Publications by authors named "Xiong Guo"

289 Publications

Meta-analysis of Association Studies of Selenoprotein Gene Polymorphism and Kashin-Beck Disease: an Updated Systematic Review.

Biol Trace Elem Res 2021 Apr 12. Epub 2021 Apr 12.

Department of Occupational and Environmental Health, School of Public Health, Zhengzhou University, Environment and Health Innovation Team, 100 Kexue Avenue, Zhengzhou, Henan, 450001, People's Republic of China.

To evaluate the association between selenoprotein gene polymorphisms and Kashin-Beck disease (KBD) susceptibility through a systematic review and updated meta-analysis. PubMed, Google Scholar, Cochrane library, and Chinese National Knowledge Infrastructure (CNKI) were electronically searched using the terms "selenoprotein" and "Kashin-Beck disease" or "KBD" with a search time from the establishment of the database to January 2021. The Newcastle-Ottawa Scale (NOS) was used for methodological quality evaluation of the included studies. Stata 14.0 software was used to pooled odds ratio (OR) and 95% confidence interval. There were a total of eight included case-control studies covering 2025 KBD patients and 1962 controls. Meta-analysis results show that the pooled odds ratios (OR) and 95% confidence intervals (CI) for DIO2 (rs225014) were 0.69 (0.52, 0.91), 0.69 (0.50, 0.96), and 0.72 (0.52, 0.99) in the allele, heterozygote, and dominant models, respectively. The OR and 95%CI for SEPS1 (-105G>A) were 2.47 (1.85, 3.29), 9.36 (4.58, 19.12), 2.17 (1.53, 3.08), and 8.60 (4.25, 17.38) in the allele, homozygote, dominant, and recessive models, respectively. In addition, the OR and 95%CI for Sep15 (rs5859) were 2.05 (1.06, 3.96) in the allele model. These results illustrate that there was a significant association between DIO2 (rs225014), SEPS1 (-105G>A), Sep15 (rs5859), and KBD. For GPX1 (rs1050450, rs1800668, rs3811699), DIO2 (rs225014, rs1352815, rs1388382), TrxR2 (rs1139793, rs5746841), GPX4 (rs713041, rs4807542), and SEPP1 (rs7579, 25191g/a), there was no significant statistical difference between the KBD and control groups (P>0.05). We conclude that the DIO2 (rs225014), SEPS1 (-105G>A), and Sep15 (rs5859) gene polymorphism are associated with susceptibility to KBD.
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http://dx.doi.org/10.1007/s12011-021-02705-2DOI Listing
April 2021

Upregulation of ZHX2 predicts poor prognosis and is correlated with immune infiltration in gastric cancer.

FEBS Open Bio 2021 Apr 10. Epub 2021 Apr 10.

Department of Gastrointestinal Surgery, Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China.

The transcriptional repressor Zinc-finger and homeoboxes 2 (ZHX2) is reported to regulate tumor progression in several human cancers, but little is known about its role in gastric cancer (GC). In this study, we examined the expression of ZHX2 and its relationship with clinicopathological characteristics and prognosis of GC patients, and examined the effect of ZHX2 overexpression in GC cell lines. We used UALCAN and Tumor Immune Estimation Resource (TIMER) to examine ZHX2 mRNA expression, and used Kaplan-Meier plotter to determine whether ZHX2 expression was related to GC prognosis. Expression of ZHX2 protein was detected using immunohistochemical (IHC) staining assays. Cell proliferation was evaluated using CCK-8 assay and colony formation assay while apoptosis was examined by flow cytometry. Wound healing assay and transwell assay were used to detect cell migration and invasion. We also performed gene set enrichment analysis (GSEA) and used The Cancer Genome Atlas (TCGA) database to examine correlation of ZHX2 with immune infiltration. We report that ZHX2 is highly expressed in GC tissues and significantly associated with clinical characteristics. Upregulation of ZHX2 predicted poor prognosis in GC. Furthermore, ZHX2 overexpression can promote proliferation, invasion, and migration, but inhibit apoptosis of GC cells. High expression of ZHX2 in GC is correlated with the presence of infiltrating immune cells, including B cells, CD4 T cells, macrophages and dendritic cells. Our data suggest that high expression of ZHX2 in GC predicts poor prognosis. In addition, ZHX2 may promotes malignant behaviors of GC cells, and immune infiltration might be related to the oncogenic role of ZHX2 in GC.
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http://dx.doi.org/10.1002/2211-5463.13160DOI Listing
April 2021

Genome-Wide Differentially Methylated Region Analysis to Reveal Epigenetic Differences of Articular Cartilage in Kashin-Beck Disease and Osteoarthritis.

Front Cell Dev Biol 2021 1;9:636291. Epub 2021 Mar 1.

School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China.

Kashin-Beck disease (KBD) is a degenerative osteoarticular disorder, and displays the significant differences with osteoarthritis (OA) regarding the etiology and molecular changes in articular cartilage. However, the underlying dysfunctions of molecular mechanisms in KBD and OA remain unclear. Here, we primarily performed the various genome-wide differential methylation analyses to reveal the distinct differentially methylated regions (DMRs) in conjunction with corresponding differentially methylated genes (DMGs), and enriched functional pathways in KBD and OA. We identified a total of 131 DMRs in KBD vs. Control, and 58 DMRs in OA vs. Controls, and the results demonstrate that many interesting DMRs are linked to DMGs, such as and , which are all key genes to regulate cartilage/skeletal physiologic and pathologic process, and are further enriched in skeletal system and limb-associated pathways. Our DMR analysis indicates that KBD-associated DMRs has higher proportion than OA-associated DMRs in gene body regions. KBD-associated DMGs were enriched in wounding and coagulation-related functional pathways that may be stimulated by trace elements. The identified molecular features provide novel clues for understanding the pathogenetic and therapeutic studies of both KBD and OA.
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http://dx.doi.org/10.3389/fcell.2021.636291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957013PMC
March 2021

An Effective Hypoxia-Related Long Non-Coding RNAs Assessment Model for Prognosis of Clear Cell Renal Carcinoma.

Front Oncol 2021 22;11:616722. Epub 2021 Feb 22.

Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Hypoxia is a significant clinical feature and regulates various tumor processes in clear cell renal carcinoma (ccRCC). Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) are closely associated with the survival outcomes of ccRCC patients and regulates hypoxia-induced tumor processes. Thus, this study aimed to develop a hypoxia-related lncRNA (HRL) prognostic model for predicting the survival outcomes in ccRCC. LncRNAs in ccRCC samples were extracted from The Cancer Genome Atlas database. Hypoxia-related genes were downloaded from the Molecular Signatures Database. A co-expression analysis between differentially expressed lncRNAs and hypoxia-related genes in ccRCC samples was performed to identify HRLs. Univariate and multivariate Cox regression analyses were performed to select nine optimal lncRNAs for developing the HRL model. The prognostic model showed good performance in predicting prognosis among patients with ccRCC, and the validation sets reached consistent results. The model was also found to be related to the clinicopathologic parameters of tumor grade and tumor stage and to tumor immune infiltration. In conclusion, our findings indicate that the hypoxia-lncRNA assessment model may be useful for prognostication in ccRCC cases. Furthermore, the nine HRLs included in the model might be useful targets for investigating the tumorigenesis of ccRCC and designing individualized treatment strategies.
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http://dx.doi.org/10.3389/fonc.2021.616722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937891PMC
February 2021

Profiling of selenium and other trace elements in breads from rice and maize cultivated in a seleniferous area of Punjab (India).

J Food Sci Technol 2021 Mar 8;58(3):825-833. Epub 2020 Jun 8.

Peoples' Friendship University of Russia (RUDN University), Moskva, Russia.

The objective of the study was to assess selenium and other elements levels in Indian Roti bread from Se-rich maize and rice using inductively coupled plasma mass-spectrometry. Se levels in Roti bread from Se-rich maize and rice exceeded those in the control samples by a factor of more than 594 and 156, respectively. Using Se-enriched maize increased bread Co, Cr, Mn, Mo, and Zn content, whereas Fe and I levels were reduced. In Se-rich rice-based bread a decrease in Co, Cr, Cu, Fe, I, Mo, and Zn contents was observed. Daily consumption of Se-rich maize and rice bread (100 g) could account for 5.665% and 4.309% from recommended dietary allowance, also exceeding the upper tolerable levels by a factor of 7.8 and 5.9, respectively. Therefore, Roti bread from both Se-rich maize and rice may be considered as an additional source of selenium. At the same time, regular intake of Se-rich grains and its products including breads may cause adverse health effects even after a few days and should be regularly monitored in order to prevent Se overload and toxicity.
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http://dx.doi.org/10.1007/s13197-020-04565-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884500PMC
March 2021

E2F7 Transcriptionally Inhibits MicroRNA-199b Expression to Promote USP47, Thereby Enhancing Colon Cancer Tumor Stem Cell Activity and Promoting the Occurrence of Colon Cancer.

Front Oncol 2020 7;10:565449. Epub 2021 Jan 7.

Department of Colorectal and Anal Surgery, Hepatobiliary and Enteric Surgery Center, Xiangya Hospital, Central South University, Changsha, China.

microRNAs (miRNAs) can modulate the expression level of genes in a post-transcription manner, which are closely related to growth and metastasis of colon cancer. Herein, we aimed to explore how miR-199b influences colon cancer and to characterize its underlying molecular mechanism associating with E2F transcription factor 7 (E2F7). Assays of RT-qPCR, Western blot, and immunohistochemistry were utilized to detect the expression of E2F7 in the tissue samples collected from 30 patients diagnosed with colon cancer. Flow analysis was utilized to detect the ratio of ALDH1 and CD133 colon cancer stem cells. The interaction between E2F7, miR-199b, USP47, and MAPK was identified by ChIP-Seq analysis, luciferase reporter, RNA pull-down, co-immunoprecipitation, as well as glutathione-S-transferase (GST) pull-down experiments. Based on the gain- and loss-of-function approaches, the cellular functions of colon cancer cells by the E2F7-regulated miR-199b/USP47/MAPK axis were assessed. It was identified that E2F7 are expressed highly in the collected colon cancer tissues. E2F7 silencing reduced the production of ALDH1 and CD133 colon cancer stem cells and antagonized the effects of 5-fluorouracil (5-FU) treatment. Besides, the silencing of E2F7 was observed to suppress the oxidative stress, proliferation, migration, as well as invasion of ALDH1 cells and tumorigenesis of colon cancer cells . Our findings reveal the pro-oncogenic effect of E2F7 on colon cancer development, highlighting E2F7 as a novel target for therapeutic strategy for colon cancer.
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http://dx.doi.org/10.3389/fonc.2020.565449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819137PMC
January 2021

First-Line Contact Aspiration vs Stent Retriever for Proximal Occlusion in Acute Ischemic Stroke: A Systemic Review and Meta-Analysis.

J Stroke Cerebrovasc Dis 2020 Dec 27;29(12):105374. Epub 2020 Oct 27.

952 hospital of the Chinese people's liberation army ground force, Neurology department, Geermu, Qinghai Province, 816000, China. Electronic address:

Introduction: The aim of this systematic review and meta-analysis was to compare the performance of first-line contact aspiration (ASP) and stent retriever (SR) in acute ischemic stroke caused by proximal large vessel occlusion.

Methods: Cochrane databases, MEDLINE and EMBASE were systematically searched for literatures reporting outcomes on thrombectomy with both first-line aspiration and first-line stent retriever in proximal occlusion.

Results: Thirteen studies with a total of 1614 patients were included. No differences were identified between the SR and ASP groups in terms of final reperfusion rate (modified thrombolysis in cerebral infarction 2b/3) (OR: 1.54, 95% CI: 0.88-2.70), complete recanalization rate (modified thrombolysis in cerebral infarction 3) (OR: 1.78, 95% CI: 0.58-5.44), and favorable outcomes (modified Rankin scale ≤2) (OR: 1.02, 95% CI: 0.79-1.32). With regard to adverse events, emboli to new territories (OR: 0.81, 95% CI: 0.31-2.14), intracranial hemorrhage (OR: 0.71, 95% CI: 0.40-1.28), 90-days mortality (OR: 1.02, 95% CI: 0.71-1.47) were similar between groups, while symptomatic intracerebral hemorrhage (OR: 0.43 95% CI: 0.21-0.86) was less seen in ASP. Subgroup analysis indicated that ASP was comparable to stent retriever with local aspiration (SRLA) (OR: 1.25 95% CI: 0.25-6.22) and superior to stent retriever alone (OR: 1.85 95% CI: 1.22-2.81). Moreover, in posterior circulation, contact aspiration achieved a significantly higher reperfusion (OR: 1.97 95% CI: 1.03-3.76) compared to stent retriever, and needed relatively less rescue therapies (21.5% vs 29.6%, p < 0.05).

