Publications by authors named "Danyang Zhou"

27 Publications

  • Page 1 of 1

Immediate effects of neuromuscular joint facilitation treatment on vertebral artery blood flow.

J Phys Ther Sci 2021 Dec 1;33(12):928-930. Epub 2021 Dec 1.

Fukuoka International University of Health and Welfare, Japan.

[Purpose] The purpose of this study was to investigate the changes in blood flow velocity and the vascular diameter of vertebral arteries before and after neuromuscular joint facilitation interventions via the cervical spine approach in healthy adults. [Participants and Methods] We included 16 healthy adults (9 males and 7 females). The interventions were performed successively, separated by a one-week interval. The order of interventions was randomized. The blood-flow velocity and diameter of the vertebral artery were measured before and after the intervention. The neuromuscular joint facilitation group underwent neuromuscular joint facilitation neck flexion pattern and extension pattern training on the right side of the cervical spine, while the control group was asked to rest for 5 min. [Results] The neuromuscular joint facilitation group showed a significant increase in systolic blood flow velocity and mean blood flow velocity of the right vertebral artery after the intervention. In contrast, the control group showed no significant differences for any of the measured parameters after the intervention. [Conclusion] Neuromuscular joint facilitation intervention via the cervical spine approach may be recommended to improve vertebral artery function.
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http://dx.doi.org/10.1589/jpts.33.928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636919PMC
December 2021

Distribution Characteristics and Prognostic Value of Immune Infiltration in Oligometastatic Breast Cancer.

Front Oncol 2021 11;11:747012. Epub 2021 Nov 11.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: To assess the distribution characteristics and the prognostic value of immune infiltration in female oligometastatic breast cancer patients.

Methods: We retrospectively analyzed the clinicopathological data of oligometastatic breast cancer (OMBC) patients diagnosed between June 2000 and January 2020. Immune markers were quantified by immunohistochemistry on FFPE tissues in paired normal breast tissues, primary breast cancers and oligometastatic lesions. Survival analyses were performed using the Kaplan-Meier curves and Cox-proportional hazards model.

Results: A total of 95 female OMBC patients visited Sun Yat-sen University Cancer Center between June 2000 and January 2020, and 33 of them had matched normal breast tissues, primary cancers and oligometastatic lesions and were reviewed in immune infiltration analysis. CD8 of primary tumors had a higher expression than that in matched normal tissues. The expressions of CD8 and FOXP3 were higher in the primary sites than that in the oligometastatic lesions. CD3, CD4 and CD8 were significantly lower in the intratumoral regions than that in the peritumoral regions both in primary and oligometastatic lesions. Notably, the high percentage of CD3 in the intratumoral oligometastatic lesions predicted the longer PFS and OS, and higher CD4 in the same lesions also predicted a better OS. There was obviously positive correlation between CD4/CD3 and Ki-67 in primary cancers and negative correlation between CD4/CD3 and ER in oligometastatic sites.

Conclusion: We explored immune distribution and evolution in time and space in OMBC to provide new understandings for biological behaviors of this disease and further divided patients in different prognosis.
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http://dx.doi.org/10.3389/fonc.2021.747012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632540PMC
November 2021

A Water-Soluble Polyacid Polymer Based on Hydrophilic Metal-Organic Frameworks Using Amphoteric Carboxylic Acid Ligands as Linkers for Hydroxycamptothecin Loading and Release In Vitro.

Nanomaterials (Basel) 2021 Oct 26;11(11). Epub 2021 Oct 26.

Henan International Joint Laboratory of Medicinal Plants Utilization, College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, China.

The poor water solubility and severe side effects of hydroxycamptothecin (HCPT) limit its clinical application; therefore, it is necessary to synthesize applicable nanodrug carriers with good solubility to expand the applications of HCPT. In this study, a hydrophilic metal-organic framework (MOF) with amphoteric carboxylic acid ligands as linkers was first synthesized and characterized. Then, water-soluble acrylamide and methacrylic acid were applied as monomers to prepare a water-soluble polyacid polymer [email protected], which had a solubility of 370 μg/mL. The effects of the [email protected] material on the HCPT loading and solubility were investigated. The results showed that the polymer material could improve the HCPT solubility in water. Moreover, the in vitro release study indicated that the [email protected] polymeric composite exhibited a sustained-release effect on HCPT, with a cumulative release rate of 30.18% in 72 h at pH 7.4. Furthermore, the cytotoxicity test demonstrated that the hydrophilic MOF and the [email protected] had low cell toxicities. The results indicate that the prepared [email protected] polymeric complex can be applied for the sustained release of HCPT in clinics.
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http://dx.doi.org/10.3390/nano11112854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618358PMC
October 2021

Identification of a risk prediction model for clinical prognosis in HER2 positive breast cancer patients.

