Publications by authors named "Hongyuan Xu"

29 Publications

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STAT3 is critical for skeletal development and bone homeostasis by regulating osteogenesis.

Nat Commun 2021 Nov 25;12(1):6891. Epub 2021 Nov 25.

Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China.

Skeletal deformities are typical AD-HIES manifestations, which are mainly caused by heterozygous and loss-of-function mutations in Signal transducer and activator of transcription 3 (STAT3). However, the mechanism is still unclear and the treatment strategy is limited. Herein, we reported that the mice with Stat3 deletion in osteoblasts, but not in osteoclasts, induced AD-HIES-like skeletal defects, including craniofacial malformation, osteoporosis, and spontaneous bone fracture. Mechanistic analyses revealed that STAT3 in cooperation with Msh homeobox 1(MSX1) drove osteoblast differentiation by promoting Distal-less homeobox 5(Dlx5) transcription. Furthermore, pharmacological activation of STAT3 partially rescued skeletal deformities in heterozygous knockout mice, while inhibition of STAT3 aggravated bone loss. Taken together, these data show that STAT3 is critical for modulating skeletal development and maintaining bone homeostasis through STAT3-indcued osteogenesis and suggest it may be a potential target for treatments.
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http://dx.doi.org/10.1038/s41467-021-27273-wDOI Listing
November 2021

Characteristics of the Dynamic Electrocardiogram in the Elderly with Nonvalvular Atrial Fibrillation Combined with Long R-R Intervals.

Evid Based Complement Alternat Med 2021 10;2021:4485618. Epub 2021 Nov 10.

ECG Diagnosis Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.

Objective: To investigate the characteristics of dynamic electrocardiogram and their clinical implications in elderly patients with nonvalvular atrial fibrillation combined with long R-R intervals.

Methods: Elderly patients diagnosed with nonvalvular atrial fibrillation who were admitted as an inpatient or attended the outpatient department from January 2015 to January 2020 were selected. Patients were divided into two groups based on the presence of a long R-R interval. The characteristics and therapeutic significance of dynamic electrocardiogram between the two groups were compared.

Results: A total of 532 patients were included in our analyses. Of these, 399 patients were in the long R-R interval group and 133 in the nonlong R-R interval group. In 399 patients, there were 48,840 long R-R intervals manifested within 24 hours. The average, slowest, and fastest ventricular rates during sleep time were higher than those in nonsleep time, while the number of long R-R intervals in sleep time was significantly smaller than that in nonsleep time ( < 0.05). Clinical parameters including dizziness/syncope, cerebral infarction, ST-segment changes, platelet count, average hematocrit, prothrombin time (PT), left ventricular systolic function, end-diastolic diameter, pulmonary artery pressure, and left ventricular ejection fraction were comparable between the groups ( > 0.05). When compared with the nonlong R-R interval group, the level of C-reactive protein was slightly lower in the long R-R interval group ( < 0.05). In addition, the long R-R interval group had a higher incidence of atrial premature beats but a lower incidence of ventricular premature beats. Furthermore, the probability of long R-R interval combined with paroxysmal atrial tachycardia, transient ventricular arrest, second-degree atrioventricular block, and complete or incomplete right bundle branch block was higher than that of nonlong R-R interval ( < 0.05). In patients with long R-R interval >3 s, the risk of having second-degree atrioventricular block and complete or incomplete right bundle branch block was significantly lower, while the risk of having transient ventricular arrest was higher when compared to patients with long R-R intervals of 2-3 s ( < 0.05).

Conclusions: Long R-R interval is a common electrocardiographic phenomenon among the elderly with nonvalvular atrial fibrillation. The long R-R interval mostly occurs in nonsleeping time. The average ventricular rate, slowest ventricular rate, and fastest ventricular rate of sleep time are higher than nonsleeping time. Analysis of the characteristics of the dynamic electrocardiogram of these patients may shed light on the mechanisms for long R-R intervals, including the likelihood of concealed conduction and physiological interference in the atrioventricular node, overspeed inhibition, increased vagus nerve tension, or pathological atrioventricular block.
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http://dx.doi.org/10.1155/2021/4485618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8598370PMC
November 2021

Comparative metabolomics analysis revealed biomarkers and distinct flavonoid biosynthesis regulation in Chrysanthemum mongolicum and C. rhombifolium.

Phytochem Anal 2021 Nov 8. Epub 2021 Nov 8.

College of Life and Health Sciences, Northeastern University, Shenyang, China.

Introduction: Chrysanthemums are traditional flowers that originated in China and have high ornamental, economic and medicinal value. They are widely used as herbal remedies and consumed as food or beverages in folk medicine. However, little is known about their metabolic composition.

Objectives: The aims of this work were to determine the metabolic composition of and natural variation among different species of Chrysanthemum and to explore new potential resources for drug discovery and sustainable utilisation of wild Chrysanthemum.

Methods: The metabolomes of Chrysanthemum mongolicum (Ling) Tzvel. and Chrysanthemum rhombifolium H. Ohashi & Yonek. were compared using a widely targeted metabolomics approach based on liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: In total, 477 metabolites were identified, of which 72 showed significant differences in expression between C. mongolicum and C. rhombifolium, mainly in flavonoids, organic acids and nucleotides. The flavone and flavonol biosynthesis pathway showed significant enrichment among the differentially expressed metabolites. The contents of genkwanin, trigonelline, diosmin, narcissoside, 3,4-dihydroxyphenylacetic acid, linarin, N',N'-p-coumarin, C-hexosyl-tricetin O-pentoside, chrysoeriol, acacetin and kaempferol-3-O-gentiobioside were significantly different between the two species and represent potential biomarkers.

Conclusion: The types of flavonoid-related metabolites in the flavonoid biosynthesis pathway differed between C. mongolicum and C. rhombifolium. The mechanisms underlying the unique adaptations of these two species to their environments may involve variations in the composition and abundance of flavonoids, organic acids, and nucleotides. These methods are promising to identify functional compounds in Chrysanthemum species and can provide potential resources for drug discovery and the sustainable utilisation of Chrysanthemum plants.
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http://dx.doi.org/10.1002/pca.3095DOI Listing
November 2021

De Novo Germline and Somatic Variants Convergently Promote Endothelial-to-Mesenchymal Transition in Simplex Brain Arteriovenous Malformation.