Conclusion: Our study suggested that contact aspiration might be advantageous over stent retriever alone and more suitable in posterior circulation. While ASP and SRLA thrombectomy were equally effective in achieving good clinical outcomes. However, further studies are needed to confirm these results.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105374DOI Listing
December 2020

The molecular mechanism study of COMP involved in the articular cartilage damage of Kashin-Beck disease.

Bone Joint Res 2020 Sep 20;9(9):578-586. Epub 2020 Sep 20.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.

Aims: Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD.

Methods: The articular cartilage specimens were collected from five KBD patients and five control subjects for cell culture. The messenger RNA (mRNA) and protein expression levels were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot. The survival rate of C28/I2 chondrocyte cell line was detected by MTT assay after T-2 toxin intervention. The cell viability and mRNA expression levels of apoptosis related genes between -overexpression groups and control groups were examined after cell transfection.

Results: The mRNA and protein expression levels of were significantly lower in KBD chondrocytes than control chondrocytes. After the T-2 toxin intervention, the mRNA expression of C28/I2 chondrocyte reduced and the protein level of COMP in three intervention groups was significantly lower than in the control group. MTT assay showed that the survival rate of overexpression KBD chondrocytes were notably higher than in the blank control group. The mRNA expression levels of , , and were also significantly different among COMP overexpression, negative control, and blank control groups.

Conclusion: Our study results confirmed the functional relevance of with KBD. may play an important role in the excessive chondrocytes apoptosis of KBD patients.Cite this article: 2020;9(9):578-586.
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http://dx.doi.org/10.1302/2046-3758.99.BJR-2019-0247.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502256PMC
September 2020

Identification of the Prognostic Value of Immune-Related Genes in Esophageal Cancer.

Front Genet 2020 21;11:989. Epub 2020 Aug 21.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Esophageal cancer (EC) is a serious malignant tumor, both in terms of mortality and prognosis, and immune-related genes (IRGs) are key contributors to its development. In recent years, immunotherapy for tumors has been widely studied, but a practical prognostic model based on immune-related genes (IRGs) in EC has not been established and reported. This study aimed to develop an immunogenomic risk score for predicting survival outcomes among EC patients. In this study, we downloaded the transcriptome profiling data and matched clinical data of EC patients from The Cancer Genome Atlas (TCGA) database and found 4,094 differentially expressed genes (DEGs) between EC and normal esophageal tissue ( < 0.05 and fold change >2). Then, the intersection of DEGs and the immune genes in the "ImmPort" database resulted in 303 differentially expressed immune-related genes (DEIRGs). Next, through univariate Cox regression analysis of DEIRGs, we obtained 17 immune genes related to prognosis. We detected nine optimal survival-associated IRGs () by using Lasso regression and multivariate Cox regression analyses. Finally, we used those survival-associated IRGs to construct a risk model to predict the prognosis of EC patients. This model could accurately predict overall survival in EC and could be used as a classifier for the evaluation of low-risk and high-risk groups. In conclusion, we identified a practical and robust nine-gene prognostic model based on immune gene dataset. These genes may provide valuable biomarkers and prognostic predictors for EC patients and could be further studied to help understand the mechanism of EC occurrence and development.
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http://dx.doi.org/10.3389/fgene.2020.00989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472890PMC
August 2020

Assessment of the Contrast-Enhanced Ultrasound in Percutaneous Nephrolithotomy for the Treatment of Patients with Nondilated Collecting System.

J Endourol 2021 Apr 30;35(4):436-443. Epub 2020 Oct 30.

Department of Urology, The Second People's Hospital of China Three Gorges University, The Second People's Hospital of Yichang, Yichang, China.

To investigate the clinical value of contrast-enhanced ultrasound (CEUS) in percutaneous nephrolithotomy (PCNL) for kidney stone patients without hydronephrosis. Patients with nondilated collecting system kidney stones who underwent PCNL between October 2018 and December 2019 at our hospital were enrolled in this study. Patients who met the inclusion criteria were randomized into two groups: a CEUS-guided PCNL group and a conventional ultrasound (US)-guided PCNL group. The operation results of the two groups were compared, including the number of attempts for effective puncture, duration to effective puncture, stone clearance rate, blood loss, postoperative complications, and hospital stay. Fifty-six patients with a nondilated collecting system who underwent PCNL for 60 kidneys were included in this study, including 4 patients who underwent bilateral PCNL due to bilateral renal stones. There were 30 kidneys in each group. All patients successfully underwent PCNL. The CEUS-guided PCNL group had more accurate punctures, with a higher effective rate of one puncture and shorter puncture time. There was no statistically significant difference in stone clearance rate between the two groups. Four cases of double channels were established in the conventional US-guided PCNL group, while there was only one case in the CEUS-guided PCNL group. In the CEUS-guided PCNL group, most cases (96.7%, 29/30) had no or only mild complications, which were significantly better than the conventional US-guided PCNL group (76.7%, 23/30). The mean postoperative hemoglobin loss in the CEUS-guided PCNL group was 9.5 (range 1-25) g/L, which was significantly lower than 15.5 (range 5-52) g/L in the conventional US-guided PCNL group. The CEUS technique can improve visibility of the nondilated renal collecting system, facilitate selection of suitable calix, and identify renal calix fornix. It also benefits needle placement in patients with a nondilated collecting system.
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http://dx.doi.org/10.1089/end.2020.0564DOI Listing
April 2021

The integrative analysis of DNA methylation and mRNA expression profiles confirmed the role of selenocompound metabolism pathway in Kashin-Beck disease.

Cell Cycle 2020 Sep 20;19(18):2351-2366. Epub 2020 Aug 20.

Department of Joint Surgery, The Red Cross Hospital of Xi'an Jiaotong University , Xi'an, China.

