modified fiber (Ca-MBF), bacterial community, and nitrogen removal performance. Results showed that Ca-MBF with hydrophilic (62.66°) and positively-charged (7.80 mV) surface accelerated bacterial attachment. Volatile suspended solids on Ca-MBF (5.46 g VSS/g fiber) were increased by 2.61 times after modification, with high bacterial activity when bio-carriers were cultured in activated sludge. Extracellular polymeric substances on Ca-MBF was 4.35 times higher and consisted of more protein. Bio-nests with unique aerobic/anaerobic structure formed on the ultrafine carriers in bioreactor. Ca-MBF bioreactor exhibited total nitrogen removal efficiency above 72.2% and COD removal efficiency above 94.2% with more stable performance than unmodified carrier in long-term treatment using synthetic domestic wastewater.16S rRNA gene sequencing revealed enhanced abundance of nitrifying and denitrifying bacteria in Ca-MBF bio-nest.
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http://dx.doi.org/10.1016/j.biortech.2021.125259DOI Listing
September 2021

ADP Induces Blood Glucose Through Direct and Indirect Mechanisms in Promotion of Hepatic Gluconeogenesis by Elevation of NADH.

Front Endocrinol (Lausanne) 2021 27;12:663530. Epub 2021 Apr 27.

Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Extracellular ADP, a derivative of ATP, interacts with the purinergic receptors in the cell membrane to regulate cellular activities. This signaling pathway remains unknown in the regulation of blood glucose . We investigated the acute activity of ADP in mice through a peritoneal injection. In the lean mice, in response to the ADP treatment, the blood glucose was elevated, and pyruvate tolerance was impaired. Hepatic gluconeogenesis was enhanced with elevated expression of glucogenic genes ( and ) in the liver. An elevation was observed in NADH, cAMP, AMP, GMP and citrate in the liver tissue in the targeted metabolomics assay. In the primary hepatocytes, ADP activated the cAMP/PKA/CREB signaling pathway, which was blocked by the antagonist (2211) of the ADP receptor P2Y13. In the circulation, gluconeogenic hormones including glucagon and corticosterone were elevated by ADP. Insulin and thyroid hormones (T3 and T4) were not altered in the blood. In the diet-induced obese (DIO) mice, NADH was elevated in the liver tissue to match the hepatic insulin resistance. Insulin resistance was intensified by ADP for further impairment in insulin tolerance. These data suggest that ADP induced the blood glucose through direct and indirect actions in liver. One of the potential pathways involves activation of the P2Y13/cAMP/PKA/CREB signaling pathway in hepatocytes and the indirect pathway may involve induction of the gluconeogenic hormones. NADH is a signal for gluconeogenesis in the liver of both DIO mice and lean mice.
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http://dx.doi.org/10.3389/fendo.2021.663530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111448PMC
April 2021

Generation and evaluation of IgY-scFv based mimetics against canine parvovirus.

Vet Res 2021 May 13;52(1):70. Epub 2021 May 13.

Chinese-German Joint Laboratory for Natural Product Research, Key Laboratory of Biological Resources and Ecological Environment of Qinba Areas, School of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong, China.

Antibody mimetics may be used for various biomedical applications, especially those for which conventional antibodies are ineffective. In this study, we developed a smaller molecular chicken IgY mimetic peptide (IgY-peptide) based on the complementarity-determining regions (CDRs) of the anti-canine parvovirus (CPV) IgY-scFv prepared previously. The mimetic peptide showed no cross-reactivity with canine distemper virus (CDV) and canine coronavirus (CCV) and showed excellent protective properties for Crandell-Rees Feline Kidney (CRFK) cells against CPV. This study is the first attempt to develop a mimetic IgY-peptide and demonstrates the ease and feasibility in generating such a novel antibody-like functional molecule for biomedical purposes.
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http://dx.doi.org/10.1186/s13567-021-00943-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116823PMC
May 2021

Heatwave distortion correction using an improved reference sample compensation method and multispectral digital image correlation.