Circ Res 2021 Oct 17;129(9):825-839. Epub 2021 Sep 17.

Neurosurgery, Beijing Tiantan Hospital (H.L., R.H., W.F., Y.J., Jiancong Weng, Z.Y., Jie Wang, H.X., S.W., J.Z., Y.C.), Capital Medical University, China.

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCRESAHA.121.319004DOI Listing
October 2021

Impaired Restoration of Global Protein Synthesis Contributes to Increased Vulnerability to Acute ER Stress Recovery in Huntington's Disease.

Cell Mol Neurobiol 2021 Aug 4. Epub 2021 Aug 4.

Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, 33431, USA.

Neurons are susceptible to different cellular stresses and this vulnerability has been implicated in the pathogenesis of Huntington's disease (HD). Accumulating evidence suggest that acute or chronic stress, depending on its duration and severity, can cause irreversible cellular damages to HD neurons, which contributes to neurodegeneration. In contrast, how normal and HD neurons respond during the resolution of a cellular stress remain less explored. In this study, we challenged normal and HD cells with a low-level acute ER stress and examined the molecular and cellular responses after stress removal. Using both striatal cell lines and primary neurons, we first showed the temporal activation of p-eIF2α-ATF4-GADD34 pathway in response to the acute ER stress and during recovery between normal and HD cells. HD cells were more vulnerable to cell death during stress recovery and were associated with increased number of apoptotic/necrotic cells and decreased cell proliferation. This is also supported by the Gene Ontology analysis from the RNA-seq data which indicated that "apoptosis-related Biological Processes" were more enriched in HD cells during stress recovery. We further showed that HD cells were defective in restoring global protein synthesis during stress recovery and promoting protein synthesis by an integrated stress response inhibitor, ISRIB, could attenuate cell death in HD cells. Together, these data suggest that normal and HD cells undergo distinct mechanisms of transcriptional reprogramming, leading to different cell fate decisions during the stress recovery.
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http://dx.doi.org/10.1007/s10571-021-01137-9DOI Listing
August 2021

RNA-seq analysis reveals significant transcriptome changes in huntingtin-null human neuroblastoma cells.

BMC Med Genomics 2021 07 2;14(1):176. Epub 2021 Jul 2.

Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, 33431, USA.

Background: Huntingtin (Htt) protein is the product of the gene mutated in Huntington's disease (HD), a fatal, autosomal dominant, neurodegenerative disorder. Normal Htt is essential for early embryogenesis and the development of the central nervous system. However, the role of Htt in adult tissues is less defined. Following the recent promising clinical trial in which both normal and mutant Htt mRNA were knocked down in HD patients, there is an urgent need to fully understand the molecular consequences of knocking out/down Htt in adult tissues. Htt has been identified as an important transcriptional regulator. Unbiased investigations of transcriptome changes with RNA-sequencing (RNA-Seq) have been done in multiple cell types in HD, further confirming that transcriptional dysregulation is a central pathogenic mechanism in HD. However, there is lack of direct understanding of the transcriptional regulation by normal Htt.

Methods: To investigate the transcriptional role of normal Htt, we first knocked out Htt in the human neuroblastoma SH-SY5Y cell line using the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) gene editing approach. We then performed RNA-seq analysis on Htt-null and wild type SH-SY5Y cells to probe the global transcriptome changes induced by Htt deletion.

Results: In general, Htt has a widespread effect on gene transcription. Functional analysis of the differentially expressed genes (DEGs) using various bioinformatic tools revealed irregularities in pathways related to cell communication and signaling, and more specifically those related to neuron development, neurotransmission and synaptic signaling. We further examined the transcription factors that may regulate these DEGs. Consistent with the disrupted pathways associated with cellular development, we showed that Htt-null cells exhibited slower cell proliferation than wild type cells. We finally validated some of the top DEGS with quantitative RT-PCR.

Conclusions: The widespread transcriptome changes in Htt-null cells could be directly caused by the loss of Htt-mediated transcriptional regulation or due to the secondary consequences of disruption in the gene regulatory network. Our study therefore provides valuable information about key genes associated with Htt-mediated transcription and improves our understanding of the molecular mechanisms underlying the cellular functions of normal and mutant Htt.
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http://dx.doi.org/10.1186/s12920-021-01022-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252266PMC
July 2021

Atorvastatin and growth, rupture of small unruptured intracranial aneurysm: results of a prospective cohort study.

Ther Adv Neurol Disord 2021 9;14:1756286420987939. Epub 2021 Apr 9.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.

Background And Aims: The role of statins in unruptured intracranial aneurysm (UIA) growth and rupture remains ambiguous. This study sought to determine whether atorvastatin is associated with aneurysm growth and rupture in patients harboring UIA <7 mm.

Methods: This prospective, multicenter cohort study consecutively enrolled patients with concurrent UIA <7 mm and ischemic cerebrovascular disease from four hospitals between 2016 and 2019. Baseline and follow-up patient information was recorded. Because of the strong anti-inflammatory effect of aspirin, patients using aspirin were excluded. Patients taking atorvastatin 20 mg daily were atorvastatin users. The primary and exploratory endpoints were aneurysm rupture and growth, respectively.

Results: Among the 1087 enrolled patients, 489 (45.0%) took atorvastatin, and 598 (55%) took no atorvastatin. After a mean follow-up duration of 33.0 ± 12.5 months, six (1.2%) and five (0.8%) aneurysms ruptured in atorvastatin and non-atorvastatin groups, respectively. In the adjusted multivariate Cox analysis, UIA sized 5 to <7 mm, current smoker, and uncontrolled hypertension were associated with aneurysm rupture, whereas atorvastatin [adjusted hazard ratio (HR) 1.495, 95% confidence interval (CI) 0.417-5.356,  = 0.537] was not. Of 159 patients who had follow-up imaging, 34 (21.4%) took atorvastatin and 125 (78.6%) took no atorvastatin. Aneurysm growth occurred in five (14.7%) and 21 (16.8%) patients in atorvastatin and non-atorvastatin groups (mean follow-up: 20.2 ± 12.9 months), respectively. In the adjusted multivariate Cox analysis, UIAs sized 5 to <7 mm and uncontrolled hypertension were associated with a high growth rate; atorvastatin (adjusted HR 0.151, 95% CI 0.031-0.729,  = 0.019) was associated with a reduced growth rate.