Kashin-Beck disease (KBD) is an endemic chronic osteochondropathy. The etiology of KBD remains unknown. In this study, we conducted an integrative analysis of genome-wide DNA methylation and mRNA expression profiles between KBD and normal controls to identify novel candidate genes and pathways for KBD. Articular cartilage samples from 17 grade III KBD patients and 17 healthy controls were used in this study. DNA methylation profiling of knee cartilage and mRNA expression profile data were obtained from our previous studies. InCroMAP was performed to integrative analysis of genome-wide DNA methylation profiles and mRNA expression profiles. Gene ontology (GO) enrichment analysis was conducted by online DAVID 6.7. The quantitative real-time polymerase chain reaction (qPCR), Western blot, immunohistochemistry (IHC), and lentiviral vector transfection were used to validate one of the identified pathways. We identified 298 common genes (such as COL4A1, HOXA13, TNFAIP6 and TGFBI), 36 GO terms (including collagen function, skeletal system development, growth factor), and 32 KEGG pathways associated with KBD (including Selenocompound metabolism pathway, PI3K-Akt signaling pathway, and TGF-beta signaling pathway). Our results suggest the dysfunction of many genes and pathways implicated in the pathogenesis of KBD, most importantly, both the integrative analysis and study in KBD cartilage highlighted the importance of selenocompound metabolism pathway in the pathogenesis of KBD for the first time.
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http://dx.doi.org/10.1080/15384101.2020.1807665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513840PMC
September 2020

The role of selenium metabolism and selenoproteins in cartilage homeostasis and arthropathies.

Exp Mol Med 2020 08 13;52(8):1198-1208. Epub 2020 Aug 13.

Center for RNA Research, Institute for Basic Science, Seoul, 08826, South Korea.

As an essential nutrient and trace element, selenium is required for living organisms and its beneficial roles in human health have been well recognized. The role of selenium is mainly played through selenoproteins synthesized by the selenium metabolic system. Selenoproteins have a wide range of cellular functions including regulation of selenium transport, thyroid hormones, immunity, and redox homeostasis. Selenium deficiency contributes to various diseases, such as cardiovascular disease, cancer, liver disease, and arthropathy-Kashin-Beck disease (KBD) and osteoarthritis (OA). A skeletal developmental disorder, KBD has been reported in low-selenium areas of China, North Korea, and the Siberian region of Russia, and can be alleviated by selenium supplementation. OA, the most common form of arthritis, is a degenerative disease caused by an imbalance in matrix metabolism and is characterized by cartilage destruction. Oxidative stress serves as a major cause of the initiation of OA pathogenesis. Selenium deficiency and dysregulation of selenoproteins are associated with impairments to redox homeostasis in cartilage. We review the recently explored roles of selenium metabolism and selenoproteins in cartilage with an emphasis on two arthropathies, KBD and OA. Moreover, we discuss the potential of therapeutic strategies targeting the biological functions of selenium and selenoproteins for OA treatment.
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http://dx.doi.org/10.1038/s12276-020-0408-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423502PMC
August 2020

Circular RNA circREPS2 Acts as a Sponge of miR-558 to Suppress Gastric Cancer Progression by Regulating RUNX3/β-catenin Signaling.

Mol Ther Nucleic Acids 2020 Sep 27;21:577-591. Epub 2020 Jun 27.

Department of Gastrointestinal Surgery, Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China. Electronic address:

Circular RNAs (circRNAs) play an essential regulatory role in multiple cancers. However, the role of a large number of circRNAs in gastric cancer (GC) is still unknown. Here, hsa_circ_0139996 (circREPS2), a novel circRNA that was significantly downregulated in GC, was selected for further investigation. circREPS2 was validated and analyzed by DNA sequencing and quantitative real-time PCR. The roles of circREPS2 in GC cells were verified by gain- and loss-of-function experiments. Bioinformatics analysis, luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays were performed to evaluate the functional mechanism of circREPS2 on microRNA-558 (miR-558)/RUNX3/β-catenin axis in GC cells. In the present study, we found that circREPS2 was downregulated in GC tissues and cell lines. Low expression of circREPS2 was associated with a higher tumor-node-metastasis (TNM) stage, poor tumor differentiation, and larger tumor size in GC patients. Functionally, circREPS2 significantly inhibited GC cell proliferation, migration, invasion, and epithelial-mesenchymal transformation (EMT) in vitro and tumorigenesis in vivo. Furthermore, our data demonstrated that circREPS2 acted as a miR-558 sponge and upregulated RUNX3 expression to inactivate β-catenin signaling in GC cells. In conclusion, circREPS2 suppresses the progression of GC via miR-558/RUNX3/β-catenin signaling and is a novel promising biomarker and target for GC treatment.
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http://dx.doi.org/10.1016/j.omtn.2020.06.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390859PMC
September 2020

α-Lactalbumin-Based Nanofiber Dressings Improve Burn Wound Healing and Reduce Scarring.

ACS Appl Mater Interfaces 2020 Oct 29;12(41):45702-45713. Epub 2020 Sep 29.

Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016 Shenyang, China.

Skin wound especially burn injury is a major threat for public health. One of the pursuits in the current wound healing research is to identify new promising biological materials, which can not only promote tissue repair but also reduce scar formation. In this current study, the potentials of α-lactalbumin (ALA), a tryptophan-rich dietary protein acting as a precursor of neurotransmitter serotonin, to promote the burn wound healing and reduce the scar formation were investigated. The ALA was initially electrospun with polycaprolactone (PCL) to accomplish electrospun nanofibrous mats (ENMs), subsequently assessed for their physicochemical attributes and wound healing efficiency on a burn rat model, and then their healing mechanisms at cellular and molecular levels were explored. The results showed that ALA and PCL were physicochemically compatible in ENMs. The average diameter of various nanofibers was within 183-344 nm. Their wettability and mechanical properties could be readily modulated by adjusting the mass ratios of ALA and PCL from 1/9 to 1/2. The selected ENMs exhibited negligible cytotoxicity and satisfactory adhesion to fibroblasts and promoting the proliferation of the fibroblasts. As compared to pristine PCL based ENMs, the composite scaffolds could accelerate the wound healing process and exhibit effects comparable to a marketed wound dressing over 16 days. Moreover, the ALA/PCL based ENMs could increase the synthesis of type I collagen and decrease the expression of α-smooth muscle actin, conferring that the novel wound dressings could reduce the formation of scars. Collectively, this study demonstrates that the ALA is a promising biological material and could promote the regeneration of burn skins with reduced scar formation, when being loaded on ultrafine fibrous scaffolds, mimicking the structure of the natural extra cellular matrix.
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http://dx.doi.org/10.1021/acsami.0c05175DOI Listing
October 2020

Comparative assessment of in vitro/in vivo performances of orodispersible electrospun and casting films containing rizatriptan benzoate.

Eur J Pharm Biopharm 2020 Sep 4;154:283-289. Epub 2020 Jul 4.

Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016 Shenyang, China; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address:

The electrospinning process is a promising approach to produce various drug-loaded orodispersible films (ODFs) with a rapid onset of their actions. However, there is only limited number of studies comparing the pharmacological performances of electrospun ODFs (eODFs) with traditional casting films (CFs). In this study, rizatriptan benzoate (RB), a pain relieving agent was formulated with PVP and PVA into ODFs using electrospinning and casting methods. The ODFs were subsequently characterized with respect to their morphology, solid state properties and mechanical characteristics. The uniformity of the dosage units, disintegration behavior and dissolution patterns of the ODFs were also evaluated prior to the pharmacokinetic study. The obtained CFs and eODFs were semitransparent and white in appearance, respectively. The scanning electron microscopy revealed that the eODFs contained nanoporous structure, while the CFs showed no observable pores. RB was amorphously dispersed in both these films without drug-polymer interactions. The uniformity of dosage units for both eODFs and CFs was complied with European Pharmacopeia. As compared to the CFs, the eODFs were more flexible and lesser rigid in nature and showed faster disintegration and dissolution rates. In addition, the eODFs exhibited a higher bioavailability with a shorter T relative to the CFs and commercial RB tablets. This study demonstrated that eODFs were superior to CFs with respect to in vivo pharmacological effects, which could be attributed to the submicron structure of eODFs obtained through the electrospinning process.
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http://dx.doi.org/10.1016/j.ejpb.2020.06.023DOI Listing
September 2020

Circular RNA circFGD4 suppresses gastric cancer progression via modulating miR-532-3p/APC/β-catenin signalling pathway.

Clin Sci (Lond) 2020 07;134(13):1821-1839

Department of Gastrointestinal Surgery, Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China.

Background: Mounting evidence has displayed critical roles of circular RNAs (circRNAs) in multiple cancers. The underlying mechanisms by which circFGD4 contributed to gastric cancer (GC) are still unclear.

Methods: The levels and clinical values of circFGD4 in GC patients were detected and analysed by quantitative real-time PCR. The biological roles of circFGD4 in GC were assessed in vitro and in vivo experiments. Dual-luciferase reporter, fluorescence in situ hybridization, RNA immunoprecipitation, biotin-coupled RNA pull-down, and TOP/Flash and FOP/Flash reporter gene assays were employed to evaluate the effects of circFGD4 on miR-532-3p-mediated adenomatous polyposis coli (APC)/β-catenin signalling in GC cells.

Results: circFGD4 expression was down-regulated the most in human GC tissues and cell lines. Low expression of circFGD4 was correlated with poor tumour differentiation, lymphatic metastasis, and poor prognosis of GC patients. circFGD4 suppressed GC cell viability, colony formation, migration, induced epithelial-mesenchymal transition (EMT), and tumorigenesis and metastasis in vivo. Next, we validated that circFGD4 acted as a sponge of miR-532-3p to relieve the tumour-promoting effects of miR-532-3p on its target APC. The mechanistic analysis demonstrated that the circFGD4 suppressed GC cell viability, migration, and EMT by modulating the miR-532-3p/APC axis to inactivate the β-catenin signalling.

Conclusion: circFGD4 suppressed GC progression through sponging miR-532-3p and enhancing APC expression to inactivate the β-catenin signalling. Thus circFGD4 provides a novel potential biomarker and valuable therapeutic strategy for GC.
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http://dx.doi.org/10.1042/CS20191043DOI Listing
July 2020

Cell cycle-related lncRNAs and mRNAs in osteoarthritis chondrocytes in a Northwest Chinese Han Population.

Medicine (Baltimore) 2020 Jun;99(24):e19905

School of Public Health, Health Science Center of Xi'an Jiaotong University.

Background: A group of differentially expressed long non-coding RNAs (lncRNAs) have been shown to play key roles in osteoarthritis (OA), although they represented only a small proportion of lncRNAs that may be biologically and physiologically relevant. Since our knowledge of regulatory functions of non-coding RNAs is still limited, it is important to gain better understanding of their relation to the pathogenesis of OA.

Methods: We performed mRNA and lncRNA microarray analysis to detect differentially expressed RNAs in chondrocytes from three OA patients compared with four healthy controls. Then, enrichment analysis of the differentially expressed mRNAs was carried out to define disease molecular networks, pathways and gene ontology (GO) function. Furthermore, target gene prediction based on the co-expression network was performed to reveal the potential relationships between lncRNAs and mRNAs, contributing an exploration of a role of lncRNAs in OA mechanism. Quantitative RT-PCR analyses were used to demonstrate the reliability of the experimental results.

Findings: Altogether 990 lncRNAs (666 up-regulated and 324 down-regulated) and 546 mRNAs (419 up-regulated and 127 down-regulated) were differentially expressed in OA samples compared with the normal ones. The enrichment analysis revealed a set of genes involved in cell cycle. In total, 854 pairs of mRNA and lncRNA were highly linked, and further target prediction appointed 12 genes specifically for their corresponding lncRNAs. The lncRNAs lncRNA-CTD-2184D3.4, ENST00000564198.1, and ENST00000520562.1 were predicted to regulate SPC24, GALM, and ZNF345 mRNA expressions in OA.

Interpretation: This study uncovered several novel genes potentially important in pathogenesis of OA, and forecast the potential function of lnc-CTD-2184D3.4, especially for the cell cycle in the chondrocytes. These findings may promote additional aspects in studies of OA.
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http://dx.doi.org/10.1097/MD.0000000000019905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302618PMC
June 2020

Circ-OXCT1 Suppresses Gastric Cancer EMT and Metastasis by Attenuating TGF-β Pathway Through the Circ-OXCT1/miR-136/SMAD4 Axis.

Onco Targets Ther 2020 11;13:3987-3998. Epub 2020 May 11.

Department of Gastrointestinal Surgery, Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People's Republic of China.

Background: Circular RNAs (circRNAs) have been proven to play important roles in tumorigenesis. However, the mechanism by which circRNAs act on gastric cancer (GC) through epithelial-to-mesenchymal transition (EMT) is unclear. In this study, we identified circ-OXCT1 and elucidated its function on EMT in GC.

Methods: Tissue circRNA microarray analysis and qRT-PCR were utilized to determine the expression level of circ-OXCT1 in GC. Luciferase reporter assay and FISH were employed to confirm the interaction between circ-OXCT1 and miR-136. CCK-8, cloning formation, transwell, wound healing, nude mice experiment, circ-OXCT1 overexpression and silencing were conducted to elucidate the function of circ-OXCT1 in vivo and in vitro. Western blot and rescue experiment were carried out to evaluate the changes of EMT-related proteins induced by circ-OXCT1 overexpression or silencing.

