Publications by authors named "Xiaoying He"

92 Publications

Elevation of Serum Cytokine Profiles and Liver Metabolomic Normalization in Early Convalescence of COVID-19 Patients.

Front Med (Lausanne) 2021 7;8:626633. Epub 2021 Jul 7.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Coronavirus disease 2019 (COVID-19) has become a global public health concern. We aimed to study the cytokine profile during the convalescent phase and its association with liver functions. We performed a retrospective study to investigate the longitudinal dynamic serum cytokine, liver function, and metabolomic profiles, as well as their potential correlations, from the viral replication phase to early convalescence. Our results demonstrated that liver injury was common. Liver injury was significantly associated with higher levels of interleukin (IL)-6 and IL-10 ( < 0.05). However, alanine aminotransferase levels decreased during the first week after hospital discharge ( < 0.01). In parallel, T-cell and B-cell immune response-stimulating cytokine IL-4, but not IL-2, was significantly elevated ( < 0.05). Furthermore, interferon-γ (IFN-γ) and tumor necrosis factor-α (TFN-α) levels increased, in contrast to the decrease in IL-6 and IL-10 levels; liver function returned to normal. The metabolomic analysis supported active recovery during early convalescence of COVID-19 patients that had distinct metabolic profiles associated with the hepatic tricarboxylic acid cycle, amino acid metabolism, and lipid metabolism. In addition, we identified a metabolomic association of IL-4 with liver repair. Our findings suggest that discharged patients continue to recover from the physiological effects of COVID-19, and the association of IL-4, IL-6, and IL-10 levels with metabolic changes and liver function repair may have important implications for clinical manifestations and treatment of COVID-19.
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http://dx.doi.org/10.3389/fmed.2021.626633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292617PMC
July 2021

Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte Development.

Front Genet 2021 2;12:679616. Epub 2021 Jul 2.

Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China.

Intrathymic differentiation of T lymphocytes begins as early as intrauterine stage, yet the T cell lineage decisions of human fetal thymocytes at different gestational ages are not currently understood. Here, we performed integrative single-cell analyses of thymocytes across gestational ages. We identified conserved candidates underlying the selection of T cell receptor (TCR) lineages in different human fetal stages. The trajectory of early thymocyte commitment during fetal growth was also characterized. Comparisons with mouse data revealed conserved and species-specific transcriptional dynamics of thymocyte proliferation, apoptosis and selection. Genome-wide association study (GWAS) data associated with multiple autoimmune disorders were analyzed to characterize susceptibility genes that are highly expressed at specific stages during fetal thymocyte development. In summary, our integrative map describes previously underappreciated aspects of human thymocyte development, and provides a comprehensive reference for understanding T cell lymphopoiesis in a self-tolerant and functional adaptive immune system.
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http://dx.doi.org/10.3389/fgene.2021.679616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284395PMC
July 2021

Association between vaginal microbiota and risk of early pregnancy miscarriage.

Comp Immunol Microbiol Infect Dis 2021 Aug 10;77:101669. Epub 2021 May 10.

Shanghai Key Laboratory of Embryo Original Diseases, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China. Electronic address:

Approximately 15 % of clinically recognized pregnancies end in miscarriage. To explore the vaginal microbiota profile in women diagnosed with early pregnancy miscarriage (including missed miscarriage [M] or empty-sac miscarriage [E]), the microbial community structure in vaginal fluid was evaluated by Illumina MiSeq sequencing of the 16S rRNA gene V4 region and compared with that in women with normal pregnancy (P). Taxa identified in samples from the P, E, and M groups formed distinct clusters. The M group had the highest bacterial species richness and diversity, with lower Lactobacillus levels and higher Bacteroides, Halomonas, Miscellaneous-Crenarchaeota, Bacillus, Staphylococcus, Escherichia/Shigella, and Acetobacter levels than in the other two groups. The vaginal community-state types differed significantly among the three groups (P = 0.02) but were similar between the P and E groups (P = 0.21). Moreover, we identified an optimal marker set composed of 12 operational taxonomic units based on a random forest model that distinguished the M and P groups, with areas under the receiver-operating characteristic curve of 86.76 % and 93.33 % in the training and test groups, respectively. In conclusion, this study highlights that patients with early pregnancy miscarriage had a significantly different vaginal microbiota profile. Microbial markers analyzed by RT-qPCR may be applied for the etiological diagnosis of miscarriage. Further studies should be performed to elucidate the possible mechanism of special strains affecting miscarriage during early pregnancy.
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http://dx.doi.org/10.1016/j.cimid.2021.101669DOI Listing
August 2021

The miR-302s/367 Cluster Inhibits the Proliferation and Apoptosis in Sheep Fetal Fibroblasts via the Cell Cycle and PI3K-Akt Pathways.

Mamm Genome 2021 Jun 6;32(3):183-194. Epub 2021 May 6.

School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China.

The miR-302s/367 family has the ability to induce mouse and human somatic cell reprogramming into induced pluripotent stem cells (iPSCs), inhibit the proliferation of several types of cancer cells, and even cause cancer cell apoptosis. However, the functions of the miR-302s/367 family in other mammals have not been explored. In the present study, the effects of miR-302s/367 on reprogramming, proliferation, and apoptosis in sheep fetal fibroblasts (SFFs) were evaluated by the delivery of a plasmid vector containing synthetic precursor miRNAs into cells, followed by the induction of mature miR-302s/367 expression. The results showed that miR-302s/367 could not reprogram SFFs into iPSCs; however, they could inhibit both the proliferation and apoptosis of SFFs by targeting CDK2, E2F1, E2F2, and PTEN in the cell cycle and PI3K-Akt pathways. Based on our findings, a novel mechanism was proposed in which the miR-302s/367 family functions in both the proliferation and apoptosis of somatic cells in mammals, suggesting that caution is needed when using miR-302s/367 as therapeutic agent.
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http://dx.doi.org/10.1007/s00335-021-09873-5DOI Listing
June 2021

Atlas of breast cancer infiltrated B-lymphocytes revealed by paired single-cell RNA-sequencing and antigen receptor profiling.

Nat Commun 2021 04 12;12(1):2186. Epub 2021 Apr 12.