Conclusions: We conclude atorvastatin use is associated with a reduced risk of UIA growth, whereas atorvastatin is not associated with UIA rupture. The Clinic Benefit and Risk of Oral Aspirin for Unruptured Intracranial Aneurysm Combined With Cerebral Ischemia http://www.clinicaltrials.gov NCT02846259.
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http://dx.doi.org/10.1177/1756286420987939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042545PMC
April 2021

Somatic MAP3K3 mutation defines a subclass of cerebral cavernous malformation.

Am J Hum Genet 2021 05 22;108(5):942-950. Epub 2021 Apr 22.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing 100050, China; Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China; Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100069, China. Electronic address:

Cerebral cavernous malformations (CCMs) are vascular disorders that affect up to 0.5% of the total population. About 20% of CCMs are inherited because of familial mutations in CCM genes, including CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10, whereas the etiology of a majority of simplex CCM-affected individuals remains unclear. Here, we report somatic mutations of MAP3K3, PIK3CA, MAP2K7, and CCM genes in CCM lesions. In particular, somatic hotspot mutations of PIK3CA are found in 11 of 38 individuals with CCMs, and a MAP3K3 somatic mutation (c.1323C>G [p.Ile441Met]) is detected in 37.0% (34 of 92) of the simplex CCM-affected individuals. Strikingly, the MAP3K3 c.1323C>G mutation presents in 95.7% (22 of 23) of the popcorn-like lesions but only 2.5% (1 of 40) of the subacute-bleeding or multifocal lesions that are predominantly attributed to mutations in the CCM1/2/3 signaling complex. Leveraging mini-bulk sequencing, we demonstrate the enrichment of MAP3K3 c.1323C>G mutation in CCM endothelium. Mechanistically, beyond the activation of CCM1/2/3-inhibited ERK5 signaling, MEKK3 p.Ile441Met (MAP3K3 encodes MEKK3) also activates ERK1/2, JNK, and p38 pathways because of mutation-induced MEKK3 kinase activity enhancement. Collectively, we identified several somatic activating mutations in CCM endothelium, and the MAP3K3 c.1323C>G mutation defines a primary CCM subtype with distinct characteristics in signaling activation and magnetic resonance imaging appearance.
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http://dx.doi.org/10.1016/j.ajhg.2021.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206158PMC
May 2021

Napabucasin Induces Mouse Bone Loss by Impairing Bone Formation via STAT3.

Front Cell Dev Biol 2021 18;9:648866. Epub 2021 Mar 18.

Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral and Cranio-maxillofacial Surgery, National Clinical Research Center of Stomatology, Center of Craniofacial Orthodontics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The novel small molecule Napabucasin (also known as BBI608) was shown to inhibit gene transcription driven by Signal Transducer and Activator of Transcription 3 (STAT3), which is considered a promising anticancer target. Many preclinical studies have been conducted in cancer patients examining the selective targeting of cancer stem cells by Napabucasin, but few studies have examined side effects of Napabucasin in the skeleton system. In the present study, we found treating bone marrow mesenchymal stem cells (BMSCs) with Napabucasin impaired their osteogenic differentiation. In terms of mechanisms, Napabucasin disrupted differentiation of BMSCs by inhibiting the transcription of osteogenic gene osteocalcin (Ocn) through STAT3. Moreover, through micro-CT analysis we found 4 weeks of Napabucasin injections induced mouse bone loss. Histological analysis revealed that Napabucasin-induced bone loss in mice was the result of impaired osteogenesis. In conclusion, this study provided evidence for the effect of Napabucasin on mouse bone homeostasis and revealed its underlying mechanisms and .
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http://dx.doi.org/10.3389/fcell.2021.648866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014090PMC
March 2021

Characterizing the Leaf Transcriptome of (Ling et C. Shih), a Drought Resistant, Endemic Plant From China.

Front Genet 2021 11;12:625985. Epub 2021 Feb 11.

College of Life and Health Sciences, Northeastern University, Shenyang, China.

(Ling et C. Shih), an endemic plant that is extremely well-adapted to harsh environments. However, little is known about its molecular biology of the plant's resistant traits against stress, or even its molecular biology of overall plant. To investigate the molecular biology of and mechanism of stress adaptation, we performed transcriptome sequencing of its leaves using an Illumina platform. A total of 130,891 unigenes were obtained, and 97,496 (~74.5%) unigenes were annotated in the public protein database. The similarity search indicated that 40,878 and 74,084 unigenes showed significant similarities to known proteins from NCBI non-redundant and Swissprot protein databases, respectively. Of these, 56,213 and 42,005 unigenes were assigned to the Gene Ontology (GO) database and Cluster of Orthologous Groups (COG), respectively, and 38,918 unigenes were mapped into five main categories, including 18 KEGG pathways. Metabolism was the largest category (23,128, 59.4%) among the main KEGG categories, suggesting active metabolic processes in . About 2,459 unigenes were annotated to have a role in defense mechanism or stress tolerance. Transcriptome analysis of revealed the presence of 12,925 microsatellites in 10,524 unigenes and mono, trip, and dinucleotides having higher polymorphism rates. The phylogenetic analysis based on gene among related species confirmed the reliability of the transcriptomic data. This work is the first genetic study of as a new plant resource of stress-tolerant genes. This large number of transcriptome sequences enabled us to comprehensively understand the basic genetics of and discover novel genes that will be helpful in the molecular improvement of chrysanthemums.
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http://dx.doi.org/10.3389/fgene.2021.625985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906282PMC
February 2021

CyTOF Analysis Reveals a Distinct Immunosuppressive Microenvironment in IDH Mutant Anaplastic Gliomas.