Results: Circ-OXCT1 was downregulated in GC tissues and cell lines. Its expression level was significantly associated with lymph node metastasis, pathologic stage and overall survival rate through clinicopathologic data analysis. Circ-OXCT1 silencing downregulated SMAD4 expression and accordingly regulated expression of E-cadherin, N-cadherin and vimentin through the transforming growth factor-beta (TGF-β)/Smad signaling pathway by a circ-OXCT1/miR-136/SMAD4 axis, resulting in enhancement of EMT and subsequent boost of cell migration, invasion and nude mice lung metastasis.

Conclusion: Our data showed that circ-OXCT1 suppresses gastric cancer EMT and metastasis through TGF-β/Smad signaling pathway. The clinicopathologic data analysis revealed that circ-OXCT1 overexpression could be a novel treatment for advanced GC especially with distant metastasis by targeting the circ-OXCT1/miR-136/SMAD4 axis.
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http://dx.doi.org/10.2147/OTT.S239789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236241PMC
May 2020

Altered Expression of Aggrecan, FAM20B, B3GALT6, and EXTL2 in Patients with Osteoarthritis and Kashin-Beck Disease.

Cartilage 2020 Jun 9:1947603520932199. Epub 2020 Jun 9.

School of Public Health, Key Laboratory of Environment and Genes Related to Diseases, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

Objective: The objective of this study was to investigate the expression of enzymes involved in synthesis and modification of chondroitin sulfate (CS) in knee cartilage tissue of patients with osteoarthritis (OA) and Kashin-Beck disease (KBD).

Methods: The knee articular cartilage samples were obtained from 18 age- and gender-matched donors with 6 each in KBD, OA, and control groups. Hematoxylin and eosin (HE) staining, toluidine blue (TB) staining, and immunohistochemical (IHC) staining were performed to estimate the expression level and localization of aggrecan, along with FAM20B, GalT-II, and EXTL2, which are associated with CS synthesis and modification. Rank-based analyses of variance test was used for the multiple comparisons of discrepancy in the positive staining rate among the 3 groups.

Results: In HE and TB staining results, damaged morphology, decreased chondrocyte numbers and proteoglycans were observed in OA and KBD groups compared with the control group. In line with these trends, the positive staining rates of aggrecan were lower in KBD and OA groups than in the control group. Meanwhile, the positive staining rates of CS chain modifying enzymes FAM20B, GalT-II, and EXTL2 decreased in OA and KBD groups.

Conclusions: In conclusion, it was demonstrated that altered expression of CS chain modifying enzymes in OA and KBD groups influenced the synthesis procession of CS and could contribute to the damage of cartilage. Further investigation of these enzymes can provide new theoretical and experimental targets for OA and KBD pathogenesis studies.
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http://dx.doi.org/10.1177/1947603520932199DOI Listing
June 2020

Construction of an Immunogenomic Risk Score for Prognostication in Colon Cancer.

Front Genet 2020 21;11:499. Epub 2020 May 21.

Department of Digestive Oncology, Three Gorges Hospital, Chongqing University, Chongqing, China.

Immune-related genes (IRGs) play regulatory roles in the immune system and are involved in the initiation and progression of colon cancer. This study aimed to develop an immunogenomic risk score for predicting survival outcomes among colon cancer patients. We analyzed the expressions of IRGs in colon specimens and discovered 484 differentially expressed IRGs when we compared specimens from colon cancer and adjacent normal tissue. Univariate Cox regression analyses were performed to identify 26 IRGs that were associated with survival. A Cox proportional hazards model with a lasso penalty identified five optimal IRGs for constructing the immunogenomic risk score (, and ). The risk score had good performance in predicting overall survival among patients with colon cancer and was correlated with the amount of tumor-infiltrating immune cells. Our findings suggest that the immunogenomic risk score may be useful for prognostication in colon cancer cases. Furthermore, the five IRGs included in the risk score might be useful targets for investigating the initiation of colon cancer and designing personalized treatments.
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http://dx.doi.org/10.3389/fgene.2020.00499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253627PMC
May 2020

Ceftazidime-related urinary calculi in a young boy: a case report.

J Int Med Res 2020 Apr;48(4):300060520921667

Department of Urology, Second People's Hospital of Yichang, Second People's Hospital of China Three Gorges University, Yichang, Hubei, China.

Certain drugs can cause kidney stones but as far as we are aware, ceftazidime-related urinary calculi have not been previously reported. We report here a case of an 8-year-old boy who developed hydronephrosis secondary to urinary calculi after receiving ceftazidime 2.0 g by intravenous infusion daily for two weeks. Previously, his left kidney showed no signs of disease. A retrograde double J ureteral stent was inserted, ceftazidime terminated, fluids increased and urine alkalised. On day 25, the patient showed no signs of kidney stones or hydronephrosis. Clinicians should be aware of the possibility of ceftazidime-related urinary calculi particularly if patients are receiving long-term treatment.
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http://dx.doi.org/10.1177/0300060520921667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223203PMC
April 2020

Proteomic analysis of knee cartilage reveals potential signaling pathways in pathological mechanism of Kashin-Beck disease compared with osteoarthritis.

Sci Rep 2020 04 22;10(1):6824. Epub 2020 Apr 22.

School of Public Health, Health Science Center; Key Laboratory of Environment and Gene Related Diseases of Ministry Education; Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P. R. China.

The pathological mechanism of Kashin-Beck disease (KBD), an endemic osteoarthritic disease, remains to be poorly understood. This study was designed to identify signaling pathways and crucial proteins involved in the pathological mechanism of KBD compared with osteoarthritis (OA). The knee cartilage samples were collected from gender- and age-matched KBD (n = 9) and OA (n = 9) patients. After pre-processing, samples were labeled with Tamdem Mass Tags 6plex multiplex kit, and analyzed by liquid chromatography-tandem mass spectrometry. Proteomic results were analyzed with gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactions (PPI). The differential abundance proteins from KBD and OA were validated using western blot analysis. As a result, A total number of 375 proteins were identified to have differential abundance between KBD and OA, of which 121 and 254 proteins were observed to be up-regulated or down-regulated in KBD group. GO analysis shows that the differential abundant proteins are associated with cell junction and signal transducer activity from extracellular to intracellular. KEGG pathways enrichment and PPI network indicate four major pathways, including extracellular matrix -receptor interaction, focal adhesion, phosphatidylinositol 3-kinase (PI3K)-Protein kinase B (Akt), and Ras signaling pathways were involved in the degeneration of cartilage. Moreover, integrins, laminins, NF-κB and other regulative molecules were found as crucial proteins. In conclusion, our results demonstrated that compared with OA, the differential abundance proteins and signaling pathways may contribute to the occurrence and development of joint damage in KBD. Further investigation of their regulative roles and interaction may provide new insights into the pathological mechanisms and therapeutic targets for KBD.
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http://dx.doi.org/10.1038/s41598-020-63932-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176695PMC
April 2020

Response to comment on 'Comparison of the toxic mechanism of T-2 toxin and deoxynivalenol on human chondrocytes by microarray and bioinformatics analysis'.

