Publications by authors named "Guohua Wang"

190 Publications

Prevalence and Predictors of Syphilis in Female Sex Workers in Eastern China: Findings from Six Consecutive Cross-Sectional Surveys.

J Multidiscip Healthc 2021 16;14:853-860. Epub 2021 Apr 16.

Tongxiang Center for Disease Prevention and Control, Jiaxing, Zhejiang, 314500, People's Republic of China.

Purpose: Female sex workers play an important role in transmitting HIV and syphilis from high-risk groups to the general population. However, epidemic trends and risk factors for syphilis in Chinese female sex workers (FSWs) remain unclear.

Methods: Using convenient sampling methods, 2482 FSWs were interviewed and tested for syphilis from 2014 to 2019, all of them were divided into two groups of high-grade FSWs and low-grade FSWs according to service solicited and clients price there were. Demographic data were collected and logistic regression analysis was used to identify risk factors for syphilis.

Results: 43.67% of participants have received free condoms, 76.15% of them engaged in peer education of the 2482 FSWs tested for syphilis, 107 (4.31%) were positive. The prevalence of syphilis in high-grade FSWs was significantly lower than that in low-grade FSWs (3.14% and 5.62%, respectively).The overall prevalence of syphilis increased from 3.19% to4.47%. The percentage of FSWs received free condoms and engaged in peer education increased significantly. With upgraded awareness of syphilis, the number of FSWs having protected sex also increased significantly. It is also found that low-grade female sex workers are at greater risk of syphilis than those high-grade ones (odds ratio (OR) = 1.76, 95% CI 1.18-2.63, p < 0.05).

Conclusion: Great awareness of syphilis and the increased utilization of condom did not reduce the prevalence of syphilis, especially in low-grade FSWs group. More effective integrated interventions should be developed for such populations.
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http://dx.doi.org/10.2147/JMDH.S305492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057824PMC
April 2021

Association of betatrophin amounts with 25-(OH)D levels in patients with gestational diabetes mellitus.

Medicine (Baltimore) 2021 Apr;100(16):e25646

Clinical Lab Department, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu Province, China.

Abstract: To determine the association of betatrophin amounts with 25-(OH)D levels in gestational diabetes mellitus (GDM) patients, and to provide new targets for the prevention and treatment of GDM.This study included 40 GDM patients (GDM group) and 37 healthy pregnant women (control group). Betatrophin, 25-(OH)D, fasting blood glucose (FBG), HbA1c, hsCRP, and FINS levels in peripheral blood, as well as betatrophin and 25-(OH)D amounts in cord blood, were measured. Then, associations of betatrophin levels with 25-(OH)D amounts and other indexes were determined.Maternal (P = .011) and cord (P = .022) blood betatrophin levels were significantly lower in the GDM group compared with control group. Cord blood betatrophin levels were higher compared with maternal blood amounts in both the GDM and control groups (both P = .000). Serum betatrophin levels were positively associated with 25-(OH)D levels (r = 0.677, P = .000), but negatively associated with hsCRP (r = -0.335, P = .037) and HOMA-IR (r = -0.346, P = .031) levels in the GDM group. Fetal weight was higher in the GDM group compared with control group (P = .023), and negatively associated with cord blood betatrophin amounts in the GDM group (r = -0.342, P = .031). However, cord blood betatrophin levels were not significantly associated with body length, Apgar score, and cord blood 25-(OH)D levels in the GDM group (all P > .05).Serum betatrophin and 25-(OH) D levels were positively associated in women with GDM, and both significantly lower compared with control values. Fetal weight was higher in the GDM group and associated with cord blood betatrophin. These findings provide insights into developing new predictive biomarkers or therapeutic targets for GDM.
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http://dx.doi.org/10.1097/MD.0000000000025646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078436PMC
April 2021

Identifying Plant Pentatricopeptide Repeat Proteins Using a Variable Selection Method.

Front Plant Sci 2021 1;12:506681. Epub 2021 Mar 1.

College of Information and Computer Engineering, Northeast Forestry University, Harbin, China.

Pentatricopeptide repeat (PPR), which is a triangular pentapeptide repeat domain, plays an important role in plant growth. Features extracted from sequences are applicable to PPR protein identification using certain classification methods. However, which components of a multidimensional feature (namely variables) are more effective for protein discrimination has never been discussed. Therefore, we seek to select variables from a multidimensional feature for identifying PPR proteins. A framework of variable selection for identifying PPR proteins is proposed. Samples representing PPR positive proteins and negative ones are equally split into a training and a testing set. Variable importance is regarded as scores derived from an iteration of resampling, training, and scoring step on the training set. A model selection method based on Gaussian mixture model is applied to automatic choice of variables which are effective to identify PPR proteins. Measurements are used on the testing set to show the effectiveness of the selected variables. Certain variables other than the multidimensional feature they belong to do work for discrimination between PPR positive proteins and those negative ones. In addition, the content of methionine may play an important role in predicting PPR proteins.
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http://dx.doi.org/10.3389/fpls.2021.506681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957076PMC
March 2021

Effects of DNA Methylation on TFs in Human Embryonic Stem Cells.

Front Genet 2021 23;12:639461. Epub 2021 Feb 23.

School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.