National Institute of Biological Sciences, Beijing, China.

To gain mechanistic insights into the functions and developmental dynamics of tumor-infiltrated immune cells, especially B-lymphocytes, here we combine single-cell RNA-sequencing and antigen receptor lineage analysis to characterize a large number of triple-negative breast cancer infiltrated immune cells and report a comprehensive atlas of tumor-infiltrated B-lymphocytes. The single-cell transcriptional profiles reveal significant heterogeneity in tumor-infiltrated B-cell subgroups. The single-cell antigen receptor analyses demonstrate that compared with those in peripheral blood, tumor-infiltrated B-cells have more mature and memory B-cell characteristics, higher clonality, more class switching recombination and somatic hypermutations. Combined analyses suggest local differentiation of infiltrated memory B-cells within breast tumors. The B-cell signatures based on the single-cell RNA-sequencing results are significantly associated with improved survival in breast tumor patients. Functional analyses of tumor-infiltrated B-cell populations suggest that mechanistically, B-cell subgroups may contribute to immunosurveillance through various pathways. Further dissection of tumor-infiltrated B-cell populations will provide valuable clues for tumor immunotherapy.
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http://dx.doi.org/10.1038/s41467-021-22300-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042001PMC
April 2021

Glucose-dependent insulinotropic polypeptide modifies adipose plasticity and promotes beige adipogenesis of human omental adipose-derived stem cells.

FASEB J 2021 05;35(5):e21534

Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

The adipocyte precursors (APs) located in white adipose tissue (WAT) are functionally significant in adipose plasticity and browning. Modifying adipogenesis or WAT browning targeted on APs is a promising mechanism for anti-obesity drug. We herein explored the in vitro actions and mechanisms of glucose-dependent insulinotropic polypeptide (GIP), a gut-derived peptide, in human adipose-derived mesenchymal stem cells (hADSCs) isolated from omentum. The hADSCs were cotreated with 100 nM GIP with or without equimolar concentration of GIP3-42 (a GIP receptor antagonist), and subsequently examined in vitro. CCK-8, EdU incorporation, and flow cytometry assays were used to assess cellular proliferation. Annexin V FTIC/PI double stain, TUNEL staining, and Western blot were applied for apoptosis evaluation. Adipogenesis was reflected by Western blot, real-time PCR, Oil Red O staining, mitochondrial staining, and mitochondrial DNA analysis. Results showed that GIP promoted proliferation and inhibited apoptosis of hADSCs via pleiotropic effects. Besides, GIP facilitated de novo beige adipogenesis, by accelerating mitotic clonal expansion (MCE), upregulating core adipogenic regulators (C/EBPα and PPARγ), augmenting beige-related genes (UCP1, PGC1α, and PRDM16), increasing mitochondrial content and improving beige adipocyte functionalities. Above all, our study expands knowledge on the mechanisms of GIP modifying adipogenesis especially in inducing beige adipogenesis, and thus provides a theoretical support for clinical usage of GIP on obesity treatment.
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http://dx.doi.org/10.1096/fj.201903253RDOI Listing
May 2021

Population pharmacokinetics and individual analysis of daptomycin in kidney transplant recipients.

Eur J Pharm Sci 2021 Jul 24;162:105818. Epub 2021 Mar 24.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. Electronic address:

Background: Little is known about the population pharmacokinetics (PPK) of daptomycin in kidney transplant patients. The present study established a pharmacokinetic model for daptomycin in kidney transplant patients in China and examinee the important factors affecting the pharmacokinetic parameters of daptomycin.

Methods: The study population included 49 kidney transplant patients with 537 daptomycin concentrations. The PPK model of daptomycin was developed using a nonlinear mixed-effects model, a two-compartment structural model, and a mixed residual error model. The stability and predictive ability of the final model were evaluated based on bootstrapping, visual prediction checks and normalized prediction distribution errors.

Results: Glomerular filtration rate (GFR) and total body weight significantly affected clearance, and body weight influenced the central volume of distribution. The average clearance of the population was 0.316 L/h, the central volume of distribution was 6.04 L, the intercompartmental clearance was 2.31 L/h, and the peripheral volume of distribution was 2.46 L. Based on the established model and the target of area under curve (AUC)/minimum inhibition concentration (MIC) ≥666, we developed a recommended dose regimen for kidney transplant patients according to their renal function and weight. The daily doses were 4.0±0.31, 4.7±0.36, 5.1±0.40, 5.5±0.43, 5.8±0.45, and 6.1±0.48 mg/kg when the GFRs were 15, 30, 45, 60, 75, and 90 ml/min/1.73 m, respectively.

Conclusion: This study provides a reference for individualized daptomycin administration in kidney transplant recipients, and it is a valuable resource for improving the treatment effect and reducing the toxic effects of daptomycin.
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http://dx.doi.org/10.1016/j.ejps.2021.105818DOI Listing
July 2021

Plasma metabolites, especially lipid metabolites, are altered in pregnant women with gestational diabetes mellitus.

Clin Chim Acta 2021 Jun 9;517:139-148. Epub 2021 Mar 9.

Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang 310000, People's Republic of China. Electronic address:

Background And Aims: Gestational diabetes mellitus (GDM) is a pathological condition of glucose intolerance associated with adverse pregnancy outcomes and increased risk of developing maternal type 2 diabetes later in life. Metabolomics is finding increasing use in the study of GDM. To date, GDM-specific metabolomic changes have not been completely elucidated.

Materials And Methods: In this pilot study, metabolomics fingerprinting data, obtained by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS), of 54 healthy pregnant women and 49 patients with GDM at the second and third gestational trimesters were analyzed. Multilevel statistical methods were used to process complex metabolomic data from the retrospective cohorts.

Results: Using univariate analysis (p < 0.05), 41 metabolites were identified as having the most significant differences between these two groups. Lipid metabolites, particularly glycerophospholipids, were the most prevalent class of altered compounds. In addition, metabolites with previously unknown connection to GDM - such as monoacylglycerol, dihydrobiopterin, and 13S-hydroxyoctadecadienoic acid - were identified with strong discriminative power. The main metabolic pathways affected by GDM included glycerophospholipid metabolism, linoleic acid metabolism, and D-arginine and D-ornithine metabolism.