Front Oncol 2020 4;10:560211. Epub 2021 Feb 4.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

The immune microenvironment is important for the development, progression, and prognosis of anaplastic glioma (AG). This complex milieu has not been fully elucidated, and a high-dimensional analysis is urgently required. Utilizing mass cytometry (CyTOF), we performed an analysis of immune cells from 5 patients with anaplastic astrocytoma, IDH-mutant (AAmut) and 10 patients with anaplastic oligodendroglioma, IDH-mutant and 1p/19q codeletion (AOD) and their paired peripheral blood mononuclear cells (PBMCs). Based on a panel of 33 biomarkers, we demonstrated the tumor-driven immune changes in the AG immune microenvironment. Our study confirmed that mononuclear phagocytes and T cells are the most abundant immunocytes in the AG immune microenvironment. Glioma-associated microglia/macrophages in both AAmut and AOD samples showed highly immunosuppressive characteristics. Compared to those in the PBMCs, the ratios of immune checkpoint-positive exhausted CD4+ T cells and CD8+ T cells were higher at the AG tumor sites. The AAmut immune milieu exhibits more immunosuppressive characteristics than that in AOD.
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http://dx.doi.org/10.3389/fonc.2020.560211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890006PMC
February 2021

The CTSC-RAB38 Fusion Transcript Is Associated With the Risk of Hemorrhage in Brain Arteriovenous Malformations.

J Neuropathol Exp Neurol 2021 01;80(1):71-78

From the Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University.

Brain arteriovenous malformations (bAVMs) are congenital anomalies of blood vessels that cause intracranial hemorrhage in children and young adults. Chromosomal rearrangements and fusion genes play an important role in tumor pathogenesis, though the role of fusion genes in bAVM pathophysiological processes is unclear. The aim of this study was to identify fusion transcripts in bAVMs and analyze their effects. To identify fusion transcripts associated with bAVM, RNA sequencing was performed on 73 samples, including 66 bAVM and 7 normal cerebrovascular samples, followed by STAR-Fusion analysis. Reverse transcription polymerase chain reaction and Sanger sequencing were applied to verify fusion transcripts. Functional pathway analysis was performed to identify potential effects of different fusion types. A total of 21 fusion transcripts were detected. Cathepsin C (CTSC)-Ras-Related Protein Rab-38 (RAB38) was the most common fusion and was detected in 10 of 66 (15%) bAVM samples. In CTSC-RAB38 fusion-positive samples, CTSC and RAB38 expression was significantly increased and activated immune/inflammatory signaling. Clinically, CTSC-RAB38 fusion bAVM cases had a higher hemorrhage rate than non-CTSC-RAB38 bAVM cases (p < 0.05). Our study identified recurrent CTSC-RAB38 fusion transcripts in bAVMs, which may be associated with bAVM hemorrhage by promoting immune/inflammatory signaling.
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http://dx.doi.org/10.1093/jnen/nlaa126DOI Listing
January 2021

Isolation and Cultivation of Mandibular Bone Marrow Mesenchymal Stem Cells in Rats.

J Vis Exp 2020 08 25(162). Epub 2020 Aug 25.

Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research center of Stomatology;

Here we present an efficient method for isolating and culturing mandibular bone marrow mesenchymal stem cells (mBMSCs) in vitro to rapidly obtain numerous high-quality cells for experimental requirements. mBMSCs could be widely used in therapeutic applications as tissue engineering cells in case of craniofacial diseases and cranio-maxillofacial regeneration in the future due to the excellent self-renewal ability and multi-lineage differentiation potential. Therefore, it is important to obtain mBMSCs in large numbers. In this study, bone marrow was flushed from the mandible and primary mBMSCs were isolated through whole bone marrow adherent cultivation. Furthermore, CD29CD90CD45 mBMSCs were purified through fluorescent cell sorting. The second generation of purified mBMSCs were used for further study and displayed potential in differentiating into osteoblasts, adipocytes, and chondrocytes. Utilizing this in vitro model, one can obtain a high number of proliferative mBMSCs, which may facilitate the study of the biological characteristics, the subsequent reaction to the microenvironment, and other applications of mBMSCs.
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http://dx.doi.org/10.3791/61532DOI Listing
August 2020

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model.

J Vis Exp 2020 07 3(161). Epub 2020 Jul 3.

Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research center of Stomatology;

Transgenic mouse models are powerful for understanding the critical genes controlling osteoclast differentiation and activity, and for studying mechanisms and pharmaceutical treatments of osteoporosis. Cathepsin K (Ctsk)-Cre mice have been widely used for functional studies of osteoclasts. The signal transducer and activator of transcription 3 (STAT3) is relevant in bone homeostasis, but its role in osteoclasts in vivo remains poorly defined. To provide the in vivo evidence that STAT3 participates in osteoclast differentiation and bone metabolism, we generated an osteoclast-specific Stat3 deletion mouse model (Stat3 ; Ctsk-Cre) and analyzed its skeletal phenotype. Micro-CT scanning and 3D reconstruction implied increased bone mass in the conditional knockout mice. H&E staining, calcein and alizarin red double staining, and tartrate-resistant acid phosphatase (TRAP) staining were performed to detect bone metabolism. In short, this protocol describes some canonical methods and techniques to analyze skeletal phenotype and to study the critical genes controlling osteoclast activity in vivo.
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http://dx.doi.org/10.3791/61390DOI Listing
July 2020

Mesenchymal Behavior of the Endothelium Promoted by SMAD6 Downregulation Is Associated With Brain Arteriovenous Malformation Microhemorrhage.

Stroke 2020 07 3;51(7):2197-2207. Epub 2020 Jun 3.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China (W.F., R.H., Z.Y, H.X., H.L., Y.J., J. Weng, J. Wang, S.W., Y.C., J.Z.).

Background And Purpose: In unruptured brain arteriovenous malformations (bAVMs), microhemorrhage portends a higher risk of future rupture and may represent a transitional state along the continuum of destabilization. Exploration of the molecular and cellular mechanisms of microhemorrhage will provide a possible target for medical treatment to prevent bAVM bleeding.

