Publications by authors named "Zhijie Dai"

13 Publications

  • Page 1 of 1

Single Dose of SHR-1222, a Sclerostin Monoclonal Antibody, in Healthy Men and Postmenopausal Women With Low Bone Mass: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Phase I Study.

Front Pharmacol 2021 20;12:770073. Epub 2021 Oct 20.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

SHR-1222 is a humanized monoclonal antibody targeting sclerostin and has the potential to promote bone formation and reduce bone resorption. This study was aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1222 in healthy men and postmenopausal women with low bone mass (BMD). It was a randomized, double-blind, placebo-controlled, dose-escalation, phase I study. Subjects received SHR-1222 at 50, 100, 200, 300, and 400 mg sequentially or matching placebo subcutaneously. Totally, 50 subjects with low BMD were enrolled and randomly assigned; 10 received placebo and 40 received SHR-1222 (50 mg, n = 4; 100, 200, 300, or 400 mg, n = 9). The most common adverse events that occurred at least 10% higher in subjects with SHR-1222 treatment than those with placebo were decreased blood calcium, blood urine present, increased blood cholesterol, electrocardiogram T wave abnormal, urinary tract infection, increased blood pressure diastolic, and positive bacterial test. All the above adverse events were mild in severity and well resolved except one of increased blood cholesterol in a subject lost to follow-up. The serum SHR-1222 concentration increased in a dose-dependent manner. Administration of SHR-1222 upregulated the bone-formation markers N-terminal propeptide of type 1 procollagen, osteocalcin, and bone-specific alkaline phosphatase, while downregulated the bone-resorption marker β-C-telopeptide. The BMD at the lumbar spine notably rose after a single dose of SHR-1222. The largest increase occurred in the 400 mg cohort (3.8, 6.7, and 6.1% on day 29, 57, and 85, respectively; compared with 1.4, 0.8, and 1.0% in the placebo group). Although 10.0% of subjects receiving SHR-1222 tested positive for anti-SHR-1222 antibodies, no obvious effects of antibody formation were found on pharmacokinetics. Overall, SHR-1222 was well tolerated at doses from 50 to 400 mg and is a promising new remedy for osteoporosis. http://www.clinicaltrials.gov, NCT03870100.
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http://dx.doi.org/10.3389/fphar.2021.770073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564351PMC
October 2021

[Retracted] CXCL5 promotes the proliferation and migration of glioma cells in autocrine‑ and paracrine‑dependent manners.

Oncol Rep 2021 Oct 9;46(4). Epub 2021 Aug 9.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting assay data shown in Fig. 7 were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 36: 3303-3310, 2016; DOI: 10.3892/or.2016.5155].
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http://dx.doi.org/10.3892/or.2021.8163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377462PMC
October 2021

Overexpression of Annexin A2 promotes proliferation by forming a Glypican 1/c-Myc positive feedback loop: prognostic significance in human glioma.

Cell Death Dis 2021 03 12;12(3):261. Epub 2021 Mar 12.

Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, China.

In order to set up a reliable prediction system for the tumor grade and prognosis in glioma patients, we clarify the complicated crosstalk of Annexin A2 (ANXA2) with Glypican 1 (GPC1) and demonstrate whether combined indexes of ANXA2 and GPC1 could improve the prognostic evaluation for glioma patients. We found that ANXA2-induced glioma cell proliferation in a c-Myc-dependent manner. ANXA2 increased the expression of GPC1 via c-Myc and the upregulated GPC1 further promoted the c-Myc level, forming a positive feedback loop, which eventually led to enhanced proliferation of glioma cells. Both mRNA and protein levels of ANXA2 were upregulated in glioma tissues and coincided with the overexpression of GPC1. Besides, we utilized tissue microarrays (TMAs) and immunohistochemistry to demonstrate that glioma patients with both high expression of ANXA2 and GPC1 tended to have higher rate of tumor recurrence and shorter overall survival (OS). In conclusion, the overexpression of ANXA2 promotes proliferation of glioma cells by forming a GPC1/c-Myc positive feedback loop, and ANXA2 together with its downstream target GPC1 could be a potential "combination biomarker" for predicting prognosis of glioma patients.
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http://dx.doi.org/10.1038/s41419-021-03547-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954792PMC
March 2021

Glioma progression is suppressed by Naringenin and APO2L combination therapy via the activation of apoptosis in vitro and in vivo.