Conclusion: Our data provide a comprehensive overview of metabolite changes at different stages of pregnancy, which offers further insights into the pathogenesis of GDM.
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http://dx.doi.org/10.1016/j.cca.2021.02.023DOI Listing
June 2021

Analyzing fundus images to detect diabetic retinopathy (DR) using deep learning system in the Yangtze River delta region of China.

Ann Transl Med 2021 Feb;9(3):226

Department of Ophthalmology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: This study aimed to establish and evaluate an artificial intelligence-based deep learning system (DLS) for automatic detection of diabetic retinopathy. This could be important in developing an advanced tele-screening system for diabetic retinopathy.

Methods: A DLS with a convolutional neural network was developed to recognize fundus images of referable diabetic retinopathy. A total data set of 41,866 color fundus images were obtained from 17 cities in the Yangtze River Delta Urban Agglomeration (YRDUA). Five experienced retinal specialists and 15 ophthalmologists were recruited to verify images. For training, 80% of the data set was used, and the other 20% served as the validation data set. To effectively understand the learning process, the DLS automatically superimposed a heatmap on the original image. The regions utilized by the DLS were highlighted for diagnosis.

Results: Using the local validation data set, the DLS achieved an area under the curve of 0.9824. Based on the manual screening criteria, an operating point was set at about 0.9 sensitivity to evaluate the DLS. Specificity was recorded at 0.9609 and sensitivity was 0.9003. The DLSs showed excellent reliability, repeatability, and high efficiency. After analyzing the misclassification, it was found that 88.6% of the false-positives were mild non-proliferative diabetic retinopathy (NPDR) whereas, 81.6% of the false-negatives were intraretinal microvascular abnormalities.

Conclusions: The DLS efficiently detected fundus images from complex sources in the real world. Incorporating DLS technology in tele-screening will advance the current screening programs to offer a cost-effective and time-efficient solution for detecting diabetic retinopathy.
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http://dx.doi.org/10.21037/atm-20-3275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940941PMC
February 2021

Optimized protocol for high-titer lentivirus production and transduction of primary fibroblasts.

J Basic Microbiol 2021 May 8;61(5):430-442. Epub 2021 Mar 8.

Department of Ophthalmology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

The lentivirus-short hairpin RNA (shRNA) system is a widely used tool for RNA interference. Multiple factors may affect the RNA interference efficiency during lentivirus production and transduction procedures. Thus, an optimized protocol is required to achieve high-titer lentivirus and efficient gene delivery. In the present study, lentivirus was produced by transfecting lentiviral transfer and packaging plasmids into HEK 293T cells. The factors affecting lentiviral titer were assessed, including lentiviral plasmid ratio, lentiviral transfer plasmid type, serum type for cell culture, transfection reagent-plasmid mixture incubation time, and the inoculation density of 293T cells for transfection. The high-titer lentivirus was achieved when plasmids were transfected at a molar ratio of 1:1:1:2, and the transfection reagent-plasmid mixture was replaced 6-8 h after transfection. The pLVX-shRNA2 lentiviral transfer plasmid was associated with the highest lentiviral titer, while both pLVX-shRNA2 and psi-LVRU6GP plasmids were associated with efficient RNA interference in target cells. The serum type for 293T cell culture affected the lentiviral titer significantly, while the inoculation density of 293T cells showed no influence on transfection efficiency or lentiviral titer. Moreover, the human primary fibroblasts infected with lentivirus, using the centrifugation method, achieved higher transduction efficiency than those infected with the non-centrifugation method. In conclusion, this study helped optimize lentiviral production and transduction procedures for more efficient gene delivery.
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http://dx.doi.org/10.1002/jobm.202100008DOI Listing
May 2021

Effect of corneal incision features on anterior and posterior corneal astigmatism and higher-order aberrations after cataract surgery.

Acta Ophthalmol 2021 Mar 4. Epub 2021 Mar 4.

The Department of Ophthalmology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Purpose: To evaluate the influence of 2.2 mm clear corneal incision (CCI) features in surgically induced astigmatism (SIA) and higher-order aberrations (HOAs) after cataract surgery.

Methods: Right eyes of 92 subjects receiving 2.2 mm incision cataract surgery were involved. A total of 38 eyes were categorized as the intact incision group, and 54 eyes were the defective incision group. Pre- and postoperative (1 month and 6 months) corneal astigmatism and HOAs on anterior and posterior corneal surfaces, corneal volume, and corneal thickness (CT) were measured using Pentacam. The CCI features including incision length (IL), incision angles, distance from incision to central cornea (Dis-En/Ex), and CT at incision site were quantified using AS-OCT.

Results: The defective incision group showed shorter IL and larger incision angles [false discovery rate (FDR) - p < 0.05]. Changes in CT at incision site were more pronounced for the defective incision group (FDR - p < 0.05). Some SIA parameters were related to the certain specific CCI features, especially IL (FDR - p < 0.05). Both groups exhibited significant increased 6 mm posterior corneal tHOAs at 1 month (Bonferroni corrected - p < 0.01) and the defective incision group showed increased 6 mm posterior tHOAs at 6 months (Bonferroni corrected - p = 0.023). There were characteristic correlations between Zernike terms and CCI features including IL, CT, Dis-En/Ex, and incision angles at 1 month, especially over 6 mm zone.

Conclusion: The CCI deformities can affect corneal recovery and induce more HOAs at 1 month postoperatively. Such effects became minor, but could persist until 6 months. The IL combined with Angle-En/Ex was important factor influencing CCI integrity and corneal optical quality.
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http://dx.doi.org/10.1111/aos.14778DOI Listing
March 2021

Chemical constituents of radix Actinidia chinensis planch by UPLC-QTOF-MS.

Biomed Chromatogr 2021 Jul 19;35(7):e5103. Epub 2021 Mar 19.

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.