Methods: We performed RNA sequencing analysis on 34 unruptured bAVM surgical samples. Functional pathway analysis was performed to identify potential signals associated with the microhemorrhagic phenotype. Candidate gene was then investigated in bAVM specimens by immunohistochemical staining. Several functional assays were used to investigate the effects of candidate genes on the phenotypic properties of cultured human umbilical vein endothelial cells. Then, Masson trichrome staining and immunofluorescence staining were used to evaluate the phenotypic and molecular changes in bAVM tissue.

Results: Via RNA sequencing, we identified differential gene expression between 18 microhemorrhagic bAVMs and 16 nonmicrohemorrhagic bAVMs. TGFβ (transforming growth factor-beta)/BMP (bone morphogenetic protein) signaling was associated with the bAVM microhemorrhage group when SMAD6 (SMAD family member 6) was downregulated. Immunohistochemical staining showed that the vascular endothelium of microhemorrhagic bAVMs exhibited decreased SMAD6 expression. Functional assays revealed that SMAD6 downregulation promoted the formation of endothelial cell tubes with deficient cell-cell junctions and facilitated the acquisition of mesenchymal behavior by endothelial cells. Masson trichrome and immunofluorescence staining demonstrated that mesenchymal phenotype of endothelial cells is promoted in microhemorrhagic bAVMs.

Conclusions: TGFβ/BMP signaling mediated by SMAD6 in vascular endothelial cells is associated with microhemorrhagic bAVMs, and mesenchymal behavior of endothelial cells induced by SMAD6 downregulation is related with bAVM microhemorrhage.
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http://dx.doi.org/10.1161/STROKEAHA.120.030046DOI Listing
July 2020

N6-methyladenosine methyltransferase METTL3 affects the phenotype of cerebral arteriovenous malformation via modulating Notch signaling pathway.

J Biomed Sci 2020 May 9;27(1):62. Epub 2020 May 9.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.119 South 4th Ring West Road, Fengtai District, Beijing, 100070, China.

Background: Cerebral arteriovenous malformation (AVM) is a serious life-threatening congenital cerebrovascular disease. Specific anatomical features, such as nidus size, location, and venous drainage, have been validated to affect treatment outcomes. Until recently, molecular biomarkers and corresponding molecular mechanism related to anatomical features and treatment outcomes remain unknown.

Methods: RNA N6-methyladenosine (mA) Methyltransferase METTL3 was identified as a differentially expressed gene in groups with different lesion sizes by analyzing the transcriptome sequencing (RNA-seq) data. Tube formation and wound healing assays were performed to investigate the effect of METTL3 on angiogenesis. In addition, Methylated RNA Immunoprecipitation Sequencing technology (MeRIP-seq) was performed to screen downstream targets of METTL3 in endothelial cells and to fully clarify the specific underlying molecular mechanisms affecting the phenotype of cerebral AVM.

Results: In the current study, we found that the expression level of METTL3 was reduced in the larger pathological tissues of cerebral AVMs. Moreover, knockdown of METTL3 significantly affected angiogenesis of the human endothelial cells. Mechanistically, down-regulation of METTL3 reduced the level of heterodimeric Notch E3 ubiquitin ligase formed by DTX1 and DTX3L, thereby continuously activating the Notch signaling pathway. Ultimately, the up-regulated downstream genes of Notch signaling pathway dramatically affected the angiogenesis of endothelial cells. In addition, we demonstrated that blocking Notch pathway with DAPT could restore the phenotype of METTL3 deficient endothelial cells.

Conclusions: Our findings revealed the mechanism by which mA modification regulated the angiogenesis and might provide potential biomarkers to predict the outcome of treatment, as well as provide suitable pharmacological targets for preventing the formation and progression of cerebral AVM.
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http://dx.doi.org/10.1186/s12929-020-00655-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210675PMC
May 2020

Wilms' tumour 1-associating protein inhibits endothelial cell angiogenesis by m6A-dependent epigenetic silencing of desmoplakin in brain arteriovenous malformation.

J Cell Mol Med 2020 05 13;24(9):4981-4991. Epub 2020 Apr 13.

Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.

Brain arteriovenous malformations (AVMs) are congenital vascular abnormality in which arteries and veins connect directly without an intervening capillary bed. So far, the pathogenesis of brain AVMs remains unclear. Here, we found that Wilms' tumour 1-associating protein (WTAP), which has been identified as a key subunit of the m6A methyltransferase complex, was down-regulated in brain AVM lesions. Furthermore, the lack of WTAP could inhibit endothelial cell angiogenesis in vitro. In order to screen for downstream targets of WTAP, we performed RNA transcriptome sequencing (RNA-seq) and Methylated RNA Immunoprecipitation Sequencing technology (MeRIP-seq) using WTAP-deficient and control endothelial cells. Finally, we determined that WTAP regulated Desmoplakin (DSP) expression through m6A modification, thereby affecting angiogenesis of endothelial cells. In addition, an increase in Wilms' tumour 1 (WT1) activity caused by WTAP deficiency resulted in substantial degradation of β-catenin, which might also inhibit angiogenesis of endothelial cells. Collectively, our findings revealed the critical function of WTAP in angiogenesis and laid a solid foundation for the elucidation of the pathogenesis of brain AVMs.
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http://dx.doi.org/10.1111/jcmm.15101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205785PMC
May 2020

High Dimensional Mass Cytometry Analysis Reveals Characteristics of the Immunosuppressive Microenvironment in Diffuse Astrocytomas.