Invest New Drugs 2020 12 7;38(6):1743-1754. Epub 2020 Aug 7.

Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.

Naringenin (NG) is a natural antioxidant flavonoid which is isolated from citrus fruits, and has been reported to inhibit colon cancer proliferation. However, the effects of NG treatment on glioma remain to be elucidated. The present study aimed to explore the effects of NG on glioma in vitro and in vivo. Also, the interactions between NG and APO2 ligand (APO2L; also known as tumor necrosis factor-related apoptosis-inducing ligand) were investigated in glioma. A synergistic effect of NG and APO2L combination on apoptotic induction was observed, though glioma cells were insensitive to APO2L alone. After NG treatment, glioma cells resumed the sensitivity to APO2L and cell apoptosis was induced via the activation of caspases, elevation of decoy receptors 4 and 5 (DR4 and DR5) and induction of p53. Coadministration of NG and APO2L decreased levels of anti-apoptotic B cell lymphoma 2 (Bcl-2) family members Bcl-2 and Bcl-extra large (Bcl-xL), while increased levels of proapoptotic factors Bcl-2-associated agonist of cell death (Bad) and Bcl-2 antagonist/killer 1 (Bak). Furthermore, an in vivo mouse xenograft model demonstrated that NG and APO2L cotreatment markedly suppressed glioma growth by activating apoptosis in tumor tissues when compared with NG or APO2L monotherapy. The present study provides a novel therapeutic strategy for glioma by potentiating APO2L-induced apoptosis via the combination with NG in glioma tumor cells.
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http://dx.doi.org/10.1007/s10637-020-00979-2DOI Listing
December 2020

Efficacy and Safety of Apatinib Combined with Etoposide in Patients with Recurrent Platinum-resistant Epithelial Ovarian Cancer: A Retrospective Study.

J Cancer 2020 9;11(18):5353-5358. Epub 2020 Jul 9.

National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Advanced epithelial ovarian cancer (EOC) eventually develops into a recurrent platinum-resistant disease. The response to standard treatment and prognosis in patients with EOC is generally unsatisfactory. This study aimed to assess the efficacy and safety of apatinib combined with etoposide in patients with recurrent platinum-resistant EOC. This is a single-center, retrospective, observational study. We have reviewed a total of 33 patients with recurrent platinum-resistant EOC from July 2017 to July 2018, who were regularly treated with apatinib and etoposide until disease progression or unacceptable toxic effects occurred. At the date of the review finished, 15 of 33 (45.5%) patients remained on the combined treatment of apatinib and etoposide, while the other 18 (54.5%) had discontinued. Although no complete response (CR) occurred, the overall response rate (ORR) and disease control rate (DCR) were 36.4% and 78.8% respectively. The median progression-free survival (PFS) was 5.6 months (95% CI, 4.1~7.1), and the median overall survival (OS) was 10.3 months (95% CI, 9.4~11.2). The most common adverse event was mucositis oral (60.6%), which caused the treatment discontinued in 4 (12.1%) patients. Other relatively common adverse events were hand-foot syndrome (42.4%), hypertension (39.4%), nausea or vomiting (30.3%), neutropenia (24.2%), fatigue (24.2%) and thrombocytopenia (21.2%). Grade 1 and 2 adverse events accounted for 63.6% (21/33). The efficacy of apatinib combined with etoposide is encouraging in patients with platinum-resistant EOC. Most adverse events of this combined therapy were mild and tolerable. Severe mucositis oral was not rare, which needs more precautions.
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http://dx.doi.org/10.7150/jca.45547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391184PMC
July 2020

Distinct two different ages associated with clinical profiles of acute onset type 1 diabetes in Chinese patients.