Genomics 2021 Nov 16;113(6):4088-4097. Epub 2021 Oct 16.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China. Electronic address:

Background New biomarkers are needed to identify different clinical outcomes for HER2+ breast cancer (BC). Methods Differential genes of HER2+ BC were screened based on TCGA database. We used WGCNA to identify the genes related to the survival. Genetic Algorithm was used to structure risk prediction model. The prognostic model was validated in GSE data. Results We constructed a risk prediction model of 6 genes to identify prognosis of HER2+ BC, including CLEC9A, PLD4, PIM1, PTK2B, AKNAD1 and C15orf27. Kaplan-Meier curve showed that the model effectively distinguished the survival of HER2+ BC patients. The multivariate Cox regression suggested that the risk model was an independent predictor for HER2+ BC. Analysis related to immune showed that significant differences in immune infiltration between high- and low-risk groups classified by the prognostic model. Conclusions Our study identified a risk prediction model of 6 genes that could distinguish the prognosis of HER2+ BC.
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http://dx.doi.org/10.1016/j.ygeno.2021.10.010DOI Listing
November 2021

Miller-Payne Grading and 70-Gene Signature Are Associated With Prognosis of Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early-Stage Breast Cancer After Neoadjuvant Chemotherapy.

Front Oncol 2021 24;11:735670. Epub 2021 Sep 24.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Introduction: HR+/HER2- breast cancer (BC) has a much lower pathological complete response (pCR) rate to neoadjuvant chemotherapy (NAC). Therefore, to better stratify the relapse risk for HR+/HER2- non-pCR populations, it is essential to accurate identification new prognostic markers.

Materials And Methods: The study retrospectively analyzed 105 stage II-III patients who were diagnosed with HR+/HER2- BC and received NAC followed by breast and axilla surgery between 2013 and 2019 in Sun Yat-Sen University Cancer Center. The Miller-Payne (MP) grading system was used to evaluate pathological responses to NAC. The 70-gene signature was used to classify the prognosis signatures.

Results: Among the 105 patients, the study demonstrated that larger tumor size and lower progesterone receptor level at baseline and larger tumor size postoperative were statistically significantly associated with worse disease-free survival (DFS) ( = 0.004, = 0.021, and = 0.001, respectively). Among 54 patients who underwent the 70-gene assays, 26 (48.1%) had a low-risk signature; 28 (51.9%) patients had a high-risk signature. Patients with poor response (MP grades 1-2) were more likely to with a high-risk 70-gene signature than those with good response (MP grades 4-5). The final analysis showed that DFS was longer in the low-risk group than in the high-risk group [52.4 vs. 36.1 months of the median DFS, hazard ratio (HR) for recurrence, 0.29; 95% confidence interval (CI), 0.10-0.80; = 0.018]. DFS was longer in the good response (MP grades 3-4) group than in the poor response (MP grades 1-2) group (94.7% vs. 60% of the patients free from recurrence; HR, 0.16; 95% CI, 0.05-0.47; = 0.037). When stratified by MP grades combined with the 70-gene signature, subgroup analyses showed the good-response low-risk group with the best DFS, whereas the poor-response high-risk group showed the worst DFS ( = 0.048). Due to the short median follow-up time of 34.5 months (5.9-75.1 months), MP grades and the 70-gene signature did not show significant prognostic value for overall survival.

Conclusion: The study showed that analysis of MP grades combined with the 70-gene signature with residual NAC-resistant breast samples has a significant correlation with DFS.
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http://dx.doi.org/10.3389/fonc.2021.735670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498026PMC
September 2021

Safety, tolerability, and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer: An open-label, dose-escalation, phase I study.

Cancer Commun (Lond) 2021 02 2;41(2):171-182. Epub 2021 Feb 2.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China.

Background: The introductions of anti- human epidermal growth factor receptor-2 (HER2) agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer. BAT8001 is a novel antibody-drug conjugate targeting human epidermal growth factor receptor-2 (HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine. This dose-escalation, phase I study was designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.

Methods: This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer (having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1) using a 3 + 3 design of escalating BAT8001 doses. Patients received BAT8001 intravenously in a 21-day cycle, with dose escalation in 5 cohorts: 1.2, 2.4, 3.6, 4.8, and 6.0 mg/kg. The primary objective was to evaluate the safety and tolerability of BAT8001. Preliminary activity of BAT8001 was also assessed as a secondary objective.