Front Oncol 2020 4;10:78. Epub 2020 Feb 4.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

The tumor immune microenvironment (TIME) plays a pivotal role in tumor development, progression, and prognosis. However, the characteristics of the TIME in diffuse astrocytoma (DA) are still unclear. Leveraging mass cytometry with a panel of 33 markers, we analyzed the infiltrating immune cells from 10 DA and 4 oligodendroglioma (OG) tissues and provided a single cell-resolution landscape of the intricate immune microenvironment. Our study profiled the composition of the TIME in DA and confirmed the presence of immune cells, such as glioma-associated microglia/macrophages (GAMs), CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), and natural killer cells. Increased percentages of PD-1+ CD8+ T cells, TIM-3+ CD4+ T cell subpopulations, Tregs and pro-tumor phenotype GAMs substantially contribute to the local immunosuppressive microenvironment in DA. DAs and OGs share similar compositions in terms of immune cells, while GAMs in DA exhibit more inhibitory characteristics than those in OG.
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http://dx.doi.org/10.3389/fonc.2020.00078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010913PMC
February 2020

Predictive value of gamma-glutamyl transpeptidase to lymphocyte count ratio in hepatocellular carcinoma patients with microvascular invasion.

BMC Cancer 2020 Feb 18;20(1):132. Epub 2020 Feb 18.

Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China.

Background: Microvascular invasion (MVI) is an independent risk factor for poor prognosis in hepatocellular carcinoma (HCC). However, there is still a lack of preoperative markers to predict MVI in HCC. This study intends to explore the potential application value of the gamma-glutamyl transpeptidase (GGT) to lymphocyte count ratio (GLR) in predicting MVI in HCC and provide guidance for clinical diagnosis and treatment.

Methods: From March 2010 to December 2015, 230 HCC patients who underwent surgical treatment in the Affiliated Hospital of Guilin Medical University were selected. Clinicopathological parameters between the MVI group (n = 115) and the non-MVI group (n = 115) were comparatively analyzed. The GLR was used as the potential risk factor for HCC with MVI, and its optimal cut-off value was estimated by using the receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to analyze the survival of HCC patients, and univariate and multivariate Cox regression analyses were used to establish independent predictors affecting postoperative HCC patients.

Results: The GLR levels in the MVI group and non-MVI group were 84.83 ± 61.84 and 38.42 ± 33.52 (p <  0.001), respectively. According to ROC curve analysis, the optimal cut-off value of GLR was 56.0, and the area under the ROC curve (AUC) was 0.781 (95% CI, 0.719-0.833) for the risk prediction of MVI in HCC patients. Multivariate analysis showed that tumor size > 5 cm, HCC combined with MVI and GLR >  56.0 were independent risk factors for poor prognosis in HCC patients. In addition, compared with the non-MVI group, patients in the MVI group had shorter progression-free survival (PFS) and overall survival (OS).

Conclusion: GLR could be a predictive biomarker of HCC after operation and a potential predictor of HCC combined with MVI.
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http://dx.doi.org/10.1186/s12885-020-6628-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029459PMC
February 2020

Icariin prevents oestrogen deficiency-induced alveolar bone loss through promoting osteogenesis via STAT3.

Cell Prolif 2020 Feb 13;53(2):e12743. Epub 2020 Jan 13.

Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China.

Objectives: Alveolar bone osteoporosis has attracted more and more attention because of its profound impact on stomatognathic function and treatment, but current treatments have not been targeted to alveolar bone and might even cause severe side effects. Thus, identifying the effects of anti-osteoporosis agents on alveolar bone is essential. Icariin ameliorates metabolic dysfunction of long bones, but its effects on alveolar bone remain unclarified.

Materials And Methods: BMSCs were isolated from rat mandibles (mBMSCs). The osteogenic potential of mBMSCs and the signalling pathway involved under icariin treatment were measured by ALP and alizarin red staining, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence. Dual-luciferase assay, chromatin immunoprecipitation (ChIP) and co-immunoprecipitation were used to investigate the molecular mechanism. Ovariectomized and sham-operated rats treated with or without icariin were analysed by micro-CT, TRAP staining and calcein double labelling.

Results: We found that icariin promoted osteoblast differentiation of mBMSCs. Furthermore, STAT3 was critical for icariin-promoted osteoblast differentiation, as indicated by increased phosphorylation levels in icariin-treated mBMSCs, while preventing STAT3 activation blocked icariin-induced osteoblast differentiation. Mechanistically, icariin-promoted transcription of the downstream osteogenic gene osteocalcin (Ocn) through STAT3 and STAT3 bound to the promoter of Ocn. Notably, icariin prevented the alveolar bone osteoporosis induced by oestrogen deficiency through promoting bone formation.

Conclusions: For the first time, our work provides evidence supporting the potential application of icariin in promoting osteogenesis and treating alveolar bone osteoporosis.
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http://dx.doi.org/10.1111/cpr.12743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048209PMC
February 2020

Mode of action of granulocyte-colony stimulating factor (G-CSF) as a novel therapy for stroke in a mouse model.

J Biomed Sci 2020 Jan 6;27(1):19. Epub 2020 Jan 6.

Department of Biomedical Sciences, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, 33431, USA.

Background: The FDA approved drug granulocyte-colony stimulating factor (G-CSF) displays anti-apoptotic and immunomodulatory properties with neurogenesis and angiogenic functions. It is known to demonstrate neuroprotective mechanisms against ischemic global stroke. Autophagy is a method for the degradation of intracellular components and in particular, unrestrained autophagy may lead to uncontrolled digestion of affected neurons as well as neuronal death in cerebral ischemia. Mitochondrial dynamics is vital for the regulation of cell survival and death after cerebral ischemia and an early upstream event in neuronal death is mitochondrial fission. We examined the pro-survival mechanisms of G-CSF against apoptosis resulting from autophagy, mitochondrial stress and endoplasmic reticulum (ER) stress.

Methods: Male Swiss Webster mice (20 weeks of age) were subjected to bilateral common carotid artery occlusion (BCAO) for 30 min. After occlusion, mice were injected with G-CSF (50 μg/kg) subcutaneously for 4 days. Behavioral analysis was carried out using the corner test and locomotor activity test before animals were sacrificed on day 4 or day 7. Key proteins in ER stress, autophagy and mitochondrial stress induced apoptosis were analyzed by immunoblotting.