Diabetes Metab Res Rev 2020 02 9;36(2):e3209. Epub 2019 Aug 9.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Background: There are abundant variations in the phenotypes and genetics of type 1 diabetes (T1D) patients across different races. This study aimed to assess differences between juvenile acute onset (JAO) and adult acute onset in Chinese T1D patients.

Methods: Seven hundred and fifty-one acute onset T1D patients were divided into two groups by the patient onset age as follows: the juvenile acute onset group (≤20 years, JAO group) and the adult acute onset group (>20 years, AAO group). Clinical characteristics, islet autoantibodies, and HLA class II haplotypes and genotypes were compared between these two groups.

Results: In comparison with AAO patients, JAO patients had significantly lower relative weights and lower triglyceride levels (P < .001, P < .01, respectively) but higher frequency of ketoacidosis (P < .001), higher daily insulin dosage (P  < .001), higher HbA1 (P  < .05), and higher HDL-cholesterol levels (P  < .01). The JAO group showed a higher prevalence of IA-2A, ZnT8A, and multiple autoantibodies than that in the AAO group (P < .001, P < .01, P < .001, respectively). Haplotypes for DRB1*0301-DQA1*03-DQB1*0201, DR3, DR4, DR9, and DR3/DR9 genotypes are highly associated with JAO susceptibility, whereas only DR3 and DR9 genotypes confer risk for AAO. In the JAO group but not the AAO group, DR3 is related to ZnT8A, and DR3/DR9 is related to IA-2A and multiple autoantibodies.

Conclusions: These observations suggest that JAO patients markedly differ from AAO patients in their clinical manifestations and genetics in the Chinese T1D population. Notably, the DR3/DR9 genotype can facilitate the appearance of IA-2A or multiple autoantibodies in JAO patients.
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http://dx.doi.org/10.1002/dmrr.3209DOI Listing
February 2020

CXCL5 promotes the proliferation and migration of glioma cells in autocrine- and paracrine-dependent manners.

Oncol Rep 2016 Dec 10;36(6):3303-3310. Epub 2016 Oct 10.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

CXCL5 and its receptor CXCR2 have been found to be involved in tumorigenesis and cancer progression. Recent studies have shown that CXCR2 is upregulated in glioma tissues, and associated with poor prognosis and recurrence. However, the role of CXCL5/CXCR2 signaling in mediating the malignant phenotypes of glioma cells, as well as the underlying mechanism, still remains unclear. In the present study, we found that CXCL5 was upregulated in glioma tissues compared to that noted in normal brain tissues. High CXCL5 levels were significantly associated with higher tumor grade, advanced clinical stage, and shorter survival time of glioma patients. In vitro studies indicated that the protein expression levels of CXCL5 and CXCR2 were markedly higher in human glioma cell lines (U87, U251, U373 and A172), when compared with those in normal human gliocyte HEB cells. Overexpression of CXLC5 significantly promoted the proliferation and migration of U87 cells, while knockdown of CXCL5 by small interfering RNA markedly inhibited U87 cell proliferation and migration. Moreover, both exogenous CXCL5 treatment and the conditioned medium of CXCL5-overexpressing HEB cells also enhanced the proliferation and migration of U87 cells. Molecular mechanism investigation revealed that CXLC5 activated the ERK, JNK, p38 MAPK signaling pathways, which play key roles in tumor growth and metastasis. According to these data, our study suggests that CXCL5 plays a promoting role in glioma in autocrine- and paracrine-dependent manners.
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http://dx.doi.org/10.3892/or.2016.5155DOI Listing
December 2016

Roles of microRNA-99 family in human glioma.

Onco Targets Ther 2016 20;9:3613-9. Epub 2016 Jun 20.

Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha.

Objective: Deregulation of microRNA (miR)-99 family members (miR-99a, miR-99b, and miR-100) has been reported to play a crucial role in many cancer types. However, their roles in human gliomas have not been fully elucidated. This study aimed to investigate the expression patterns of miR-99a, miR-99b, and miR-100 in glioma tissues and to evaluate their expression profiles with respect to tumor progression.