DNA methylation is an important epigenetic mechanism for gene regulation. The conventional view of DNA methylation is that DNA methylation could disrupt protein-DNA interactions and repress gene expression. Several recent studies reported that DNA methylation could alter transcription factors (TFs) binding sequence specificity . Here, we took advantage of the large sets of ChIP-seq data for TFs and whole-genome bisulfite sequencing data in many cell types to perform a systematic analysis of the protein-DNA methylation . We observed that many TFs could bind methylated DNA regions, especially in H1-hESC cells. By locating binding sites, we confirmed that some TFs could bind to methylated CpGs directly. The different proportion of CpGs at TF binding specificity motifs in different methylation statuses shows that some TFs are sensitive to methylation and some could bind to the methylated DNA with different motifs, such as CEBPB and CTCF. At the same time, TF binding could interactively alter local DNA methylation. The TF hypermethylation binding sites extensively overlap with enhancers. And we also found that some DNase I hypersensitive sites were specifically hypermethylated in H1-hESC cells. At last, compared with TFs' binding regions in multiple cell types, we observed that CTCF binding to high methylated regions in H1-hESC were not conservative. These pieces of evidence indicate that TFs that bind to hypermethylation DNA in H1-hESC cells may associate with enhancers to regulate special biological functions.
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http://dx.doi.org/10.3389/fgene.2021.639461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940757PMC
February 2021

The stacking strategy-based hybrid framework for identifying non-coding RNAs.

Brief Bioinform 2021 Mar 10. Epub 2021 Mar 10.

School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.

With the development of next-generation sequencing technology, a large number of transcripts need to be analyzed, and it has been a challenge to distinguish non-coding ribonucleic acid (RNAs) (ncRNAs) from coding RNAs. And for non-model organisms, due to the lack of transcriptional data, many existing methods cannot identify them. Therefore, in addition to using deoxyribonucleic acid-based and RNA-based features, we also proposed a hybrid framework based on the stacking strategy to identify ncRNAs, and we innovatively added eight features based on predicted peptides. The proposed framework was based on stacking two-layer classifier which combined random forest (RF), LightGBM, XGBoost and logistic regression (LR) models. We used this framework to build two types of models. For cross-species ncRNAs identification model, we tested it on six different species: human, mouse, zebrafish, fruit fly, worm and Arabidopsis. Compared with other tools, our model was the best in datasets of Arabidopsis, worm and zebrafish with the accuracy of 98.36%, 99.65% and 94.12%. For performance metrics analysis, the datasets of the six species were considered as a whole set, and the sensitivity, accuracy, precision and F1 values of our model were the best. For the plant-specific ncRNAs identification model, the average values of the six metrics of the two experiments were all greater than 95%, which demonstrated it can be used to identify ncRNAs in plants. The above indicates that the hybrid framework we designed is universal between animals and plants and has significant advantages in the identification of cross-species ncRNAs.
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http://dx.doi.org/10.1093/bib/bbab023DOI Listing
March 2021

Mapping the Worldwide Trends on Energy Poverty Research: A Bibliometric Analysis (1999-2019).

Int J Environ Res Public Health 2021 02 11;18(4). Epub 2021 Feb 11.

College of Public Administration, Huazhong University of Science and Technology, Wuhan 430074, China.

Energy poverty is one of the main challenges facing humanity in the 21st century. Research on energy poverty is becoming a common focus of scholars in many areas. Bibliometrics can help researchers dig deep into the information of specific research fields from a quantitative perspective. In this study, we collected 1018 research papers in the field of energy poverty published in the period 1999-2019 from the Web of Science databases and conducted a bibliometric analysis on them. Cleaning and screening of sample papers, matrix construction, and visualization were performed using Bibliometrix, VOSviewer, and HistCite, summarizing the internal and external characteristics of the papers. With regard to external characteristics, a total of 982 research institutions in 80 regions conducted research in this field. There is extensive cooperation between the countries, and the UK, the USA, Australia, and Italy play the most active role in the cooperation network. With regard to internal characteristics, we found the two most representative citation paths: one path starts from the concerns of energy-poor groups and stops at an ethical discussion on energy poverty; the second path is based on the existing technological path, continuously developing coping policies, evaluation methods, and a conceptual framework for dealing with energy poverty. Furthermore, through coupling analysis, we discovered four focuses of energy poverty research: improvement of definition, improvement of evaluation methods, effects of coping policy, and energy justice. Through a comprehensive analysis of existing papers, this paper reveals some limitations of previous studies and recommends some promising directions for future research on energy poverty.
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http://dx.doi.org/10.3390/ijerph18041764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918555PMC
February 2021

AlignGraph2: similar genome-assisted reassembly pipeline for PacBio long reads.

Brief Bioinform 2021 Feb 23. Epub 2021 Feb 23.

Interdisciplinary Information Sciences, School of Software Engineering, Beijing Jiaotong University, China.

Contigs assembled from the third-generation sequencing long reads are usually more complete than the second-generation short reads. However, the current algorithms still have difficulty in assembling the long reads into the ideal complete and accurate genome, or the theoretical best result [1]. To improve the long read contigs and with more and more fully sequenced genomes available, it could still be possible to use the similar genome-assisted reassembly method [2], which was initially proposed for the short reads making use of a closely related genome (similar genome) to the sequencing genome (target genome). The method aligns the contigs and reads to the similar genome, and then extends and refines the aligned contigs with the aligned reads. Here, we introduce AlignGraph2, a similar genome-assisted reassembly pipeline for the PacBio long reads. The AlignGraph2 pipeline is the second version of AlignGraph algorithm proposed by us but completely redesigned, can be inputted with either error-prone or HiFi long reads, and contains four novel algorithms: similarity-aware alignment algorithm and alignment filtration algorithm for alignment of the long reads and preassembled contigs to the similar genome, and reassembly algorithm and weight-adjusted consensus algorithm for extension and refinement of the preassembled contigs. In our performance tests on both error-prone and HiFi long reads, AlignGraph2 can align 5.7-27.2% more long reads and 7.3-56.0% more bases than some current alignment algorithm and is more efficient or comparable to the others. For contigs assembled with various de novo algorithms and aligned to similar genomes (aligned contigs), AlignGraph2 can extend 8.7-94.7% of them (extendable contigs), and obtain contigs of 7.0-249.6% larger N50 value and 5.2-87.7% smaller number of indels per 100 kbp (extended contigs). With genomes of decreased similarities, AlignGraph2 also has relatively stable performance. The AlignGraph2 software can be downloaded for free from this site: https://github.com/huangs001/AlignGraph2.
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http://dx.doi.org/10.1093/bib/bbab022DOI Listing
February 2021

Surgical repair of mitral valve bileaflet prolapse in pediatric patients.