Results: Between March 2017 to May 2018, 29 HER2-positive breast cancer patients were enrolled. The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase. The maximum tolerated dose was determined to be 3.6 mg/kg. Grade 3 or greater adverse events (AEs) occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) patients, aspartate aminotransferase increased in 4 (13.8%) patients, γ-glutamyl transferase increased in 2 (6.9%) patients, alanine aminotransferase increased in 2 (6.9%) patients, diarrhea in 2 (6.9%) patients. Objective response was observed in 12 (41.4%; 95% confidence interval [CI] = 23.5%-61.1%) and disease control (including patients achieving objective response and stable disease) was observed in 24 (82.8%; 95% CI = 64.2%-94.2%) patients.

Conclusions: BAT8001 demonstrated favorable safety profiles, with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer. BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.
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http://dx.doi.org/10.1002/cac2.12135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896747PMC
February 2021

Surveillance Strategy for Patients With BCLC Stage B Hepatocellular Carcinoma After Achieving Complete Remission: Data From the Real World.

Front Oncol 2020 29;10:574804. Epub 2020 Sep 29.

Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.

There is a lack of consensus on the surveillance strategy for Barcelona Clinic liver cancer (BCLC) stage B hepatocellular carcinoma (HCC) patients with complete remission (CR). We performed a real-world, retrospective analysis of the surveillance strategy for BCLC stage B HCC patients after radical therapy with CR to support clinical decision-making. We analyzed 546 BCLC stage B HCC patients with CR after radical treatments (surgery/ablation) at Sun Yat-sen University Cancer Center, from January 2007 to December 2019. The intensity of surveillance interval was defined as the mean of surveillance interval within 2 years. The primary endpoint of the study was overall survival (OS) and extra-Milan criteria relapse. During a median follow-up time of 23.9 months (range = 3.1-148.3 months), there were 11.9% of patients died, 56.6% of patients developed recurrence, the vast majority of patients experienced recurrence within 2 years, and 27.8% patients developed extra-Milan criteria recurrence. The median disease-free survival and OS were 33.6 and 60.0 months, respectively. Patients were divided into regular surveillance group (RS) (≤4.3 months) and irregular surveillance (IRS) group (>4.3 months) based on the optimal cutoff value of the intensity of surveillance interval. The RS group owned a lower incident of extra-Milan criteria relapse and smaller and fewer tumors at recurrence than IRS group, which contributed to the prolonged OS. Besides, the cutoff values of surveillance interval that could lead to significant differences in the incidence of extra-Milan criteria relapse during 0-6, 6-12, and 12-18 months after CR were 2.6, 2.9, and 3 months, respectively. The average surveillance interval for patients with BCLC stage B HCC achieved CR should not exceed 4.3 months during the first 2 years' follow-up. During three different phases of the initial 18 months after CR, individualized surveillance showed intervals no more than 3 months were required to reduce the incidence of extra-Milan criteria relapse.
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http://dx.doi.org/10.3389/fonc.2020.574804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550758PMC
September 2020

prediction and validation of potential therapeutic genes in pancreatic β-cells associated with type 2 diabetes.

Exp Ther Med 2020 Nov 4;20(5):60. Epub 2020 Sep 4.

Department of Endocrinology, Zhejiang Integrated Traditional and Western Medicine Hospital, Hangzhou, Zhejiang 310003, P.R. China.

Diabetes mellitus is becoming a major health burden worldwide. Pancreatic β-cell death is a characteristic of type 2 diabetes (T2D), but the underlying mechanisms of pancreatic β-cell death remain unknown. Therefore, the aim of the present study was to identify potential targets in the pancreatic islet of T2D. The GSE20966 dataset was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified by using the GEO2R tool. The Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analysis of DEGs were further assessed using the Database for Annotation, Visualization and Integrated Discovery. Furthermore, protein-protein interaction (PPI) networks were constructed for the up- and downregulated genes using STRING databases and were then visualized with Cytoscape. The body weight, fasting blood glucose (FBG), pancreatic index and biochemistry parameters were measured in db/db mice. Moreover, the morphology of the pancreas was detected by hematoxylin and eosin staining, and hub genes were assessed using reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. In total, 570 DEGs were screened, including 376 upregulated and 194 downregulated genes, which were associated with 'complement activation, classical pathway', 'proteolysis', 'complement activation' and 'pancreatic secretion pathway'. It was found that the body weight, FBG, alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, blood urea nitrogen, creatinine, fasting serum insulin, glucagon and low-density lipoprotein cholesterol levels were significantly higher in db/db mice, while high-density lipoprotein cholesterol levels and the pancreatic index were significantly decreased. Furthermore, albumin, interleukin-8, CD44, C-C motif chemokine ligand 2, hepatocyte growth factor, cystic fibrosis transmembrane conductance regulator, histone cluster 1 H2B family member n, mitogen-activated protein kinase 11 and neurotrophic receptor tyrosine kinase 2 were identified as hub genes in PPI network. RT-qPCR and western blotting results demonstrated the same expression trend in hub genes as found by the bioinformatics analysis. Therefore, the present study identified a series of hub genes involved in the progression of pancreatic β-cell, which may help to develop effective therapeutic strategy for T2D.
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http://dx.doi.org/10.3892/etm.2020.9188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485321PMC
November 2020