Radix Actinidia decoction and its prescriptions are used to treat tumors and other diseases. Although some chemical components have been isolated from Radix Actinidia, systematic analysis of its chemical components has not been reported, which hinders the basic research on its effective substances and its quality control. In this work, a UPLC-QTOF-MS method was employed to profile and characterize the chemical constituents of water extracts from Radix Actinidia Chinensis Planch (RACP). We unambiguously or tentatively identified 295 chemical components from RACP, including 46 pentacyclic triterpenes, 72 flavonoids, 53 phenolic acids, 24 coumarins, three anthraquinones and other compounds. Most of the chemical components have not been described so far in Actinidia. More than 180 phytochemicals are reported in Actinidia for the first time. 2α,3α,24-trihydroxyurs-12-en-28-oic acid, asiatic acid, syringic acid, fraxin, esculetin, 5,7-dihydroxychromone, esculin, (+)-catechin, (-)-epi-catechin, vanillic acid, ferulic acid, protocatechuic acid and rutin were unambiguously identified by comparison with the reference standards. Catechin derivatives, coumarin derivatives and phenolic acid derivatives were the main water-soluble components in RACP. This study broadened the chemical profiles of RACP, and laid the foundation for subsequent research on the effective components and their mechanism of action. This work also provides an important reference for the quality control and evaluation of RACP.
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http://dx.doi.org/10.1002/bmc.5103DOI Listing
July 2021

Discovering and efficiently promoting the extracellular secretory expression of Thermobacillus sp. ZCTH02-B1 sucrose phosphorylase in Escherichia coli.

Int J Biol Macromol 2021 Mar 19;173:532-540. Epub 2021 Jan 19.

College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, China.

Sucrose phosphorylase (SPase, EC2.4.1.7) is a promising transglycosylation biocatalyst used for producing glycosylated compounds that are widely used in the food, cosmetics, and pharmaceutical industries. In this study, a recombinant SPase from the Thermobacillus sp. ZCTH02-B1 (rTSPase), which was previously reported to have high thermostability and the catalytic ability to synthesize ascorbic acid 2-glucoside, was attempted to be extracellularly expressed in Escherichia coli BL21(DE3) by fusion of endogenous osmotically-inducible protein Y. Unexpectedly, the rTSPase itself was produced outside the cells with an underestimated performance, although no typical signal peptide was predicted. Further N- and C-terminal truncation experiments revealed that both termini of rTSPase have an important role in protein folding and enzymatic activity, while its secretion was N-terminus associated. Extracellular protein concentration and rTSPase activity achieved 1.8 mg/mL and 6.2 U/mL after induction of 36 h in a 5-L fermenter. High-level extracellular rTSPase production could also be obtained from E. coli within 24 h by inducing overexpression of D, D-carboxypeptidase for cell lysis.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.115DOI Listing
March 2021

Single-course antenatal corticosteroids is related to faster growth in very-low-birth-weight infant.

BMC Pregnancy Childbirth 2021 Jan 12;21(1):50. Epub 2021 Jan 12.

Department of Maternal and Child Health, School of Public Health, Sun Yat-sen University, No. 74 Zhongshang 2nd Road, Guangzhou, 510080, China.

Background: Antenatal corticosteroids (ACS) treatment is critical to support survival and lung maturation in preterm infants, however, its effect on feeding and growth is unclear. Prior preterm delivery, it remains uncertain whether ACS treatment should be continued if possible (repeated course ACS), until a certain gestational age is reached. We hypothesized that the association of single-course ACS with feeding competence and postnatal growth outcomes might be different from that of repeated course ACS in very-low-birth-weight preterm infants.

Methods: A multicenter retrospective cohort study was conducted in very-low-birth-weight preterm infants born at 23-37 weeks' gestation in South China from 2011 to 2014. Data on growth, nutritional and clinical outcomes were collected. Repeated course ACS was defined in this study as two or more courses ACS (more than single-course). Infants were stratified by gestational age (GA), including GA < 28 weeks, 28 weeks ≤ GA < 32 weeks and 32 weeks ≤ GA < 37 weeks. Multiple linear regression and multilevel model were applied to analyze the association of ACS with feeding and growth outcomes.

Results: A total of 841 infants were recruited. The results, just in very-low-birth-weight preterm infants born at 28-32 weeks' gestation, showed both single and repeated course of ACS regimens had shorter intubated ventilation time compared to non-ACS regimen. Single-course ACS promoted the earlier application of amino acid and enteral nutrition, and higher rate of weight increase (15.71; 95%CI 5.54-25.88) than non-ACS after adjusting for potential confounding factors. No associations of repeated course ACS with feeding, mean weight and weight increase rate were observed.

Conclusions: Single-course ACS was positively related to feeding and growth outcomes in very-low-birth-weight preterm infants born at 28-32 weeks' gestation. However, the similar phenomenon was not observed in the repeated course of ACS regimen.
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http://dx.doi.org/10.1186/s12884-020-03510-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801876PMC
January 2021

Pharmacokinetics and Pharmacodynamics of the Combination of Rhein and Curcumin in the Treatment of Chronic Kidney Disease in Rats.

Front Pharmacol 2020 23;11:573118. Epub 2020 Dec 23.

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.

The interaction between the components of traditional Chinese medicine (TCM) is an important basis for their synergy. Rhein and curcumin exert various pharmacological activities, including anti-tumour, anti-inflammatory, antioxidant, anti-fibrosis and renoprotective effects. However, no investigation has reported the synergistic anti-fibrosis effect yet. This study aims at determine the pharmacokinetics and pharmacodynamics of the combination of rhein and curcumin in the treatment for chronic kidney disease in rats. Fifty two male Sprague-Dawley (SD) rats were randomly divided into rhein group, curcumin group and their combination group for pharmacodynamics studies. HE and Masson staining was conducted to observe the changes of renal morphology. Kits were used to detect the level of urea nitrogen (BUN) and creatinine (Scr). For pharmacokinetic study, 36 SD rats were randomly divided into rhein group, curcumin group and a combination group, the content of rhein and curcumin in plasma and renal tissue was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In additon, molecular docking method and cell experiments was used to disclose the interaction mechanism between curcumin and rhein. The pharmacodynamic results showed that the degree of renal fibrosis was improved obviously by co-administration rhein and curcumin. Meanwhile, compared to single administration, the Cmax and AUC of rhein and curcumin in plasma and renal tissue were enhanced significantly after co-administration. Moreover, the result of molecular docking and cell experiments showed that both two compounds could interact with P-gp, CYP2C9 and CYP2C19. Together, these findings demonstrated that rhein and curcumin had a synergistic effect in ameliorateing chonic kidney disease, providing an important explanation on the synergistic mechanism of curcumin and rhein from a pharmacokinetic viewpoint.
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http://dx.doi.org/10.3389/fphar.2020.573118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785804PMC
December 2020

Effects of contaminated surface water and groundwater from a rare earth mining area on the biology and the physiology of Sprague-Dawley rats.