J Card Surg 2021 Feb 18. Epub 2021 Feb 18.

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Pediatric mitral regurgitation (MR), especially with bileaflet prolapse, is relatively rare, of high complexity, and frequently associated with other congenital cardiac abnormalities. It remains a major therapeutic challenge for surgeons. This study reports our experience of surgical treatment of this mitral disease and midterm follow-up results.

Methods: Between January 2016 and April 2020, nine pediatric patients, six females and three males, age ranged from 3 to 12 years (median age was 6 years) with a weight range of 12-36 kg (median weight was 25 kg), who all had over moderate regurgitation caused by bileaflet prolapse with mean distance of leaflet coaptation beyond annular plane 5.89 ± 1.66 mm (4-9 mm), received mitral valve (MV) repair. Various surgical techniques were used to repair MV.

Results: The median follow-up period was 23(6-51) months, only one patient had moderately severe recurrent of MR, no patient developed systolic anterior motion (SAM) or mitral stenosis. Freedom from reoperation was 100% during the follow-up period. Compared to preoperation, the left atrial (LA) diameter and left ventricular end-diastolic diameter (LVEDD) decreased significantly from 2.94 ± 0.49 cm to 2.37 ± 0.38 cm (LA, p < .01) and from 4.13 ± 0.73 cm to 3.62 ± 0.49 cm (LVEDD, p < .01) respectively, ejection fraction (EF) decreased significantly (p < .05) from 68.56 ± 3.98% to 62.89 ± 4.48% before discharged.

Conclusion: We share our experience of surgical repair of mitral valve bileaflet prolapse in pediatric patients. Several surgical methods are considered to be used to repair the MV due to the high complexity of lesions. Anatomic correction or functional correction in our reports almost reaches the same result, while functional correction means simpler operation.
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http://dx.doi.org/10.1111/jocs.15432DOI Listing
February 2021

An all-to-all approach to the identification of sequence-specific readers for epigenetic DNA modifications on cytosine.

Nat Commun 2021 02 4;12(1):795. Epub 2021 Feb 4.

Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Epigenetic modifications of DNA play important roles in many biological processes. Identifying readers of these epigenetic marks is a critical step towards understanding the underlying mechanisms. Here, we present an all-to-all approach, dubbed digital affinity profiling via proximity ligation (DAPPL), to simultaneously profile human TF-DNA interactions using mixtures of random DNA libraries carrying different epigenetic modifications (i.e., 5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine) on CpG dinucleotides. Many proteins that recognize consensus sequences carrying these modifications in symmetric and/or hemi-modified forms are identified. We further demonstrate that the modifications in different sequence contexts could either enhance or suppress TF binding activity. Moreover, many modifications can affect TF binding specificity. Furthermore, symmetric modifications show a stronger effect in either enhancing or suppressing TF-DNA interactions than hemi-modifications. Finally, in vivo evidence suggests that USF1 and USF2 might regulate transcription via hydroxymethylcytosine-binding activity in weak enhancers in human embryonic stem cells.
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http://dx.doi.org/10.1038/s41467-021-20950-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862700PMC
February 2021

Inhibition of S-adenosyl-L-homocysteine hydrolase alleviates alloimmune response by down-regulating CD4 T-cell activation in a mouse heart transplantation model.

Ann Transl Med 2020 Dec;8(23):1582

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Transmethylation reactions play an important role on lymphocyte activation and function. S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitors prevent the feedback of transmethylation reactions by S-adenosyl-L-homocysteine (SAH) accumulation, a competitive antagonist of S-adenosylmethionine (SAM)-dependent methyltransferases. However, the role of SAH in solid organ transplantation is currently unclear.

Methods: A murine model of cardiac transplantation (BALB/C to C57B/6) was established to assess allograft survival, histology, and T cell infiltration. The reversible SAHH inhibitor, DZ2002, and irreversible SAHH inhibitor, adenosine dialdehyde (AdOx), were used to assess their immunosuppressive effects in murine cardiac transplantation, compared with mice with DMSO.

Results: Both SAHH inhibitors prolonged the survival of cardiac allografts and alleviated alloimmune response. Notably, AdOx and DZ2002 both eliminated frequencies of Th1 and Th17 in CD4 T cells in cardiac transplantation, and reduced the frequency of active CD4 T cell (CD44 CD62L). The irreversible SAHH inhibitor facilitated the differentiation of regulatory T cells (Tregs) and increased Bim expression. Furthermore, both SAHH inhibitors alleviated infiltration of CD4 T cells in cardiac allografts.

Conclusions: The SAHH inhibitors (AdOx and DZ2002) alleviates allograft rejection in cardiac transplantation by inhibition of CD4 T alloimmune response. SAHH inhibitors, especially DZ2002, is a promising complementary therapeutic agent in organ transplantation.
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http://dx.doi.org/10.21037/atm-20-2899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791210PMC
December 2020

Orbital competition of Mnand Vions in MnVO.

J Phys Condens Matter 2021 Jan 7. Epub 2021 Jan 7.