Results: G-CSF improved neurological deficits and improved behavioral performance on corner and locomotor test. G-CSF binds to G-CSF receptors and its activation leads to upregulation of Akt phosphorylation (P-Akt) which in turn decreases levels of the ER stress sensor, GRP 78 and expression of proteins involved in ER stress apoptosis pathway; ATF6, ATF4, eIF2α, XBP1, Caspase 12 and CHOP. G-CSF treatment significantly decreased Beclin-1, an autophagy marker, and decreased mitochondrial stress biomarkers DRP1 and P53. G-CSF also up-regulated the mitochondrial fusion protein, OPA1 and anti-apoptotic protein Bcl-2 while down-regulating the pro-apoptotic proteins Bax, Bak and PUMA.

Conclusions: G-CSF is an endogenous ligand in the CNS that has a dual activity that is beneficial both in reducing acute neuronal degeneration and adding to long-term plasticity after cerebral ischemia. G-CSF treatment exerts neuroprotective effects on damaged neurons through the suppression of the ER stress and mitochondrial stress and maintains cellular homeostasis by decreasing pro-apoptotic proteins and increasing of anti-apoptotic proteins.
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http://dx.doi.org/10.1186/s12929-019-0597-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943893PMC
January 2020

A Retrospective Cohort Study of Risk Factors for Descending Necrotizing Mediastinitis Caused by Multispace Infection in the Maxillofacial Region.

J Oral Maxillofac Surg 2020 Mar 26;78(3):386-393. Epub 2019 Nov 26.

Attending Physician, Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, People's Republic of China. Electronic address:

Purpose: Descending necrotizing mediastinitis (DNM) has been the most common life-threatening complication of multispace infection (MSI) in the maxillofacial region owing to the lack of a timely diagnosis and treatment. We assessed the clinical characteristics and diagnosis of odontogenic MSI and evaluated the risk factors for DNM caused by MSI.

Patients And Methods: We performed a retrospective cohort study of inpatients with MSI in the maxillofacial region from January 2012 to October 2016. The patients were classified into a non-DNM group and a secondary DNM group. The information collected included gender, age, systemic comorbidities, source of maxillofacial infection, computed tomography imaging data, and laboratory test results. Univariate analysis (t test and χ test, or the Fisher exact test) and logistic regression analysis were applied.

Results: A total of 296 patients were included. The mortality was 6.3%. On univariate analysis, the following factors were statistically significant: gender (P = .001); age (P = .003); source of infection (P = .004); number of affected spaces (P < .001); involvement of the parotid space (P < .001), submandibular space (P < .001), subgingival space (P < .001), pterygomandibular space (P < .001), parapharyngeal space (P < .001), and retropharyngeal space (P < .001); and percentage of neutrophils (P < .001). On multivariate analysis, the parapharyngeal space (P = .008), source of infection (P = .037), and number of affected spaces (P < .001) were statistically significant.

Conclusions: Glandular infection, parapharyngeal space involvement, and the presence of multiple affected spaces were risk factors for DNM. Clinicians should vigilantly watch for these factors during clinical treatment and effective measures taken to prevent the occurrence of DNM as soon as possible.
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http://dx.doi.org/10.1016/j.joms.2019.11.017DOI Listing
March 2020

STAT3 controls osteoclast differentiation and bone homeostasis by regulating NFATc1 transcription.

J Biol Chem 2019 10 28;294(42):15395-15407. Epub 2019 Aug 28.

Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai 200011, China

The transcription factor signal transducer and activator of transcription 3 (STAT3) plays a central role in cell survival and function. STAT3 has been demonstrated to participate in the maintenance of bone homeostasis in osteoblasts, but its role in osteoclasts remains poorly defined. Here, we generated a conditional knockout mouse model in which was deleted in osteoclasts using a cathepsin K-Cre (Ctsk-Cre) driver. We observed that osteoclast-specific deficiency caused increased bone mass in mice, which we attributed to impaired bone catabolism by osteoclasts. -deficient bone marrow macrophages (BMMs) showed decreased expression of nuclear factor of activated T cells, cytoplasm 1 (NFATc1), and reduced osteoclast differentiation determined by decreases in osteoclast number, tartrate-resistant acid phosphatase activity, and expression of osteoclast marker genes. Enforced expression of NFATc1 in -deficient BMMs rescued the impaired osteoclast differentiation. Mechanistically, we revealed that STAT3 could drive the transcription of NFATc1 by binding to its promoter. Furthermore, preventing STAT3 activation by using an inhibitor of upstream phosphorylases, AG490, also impaired osteoclast differentiation and formation in a similar way as gene deletion of In summary, our data provide the first evidence that STAT3 is significant in osteoclast differentiation and bone homeostasis , and it may be identified as a potential pharmacological target for the treatment of bone metabolic diseases through regulation of osteoclast activity.
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http://dx.doi.org/10.1074/jbc.RA119.010139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802509PMC
October 2019

Early cross-modal interactions underlie the audiovisual bounce-inducing effect.

Neuroimage 2018 07 20;174:208-218. Epub 2018 Mar 20.

Department of Psychology, School of Education, SooChow University, Suzhou, Jiangsu, 215123, China. Electronic address:

Two identical visual disks moving towards one another on a two-dimensional display can be perceived as either "streaming through" or "bouncing off" each other after their coincidence/overlapping. A brief sound presented at the moment of the coincidence of the disks could strikingly bias the percept towards bouncing, which was termed the audiovisual bounce-inducing effect (ABE). Although the ABE has been studied intensively since its discovery, the debate about its origin is still unresolved so far. The present study used event-related potential (ERP) recordings to investigate whether or not early neural activities associated with cross-modal interactions play a role on the ABE. The results showed that the fronto-central P2 component ∼200 ms before the coincidence of the disks was predictive of subsequent streaming or bouncing percept in the unimodal visual display but not in auditory-visual display. More importantly, the cross-modal interactions revealed by the fronto-central positivity PD170 (125-175 ms after sound onset), as well as the occipital positivity PD190 (180-200 ms), were substantially enhanced on bouncing trials compared to streaming trials in the auditory-visual display. These findings provide direct electrophysiological evidence that early cross-modal interactions contribute to the origin of ABE phenomenon at the perceptual stage of processing.
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http://dx.doi.org/10.1016/j.neuroimage.2018.03.036DOI Listing
July 2018

Global transcriptome‑wide analysis of the function of GDDR in acute gastric lesions.