Sci Total Environ 2021 Mar 14;761:144123. Epub 2020 Dec 14.

School of Energy and Environment, Inner Mongolia University of Science & Technology, Baotou 014010, China. Electronic address:

Previous studies have shown that an effective damage detection method for model rats from macro individual to micro cellular, was applied to assess the groundwater quality from rare earth metals tailings seepage. To determine whether it is universal method for measuring the toxicological damage caused by contaminated water around other mining areas to organisms at the organ-tissue-cell-chromosome-gene level. In this study, a rare earth mining area in North China was used as research base. Firstly, the core pollution factors in surface water and groundwater from five different sites were analyzed. Then, the degree of toxicological damage to Sprague-Dawley (SD) rats caused by contaminated water were systematically assessed using biological methods. Finally, the possible molecular mechanism of toxicological damage was further discussed. The synthesis results showed that the main pollution factors were some metal elements (Mn, Zn, Co, Ni) and rare earth elements (Sc, Nb, La, Ce, Pr, Dy and Y), which might cause significant DNA genetic damage to SD rats. Further, differential gene expression profile showed that DNA damage-inducible genes (Gadd45g and Ddit4), immunity-related genes (Mpo, Slpi and Elane) and two cancer-related genes (Mmp8 and Ltf) were used as a new prognostic and predictive biomarker for biosafety assessment. Therefore, this study provides a possible molecular mechanism for the toxicological damage, and also it provides a universal method to scientifically and effectively evaluate the water pollution risk for other mining areas.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144123DOI Listing
March 2021

Promoting TTC4 and HSP70 interaction and translocation of annexin A7 to lysosome inhibits apoptosis in vascular endothelial cells.

FASEB J 2020 09 9;34(9):12932-12945. Epub 2020 Aug 9.

Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, P.R. China.

We previously demonstrated that Tetraticopeptide 4 (TTC4) inhibited apoptosis in vascular endothelial cells (VEC) deprived of serum and fibroblast growth factor 2 (FGF-2). In this study, we aimed to resolve the mechanism of TTC4 inhibiting VEC apoptosis. TTC4, predicted as a HSP70 co-chaperone protein, may regulate the fate of cells by affecting the activity of HSP70, however, there is no experimental evidence showing the interaction of TTC4 and HSP70. Using Co-immunoprecipitation (Co-IP), we demonstrated that TTC4 interacted with HSP70. If HSP70 was knockdown, TTC4 no longer suppressed apoptosis. Furthermore, we found ABO, an inhibitor of annexin A7 (ANXA7) GTPase, could promote the interaction of TTC4 and HSP70 and the translocation of ANXA7 to lysosome. At the same time, ABO inhibited the interaction of HSP70 and ANXA7. Moreover, Akt, as a downstream effector of HSP70 was upregulated, and ANXA7 translocating to lysosome protected the stability of lysosomal membrane. Here, we discovered a special mechanism by which TTC4 inhibited apoptosis via HSP70 in VECs. On the one hand, increasing TTC4 and HSP70 interaction upregulated Akt that inhibited apoptosis. On the other hand, decreasing HSP70 and ANXA7 interaction promoted the translocation of ANXA7 to lysosome, which inhibited apoptosis through protecting the lysosomal membrane stability.
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http://dx.doi.org/10.1096/fj.202000067RDOI Listing
September 2020

Distinct mRNA and long non-coding RNA expression profiles of decidual natural killer cells in patients with early missed abortion.

FASEB J 2020 11 11;34(11):14264-14286. Epub 2020 Sep 11.

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Early non-chromosome-related missed abortion (MA) is commonly associated with an altered immunological environment during pregnancy. Human decidual natural killer (dNK) cells, the most abundant lymphocyte population within the first-trimester maternal-fetal interface, are vital maternal regulators of immune tolerance mediating successful embryo implantation and placentation. Previous studies have shown that dNK cells may play a role in MA. However, the gene expression status and specific altered manifestations of dNK cells in patients with early MA remain largely unknown. Here, we show that MA dNK cells have distinct mRNA and lncRNA expression profiles through RNA sequencing, with a total of 276 mRNAs and 67 lncRNAs being differentially expressed compared with controls. Protein-protein interaction analysis of differentially expressed mRNAs was performed to identify hub genes and key modules. An lncRNA-mRNA regulatory network characterized by the small-world property was constructed to reveal the regulation of mRNA transcription by differential hub lncRNAs. Functional annotation of differentially expressed mRNAs and lncRNAs was performed to disclose their potential roles in MA pathogenesis. Our data highlight several enriched biological processes (immune response, inflammatory response, cell adhesion, and extracellular matrix [ECM] organization) and signaling pathways (cytokine-cytokine receptor interaction, ECM-receptor interaction, Toll-like receptor signaling pathway, and phosphatidylinositol signaling system) that may influence MA. This study is the first to demonstrate the involvement of altered mRNA and lncRNA expression profiles in the dNK cell pathogenesis of early MA, facilitating a better understanding of the underlying molecular mechanisms and the development of novel MA therapeutic strategies targeting key mRNAs and lncRNAs.
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http://dx.doi.org/10.1096/fj.202000621RDOI Listing
November 2020

Associations of mitochondrial DNA copy number and deletion rate with early pregnancy loss.

Mitochondrion 2020 11 30;55:48-53. Epub 2020 Jul 30.

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.