Shanghai Jiao Tong University, 5-720 New Buildings of Sciences No. 800 Dongchuan Road, Shanghai, 200240, CHINA.

The structure and magnetic properties of MnVO(0 < x ≤1) have been investigated by the heat capacity, magnetization, x-ray diffraction and neutron diffraction measurements, and a phase diagram of temperature versus composition was built up: For x ≤ 0.3, a cubic-to-tetragonal (c > a) phase transition was observed; For x > 0.3, the system kept the tetragonal lattice. Although the collinear and noncollinear magnetic transition of Vions was obtained in all compositions, the canting angles between Vions decreased with Mn-doping and the ordering of Mnions was only observed as x > 0.4. In order to study the dynamics of the ground state, the first principle simulation was applied to analyze not only the orbital effects of Mn, Mn, and Vions, but also the related exchange energies.
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http://dx.doi.org/10.1088/1361-648X/abd9a1DOI Listing
January 2021

A deep learning approach for filtering structural variants in short read sequencing data.

Brief Bioinform 2020 Dec 30. Epub 2020 Dec 30.

School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150001, China.

Short read whole genome sequencing has become widely used to detect structural variants in human genetic studies and clinical practices. However, accurate detection of structural variants is a challenging task. Especially existing structural variant detection approaches produce a large proportion of incorrect calls, so effective structural variant filtering approaches are urgently needed. In this study, we propose a novel deep learning-based approach, DeepSVFilter, for filtering structural variants in short read whole genome sequencing data. DeepSVFilter encodes structural variant signals in the read alignments as images and adopts the transfer learning with pre-trained convolutional neural networks as the classification models, which are trained on the well-characterized samples with known high confidence structural variants. We use two well-characterized samples to demonstrate DeepSVFilter's performance and its filtering effect coupled with commonly used structural variant detection approaches. The software DeepSVFilter is implemented using Python and freely available from the website at https://github.com/yongzhuang/DeepSVFilter.
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http://dx.doi.org/10.1093/bib/bbaa370DOI Listing
December 2020

A meta-analysis of complications associated with the use of cement-augmented pedicle screws in osteoporosis of spine.

Orthop Traumatol Surg Res 2020 Dec 15:102791. Epub 2020 Dec 15.

Department of Orthopedics, Shengli Oilfield Central Hospital, No.31, Jinan Road, 257000 Dongying City, Shandong Province, China.

Purpose: Our study aimed to provide updated and comprehensive evidence on the complications associated with the use of cement-augmented pedicle screws (CAPS) in osteoporosis patients undergoing spinal instrumentation.

Methods: Databases of PubMed, Embase, Ovoid, and Google Scholar were screened from January 2000-February 2020 for studies reporting complications of CAPS in osteoporosis patients. Pooled estimates (with 95% confidence intervals) were calculated.

Results: Twenty studies were included. The pooled risk of screw loosening, screw breakage and screw migration was 2.0% (0.2%-4.9%), 0.6% (0%-2.0%) and 0.2% (0%-1.2%) respectively. On pooling of data from 1277 patients, we found the risk of all cement leakage to be 21.8% (6%-43.1%). However, data from 1654 patients indicated the risk of symptomatic cement leakage was 1.2% (0.6%-1.9%). The incidence of pulmonary embolism was 3.0% (0.5%-6.8%) while the risk of symptomatic pulmonary embolism was 0.8% (0.2%-1.5%). Pooled risk of neurovascular complications was 1.6% (0.3%-3.6%), adjacent compression fracture was 3.3% (1.2%-6.2%) and infectious complications was 3.1% (1.1%-5.7%). There were high heterogeneity and variability in the study outcomes.

Conclusion: The incidence of screw-related complications like loosening, breakage, and migration with the use of CAPS in spinal instrumentation of osteoporotic patients is low. The risk of cement leakage is high and variable but the incidence of symptomatic cement leakage and related neurovascular or pulmonary complications is low. Further studies using homogenous methods of reporting are needed to strengthen current evidence.

Level Of Evidence: II, Systematic Review and Meta-analysis.
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http://dx.doi.org/10.1016/j.otsr.2020.102791DOI Listing
December 2020

Preparation, optimization, and evaluation of an inhaled solution of total saponins of and its protective effect against idiopathic pulmonary fibrosis.

Drug Deliv 2020 Nov;27(1):1718-1728

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive pulmonary disease that can cause fibrotic remodeling of the surrounding lung, thus leading to respiratory failure. Although IPF is the most common form of idiopathic interstitial pneumonia, the precise mechanisms underlying this condition remain unknown. In this study, we used total saponins of inhalation solution (TIS) to induce idiopathic bleomycin-induced pulmonary fibrosis in rats. The uniformity of delivery dose was investigated by analyzing the aerodynamic particle size distribution and drug stability. The potential of hydrogen potential of hydrogen (pH) of the inhalation solution was 7.0 and the solvent 0.9% NaCl solution, thus meeting physiological requirements for pulmonary drug administration. The delivery rate was 1.94 ± 0.16 mg·min and the total dose was 17.40 ± 0.04 mg. TIS was composed of five key components: notoginsenoside R, ginsenosides Rg, ginsenosides Re, ginsenosides Rb, and ginsenosides Rd. The mass median aerodynamic diameter (MMAD) for these five components were 3.62 ± 0.05 µm, 3.62 ± 0.06 µm, 3.65 ± 0.10 µm, 3.62 ± 0.06 µm, and 3.61 ± 0.05 µm, respectively. Fine particle fraction (FPF) was 66.24 ± 0.73%, 66.20 ± 0.89%, 66.07 ± 1.42%, 66.18 ± 0.79%, and 66.29 ± 0.70%, respectively. The MMAD for inhalation solutions needs to be 1-5 µm, which indicates that the components of TIS are suitable for inhalation. It is important to control the particle size of targeted drugs to ensure that the drug is delivered to the appropriate target tissue. experiments indicated that TIS exhibited high rates of deposition in lung tissue, thus indicating that pulmonary delivery systems may represent a good therapeutic option for patients.
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http://dx.doi.org/10.1080/10717544.2020.1856222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738294PMC
November 2020

Circadian clock disruption attenuated growth hormone(GH)-mediated signalling.