Mol Med Rep 2017 Dec 2;16(6):8673-8684. Epub 2017 Oct 2.

Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.

Acute gastric lesions induced by stress are frequent occurrences in medical establishments. The gastric dramatic downrelated gene (GDDR) is a secreted protein, which is abundantly expressed in normal gastric epithelia and is significantly decreased in gastric cancer. In our previous study, it was found that GDDR aggravated stress‑induced acute gastric lesions. However, the role of GDDR in acute gastric lesions remains to be fully elucidated. In the present study, RNA sequencing was performed in order to examine the gene expression profile regulated by GDDR in acute gastric lesions. The dataset comprised four stomach samples from wild-type (WT) mice and four stomach samples from GDDR‑knockout mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to analyze the differentially-expressed genes (DEGs). Weighted correlation network analysis was used to identify clusters of highly correlated genes. Cytoscape was used to construct a protein‑protein interaction network (PPI) of the DEGs. Based on the GO analysis, the upregulated DEGs were distinctly enriched in muscle contraction and response to wounding; and the downregulated DEGs were significantly enriched in the regulation of nitrogen compound metabolic process and regulation of RNA metabolic process. The results of the KEGG pathway analysis showed that the upregulated DEGs were enriched in ECM‑receptor interaction and the signaling pathway of cGMP‑PKG, and the downregulated DEGs were enriched in the renin‑angiotensin system and glycerolipid metabolism. The co‑expression network revealed a group of genes, which were associated with increased wound healing in the WT mice. Significant pathways were identified through the PPI network, including negative regulation of the signaling pathway of glucocorticoid receptor, regulation of cellular stress response, and regulation of hormone secretion. In conclusion, the present study improves current understanding of the molecular mechanism underlying acute gastric lesions and may assist in the treatment of gastric lesions.
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http://dx.doi.org/10.3892/mmr.2017.7687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779945PMC
December 2017

Gait-force model and inertial measurement unit-based measurements: A new approach for gait analysis and balance monitoring.

J Exerc Sci Fit 2016 Dec 4;14(2):60-66. Epub 2016 Nov 4.

Department of Physics, Hong Kong Baptist University, Kowloon Tong, Hong Kong.

Background/objective: This work describes a new approach for gait analysis and balance measurement. It uses an inertial measurement unit (IMU) that can either be embedded inside a dynamically unstable platform for balance measurement or mounted on the lower back of a human participant for gait analysis.

Methods And Results: The acceleration data along three Cartesian coordinates is analyzed by the gait-force model to extract bio-mechanics information in both the dynamic state as in the gait analyzer and the steady state as in the balance scale. For the gait analyzer, the simple, noninvasive and versatile approach makes it appealing to a broad range of applications in clinical diagnosis, rehabilitation monitoring, athletic training, sport-apparel design, and many other areas. For the balance scale, it provides a portable platform to measure the postural deviation and the balance index under visual or vestibular sensory input conditions. Despite its simple construction and operation, excellent agreement has been demonstrated between its performance and the high-cost commercial balance unit over a wide dynamic range.

Conclusion: The portable balance scale is an ideal tool for routine monitoring of balance index, fall-risk assessment, and other balance-related health issues for both clinical and household use.
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http://dx.doi.org/10.1016/j.jesf.2016.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801712PMC
December 2016

[Effects of lingfasu on embryoid and plantlet formation of Panax notoginseng in vitro].

Zhong Yao Cai 2004 Oct;27(10):711-2

Agricultural College, Guangxi University, Nanning 530005.

On the medium MS added the right amount of 2,4-D and LFS (Angustmycin) and cultured under dark condition, the callus from stem segments of Panax notoginseng could induce a lot of embryoids. In 2-3 months, the ratio of embryoid formation reached about 90%. Then transplanted on MS + 2,4-D 1.5 mg/L + LFS 2 mg/L and cultured under light 20001x, near 30% embryoids could grow and develop as robust plantlets.
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October 2004

[Comparative analysis on effective compositions from tissue-cultured and wild Sophora tonkinensis].

Zhong Yao Cai 2004 Aug;27(8):552-3

Guangxi University, Nanning.

The qualitative analysis of the effective composition, matrine and oxymatrine in tissue-cultured and wild Sophora tonkinsis was done through thin-layer chromatography. The results showed that the tissue-cultured plants were almost as same as the wild plants in the ability to bio-synthesize matrine and oxymatrine. So, the tissue-cultured plants could be used as planting materials for artificial cultivation.
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August 2004

[Effects of angustmycin on callus occurrence and proliferation of Panax notogingseng in vitro].

Zhong Yao Cai 2004 Jan;27(1):1-3

Agricultural College, Guangxi University, Nanning 530005.

In order to explore quick, efficient inducement and proliferation of Panax notogingseng callus, the stem sections were taken as explants in the following 5 groups of medium: 1. MS + 2,4-D 2 mg/L (CK), 2. MS + 2,4-D 2 mg/L + N6-BA 2 mg/L, 3. MS + 2,4-D 2 mg/L + KT 2 mg/L, 4. MS + 2,4-D 2 mg/L + ZT 2 mg/L, 5. MS + 2,4-D 2 mg/L + LFS 2 mg/L. The results showed: 1. LFS (Lingfasu, a new kind of CTK) was able to promote the callus formation earlier 1-2 week than CK and to raise the rate of induced callus as high as 81%, higher 30% than that on other 4 mediums; 2. On medium 5, the fresh weight of callus increased 360.2% after being cultured 40 d, on other 4 mediums increased only 13.4%-21.8%. At the same time, 1 g callus cultured 40 d could obtain dry material 81.5 mg on medium 5, but on other 4 mediums only 21.5-25.9 mg; 3. The callus cultured on medium 5. continual generation to generation could live as long as more than 3 years, on other 4 mediums the callus hardened and aged quickly.
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January 2004
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