TACE-Sorafenib With Thermal Ablation Has Survival Benefits in Patients With Huge Unresectable Hepatocellular Carcinoma.

Front Pharmacol 2020 29;11:1130. Epub 2020 Jul 29.

Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.

Purpose: To investigate the effectiveness and safety of transarterial chemoembolization (TACE) combined with sorafenib and thermal ablation in patients with huge hepatocellular carcinoma (HCC).

Materials And Methods: This retrospective study examined 50 patients with huge unresectable HCC treated from January 2009 to December 2015. Among them, 28 cases received TACE-sorafenib treatment (TACE-sorafenib group), and 22 cases received TACE-sorafenib plus thermal ablation treatment (TACE-sorafenib-thermal ablation group). The Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared.

Results: The median follow-up was 13.5 months (ranges 4.2 to 96.7 months). The median OS was significantly longer in the TACE-sorafenib-thermal ablation group than that in the TACE-sorafenib group (20.8 vs. 10.4 months, =0.003). The median PFS of the ablation and no ablation groups were 4.3 vs. 7.1 months (=0.546). The treatment modality was an independent predictor of OS (=0.004). There were no notable drug-related high grade adverse events or permanent adverse sequelae.

Conclusion: TACE-sorafenib-thermal ablation provided extended OS to patients with huge unresectable HCC and could be a better choice than TACE-sorafenib.
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http://dx.doi.org/10.3389/fphar.2020.01130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438914PMC
July 2020

A novel identified circular RNA, circ_0000491, aggravates the extracellular matrix of diabetic nephropathy glomerular mesangial cells through suppressing miR‑101b by targeting TGFβRI.

Mol Med Rep 2020 Nov 2;22(5):3785-3794. Epub 2020 Sep 2.

Department of Endocrinology, Zhejiang Integrated and Western Medicine Hospital, Hangzhou, Zhejiang 310003, P.R. China.

Circular RNAs (circRNAs) have crucial roles in various diseases; however, the mechanisms of action underlying circRNAs in the occurrence and development of diabetic nephropathy (DN) remains largely unknown. The present study investigated the differentially expressed circRNAs in the DN mice kidney cortex using circRNA sequencing and elucidated the role of circRNAs in mesangial cells. It was revealed that 40 circRNAs were unconventionally expressed, including 18 upregulated circRNAs and 22 downregulated circRNAs. Furthermore, circ_0000491 levels were significantly augmented in both DN mice and high glucose (HG, 30 mM)‑induced mouse mesangial cells (MES13 cells). Knockdown of circ_0000491 significantly suppressed the increase of vimentin, fibronectin and α‑smooth muscle actin, as well as collagen type I, III and IV, whilst reversing the decrease of E‑cadherin in HG‑induced MES13 cells. It was further revealed that circRNA_0000491 sponged miR‑101b and that miR‑101b directly targets TGFβRI. In addition, the expression levels of miR‑101b were negatively associated with the transcriptional level of circRNA_0000491 and miR‑101b inhibitors reversed the suppression of extracellular matrix (ECM)‑associated protein synthesis mediated by knocking‑down circRNA_0000491. In conclusion, the present study investigated the circRNA_0000491/miR‑101b/TGFβRI axis in ECM accumulation and fibrosis‑associated protein expression levels of mesangial cells, which suggested that circRNA_0000491 may be beneficial for the development of an effective therapeutic target for DN.
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http://dx.doi.org/10.3892/mmr.2020.11486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533486PMC
November 2020

The Prognostic Value of Neutrophil-to-lymphocyte Ratio and Monocyte-to-lymphocyte Ratio in Metastatic Gastric Cancer Treated with Systemic Chemotherapy.