Methods: Quantitative real-time polymerase chain reaction was performed to detect the expression levels of miR-99a, miR-99b, and miR-100 in glioma and matched non-neoplastic brain tissues. Then, the associations of their expression with various clinicopathological features of glioma patients were statistically analyzed. Moreover, the roles of miR-99a, miR-99b, and miR-100 in regulating glioma cell migration and invasion were determined via transwell assay in vitro.

Results: Compared with non-neoplastic brain tissues, miR-99a, miR-99b, and miR-100 expression levels were all significantly decreased in glioma tissues (all P<0.001). miR-99a-low, miR-99b-low, and miR-100-low expression more frequently occurred in glioma patients with low Karnofsky performance score (<90) and high World Health Organization grade (III-IV). Further functional experiments revealed that the enforced expression of miR-99a, miR-99b, and miR-100 resulted in the inhibition of cellular migration and invasion in glioma cells.

Conclusion: Our results strongly suggest that the aberrant expression of miR-99a, miR-99b, and miR-100 may be a common feature in human gliomas with aggressive clinicopathological features and may participate in malignant phenotypes of the tumors. These findings highlight the potential of the three miR-99 family members as novel therapeutic targets for human gliomas.
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http://dx.doi.org/10.2147/OTT.S99363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920231PMC
July 2016

Immunological Aspects of Fulminant Type 1 Diabetes in Chinese.

J Immunol Res 2016 14;2016:1858202. Epub 2016 Feb 14.

Diabetes Center, 2nd Xiangya Hospital and Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011, China.

Background. Fulminant type 1 diabetes (FT1D) is a novel subtype of type 1 diabetes characterized by extremely rapid onset and complete deficiency of insulin due to the destruction of pancreatic β cells. However, the precise mechanisms underlying the etiology of this disease remain unclear. Methods. A total of 22 patients with FT1D and 10 healthy subjects were recruited. Serum antibodies to GAD, IA2, and ZnT8 in patients were tested. And peripheral T cell responses to GAD65, insulin B9-23 peptide, or C peptide were determined in 10 FT1D patients and 10 healthy controls. The mRNA levels of several related cytokines and molecules, such as IFN-γ, IL-4, RORC, and IL-17 in PBMCs from FT1D patients were analyzed by qRT-PCR. Result. We found that a certain proportion of Chinese FT1D patients actually have developed islet-related autoantibodies after onset of the disease. The GAD, insulin, or C peptide-reactive T cells were found in some FT1D patients. We also detected a significant increase for IFN-γ expression in FT1D PBMCs as compared with that of healthy controls. Conclusion. Autoimmune responses might be involved in the pathogenesis of Chinese FT1D.
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http://dx.doi.org/10.1155/2016/1858202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769748PMC
November 2016

miR-101a and miR-30b contribute to inflammatory cytokine-mediated β-cell dysfunction.

Lab Invest 2015 Dec 14;95(12):1387-97. Epub 2015 Sep 14.

Diabetes Center, 2nd Xiangya Hospital, and Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, Changsha, Hunan, China.

Inflammatory cytokines have a critical role in the progressive deterioration of pancreatic β-cell function and development of type 1 diabetes. Prolonged exposure of β-cells to inflammatory cytokines results in gene expression modifications, leading to loss of β-cell function. MicroRNAs (miRNAs) are small non-coding RNAs acting as key regulators of gene expression. Here, we demonstrate that miR-101a and miR-30b are key players in cytokine-mediated β-cell dysfunction. We found that IL-1β induces an increase in miR-101a and miR-30b in MIN6 cells, and that the two miRNAs participate in β-cell dysfunction, including decreased insulin content, gene expression, and increased β-cell death. miR-101a and miR-30b reduce proinsulin expression and insulin content by directly targeting the transcriptional factor Neurod1. In addition, β-cell apoptosis mediated by miR-101a and miR-30b is associated with diminished expression level of the antiapoptotic protein Bcl2. Moreover, we show that miR-101a causes an impairment in glucose-induced insulin secretion by decreasing the expression of the transcription factor Onecut2. Taken together, our findings suggest that changes in the levels of miR-101a and miR-30b contribute to cytokine-mediated β-cell dysfunction occurring during the development and progression of type 1 diabetes.
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http://dx.doi.org/10.1038/labinvest.2015.112DOI Listing
December 2015

Gambling, Delay, and Probability Discounting in Adults With and Without ADHD.