Appl Opt 2021 May;60(13):3716-3723

Heatwave distortions, caused by unevenly distributed temperature and refractive index in the optical path, unavoidably occur in high-temperature digital image correlation (DIC) measurement. To eliminate these distortions, a multispectral DIC-aided reference sample compensation method is proposed. The proposed method first adheres a correcting transparent glass (decorated with fluorescent speckle patterns) onto the test specimen (sprayed with red speckle patterns). Then, by illuminating the specimen with ultraviolet- and red-light sources, the blue light excited from the correcting glass and the red light reflected from the specimen surface can be captured by a 3CCD camera, forming a color image. After separating the recorded color images into red and blue subimages, the original and the correcting displacement fields can be calculated from these two sets of subimages using the subset-based local 2D-DIC algorithm. By point-to-point subtracting the correcting displacement fields from the original ones, the heatwave distortions can be eliminated, and the corrected real displacement fields can be obtained. For validation, static heatwave experiments show the feasibility and accuracy of the proposed method in correcting heatwave distortions. A uniaxial tensile test of an aluminum specimen with a central hole was also performed, further confirming the practicality of the proposed method in correcting heatwave distortions and revealing heatwave-hidden deformation.
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http://dx.doi.org/10.1364/AO.420124DOI Listing
May 2021

The perioperative application of continuous cerebral autoregulation monitoring for cerebral protection in elderly patients.

Ann Palliat Med 2021 Apr;10(4):4582-4592

Department of Anesthesiology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.

Background: The majority of surgical patients aged 65 years and over are accompanied with underlying conditions, making them susceptible to perioperative cerebral complications. Here, we investigated the clinical value of continuous cerebral autoregulation (CA) monitoring in protecting against cerebral dysfunction in elderly patients undergoing surgery.

Methods: This study enrolled 40 elderly patients (aged ≥65 years) and 40 middle-aged patients (aged 45 to 64 years) selected to undergo robotic-assisted laparoscopic radical prostatectomy. Cerebral oxygenation was assessed by regional cerebral oxygen saturation (rScO2) using near-infrared spectroscopy (NIRS). CA function was estimated using the cerebral oximetry index (COX), which is the rolling correlation between rScO2 and the mean arterial pressure (MAP). With the patient in the Trendelenburg position, the rScO2, MAP, calculated COX, HR, end-tidal CO2, and sevoflurane concentrations were continuously recorded. Standardized anesthesia was administered to all patients (sevoflurane, propofol, remifentanil, and rocuronium). Postoperative delirium (POD) was screened for daily using the Confusion Assessment Method (CAM). The primary outcome was the difference in periods of CA dysfunction between the elderly and middle-aged groups. Secondary outcomes included the incidence of POD and the optimal MAP range in the 2 groups.

Results: Taking positive COX values (cutoff ≥0.3) to reflect periods of CA dysfunction, we found that the cumulative duration of CA dysfunction in the Trendelenburg position was longer in elderly patients than in middle-aged patients [ratio of cumulative time of CA dysfunction: middle-aged group, 32.8% (26.3%, 43.1%) vs. elderly group, 42.2% (33.1%, 51.2%)] (P<0.01), which showed that CA function was less efficient in elderly patients. Three patients (7.5%) in the elderly group and 1 patient (2.5%) in the middle-aged group screened positive for POD on at least 1 day during their hospital stay. Additionally, using the COX-based method, we estimated the optimal MAP targets in the middle-aged and elderly groups to be (67.8±8.9, 116.4±10.5) and (71.2±12.5, 111.3±8.9) mmHg, respectively.

Conclusions: The brains of patients ≥65 years are more vulnerable to systemic insult compared with those of middle-aged patients. POD may be associated with CA dysfunction. NIRS-derived COX can be used to identify the optimal MAP range.
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http://dx.doi.org/10.21037/apm-21-707DOI Listing
April 2021

Immunomodulatory effect of pentagalloyl glucose in LPS-stimulated RAW264.7 macrophages and PAO1-induced Caenorhabditis elegans.

Exp Gerontol 2021 07 3;150:111388. Epub 2021 May 3.

Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, Guangdong, China. Electronic address:

Pentagalloyl glucose (PGG) is a valuable natural compound with an array of biological activities, but the immunomodulatory effect and mechanism have not been fully validated yet. In this study, to elucidate comprehensively the function of immunomodulation and its underlying mechanism of PGG in vitro and in vivo, two model systems were conducted, which including lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages cells and Pseudomonas aeruginosa (PAO1)-induced Caenorhabditis elegans (C. elegans). Current results showed that PGG significantly inhibited secretions of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and mediator nitric oxide (NO) in LPS-stimulated RAW264.7 cells. In addition, the expression of genes nitric oxide synthase (iNOS), TNF-α, IL-1β and IL-6 in LPS- stimulated RAW264.7 cells was reduced by PGG. In vivo assay showed that lifespan of PAO1-induced C. elegans was enhanced significantly by 14.1% under the pre-treatment of PGG, which was abrogated in toxin sensitive mdt-15 mutant. Similarly, the PGG showed a benefit on 41.2% significant extension longevity in C. elegans under pathogenic PA14. And the nuclear localization of DAF-16 of strain TJ356 was significantly increased in PAO1-induced C. elegans by PGG. Further, PGG modulated several signaling pathways to enhance immunomodulation in C. elegans including DBL-1, DAF-2/DAF-16, and mitogen-activated protein (MAP) kinase pathways. Furthermore, other genes involved in immunomodulatory response in C. elegans were remarkably regulated such as lys-1, lys-2, spp-18, egl-9, and hif-1. Our study suggested that PGG have potential to develop into novel immunomodulatory nutraceutical.
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http://dx.doi.org/10.1016/j.exger.2021.111388DOI Listing
July 2021

Neuroprotective effects of short-chain fatty acids in MPTP induced mice model of Parkinson's disease.

Exp Gerontol 2021 07 24;150:111376. Epub 2021 Apr 24.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; Key Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. Electronic address:

Gut microbial metabolites, SCFAs, were related with the occurrence and development of Parkinson's disease (PD). But the effects of different short-chain fatty acids (SCFAs) on PD and involving mechanisms are still undefined. In this study we evaluate the effects of three dominant SCFAs (acetate, propionate and butyrate) on motor damage, dopaminergic neuronal degeneration and underlying neuroinflammation related mechanisms in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. High (2.0 g/kg) or low doses (0.2 g/kg) of sodium acetate (NaA), sodium propionate (NaP) or sodium butyrate (NaB) were gavaged into PD mice for 6 weeks. High doses of NaA reduced the turning time of PD mice. NaB significantly reduced the turning and total time in pole test, and increased the average velocity in open field test when compared with PD mice, indicating the most effective alleviation of PD-induced motor disorder. Low and high doses of NaB significantly increased the content of tyrosine hydroxylase (TH) by 12.3% and 20.2%, while reduced α-synuclein activation by 159.4% and 132.7% in the substantia nigra pars compacta (SNpc), compared with PD groups. Butyrate reached into the midbrain SNpc and suppressed microglia over-activation. It inhibited the levels of pro-inflammatory factors (IL-6, IL-1β and TNF-α) (P < 0.01) and iNOS. Besides, butyrate inhibited the activation of NF-κB and MAPK signaling pathways in the SNpc region. Consequently, sodium butyrate could inhibit neuroinflammation and alleviate neurological damage of PD.
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http://dx.doi.org/10.1016/j.exger.2021.111376DOI Listing
July 2021

Resilience Predicts the Trajectories of College Students' Daily Emotions During COVID-19: A Latent Growth Mixture Model.

Front Psychol 2021 30;12:648368. Epub 2021 Mar 30.

School of Psychology, Shandong Normal University, Jinan, China.

The objective of this study was to examine the association between resilience and trajectories of college students' negative and positive affect during the COVID-19 pandemic. A total of 391 college students recruited from China completed a daily online negative and positive affect scale for 1 week, and their resilience was also measured. Profiles of brief trajectories of negative and positive affect over time were identified using the latent growth mixture model, and the effect of resilience on these trajectories was further explored. Two latent profiles of negative affect were found: a constant high negative affect profile and a slowly decreasing low negative affect profile, while three latent profiles of positive affect were identified: a slowly increasing high positive affect profile, a rapidly decreasing medium positive affect profile, and a constant medium positive affect profile. The optimism dimension of resilience predicted the membership in the various profiles significantly, whereas the prediction of tenacity and strength dimensions of resilience was not significant. Activities that promote resilience, especially optimism, should be included to improve the daily emotions of college students during COVID-19.
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http://dx.doi.org/10.3389/fpsyg.2021.648368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042211PMC
March 2021

Dynamic Tumorigenic Trajectory and Transitional Signatures of Oncogenic Evolution by Single-Cell Transcriptomic Profiling of Esophageal Squamous Cell Carcinoma.