J Cancer 2020 25;11(14):4205-4212. Epub 2020 Apr 25.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

The prognostic value of neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) in metastatic gastric cancer (mGC) treated with systemic chemotherapy is largely unknown, especially second-line chemotherapy. We retrospectively investigated the prognostic value of baseline NLR and MLR in the progression of mGC with systemic chemotherapy. Patients with mGC diagnosed by pathology from January 2010 to December 2018 were identified. Baseline NLR and MLR were collected before treatment. The time to progression during or after first-line therapy from diagnosis (PFS1), and during or after second-line chemotherapy (PFS2) were primary endpoint. Overall survival (OS) was calculated from diagnosis to the date of death or final follow-up. 537 patients with first-line chemotherapy were included in the retrospective study. The cutoff values of NLR and MLR were 2.610 and 0.285, respectively. Pretreatment NLR and MLR were significantly independent prognostic factors for PFS1 (hazard ratio [HR]=1.597, 95% CI 1.261-2.022, <0.001 and HR=1.574, 95% CI 1.239-1.999, <0.001) and OS (HR=1.448, 95% CI 1.030-2.034, =0.033 and HR=1.622, 95% CI 1.148-2.291, =0.006). For 172 patients treated with second-line chemotherapy, the cutoff value of MLR was 0.355 and MLR maintained a significant association with PFS2 (HR=1.589, 95% CI 1.073-2.354, =0.021) in multivariate analysis. Elevated NLR and MLR were markedly related to the worse PFS1 and OS in mGC performed with first-line chemotherapy. In patients with second-line therapy, MLR was more closely connected to prognosis and was a significantly independent prognostic factor for PFS2.
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http://dx.doi.org/10.7150/jca.39575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196266PMC
April 2020

A predictive analysis approach for paediatric and adult high-grade glioma: miRNAs and network insight.

Ann Transl Med 2020 Mar;8(5):242

Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing 163319, China.

Background: Brain tumours are the most common solid tumour in children and are a cause of mortality in adults. Most cases of brain tumour-related death are attributed to glioblastoma (GBM), with an elevated rate for high-grade glioma (HGG). Showing strong heterogeneity, the lesion location, molecule expression and type of HGG differ between adults and children. However, with regard to pathogenesis, brain tumours are expected to have the same underlying molecular processes.

Methods: In this study, we obtained data from the Gene Expression Omnibus (GEO) database to analyse molecular expression in HGG between adults and children. The same and different mutations were identified in these groups, and the genes involved were compared using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Molecular analysis revealed the same trend of differences between children and adults, which was verified in The Cancer Genome Atlas (TCGA).

Results: A total of 12 microarrays including 455 HGG patients were screened. Through a rigorous intersecting process, we identified miR-10a, miR-10b, and miR-139 as having common differences, as well as 6 target genes, such as and , etc. And 12 long noncoding RNAs (lncRNAs).

Conclusions: We identified that these key molecules are involved in development and progression of HGG between adults and children. The findings provide a comprehensive description of the similarities in advanced diseases between adults and children and molecular diagnostic directions for precision small-molecule medicine to treat HGG in different age populations.
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http://dx.doi.org/10.21037/atm.2020.01.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154480PMC
March 2020

A bioinformatics and network pharmacology approach to the mechanisms of action of Shenxiao decoction for the treatment of diabetic nephropathy.

Phytomedicine 2020 Apr 22;69:153192. Epub 2020 Feb 22.

Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang, Hangzhou, Zhejiang 310053, PR China. Electronic address:

Background: The epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells is the main pathological alteration in diabetic nephropathy (DN). Traditional Chinese medicine (TCM) has been used for the treatment of DN in clinical practice and has been proven to be effective.

Purpose: This aim of this study was to shed light on the efficacy of Shenxiao decoction (SXD) on the EMT of renal tubular epithelial cells and the molecular mechanisms of SXD in mice with DN, as well as on the high glucose (HG)- and TGF-β1-induced EMT of NRK-52E and HK-2 cells.

Study Design And Methods: A bioinformatics and network pharmacology method were utilized to construct the active ingredient-target networks of SXD that were responsible for the beneficial effects against DN. The effects of RUNX3 were validated in HG- and TGF-β1-induced EMT processes in NRK-52E and HK-2 cells.

Results: Bioinformatics analysis revealed that 122 matching targets were closely associated with the regulation of cell migration and the AGE-RAGE signaling pathway in diabetic complications. The results also revealed that, relative to the mice with DN, the mice in the treatment group had an improved general state and reduced blood glucose levels. The degradation of renal function was ameliorated by SXD. Moreover, the protective effects of SXD were also observed on renal structural changes. Furthermore, SXD suppressed the activation of the transforming growth factor (TGF)-β1/Smad pathway and upregulated the RUNX3 and E-cadherin levels and downregulated the extracellular matrix (ECM) protein levels in mice with DN. SXD was further found to prevent the HG- and TGF-β1-induced EMT processes in NRK-52E and HK-2 cells. Additionally, the overexpression of RUNX3 markedly inhibited the EMT and TGF-β1/Smad pathway induced by HG and TGF-β1 in NRK-52E and HK-2 cells.