Authors:
Lei Yang Xiong Guo

Toxicol Lett 2020 07 24;327:32. Epub 2020 Mar 24.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, Xi'an, Shaanxi, PR China.

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http://dx.doi.org/10.1016/j.toxlet.2020.03.014DOI Listing
July 2020

Comparison of the responsiveness of the WOMAC and the 12-item WHODAS 2.0 in patients with Kashin-Beck disease.

BMC Musculoskelet Disord 2020 Mar 25;21(1):188. Epub 2020 Mar 25.

School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, Xi'an Jiaotong University, No.76 Yanta West Road, Xi'an, Shaanxi, 710061, People's Republic of China.

Background: Several questionnaires have been used to assess the health status of patients with Kashin-Beck disease (KBD) in clinical trials, but the evidence regarding the responsiveness of these instruments in KBD patients is limited. Therefore, the aim of this study was to evaluate and compare the responsiveness of the Chinese version of the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) in KBD patients undergoing intra-articular injection of hyaluronic acid (HA).

Methods: A sample of 232 KBD patients treated with intra-articular injection of HA completed the WOMAC, 12-item WHODAS 2.0 and joint dysfunction index (JDI) both pre- and post-treatment. Responsiveness was assessed using correlation and receiver operating characteristic (ROC) curve analyses following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist.

Results: Overall, there were significant improvements in the mean scores on the WOMAC and on the 12-item WHODAS 2.0, except for in the cognition domain. Correlation analysis showed that changes in the WOMAC and 12-item WHODAS 2.0 scores had moderate or weak positive associations with the changes in the JDI. However, acceptable areas under the ROC curve (value > 0.7) were found for all domains and for the total score on the WOMAC, but only for the mobility domain and the total score on the 12-item WHODAS 2.0.

Conclusions: These results demonstrated that the WOMAC was more responsive than the 12-item WHODAS 2.0 in KBD patients treated with intra-articular injection of HA. Our findings support the continued use of the WOMAC as an outcome measure in assessing disability in KBD patients.
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http://dx.doi.org/10.1186/s12891-020-03210-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098162PMC
March 2020

HNF1A-AS1 Regulates Cell Migration, Invasion and Glycolysis via Modulating miR-124/MYO6 in Colorectal Cancer Cells.

Onco Targets Ther 2020 18;13:1507-1518. Epub 2020 Feb 18.

Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital Central South University, Changsha 410008, People's Republic of China.

Background: Accumulating evidence determined that lncRNAs play multiple roles in cell progression in colorectal cancer (CRC). Long noncoding RNA (lncRNA) hepatocyte nuclear factor 1 homeobox A (HNF1A)-antisense RNA 1 (AS1) has been identified to affect cell growth and disease diagnosis in various cancers, including CRC. However, the underlying regulatory mechanism of HNF1A-AS1 in cell progression and glycolysis has not been fully explored in CRC.

Materials And Methods: The expression of HNF1A-AS1, microRNA-124 (miR-124) and Myosins of class VI (MYO6) was detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The analysis of glucose consumption, lactate production and hexokinase 2 (HK2) protein level was used to assess glycolysis in cells. The protein level of HK2 and MYO6 was measured with Western blot. Cell migration and invasion were evaluated using the transwell assay. The relationship among HNF1A-AS1, miR-124 and MYO6 was determined via luciferase reporter and RNA immunoprecipitation (RIP) assay.

Results: In this study, we found that HNF1A-AS1 was upregulated in CRC tissues and cell lines. Functional experiments determined that reduction of HNF1A-AS1 or promotion of miR-124 inhibited cell migration and invasion as well as glycolysis in CRC cells. What' more, luciferase reporter assay manifested that miR-124 was a target of HNF1A-AS1 and MYO6 was a target mRNA of miR-124 in CRC cells. Additionally, reverse experiments showed that the effects of si-HNF1A-AS1 on colorectal cancer cells were impaired by anti-miR-124 and the effects of high miR-124 expression on CRC cells were rescued by upregulating MYO6. HNF1A-AS1 regulated MYO6 expression via targeting miR-124 in CRC cells.

Conclusion: In this study, we first found that HNF1A-AS1 regulated cell migration, invasion and glycolysis via modulating miR-124/MYO6 in CRC cells.
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http://dx.doi.org/10.2147/OTT.S231249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035897PMC
February 2020

Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors.

Asian J Pharm Sci 2019 Jan 17;14(1):78-85. Epub 2018 Mar 17.

Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, Shenyang 110016, China.

Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment. This study was aiming to investigate the potential of concurrent delivery of resveratrol (RES) and docetaxel (DTX) via polymeric nanocarriers to treat breast cancer. To this end, methoxyl poly(ethylene glycol)-poly(d,l-lactide) copolymer (mPEG-PDLA) was prepared and characterized using FTIR and H NMR, and their molecular weights were determined by GPC. Isobologram analysis and combination index calculation were performed to find the optimal ratio between RES and DTX to against human breast adenocarcinoma cell line (MCF-7 cells). Subsequently, RES and DTX were loaded in the mPEG-PDLA micelles simultaneously, and the morphology, particle size distribution, release, pharmacokinetic profiles, as well as cytotoxicity to the MCF-7 cells were characterized. IC of RES and DTX in MCF-7 cells were determined to be 23.0 µg/ml and 10.4 µg/ml, respectively, while a lower IC of 4.8 µg/ml of the combination of RES and DTX was obtained. The combination of RES and DTX at a ratio of 1:1 (w/w) generated stronger synergistic effect than other ratios in the MCF-7 cells. RES and DTX loaded mPEG-PDLA micelles exhibited prolonged release profiles, and enhanced cytotoxicity against MCF-7 cells. The AUC of DTX and RES in mPEG-PDLA micelles after i.v. administration to rats were 3.0-fold and 1.6-fold higher than that of i.v. injections of the individual drugs. These findings indicated that the co-delivery of RES and DTX using mPEG-PDLA micelles could have better treatment of tumors.
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http://dx.doi.org/10.1016/j.ajps.2018.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032195PMC
January 2019

[Stepwise treatment for knee lesion of adult Kashin-Beck disease].