Early pregnancy loss (EPL) is a common event worldwide. Previous studies show that mitochondrial DNA (mtDNA) copy number (CN) is associated with semen parameters and preimplantation embryo viability, indicating the predictive potential of mtDNA CN for ongoing pregnancy outcomes. However, no relevant study has assessed the relationship between mtDNA CN and EPL. Thus, we aimed to determine whether mtDNA CN and mtDNA 4977-bp deletion rate (DR) in chorionic villous tissue are associated with EPL. Chorionic villous tissue total DNA was extracted from 75 EPL cases and 75 healthy controls. Chromosomal analysis was conducted using copy number variation (CNV) sequencing. The mtDNA CN and DR were measured in samples without pathogenic CNVs. The association between mtDNA CN or DR and EPL risk were estimated using logistic regression. The EPL group had a significantly different mtDNA CN (P < 0.001) and DR (P = 0.005) compared to the control group. Both biomarkers were independent risk factors for EPL (CN odds ratio 1.71, 95% confidence interval 1.17 to 2.49, P = 0.005; DR odds ratio 1.07, 95% confidence interval 1.02 to 1.12, P = 0.006). These results suggest that higher mtDNA CN and DR levels are strongly associated with EPL and represent independent risk factors for EPL. Further studies validating these findings and exploring the underlying biological mechanisms are warranted.
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http://dx.doi.org/10.1016/j.mito.2020.07.006DOI Listing
November 2020

Curcumin-Induced DNA Demethylation in Human Gastric Cancer Cells Is Mediated by the DNA-Damage Response Pathway.

Oxid Med Cell Longev 2020 17;2020:2543504. Epub 2020 Jun 17.

School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, China.

Curcumin, a natural polyphenol antioxidant extracted from the root of turmeric (), can induce apoptosis and DNA demethylation in several types of cancer cells. However, the mechanism of its anticancer potentials and DNA demethylation effects and the potential relationships between these outcomes have not been clearly elucidated. In the present study, the effects of curcumin on the proliferation, colony formation, and migration of human gastric cancer cells (hGCCs) were explored. Reactive oxygen species (ROS) levels, mitochondrial damage, DNA damage, and apoptosis of curcumin-treated hGCCs were analyzed. Changes in the expression of several genes related to DNA damage repair, the p53 pathway, cell cycle, and DNA methylation following curcumin treatment were also evaluated. We observed that curcumin inhibited the proliferation, colony formation, and migration of hGCCs in a dose- and time-dependent fashion. A high concentration of curcumin elevated ROS levels and triggered mitochondrial damage, DNA damage, and apoptosis of hGCCs. Further, curcumin-induced DNA demethylation of hGCCs was mediated by the damaged DNA repair-p53-p21/GADD45A-cyclin/CDK-Rb/E2F-DNMT1 axis. We propose that the anticancer effect of curcumin could largely be attributed to its prooxidative effect at high concentrations and ROS elevation in cancer cells. Moreover, we present a novel mechanism by which curcumin induces DNA demethylation of hGCCs, suggesting the need to further investigate the demethylation mechanisms of other DNA hypomethylating drugs.
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http://dx.doi.org/10.1155/2020/2543504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317311PMC
February 2021

Novel Roles of Chloroquine and Hydroxychloroquine in Graves' Orbitopathy Therapy by Targeting Orbital Fibroblasts.

J Clin Endocrinol Metab 2020 06;105(6)

Department of Endocrinology and Diabetes Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Context: Graves' orbitopathy (GO) causes infiltrative exophthalmos by inducing excessive proliferation, adipogenesis, and glycosaminoglycan production in orbital fibroblasts (OFs). Interference with OF autophagy is a potential therapy for proptosis.

Objectives: Here, we aimed to evaluate the effects of chloroquine (CQ) and hydroxychloroquine (HCQ), the autophagy inhibitors commonly used in clinical practice, on OFs.

Design/setting/participants: OFs isolated from patients with GO (GO-OFs) or control individuals (non-GO-OFs) were cultured in proliferation medium (PM) or subjected to differentiation medium. OFs were treated with CQ or HCQ (0, 0.5, 2, and 10 μM), and subsequently examined in vitro.

Main Outcome Measures: CCK-8, EdU incorporation, and flow cytometry assays were used to assess cellular viability. Adipogenesis was assessed with Western blot analysis, real-time polymerase chain reaction (PCR) , and Oil Red O staining. Hyaluronan production was determined by real-time PCR and enzyme-linked immunosorbent assay. Autophagy flux was detected through red fluorescent protein (RFP)-green fluorescent protein (GFP)-LC3 fluorescence staining and Western blot analyses.

Results: CQ/HCQ halted proliferation and adipogenesis in GO-OFs in a concentration-dependent manner through blockage of autophagy, phenotypes that were not detected in non-GO-OFs. The inhibitory effect of CQ/HCQ on hyaluronan secretion of GO-OFs was also concentration dependent, mediated by downregulation of hyaluronan synthase 2 rather than hyaluronidases. Moreover, CQ (10 μM) induced GO-OF apoptosis without aggravating oxidative stress.

Conclusions: The antimalarials CQ/HCQ affect proliferation, adipogenesis, and hyaluronan generation in GO-OFs by inhibiting autophagy, providing evidence that they can be used to treat GO as autophagy inhibitors.
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http://dx.doi.org/10.1210/clinem/dgaa161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183395PMC
June 2020

[Detection of a BRCA1 c.2013_2014ins GT variant an ethnic Han Chinese pedigree affected with breast cancer].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Apr;37(4):415-418

Department of Head, Neck and Breast Surgery, Xinxiang Central Hospital, Henan 453000, China.

Objective: To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer.

Methods: The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes. Candidate variants were selected by analysis of their type, frequency in population, and segregation with the phenotype. Candidate variant was verified by Sanger sequencing and TA cloning.

Results: A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females. The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium (ExAC) database. The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein.

Conclusion: The BRCA1 c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.04.012DOI Listing
April 2020

SPRY4 regulates trophoblast proliferation and apoptosis via regulating IFN-γ-induced STAT1 expression and activation in recurrent miscarriage.

Am J Reprod Immunol 2020 06 6;83(6):e13234. Epub 2020 Apr 6.

Shanghai Key Laboratory of Embryo Original Diseases, the International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Problem: The dysregulation of trophoblast functions is one of the leading causes of recurrent miscarriage (RM), which frustrates 1%-5% of couples of childbearing ages. Sprouty 4 (SPRY4) is considered as a tumour suppressor and exerts a negative role in cell viability. However, its role in regulating trophoblast behaviors at the maternal-fetal interface remains largely unknown.