Conclusion: Taken together, these results suggest that SXD maybe alleviate EMT in DN via the inhibition of the TGF-β1/Smad/RUNX3 signaling pathway under hyperglycemic conditions.
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http://dx.doi.org/10.1016/j.phymed.2020.153192DOI Listing
April 2020

Immediate effects of lumbar spine patterns after neuromuscular joint facilitation on balance in stroke patients.

J Phys Ther Sci 2019 Dec 3;31(12):979-982. Epub 2019 Dec 3.

Department of Physical Therapy, International University of Health and Welfare: 2600-1 Kitakanemaru Otawara city, Tochigi 324-8501, Japan.

[Purpose] The present study investigated changes in the balance function of stroke patients after neuromuscular joint facilitation treatment. [Participants and Methods] Fourteen stroke patients were randomly subjected to neuromuscular joint facilitation intervention (neuromuscular joint facilitation intervention group) and no intervention (control group), with a 1-day interval between treatments. The interventions were performed consecutively. The order of interventions was completely randomized. Before and after one neuromuscular joint facilitation and control intervention, the functional reach test, and body sway were measured. [Results] Functional reach test values were significantly increased and peripheral area was significantly reduced in the neuromuscular joint facilitation intervention group than in the control group. [Conclusion] These results suggest that neuromuscular joint facilitation of the trunk has an immediate effect on balance and function in stroke patients.
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http://dx.doi.org/10.1589/jpts.31.979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893158PMC
December 2019

The schizophrenia risk isoform ZNF804A affects dendritic spine.

Schizophr Res 2020 04 16;218:324-325. Epub 2020 Jan 16.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China. Electronic address:

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http://dx.doi.org/10.1016/j.schres.2019.12.038DOI Listing
April 2020

The depression GWAS risk allele predicts smaller cerebellar gray matter volume and reduced SIRT1 mRNA expression in Chinese population.

Transl Psychiatry 2019 12 9;9(1):333. Epub 2019 Dec 9.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Major depressive disorder (MDD) is recognized as a primary cause of disability worldwide, and effective management of this illness has been a great challenge. While genetic component is supposed to play pivotal roles in MDD pathogenesis, the genetic and phenotypic heterogeneity of the illness has hampered the discovery of its genetic determinants. In this study, in an independent Han Chinese sample (1824 MDD cases and 3031 controls), we conducted replication analyses of two genetic loci highlighted in a previous Chinese MDD genome-wide association study (GWAS), and confirmed the significant association of a single nucleotide polymorphism (SNP) rs12415800 near SIRT1. Subsequently, using hypothesis-free whole-brain analysis in two independent Han Chinese imaging samples, we found that individuals carrying the MDD risk allele of rs12415800 exhibited aberrant gray matter volume in the left posterior cerebellar lobe compared with those carrying the non-risk allele. Besides, in independent Han Chinese postmortem brain and peripheral blood samples, the MDD risk allele of rs12415800 predicted lower SIRT1 mRNA levels, which was consistent with the reduced expression of this gene in MDD patients compared with healthy subjects. These results provide further evidence for the involvement of SIRT1 in MDD, and suggest that this gene might participate in the illness via affecting the development of cerebellum, a brain region that is potentially underestimated in previous MDD studies.
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http://dx.doi.org/10.1038/s41398-019-0675-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901563PMC
December 2019

The genome-wide risk alleles for psychiatric disorders at 3p21.1 show convergent effects on mRNA expression, cognitive function, and mushroom dendritic spine.