Gen Comp Endocrinol 2021 Feb 24;302:113670. Epub 2020 Nov 24.

Department of Pediatric Gastroenterology, The First Hospital of Jilin University, Changchun 130021, People's Republic of China. Electronic address:

The circadian molecular clock is an internal time-keeping system, which regulates various physiological processes through the generation of approximately 24-hour circadian rhythms. BMAL1 (brain and muscle arnt-like 1) is a core component of the circadian clock. Previous studies have shown that the circadian clock correlates with rhythmic secretion of endocrine hormone (such as growth hormone, GH). Currently, the effect of circadian clock on the GH-mediated biological activities is not fully understood. In this work, we used BMAL1 gene knockout mice (BMAL mice) model to explore the effect of circadian clock dysfunction on GH's activities, and the results from in vivo and in vitro experiments showed that GH-induced signaling is down-regulated. In vivo, GH/GHR-mediated tyrosine phosphorylation of signaling molecules (such as the Janus kinase-signal transducer and activator of transcription, JAK-STAT) in BMAL mice was significantly lower compared to control mice. In vitro, GH/GHR-mediated signaling in the hepatocytes from BMAL mice is decreased compared to hepatocytes from control mice. Furthermore, we explore the mechanism by which GH/GHR-mediated signalling is down-regulated in BMAL mice, and results indicated that the expression levels of negative regulators of cytokine signaling (such as the suppressor of cytokine signaling (SOCS) and protein phosphatase) were increased, which may be one of the factors that cause the GH signaling downregulation. In summary, our results show that the circadian clock affects the biological activities of GH. This finding lays the foundation for future investigations into the relationship between the circadian clock and biological activities of GH.
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http://dx.doi.org/10.1016/j.ygcen.2020.113670DOI Listing
February 2021

Effects of rhodioloside on the neurological functions of rats with total cerebral ischemia/reperfusion and cone neuron injury in the hippocampal CA1 region.

PeerJ 2020 9;8:e10056. Epub 2020 Nov 9.

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

Rhodioloside, the main effective constituent of , demonstrates antiaging and antioxidative stress functions and inhibits calcium overloading in cells. These functions imply that rhodioloside may exert protective effects on hippocampal neurons after total cerebral ischemia/reperfusion injury. In this study, male Wistar rat models of total cerebral ischemia were constructed and randomly divided into four groups: sham-operation, ischemia/reperfusion, low-dosage, and high-dosage groups. The result showed that rhodioloside treatment reduced the apoptosis rates of hippocampal neurons and the histological grades of cone cells in the hippocampal CA1 region, but neuronal density was significantly increased. Besides, the protein expressions of Bcl-2/Bax and p53 were measured and found Bcl-2/Bax was increased and p53 protein level was reduced. Therefore, rhodioloside might have protective effects on rats with ischemia/reperfusion brain injury.
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http://dx.doi.org/10.7717/peerj.10056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659626PMC
November 2020

Gene regulatory networks controlling vertebrate retinal regeneration.

Science 2020 11 1;370(6519). Epub 2020 Oct 1.

Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Injury induces retinal Müller glia of certain cold-blooded vertebrates, but not those of mammals, to regenerate neurons. To identify gene regulatory networks that reprogram Müller glia into progenitor cells, we profiled changes in gene expression and chromatin accessibility in Müller glia from zebrafish, chick, and mice in response to different stimuli. We identified evolutionarily conserved and species-specific gene networks controlling glial quiescence, reactivity, and neurogenesis. In zebrafish and chick, the transition from quiescence to reactivity is essential for retinal regeneration, whereas in mice, a dedicated network suppresses neurogenic competence and restores quiescence. Disruption of nuclear factor I transcription factors, which maintain and restore quiescence, induces Müller glia to proliferate and generate neurons in adult mice after injury. These findings may aid in designing therapies to restore retinal neurons lost to degenerative diseases.
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http://dx.doi.org/10.1126/science.abb8598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899183PMC
November 2020

BP4RNAseq: a babysitter package for retrospective and newly generated RNA-seq data analyses using both alignment-based and alignment-free quantification method.

Bioinformatics 2020 Sep 25. Epub 2020 Sep 25.

State Key Laboratory of Tree Genetics and Breeding, Northeast Forestry University, Harbin, China.

Summary: Processing raw reads of RNA sequencing (RNA-seq) data, no matter public or newly sequenced data, involves a lot of specialized tools and technical configurations that are often unfamiliar and time-consuming to learn for non-bioinformatics researchers. Here, we develop the R package BP4RNAseq, which integrates the state-of-art tools from both alignment-based and alignment-free quantification workflows. The BP4RNAseq package is a highly automated tool by using an optimized pipeline to improve the sensitivity and accuracy of RNA-seq analyses. It can take only two nontechnical parameters and output six formatted gene expression quantification at gene and transcript levels. The package applies to both retrospective and newly generated bulk RNA-seq data analyses and is also applicable for single-cell RNA-seq analyses. It, therefore, greatly facilitates the application of RNA-seq.