Method Of Study: First-trimester villous samples were collected from RM patients and healthy controls (HCs) to determine the SPRY4 expression in human placenta during early pregnancy. The HTR8/SVneo cell line was introduced to clarify trophoblast cell functions via transfecting with specific short interfering RNA against SPRY4 or SPRY4-overexpressing lentivirus in vitro. In addition, gene expression microarray analysis was performed to explore the downstream molecules and pathways.

Results: Our results revealed that SPRY4 expression was significantly increased in the first-trimester cytotrophoblasts of RM patients compared with HCs. Furthermore, SPRY4 overexpression inhibited trophoblast proliferation and accelerated apoptosis in vitro, while SPRY4 knockdown reversed these effects. Mechanistically, IFN-γ -induced STAT1 expression and activation were involved in the regulation of trophoblast proliferation and apoptosis by SPRY4, and IFN-γ promoted SPRY4 expression and STAT1 phosphorylation through PI3K/AKT pathway. Additionally, both STAT1 and phosphorylated STAT (p-STAT) levels were also upregulated in trophoblasts from RM patients and positively correlated with SPRY4 expression.

Conclusion: Our findings indicate that SPRY4 may act as a negative regulator of trophoblast functions through upregulating IFN-γ/PI3K/AKT-induced STAT1 activation. High levels of SPRY4 and STAT1 may contribute to RM development and progression, and blocking of either target could be a novel therapeutic strategy for RM patients.
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http://dx.doi.org/10.1111/aji.13234DOI Listing
June 2020

Artificial intelligence and convolution neural networks assessing mammographic images: a narrative literature review.

J Med Radiat Sci 2020 Jun 5;67(2):134-142. Epub 2020 Mar 5.

Discipline of Medical Imaging Sciences, The University of Sydney, Lidcombe, New South Wales, Australia.

Studies have shown that the use of artificial intelligence can reduce errors in medical image assessment. The diagnosis of breast cancer is an essential task; however, diagnosis can include 'detection' and 'interpretation' errors. Studies to reduce these errors have shown the feasibility of using convolution neural networks (CNNs). This narrative review presents recent studies in diagnosing mammographic malignancy investigating the accuracy and reliability of these CNNs. Databases including ScienceDirect, PubMed, MEDLINE, British Medical Journal and Medscape were searched using the terms 'convolutional neural network or artificial intelligence', 'breast neoplasms [MeSH] or breast cancer or breast carcinoma' and 'mammography [MeSH Terms]'. Articles collected were screened under the inclusion and exclusion criteria, accounting for the publication date and exclusive use of mammography images, and included only literature in English. After extracting data, results were compared and discussed. This review included 33 studies and identified four recurring categories of studies: the differentiation of benign and malignant masses, the localisation of masses, cancer-containing and cancer-free breast tissue differentiation and breast classification based on breast density. CNN's application in detecting malignancy in mammography appears promising but requires further standardised investigations before potentially becoming an integral part of the diagnostic routine in mammography.
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http://dx.doi.org/10.1002/jmrs.385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276180PMC
June 2020

Determination and pharmacokinetic study of skimmin by UHPLC-MS/MS in rat plasma.

J Pharm Biomed Anal 2020 Feb 6;179:112969. Epub 2019 Nov 6.

Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University, Zhejiang, People's Republic of China. Electronic address:

Skimmin, a major active ingredient derived from Hydrangea paniculata, has been considered to possess various pharmacological activities, including renoprotective activity, anti-inflammatory, anti-cancer, and antiamoebic properties. However, no investigation has reported the quantification and pharmacokinetics of skimmin in biomatrices. In the present study, we established and validated an ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the estimation of skimmin in rat plasma, which was successfully applied to explore the oral and intravenous pharmacokinetics of skimmin. All plasma samples were obtained following blood collection from the rat' tail vein and prepared using the protein precipitation method with acetonitrile. Separation of the analyte and internal standard (IS) magnoflorine was achieved by a reversed phase T3 column. The mobile phase consisted of water containing 0.1 % formic acid and acetonitrile with a gradient elution program. The analytical run time was 4 min with a flow rate of 0.3 mL/min. Detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI).Multiple reaction monitoring transitions were performed at m/z of 325.34 → 163.00 and 342.24 → 57.98 for skimmin and IS, respectively. The method demonstrated good linearity in the range of 2-2000 ng/mL and was validated by US FDA bioanalytical guidelines. A pharmacokinetic study of skimmin was then successfully conducted using the validated method. Hence, the absolute bioavailability of skimmin was approximately 25.08 % with rapid absorption and elimination. This study will be beneficial in better understanding the pharmacological properties and the further development of skimmin.
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http://dx.doi.org/10.1016/j.jpba.2019.112969DOI Listing
February 2020

Dual-channel design to suppress buffer induced current degradation in AlGaN/GaN heterostructures on Si.

Nanotechnology 2020 Mar 25;31(11):115202. Epub 2019 Nov 25.

State Key Laboratory for Information Photonics and Optical communications, School of Electronic Engineering, Beijing University of Posts and Telecommunications, Beijing 100876, People's Republic of China.

We design a dual-2DEG (Two dimensional electron gas) channel structure to suppress the buffer induced current degradation in AlGaN/GaN based heterostructures on Si. The epitaxial structure includes two AlGaN/GaN interfaces, and therefore induces two 2DEG channels at each interface. The upper 2DEG channel acts as the current transport channel (the working channel) while the bottom channel is used to shield the buffer charge induced electric field. Thus, the current in the upper channel keeps stable in regard of the trapping phenomenon in the buffer layers. Pulse stress measurements and back-gating sweep measurements are conducted to evaluate the current stability in the dual-channel structure. A normal single-channel AlGaN/GaN heterostructure is also tested as comparison. The current stability of the dual-channel structure in the pulsed stress measurement is better than the single-channel sample. The back-gating sweep measurement results further confirm the electric filed shielding mechanism of the bottom channel.
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http://dx.doi.org/10.1088/1361-6528/ab5b3eDOI Listing
March 2020

Loss of HMBOX1 promotes LPS-induced apoptosis and inhibits LPS-induced autophagy of vascular endothelial cells in mouse.