Mol Psychiatry 2020 01 13;25(1):48-66. Epub 2019 Nov 13.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Schizophrenia and bipolar disorder (BPD) are believed to share clinical features, etiological factors, and disease pathologies (such as impaired cognitive functions and dendritic spine pathology). Meanwhile, there is growing evidence of shared genetic risk between schizophrenia and BPD, despite that our knowledge of the functional risk variations and biological mechanisms is still limited. Here, we conduct summary data-based Mendelian randomization (SMR) analyses through combining the statistical data from genome-wide association studies (GWAS) of both schizophrenia and BPD and multiple expression quantitative trait loci (eQTL) datasets of the human brain dorsolateral prefrontal cortex (DLPFC) tissues. These integrative investigations identify a lead risk locus at the chromosome 3p21.1 region, which contains numerous single-nucleotide polymorphisms (SNPs) in varied linkage disequilibrium (LD) and encompasses more than 20 genes. Further analyses suggest that many SNPs at 3p21.1 are significantly associated with both schizophrenia and BPD, and even depression, and the psychiatric risk alleles at 3p21.1 are correlated with mRNA expression of multiple genes such as NEK4, GNL3, and PBRM1. We also identify a 335-bp functional Alu polymorphism rs71052682 in significant LD with the psychiatric GWAS risk SNP rs2251219, and confirm the regulatory effects of this Alu polymorphism on transcription activities. We then explore the involvement of the 3p21.1 locus in the common clinical features and etiology of these illnesses. We reveal that psychiatric risk alleles at 3p21.1 in low-to-high LD consistently predict worse cognitive functions in humans, and manipulating the gene expression (NEK4, GNL3, and PBRM1) linked with higher genetic risk could reduce the density of mushroom dendritic spines in rat primary cortical neurons, mirroring the spine pathology in the prefrontal cortex of psychiatric patients. Our results find that, although the risk alleles at 3p21.1 are in low-to-moderate LD spanning a large genomic area, their underlying biological mechanisms in psychiatric disorders likely converge. These results provide essential insights into the neural mechanisms underlying the chromosome 3p21.1 risk locus in the shared pathological and etiological features of both schizophrenia and BPD.
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http://dx.doi.org/10.1038/s41380-019-0592-0DOI Listing
January 2020

Association Between Transforming Growth Factor-β1 T869C Gene Polymorphism and Diabetic Nephropathy: A Meta-Analysis in the Chinese Population.

Clin Lab 2019 Jul;65(7)

Background: An updated meta-analysis was performed to clarify the effects of TGF-β1 T869C polymorphism on the risk of diabetic nephropathy (DN) in the Chinese population.

Methods: The studies were searched using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Ser-vice Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) up to October 2018.

Results: A total of 8 studies including 1,075 DN cases, 610 healthy controls, and 901 diabetes mellitus (DM) con-trols were involved in this meta-analysis. Overall, a significantly decreased risk of DN was associated with all vari-ants of TGF-β1 T869C when compared with the healthy group (T vs. C, OR = 0.71, 95% CI = 0.61 - 0.83; TT vs. CC, OR = 0.51, 95% CI = 0.37 - 0.69; TT + CT vs. CC, OR = 0.64, 95% CI = 0.51 - 0.82; TT vs. CC + CT, OR = 0.62, 95% CI = 0.48 - 0.82) or DM (T vs. C, OR = 0.65, 95% CI = 0.56 - 0.76; TT vs. CC, OR = 0.31, 95% CI = 0.17 - 0.55; TT + CT vs. CC, OR = 0.67, 95% CI = 0.54 - 0.84; TT vs. CC + CT, OR = 0.27, 95% CI = 0.13 - 0.55), as well as their combinations (T vs. C, OR = 0.67, 95% CI = 0.60 - 0.76; TT vs. CC, OR = 0.34, 95% CI = 0.21 - 0.56; TT + CT vs. CC, OR = 0.67, 95% CI = 0.56 - 0.80; TT vs. CC + CT, OR = 0.32, 95% CI = 0.17 - 0.57). The sub-group analyses stratified by geographic areas revealed significant results in South China.

Conclusions: This meta-analysis showed that the TGF-β1 T869C variants may influence DN risk in Chinese, and further studies with gene-gene and gene-environment interactions are required to confirm this conclusion.
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http://dx.doi.org/10.7754/Clin.Lab.2019.181238DOI Listing
July 2019

Identification of potential therapeutic target genes in mouse mesangial cells associated with diabetic nephropathy using bioinformatics analysis.

Exp Ther Med 2019 Jun 23;17(6):4617-4627. Epub 2019 Apr 23.

Department of Endocrinology, Zhejiang Integrated and Western Medicine Hospital, Hangzhou, Zhejiang 310003, P.R. China.