Zhongguo Gu Shang 2019 12;32(12):1082-1084

Department of Joint Surgery, Xi'an Honghui Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an 710054, Shaanxi, China;

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http://dx.doi.org/10.3969/j.issn.1003-0034.2019.12.002DOI Listing
December 2019

Comparison of the toxic mechanism of T-2 toxin and deoxynivalenol on human chondrocytes by microarray and bioinformatics analysis.

Toxicol Lett 2020 Mar 19;321:61-68. Epub 2019 Dec 19.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, Xi'an, Shaanxi, PR China. Electronic address:

T-2 toxin and deoxynivalenol (DON) are two representative mycotoxins that are commonly found in cereals and agricultural products. As T-2 toxin and DON are considered the cause of Kashin-Beck disease, a special osteoarticular disease, chondrocytes would be a vital target site for these toxins. To fully understand the toxicity effects of T-2 toxin and DON on chondrocytes, the present study investigated and compared the gene expression profiles and underlying mechanisms of T-2 toxin and DON on cultured human chondrocytes by microarray and bioinformatics analysis. Normal human chondrocytes were treated with T-2 toxin at 0.01 μg/ml and DON at 1.0 μg/ml for 72 h and analyzed by microarray using Affymetrix Human Gene Chip. Comprehensive analysis, including gene ontology, pathways and gene-gene networks was performed to identify the crucial gene functions, related signal pathways and key genes. A total of 175 and 237 differentially expressed genes were identified in human chondrocytes for T-2 toxin and DON treatment, respectively. Of these, 47 had the same expression tendencies in the two groups. The protein-protein interaction network analysis showed that the 10 hub genes were different between the two groups. Our results provide a comprehensive understanding of the toxic mechanism of T-2 toxin and DON on human chondrocytes and suggest that although T-2 toxin and DON showed some similar toxic mechanisms in human chondrocytes, they also had different toxic characteristics.
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http://dx.doi.org/10.1016/j.toxlet.2019.12.024DOI Listing
March 2020

Abnormal expression of chondroitin sulfate sulfotransferases in the articular cartilage of pediatric patients with Kashin-Beck disease.

Histochem Cell Biol 2020 Mar 16;153(3):153-164. Epub 2019 Dec 16.

Department of Integrative Medical Biology, Umeå University, 90187, Umeå, Sweden.

The objective of this study is to investigate the expression of enzymes involved in the sulfation of articular cartilage from proximal metacarpophalangeal (PMC) joint cartilage and distal metacarpophalangeal (DMC) joint cartilage in children with Kashin-Beck disease (KBD). The finger cartilage samples of PMC and DMC were collected from KBD and normal children aged 5-14 years old. Hematoxylin and eosin staining as well as immunohistochemical staining were used to observe the morphology and quantitate the expression of carbohydrate sulfotransferase 3 (CHST-3), carbohydrate sulfotransferase 12 (CHST-12), carbohydrate sulfotransferase 13 (CHST-13), uronyl 2-O-sulfotransferase (UST), and aggrecan. In the results, the numbers of chondrocyte decreased in all three zones of PMC and DMC in the KBD group. Less positive staining cells for CHST-3, CHST-12, CHST-13, UST, and aggrecan were observed in almost all three zones of PMC and DMC in KBD. The positive staining cell rates of CHST-12 were higher in superficial and middle zones of PMC and DMC in KBD, and a significantly higher rate of CHST-13 was observed only in superficial zone of PMC in KBD. In conclusion, the abnormal expression of chondroitin sulfate sulfotransferases in chondrocytes of KBD children may provide an explanation for the cartilage damage, and provide therapeutic targets for the treatment.
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http://dx.doi.org/10.1007/s00418-019-01833-0DOI Listing
March 2020

Evaluating the Correlations Between Osteoporosis and Lifestyle-Related Factors Using Transcriptome-Wide Association Study.

Calcif Tissue Int 2020 03 12;106(3):256-263. Epub 2019 Dec 12.

Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, No. 76 Yan Ta West Road, Xi'an, 710061, People's Republic of China.

Osteoporosis (OP) is a multi-factorial bone disease influenced by genetic factors, age, and lifestyles. The aim of this study is to evaluate the genetic correlations between OP and multiple lifestyle-related factors, and explore the genes underlying the detected genetic correlations. Linkage disequilibrium score regression (LDSC) analysis was applied to evaluate the genetic correlations of total body bone mineral density (TB-BMD) of different ages (including 15-30 years, 30-45 years, 45-60 years, and over 60 years) with four common lifestyle/environment-related factors (including serum 25-hydroxyvitamin D, cigarette smoking, alcohol dependence, and caffeine metabolites). Transcriptome-wide association studies (TWAS) of TB-BMD (30-45 years) and smoking were conducted in peripheral blood (PB), whole blood (WB), and adipose tissues. The identified candidate genes were also subjected to gene set enrichment analysis (GSEA). Genetic correlation was only observed between TB-BMD (30-45 years) and cigarette smoking status (P = 0.01, LD score = 0.11 ± 0.04). No significant genetic correlation was detected for other lifestyle/environmental factors, including serum 25-hydroxyvitamin D, alcohol dependence, and caffeine metabolites for TB-BMD within all of the four age groups. TWAS identified 85 genes in PB and 163 genes in WB for TB-BMD, as well as 123 genes in PB and 257 genes in WB for smoking. Multiple common candidate genes shared by both TB-BMD and smoking were detected, such as MAP1LC3B (P = 1.00 × 10, P = 9.62 × 10, P = 2.99 × 10) and SLC23A3 (P = 1.48 × 10, P = 8.76 × 10). GSEA detected one GO terms for TB-BMD (cytosol) in WB, one GO term for smoking (mitochondrion) in PB, and one pathway (oocyte meiosis) for smoking in WB.
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http://dx.doi.org/10.1007/s00223-019-00640-yDOI Listing
March 2020