Asia Pac J Oncol Nurs 2021 May-Jun;8(3):225-227. Epub 2021 Mar 26.

Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, China.

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http://dx.doi.org/10.4103/apjon.apjon-2096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030599PMC
March 2021

Synthesis of OmpA Oral Nanoparticles and Evaluation of Immune Functions against the Major Etiologic Agent of Cow Mastitis.

Vaccines (Basel) 2021 Mar 23;9(3). Epub 2021 Mar 23.

College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.

is a major etiologic agent of cow mastitis, a condition that results in huge economic losses. There is a lack of an oral vaccine for cow mastitis. Previous studies have confirmed that the outer membrane protein A (OmpA) of is immunogenic and can be used for vaccine design. In the present study, OmpA was encapsulated into nanoparticles (NP-OmpA) for an oral vaccine for cow mastitis. OmpA was purified with Ni-NTA flow resin and encapsulated with chitosan (CS) to prepare NP-OmpA nanoparticles. The gastrointestinal tract was simulated in vitro (PBS, pH 1.2) to measure the protein release rate. The optimal preparation conditions for NP-OmpA were determined by analyzing the concentrations of OmpA and CS, magnetic mixing speed, mixing time, and the ratio of tripolyphosphate (TPP)/CS (). NP-OmpA safety was assessed by function factors and histopathological examination of livers and kidneys. The immune activity of NP-OmpA was determined using qRT-PCR to assess immune-related gene expression, leukocyte phagocytosis of , ELISA to evaluate antiserum titer and immune recognition of , and the organ index. The immune protection function of NP-OmpA was assessed by the protection rate of NP-OmpA to in mice, qRT-PCR for inflammation-related gene expression, assay kits for antioxidant factors, and visceral injury in the histopathological sections. NP-OmpA nanoparticles had a diameter of about 700 nm, loading efficiency (LE) of 79.27%, and loading capacity (LC) of 20.31%. The release rate of NP-OmpA (0~96 h) was less than 50% in vitro. The optimal preparation conditions for NP-OmpAs were OmpA protein concentration of 2 mg/mL, CS concentration of 5 mg/mL, TPP/CS () of 1:1, magnetic mixing speed of 150 r/min, and mixing time of 15 min. Histopathological sections and clinical analytes of uric acid (UA), creatinine (Cr), alanine aminotransferase (ALT), aspartate transaminase (AST), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) showed NP-OmpA did not damage mice livers or kidneys. NP-OmpA could enhance the immune-related gene expression of IFN-γ and HSP70 in the spleen, liver, and kidney and the leukocyte phagocytosis of . The antiserum titer (1:3200) was obtained from mice immunized with NP-OmpA, which had an immune recognition effect to . The immune protection rate of NP-OmpA was 71.43% ( < 0.05) to . NP-OmpA could down-regulate the inflammation-related gene expression of TNF-a, IL-6, and IL-10 in the spleen, liver, and kidney, and the antioxidant factors MDA and SOD in the liver, and reduce injury in the liver and kidney of mice induced by . A novel NP-OmpA nanoparticle was encapsulated, and the optimal preparation conditions were determined. The NP-OmpA was safe and had good immune functions. They are expected to induce a response that resists infection with the major etiologic agent () of cow mastitis.
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http://dx.doi.org/10.3390/vaccines9030304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005184PMC
March 2021

CCL26 is upregulated by nab-paclitaxel in pancreatic cancer-associated fibroblasts and promotes PDAC invasiveness through activation of the PI3K/AKT/mTOR pathway.

Acta Biochim Biophys Sin (Shanghai) 2021 Apr;53(5):612-619

Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213000, China.