Availability: The BP4RNAseq package for R and its documentation are freely available at https://github.com/sunshanwen/BP4RNAseq.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa832DOI Listing
September 2020

Study on the levels of 25(OH)D, inflammation markers and glucose and fat metabolism indexes in pregnant women of Han nationality in Jiangsu province with gestational diabetes mellitus.

Medicine (Baltimore) 2020 Aug;99(35):e21654

Department of Obstetrics, the First People's Hospital of Lianyungang City, China.

The aim of this study is to investigate the levels of 25(OH)D, inflammation markers and glucose and fat metabolism indexes in pregnant women with Gestational diabetes mellitus (GDM).One hundred and ten cases GDM and 100 cases healthy pregnant women in the First People's Hospital of Lianyungang City from October 2016 to December 2018 were recruited for this observational cross-sectional study. Each participant's anthropometric and demographic data was recorded. Blood samples were collected and analyzed to determine the levels of 25(OH)D, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), fasting blood glucose, fasting blood insulin, hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol and triglycerides.Inflammatory markers and glucose and fat metabolism indexes were all significantly higher in the GDM group than that in the control group, while Serum 25(OH)D level in the GDM group was significantly lower. Serum 25(OH)D levels were negatively correlated with hs-CRP, while not with TNF-α. Furthermore, Serum 25(OH)D, hs-CRP and TNF-α levels were all associated with increased risk of developing GDM.Nowadays, the reports on the association between 25(OH)D level and GDM were controversial. Our results are consistent with the view that there was association between 25(OH)D level and GDM, and expand the literature by showing the roles of 25(OH)D, inflammation markers as well as glucose and fat metabolism indexes in the risk of developing GDM in the pregnant women with the low overall levels of 25(OH)D before delivery. This broadens our knowledge on the pathophysiology of GDM, which may be helpful in prevention and treatment of GDM.
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http://dx.doi.org/10.1097/MD.0000000000021654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458183PMC
August 2020

PPAR-γ Is Critical for HDAC3-Mediated Control of Oligodendrocyte Progenitor Cell Proliferation and Differentiation after Focal Demyelination.

Mol Neurobiol 2020 Nov 15;57(11):4810-4824. Epub 2020 Aug 15.

Department of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong, 226019, Jiangsu, China.

Disruption of remyelination contributes to neurodegeneration and cognitive impairment in chronically disabled patients. Valproic acid (VPA) inhibits histone deacetylase (HDAC) function and probably promotes oligodendrocyte progenitor cell (OPC) proliferation and differentiation; however, the relevant molecular mechanisms remain unknown. Here, focal demyelinating lesions (FDLs) were generated in mice by two-point stereotactic injection of lysophosphatidylcholine (LPC) into the corpus callosum. Cognitive functions, sensorimotor abilities and histopathological changes were assessed for up to 28 days post-injury with or without VPA treatment. Primary OPCs were harvested and used to study the effect of VPA on OPC differentiation under inflammatory conditions. VPA dose-dependently attenuated learning and memory deficits and robustly protected white matter after FDL induction, as demonstrated by reductions in SMI-32 and increases in myelin basic protein staining. VPA also promoted OPC proliferation and differentiation and increased subsequent remyelination efficiency by day 28 post-FDL induction. VPA treatment did not affect HDAC1, HDAC2 or HDAC8 expression but reduced HDAC3 protein levels. In vitro, VPA improved the survival of mouse OPCs and promoted their differentiation into oligodendrocytes following lipopolysaccharide (LPS) stimulation. LPS caused OPCs to overexpress HDAC3, which translocated from the cytoplasm into the nucleus, where it directly interacted with the nuclear transcription factor PPAR-γ and negatively regulated PPAR-γ expression. VPA decreased the expression of HDAC3 and promoted remyelination and functional neurological recovery after FDL. These findings may support the use of strategies modulating HDAC3-mediated regulation of protein acetylation for the treatment of demyelination-related cognitive dysfunction.
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http://dx.doi.org/10.1007/s12035-020-02060-8DOI Listing
November 2020

BYASE: a Python library for estimating gene and isoform level allele-specific expression.

Bioinformatics 2020 12;36(19):4955-4956

School of Computer Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China.

Summary: Allele-specific expression (ASE) is involved in many important biological mechanisms. We present a python package BYASE and its graphical user interface (GUI) tool BYASE-GUI for the identification of ASE from single-end and paired-end RNA-seq data based on Bayesian inference, which can simultaneously report differences in gene-level and isoform-level expression. BYASE uses both phased SNPs and non-phased SNPs, and supports polyploid organisms.

Availability And Implementation: The source codes of BYASE and BYASE-GUI are freely available at https://github.com/ncjllld/byase and https://github.com/ncjllld/byase_gui.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa636DOI Listing
December 2020

Familial Hemophagocytic Lymphohistiocytosis Type 2 in a Chinese Infant with PRF1 Homozygous Mutation: a Case Report.

Clin Lab 2020 Jul;66(7)

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and histiocytes. Familial HLH (fHLH) is an autosomal recessive disease.

Methods: We report a case of fHLH in a 45-day-old Chinese female infant presenting with fever, hepatosplenomegaly, and pancytopenia. Typical laboratory findings were detected for the infant, and fHLH was diagnosed according to the HLH-2004 guidelines. The infant was initially treated with antibiotics and ganciclovir prior to diagnosis of HLH. No response to glucocorticoid and intravenous immunoglobulin treatment was observed, and the infant died of disseminated intravascular coagulation.

Results: A mutation in the perforin gene was identified in this patient. Direct sequencing analysis revealed a deleterious homozygous mutation of PRF1, c.65delC [p.P22Rfs*29], and her parents were heterozygous carriers of the mutant alleles.