Apoptosis 2019 12;24(11-12):946-957

Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, 266237, People's Republic of China.

Our previous study revealed that Homeobox containing 1 (HMBOX1), essential for the survival of vascular endothelial cells (VECs), was involved in the progression of atherosclerosis. Knockdown of HMBOX1 promoted apoptosis and inhibited autophagy through regulating intracellular free zinc level in cultured VECs. In current study, in order to investigate the roles of HMBOX1 in vivo and in endothelium, we generated a knockout (KO) mouse for HMBOX1 by using transcription activator-like effector nucleases (TALENs) technology. Herein, we reported that the protein level of HMBOX1 was gradually increased during mouse development. The HMBOX1 KO mouse was viable and fertile. There existed no differences in apoptosis and autophagy of aortic endothelial cells between wild type and KO mouse. Whereas, loss of HMBOX1 promoted apoptosis and inhibited autophagy of aortic endothelial cells under lipopolysaccharide (LPS) stimulation in mouse. We also demonstrated that HMBOX1 deletion had no influence on the secretion of inflammatory cytokines TNF-α and IL-6. Moreover, overexpression or knockdown of HMBOX1 failed to regulate multiple pro-apoptotic genes expression in vitro. In conclusion, HMBOX1 participated in the functional maintenance of mouse aortic endothelial cells, the aortic endothelial cells of HMBOX1 KO mouse showed increased apoptosis and decreased autophagy with LPS treatment.
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http://dx.doi.org/10.1007/s10495-019-01572-6DOI Listing
December 2019

Metabolic Profiling of Alpinetin in Rat Plasma, Urine, Bile and Feces after Intragastric Administration.

Molecules 2019 Sep 24;24(19). Epub 2019 Sep 24.

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.

Alpinetin, a bioactive flavonoid, has been known to have a diverse therapeutic effect, with namely anti-inflammatory, anticancer and antioxidant effects with low systemic toxicity. This study aimed to obtain metabolic profiles of alpinetin in orally administrated rats. The metabolites of alpinetin were systematically analyzed and identified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The chromatographic separation was achieved on a High Strength Silica (HSS) T3 (1.8 μm, 2.1 × 100 mm) column with the mobile phase consisting of water containing 0.1% formic acid and acetonitrile with 0.1% formic acid via gradient elution. An extracted ion chromatogram strategy based on multiple prototype/metabolite intermediate templates and 71 typical metabolic reactions was proposed to comprehensively profile the metabolites of alpinetin. With the metabolite profiling strategy, altogether 15 compounds were recognized from urine, plasma, bile and feces of rats after intragastric administration of alpinetin for the first time. The prototype, glucuronide conjugates and phenolic acids metabolites were the probable predominant form of alpinetin in rats. This work showed a comprehensive study of the probable metabolic pathways of alpinetin in vivo, which could provide meaningful information for future pharmacological studies.
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http://dx.doi.org/10.3390/molecules24193458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804159PMC
September 2019

Characterisation of a Thermobacillus sucrose phosphorylase and its utility in enzymatic synthesis of 2-O-α-d-glucopyranosyl-l- ascorbic acid.

J Biotechnol 2019 Nov 27;305:27-34. Epub 2019 Aug 27.

College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211800, China. Electronic address:

Sucrose phosphorylase (SPase) is capable of specifically catalysing transglucosylation reactions and can be employed in the enzymatic synthesis of α-D-glycosides. In the present study, a putative Thermobacillus SPase gene (TSPase) was synthesised with optimised codons and overexpressed in Escherichia coli. The 1467 bp gene encodes a 488-amino acid protein with a calculated molecular mass of 55.8 kDa. The specific activity of the recombinant TSPase (rTSPase) was 6.42 U/mg for sucrose, and the optimum temperature and pH were 65 °C and pH 7.0. The T value of the rTSPase was 212 h at 50 °C and 98 h at 60 °C. A stimulating effect on the activity of the rTSPase was observed in the presence of 5 mM Co. The rTSPase showed increased stability against DMSO as organic co-solvent at 50 °C. The K and k of the rTSPase with sucrose were determined as 6.24 mM and 5.73 s respectively. The rTSPase produced 2-O-α-D-Glucopyranosyl-L-ascorbic acid (AA-2 G) from ascorbic acid in both crude extract and whole-cell forms. A maximum yield of 19.7% (39.94 ± 0.17 g/L) was achieved after incubation of ascorbic acid sodium salt and sucrose (1:2) with 19.76 U/mL of the rTSPase at pH 7.0 and 50 °C for 24 h.
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http://dx.doi.org/10.1016/j.jbiotec.2019.08.018DOI Listing
November 2019

MROH7-TTC4 read-through lncRNA suppresses vascular endothelial cell apoptosis and is upregulated by inhibition of ANXA7 GTPase activity.

FEBS J 2019 12 24;286(24):4937-4950. Epub 2019 Aug 24.

Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, China.

Apoptosis of vascular endothelial cells (VEC) is the main form of vascular injury that is closely linked to numerous cardiovascular diseases. Therefore, it is important to find new factors that can suppress VEC apoptosis. By using long noncoding RNA (lncRNA) microarray analysis, we found a new read-through lncRNA, MROH7-TTC4, which acted as an apoptosis inhibitor in VECs. Furthermore, by using the inhibitor (ABO) of annexin A7 (ANXA7) GTPase, we discovered that ANXA7 translocated into nucleus and interacted with 5'→3' exoribonuclease (XRN2). The decreased XRN2 phosphorylation induced by ANXA7 GTPase activity inhibition, promoted MROH7-TTC4 expression. Moreover, T-cell intracellular antigen-1 (TIA1), a binding protein of MROH7-TTC4, processed it into MROH7 and TTC4 that could inhibit VEC apoptosis. Here, we conclude that inhibiting ANXA7 GTPase activity promotes the interaction of ANXA7 and XRN2 in nucleus, which regulates the read-through transcription of MROH7-TTC4, and TIA1 is responsible for the process of MROH7-TTC4 that inhibits apoptosis through MROH7 and TTC4.
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http://dx.doi.org/10.1111/febs.15038DOI Listing
December 2019
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