Recently, the combined use of FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) and gemcitabine plus nab-paclitaxel has significantly improved the prognosis of patients with pancreatic cancer. However, there is still a high proportion of patients who develop metastatic pancreatic cancer in the course of chemotherapy or within a short period after chemotherapy. Previous reports have shown that chemotherapy-driven cytokine storms or the direct effects of certain chemotherapeutics on stromal and/or immune cells collectively change the microenvironment of the primary tumor, thus indirectly promoting metastasis. However, the mechanism underlying chemotherapy-induced metastasis in the course of chemotherapy, and afterwards, remains elusive in pancreatic cancer. In the present study, we aimed to determine the expression of CCL26 in the pancreatic cancer-associated fibroblasts (CAFs) after nab-paclitaxel treatment and to explore the role of CCL26 in the pancreatic adenocarcinoma (PDAC) invasion. Our results showed that nab-paclitaxel increased CCL26 mRNA and protein expression levels in a dose- and time-dependent manner. Subsequently, PDAC cell lines were treated with recombinant CCL26 for 48 h. The transwell migration assay showed that recombinant CCL26 enhanced the invasion of PDAC cells. Western blot analysis showed that the protein expression levels of phospho-(p-)PI3K, p-AKT, and p-mTOR were increased by CCL26 in PDAC cells. CCL26 expressions in 95 PDAC tissues and adjacent normal tissues were evaluated using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. CCL26 was found to be overexpressed in PDAC samples, and upregulated CCL26 expression was significantly associated with advanced perineural invasion, lymph node metastasis, and poor differentiation. In summary, our results showed that nab-paclitaxel increased the expression of CCL26 in CAFs, and CCL26 enhanced the invasive potential of pancreatic cancer cells by activating the PI3K/AKT/mTOR axis. Thus, CCL26 may be a potential prognostic biomarker for pancreatic cancer.
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http://dx.doi.org/10.1093/abbs/gmab032DOI Listing
April 2021

Integrated MicroRNA-mRNA Analyses of Distinct Expression Profiles in Hyperoxia-Induced Bronchopulmonary Dysplasia in Neonatal Mice.

Am J Perinatol 2021 Mar 23. Epub 2021 Mar 23.

Public Health, Guilin Medical University, Lingui, Guilin, People's Republic of China.

Objective:  Bronchopulmonary dysplasia (BPD) is a common chronic lung disease of preterm neonates; the underlying pathogenesis is not fully understood. Recent studies suggested microRNAs (miRNAs) may be involved in BPD.

Study Design:  miRNA and mRNA microarrays were performed to analyze the expression profiles of miRNA and mRNA in BPD and control lung tissues after oxygen and air exposure on day 21. Bioinformatics methods, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were performed to predict the potential functions of differentially expressed genes. Then, miRNA-mRNA regulatory network was constructed by protein-protein interaction (PPI) data and TarBase data.

Results:  Our results showed that a total of 192 differentially expressed miRNAs (74 downregulated and 118 upregulated) and 1,225 differentially expressed mRNAs (479 downregulated and 746 upregulated) were identified between BPD mice and normoxia-control mice. GO and KEGG analysis showed that for downregulated genes, the top significant enriched GO terms and KEGG pathways were both mainly related to immune and inflammation processes; for upregulated genes, the top significant enriched GO terms and KEGG pathways were both mainly related to extracellular matrix (ECM) remodeling. PPI network and miRNA-mRNA regulatory network construction revealed that the key genes and pathways associated with inflammation and immune regulation.

Conclusion:  Our findings revealed the integrated miRNA-mRNA data of distinct expression profiles in hyperoxia-induced BPD mice, and may provide some clues of the potential biomarkers for BPD, and provide novel insights into the development of new promising biomarkers for the treatment of BPD.

Key Points: · Integrated advanced bioinformatics methods may offer a better way to understand the molecular expression profiles involved in BPD.. · ECM remodeling, inflammation, and immune regulation may be essential to BPD.. · The miRNA-mRNA regulatory network construction may contribute to develop new biomarkers for the treatment of BPD..
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http://dx.doi.org/10.1055/s-0041-1726124DOI Listing
March 2021
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