Conclusions: Therefore, familial HLH is still a potentially lethal childhood illness, and appropriate individualized therapies, including cell therapy and gene targeting therapy, need to be established.
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http://dx.doi.org/10.7754/Clin.Lab.2019.191136DOI Listing
July 2020

Acute sleep deprivation leads to growth hormone (GH) resistance in rats.

Gen Comp Endocrinol 2020 09 3;296:113545. Epub 2020 Jul 3.

Department of Pediatric Gastroenterology, The First Hospital of Jilin University, Changchun 130021, People's Republic of China. Electronic address:

Sleep is an essential physiological process that is required by all higher animals. Sleep has many important physiological functions. Previous studies have focused on the relationship between sleep and growth hormone secretion patterns. However, to date, whether sleep affects the biological activities of GH remains unclear. Here, we investigated this issue by evaluating the growth hormone receptor (GHR)-mediated intracellular signalling pathway in a sleep-deprived rat model. The results showed that GH's signalling ability is decreased in an acute sleep deprivation rat model. JAK2-STAT signalling was decreased significantly compared to that in control rats. We further analysed the possible molecular mechanism of GH signal inhibition in sleep-deprived rats. The results showed that the protein expression levels of SOCS3 (suppressors of cytokine signalling 3, which functions as the negative regulatory molecule of GH's signalling) increased; however, other negative regulatory proteins, such as protein phosphatase (PTP1B), did not change. In addition, acute sleep deprivation results in a significant increase in serum FFA (free fatty acid) level, which is also one of the factors contributing to GH inhibition. These findings suggest that GH signal resistance may be caused by a combination of factors. This study could serve as an important reference for related studies on the effect of sleep deprivation on endocrine systems.
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http://dx.doi.org/10.1016/j.ygcen.2020.113545DOI Listing
September 2020

Orthotopic Heart Transplantation for Congenital Heart Disease with Dextrocardia: A Single-Center Clinic Experience.

Biomed Res Int 2020 31;2020:3487635. Epub 2020 May 31.

Cardiovascular Surgery, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan, China.

Background: We report a modified transplantation surgical technique for CHD with dextrocardia which is rare and surgically challenging.

Methods: From January 2015 to May 2018, 5 patients with end-stage CHD with dextrocardia underwent heart transplantation at our institute. They were 10, 29, 13, 15, and 22 years old, respectively; 3 of them had dextroversion, and the other 2 had mirror-image dextrocardia and post-TCPC. The atrial-atrial anastomosis was performed first between the donor's upper-left PVO and the recipient's lower-left PVO. The apex thereby rotated approximately 90° clockwise (to the right). The end-to-end donor and recipient aortas, vena cava, and pulmonary arteries were then anastomosed.

Results: The cold ischemic time of the donor heart was 284.6 ± 108.3 min, and the CPB time was 190.2 ± 43.8 min. The postoperative X-ray showed the apex on the right. Four patients were successfully discharged, and the follow-up times were 47 months, 36 months, 12 months, and 12 months. One post-TCPC patient died because of pneumonia and hypoxia at 59 postoperative days.

Conclusions: Heart transplantation with dextrocardial CHD is rare. A 90° rotation at the left atrial level, aortic end-to-end anastomosis, and vena cava reconstruction by vascular prosthesis or systemic atrial cuff is a simple and effective surgical strategy.
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http://dx.doi.org/10.1155/2020/3487635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285252PMC
March 2021

Evaluating individual genome similarity with a topic model.

Bioinformatics 2020 09;36(18):4757-4764

School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150001, China.

Motivation: Evaluating genome similarity among individuals is an essential step in data analysis. Advanced sequencing technology detects more and rarer variants for massive individual genomes, thus enabling individual-level genome similarity evaluation. However, the current methodologies, such as the principal component analysis (PCA), lack the capability to fully leverage rare variants and are also difficult to interpret in terms of population genetics.

Results: Here, we introduce a probabilistic topic model, latent Dirichlet allocation, to evaluate individual genome similarity. A total of 2535 individuals from the 1000 Genomes Project (KGP) were used to demonstrate our method. Various aspects of variant choice and model parameter selection were studied. We found that relatively rare (0.001 20 000 bp) variants are more efficient for genome similarity evaluation. At least 100 000 such variants are necessary. In our results, the populations show significantly less mixed and more cohesive visualization than the PCA results. The global similarities among the KGP genomes are consistent with known geographical, historical and cultural factors.

Availability And Implementation: The source code and data access are available at: https://github.com/lrjuan/LDA_genome.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa583DOI Listing
September 2020

LncRNA LBX2-AS1 facilitates abdominal aortic aneurysm through miR-4685-5p/LBX2 feedback loop.

Biomed Pharmacother 2020 Sep 16;129:109904. Epub 2020 Jun 16.

Department of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, No.1095 Jiefang Ave, Hankou, 430000 Hubei, China. Electronic address:

Long noncoding RNAs (LncRNAs) are involved in multiple processes of human malignancy, and emerge as crucial molecules in RNA biology. However, the function of lncRNAs has not been well illustrated in abdominal aortic aneurysm (AAA). In this research, the effects of dysregulated ladybird homeobox 2 antisense RNA 1 (LBX2-AS1) or ladybird homeobox 2 (LBX2) on vascular smooth muscle cell (VSMC) biological processes were surveyed via cell counting kit-8 (CCK-8), methyl thiazolyl tetrazolium (MTT), terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and caspase-3 activity assays. LBX2-AS1 and LBX2 both possessed pro-apoptosis and anti-proliferation functions in AAA. Mechanically, the regulation role of LBX2-AS1 on miR-4685-5p or that of miR-4685-5p on LBX2 was investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the competing endogenous RNA (ceRNA) network was confirmed by luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. LBX2-AS1 sequestered miR-4685-5p to release LBX2 expression via ceRNA mechanism. Further, LBX2 could act as a transcriptional activator of LBX2-AS1. A positive feedback loop was formed by LBX2-AS1, miR-4685-5p and LBX2, deteriorating AAA formation and progression. To sum up, our data suggested that LBX2-AS1, miR-4685-5p and LBX2 constituted a positive feedback loop in promoting AAA development, implying a potential usage of LBX2-AS1/miR-4685-5p/LBX2 axis in AAA management.
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http://dx.doi.org/10.1016/j.biopha.2020.109904DOI Listing
September 2020