J Atten Disord 2016 11 21;20(11):968-978. Epub 2013 Aug 21.

University of Canterbury, Christchurch, New Zealand University of Minho, Braga, Portugal

Objective: We investigated the relationship between impulsivity, as measured by delay and probability discounting, and gambling-related cognitions and behavior in adults with and without ADHD.

Method: Adults who met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnostic criteria for ADHD (n = 31) and controls (n = 29) were recruited from the community. All completed an interview that included an assessment of psychiatric disorders, gambling questionnaires, and simulated gambling, delay, and probability discounting tasks.

Results: The ADHD group was more likely to meet the criteria for problem gambling and was more impulsive than controls based on a composite discounting measure. ADHD symptoms were correlated with gambling-related cognitions and behavior. Probability, but not delay discounting, explained significant variance in gambling-related measures after controlling for ADHD symptoms.

Discussion: Results confirm an association between adult ADHD and gambling, and suggest that the facets of impulsivity related to risk proneness may be an independent risk factor for problem gambling in this population.
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http://dx.doi.org/10.1177/1087054713496461DOI Listing
November 2016

Sodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation.

J Bone Miner Res 2011 Mar;26(3):582-90

Departments of Medicine,Anatomy, Hong Kong, China.

myo-Inositol (MI) plays an essential role in several important processes of cell physiology, is involved in the neural system, and provides an effective treatment for some psychiatric disorders. Its role in osteogenesis and bone formation nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter of MI) knockout (SMIT1(-/-)) mice with markedly reduced tissue MI levels were used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1(-/-) embryos had a dramatic delay in prenatal mineralization and died soon after birth owing to respiratory failure, but this could be rescued by maternal MI supplementation. The rescued SMIT1(-/-) mice had shorter limbs, decreased bone density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted in retarded postnatal osteoblastic differentiation and bone formation in vivo and in vitro. Continuous MI supplementation partially restored the abnormal bone phenotypes in adult SMIT1(-/-) mice and strengthened bone structure in SMIT1(+/+) mice. Although MI content was much lower in SMIT1(-/-) mesenchymal cells (MSCs), the I(1,4,5)P(3) signaling pathway was excluded as the means by which SMIT1 and MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp, and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3-E1 cells and could be upregulated during bone morphogenetic protein 2 (BMP-2)-induced osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and MI has a detrimental impact on prenatal skeletal development and postnatal bone remodeling and confirmed their essential roles in osteogenesis, bone formation, and bone mineral density (BMD) determination.
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http://dx.doi.org/10.1002/jbmr.240DOI Listing
March 2011

Reward contrast in delay and probability discounting.

Learn Behav 2009 Aug;37(3):281-8

University of Canterbury, Christchurch, New Zealand.

In this study, we examined whether reward contrast influences choice between delayed and probabilistic outcomes. Specifically, we predicted that the subjective value of an intermediate reward would seem relatively larger or smaller, respectively, if it followed choices involving a smaller or larger reward and would produce corresponding changes in rates of delay and probability discounting. In Experiment 1, subjects made choices about hypothetical $5,000 or $50 outcomes and then made choices about $500 outcomes. Delay-discounting rates for the $500 outcome were larger for Group $5,000 than for Group $50, whereas the opposite result was obtained for probability-discounting rates. In Experiment 2, we used a design that allowed for contrast effects to be assessed within subjects. Two groups made choices about delayed or probabilistic rewards. After completing question blocks in which the amount was $5,000 or $50, subjects responded to questions with an intermediate amount ($475/$525). For Group Delay, the present value of the intermediate reward was greater after the $50 block than after the $5,000 block, whereas the opposite was obtained for Group Probability. The results from both experiments confirmed the predictions of reward contrast and suggested that the subjective value of a monetary reward varies inversely with the prior reward amount.
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http://dx.doi.org/10.3758/LB.37.3.281DOI Listing
August 2009
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