A Visual Approach for the SARS (Severe Acute Respiratory Syndrome) Outbreak Data Analysis.

Int J Environ Res Public Health 2020 06 3;17(11). Epub 2020 Jun 3.

Faculty of Information Engineering, Shaoyang University, Shaoyang 422000, China.

Virus outbreaks are threats to humanity, and coronaviruses are the latest of many epidemics in the last few decades in the world. SARS-CoV (Severe Acute Respiratory Syndrome Associated Coronavirus) is a member of the coronavirus family, so its study is useful for relevant virus data research. In this work, we conduct a proposed approach that is non-medical/clinical, generate graphs from five features of the SARS outbreak data in five countries and regions, and offer insights from a visual analysis perspective. The results show that prevention measures such as quarantine are the most common control policies used, and areas with strict measures did have fewer peak period days; for instance, Hong Kong handled the outbreak better than other areas. Data conflict issues found with this approach are discussed as well. Visual analysis is also proved to be a useful technique to present the SARS outbreak data at this stage; furthermore, we are proceeding to apply a similar methodology with more features to future COVID-19 research from a visual analysis perfective.
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http://dx.doi.org/10.3390/ijerph17113973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312089PMC
June 2020

Modelling biological age based on plasma peptides in Han Chinese adults.

Aging (Albany NY) 2020 06 5;12(11):10676-10686. Epub 2020 Jun 5.

Department of Epidemiology and Health Statistics, School of Public Health, Beijing Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing 100069, China.

Age-related disease burdens increased over time, and whether plasma peptides can be used to accurately predict age in order to explain the variation in biological indicators remains inadequately understood. Here we first developed a biological age model based on plasma peptides in 1890 Chinese Han adults. Based on mass spectrometry, 84 peptides were detected with masses in the range of 0.6-10.0 kDa, and 13 of these peptides were identified as known amino acid sequences. Five of these thirteen plasma peptides, including fragments of apolipoprotein A-I (m/z 2883.99), fibrinogen alpha chain (m/z 3060.13), complement C3 (m/z 2190.59), complement C4-A (m/z 1898.21), and breast cancer type 2 susceptibility protein (m/z 1607.84) were finally included in the final model by performing a multivariate linear regression with stepwise selection. This biological age model accounted for 72.3% of the variation in chronological age. Furthermore, the linear correlation between the actual age and biological age was 0.851 (95% confidence interval: 0.836-0.864) and 0.842 (95% confidence interval: 0.810-0.869) in the training and validation sets, respectively. The biological age based on plasma peptides has potential positive effects on primary prevention, and its biological meaning warrants further investigation.
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http://dx.doi.org/10.18632/aging.103286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346055PMC
June 2020

Hypoxic preconditioning enhances the differentiation of bone marrow stromal cells into mature oligodendrocytes via the mTOR/HIF-1α/VEGF pathway in traumatic brain injury.

Brain Behav 2020 07 30;10(7):e01675. Epub 2020 May 30.

Department of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Objective: Traumatic brain injury (TBI) results not only in gray matter damage, but also in severe white matter injury (WMI). Previous findings support hypoxic preconditioning (HP) could augment the efficacy of bone marrow stromal cell (BMSC) transplantation in a TBI mouse model. However, whether HP-treated BMSCs (H-BMSCs) could overcome remyelination failure after WMI is unclear, and the molecular mechanisms remain to be explored. Here, we focused on the therapeutic benefits of H-BMSC transplantation for treating WMI, as well as its underlying mechanisms.

Methods: In vitro, BMSCs were incubated at passage 4 in the hypoxic preconditioning (1.0% oxygen) for 8 hr. In vivo, a TBI mouse model was established, and DMEM cell culture medium (control), normal cultured BMSCs (N-BMSCs), or H-BMSCs were transplanted to mice 24 hr afterward. Neurobehavioral function, histopathological changes, and oligodendrogenesis were assessed for up to 35 days post-TBI.

Results: Compared with the control group, improvement of cognitive functions and smaller lesion volumes was observed in the two BMSC-transplanted groups, especially the H-BMSC group. H-BMSC transplantation resulted in a greater number of neural/glial antigen 2 (NG2)-positive and adenomatous polyposis coli (APC)-positive cells than N-BMSC transplantation in both the corpus callosum and the striatum. In addition, we observed that the expression levels of hypoxia-inducible factor-1a (HIF-1α), phosphorylated mechanistic target of rapamycin (p-mTOR), and vascular endothelial growth factor (VEGF) were all increased in H-BMSC-transplanted mice. Furthermore, the mTOR pathway inhibitor rapamycin attenuated the impact of HP both in vivo and in vitro.

Conclusion: The results provided mechanistic evidences suggesting that HP-treated BMSCs promoted remyelination partly by modulating the pro-survival mTOR/HIF-1α/VEGF signaling pathway.
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http://dx.doi.org/10.1002/brb3.1675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375110PMC
July 2020