The aim of the present study was to identify genes under the effect of transforming growth factor-β (TGF-β1), high glucose (HG) and glucosamine (GlcN) in MES-13 mesangial cells and elucidate the molecular mechanisms of diabetic nephropathy (DN). The gene expression datasets GSE2557 and GSE2558 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were independently screened using the GEO2R online tool. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery. The protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape software. The hub genes were identified by the NetworkAnalyzer plugin. Overlapping genes were subjected to molecular docking analysis using SystemsDock. A total of 202 upregulated and 158 downregulated DEGs from the HG-treated groups, 138 upregulated and 103 downregulated DEGs from the GlcN-treated groups, and 81 upregulated and 44 downregulated DEGs from the TGF-β1-treated groups were identified. The majority of the DEGs were independently enriched in 'nucleosome assembly', 'chromatin silencing' and 'xenobiotic glucuronidation'. In addition, KEGG pathways were significantly enriched in 'systemic lupus erythematosus', 'protein processing in endoplasmic reticulum' and 'aldarate metabolism pathway', and 'TNF signaling pathway' intersected in the TGF-β1-treated and HG-treated groups. In total, eight hub genes, Jun, prostaglandin-endoperoxide synthase 2 (Ptgs2), fibronectin 1 (Fn1), cyclin-dependent kinase (Cdk)2, Fos, heat shock protein family A (Hsp70) member 5 (Hspa5), Hsp90b1 and homo sapiens hypoxia upregulated 1 (Hyou1), and three overlapping genes, Ras homolog gene family, member B (RHOB), complement factor H (CFH) and Krüppel-like factor 15 (KLF15), were selected. Valsartan with RHOB, and fosinopril with CFH and KLF15 had preferential binding activity. In conclusion, Jun, Ptgs2, Fn1, Cdk2, Fos, Hspa5, Hsp90b1, Hyou1, RHOB, CFH and KLF15 may be potential therapeutic targets for mesangial cells associated with DN, which may provide insight into DN treatment strategies.
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http://dx.doi.org/10.3892/etm.2019.7524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507521PMC
June 2019

Serum miR-515-3p, a potential new RNA biomarker, is involved in gastric carcinoma.

J Cell Biochem 2019 09 12;120(9):15834-15843. Epub 2019 May 12.

Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, China.

Objectives: microRNAs (miRNAs) have provided a new opportunity for developing diagnostic biomarkers and effective therapeutic targets in gastric cancer (GC). In this study, we aimed to investigate the relationship between miR-515-3p and GC development.

Experimental Design: The Gene Expression Omnibus (GEO) database was used for screening genes and miRNA and for 2R analysis. miRNA prediction target genes and screening key genes were analyzed using protein interactions (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A network of miRNA-mRNA interactions was predicated by Cytoscape (v.3.5.1), Institute of Systems Biology & University of California, San Diego & Pasteur institute & University of California, San Francisco. Finally, miR-515-3p levels were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in gastric cells and plasma levels. Then, the association between the expression level of miR-515-3p and the clinicopathological features of patients with GC was further analyzed.

Observations And Conclusions: We found that miR-515-3p was markedly overexpressed in individuals with GC compared with that in normal gastric cells (NCs) and the surgery group (P < 0.0001). In addition, receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) value of 0.8555 for miR-515-3p.

Significance: Our results present new information to the field of gastric cancer and has done a good job of creating an initial hypothesis using the database as well as validate their initial results. These results suggest that serum miR-515-3p is a novel potential biomarker for the detection of GC.
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http://dx.doi.org/10.1002/jcb.28854DOI Listing
September 2019

Preoperative Serum Platelet-Lymphocyte Ratio as a Prognostic Factor in Cholangiocarcinoma Patients after Radical Resection: A Retrospective Analysis of 119 Patients.

Gastroenterol Res Pract 2019 28;2019:8506967. Epub 2019 Jan 28.

Department of Oncology, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, Jiangxi 330006, China.

Aims: Although prognostic markers are important to establish therapeutic strategies in patients for conducting radical resection of cholangiocarcinoma (CCA), there is still a lack of simple, valid, and repeatable markers in clinical settings. We aim to evaluate the prognostic value of the preoperative serum platelet-lymphocyte ratio (PLR) in CCA patients who underwent radical resection.

Methods: We retrospectively analyzed CCA patients who underwent radical resection surgery in our institution from January 2011 to June 2016. Baseline PLR and other clinical pathological data were measured when patients were diagnosed initially. The prognostic value of PLR in overall survival (OS) and progression-free survival (PFS) were analyzed with the Cox proportional hazard model and the Kaplan-Meier method.

Results: This study retrospectively analyzed 119 patients who underwent radical resection of CCA. During a median follow-up time of 11.0 months, there were 99.2% recurrences and 42.9% who died, and the median OS and PFS were 9.4 months and 7.4 months, respectively. Multivariate Cox analysis identified that elevated levels of PLR (PLR > 157.25) as a significant factor predicted poorer OS ( = 0.018, HR: 2.160, 95% CI: 1.139-4.096) and PFS ( = 0.005, HR: 1.930, 95% CI: 1.220-3.053). In subgroup analysis, PLR also effectively predicted OS ( = 0.016, HR: 2.515, 95% CI: 1.143-5.532) and PFS ( = 0.042, HR: 1.908, 95% CI: 0.982-3.713) in CCA patients with positive lymphatic metastasis and/or positive surgical margin who required adjuvant therapy.

Conclusions: The preoperative serum PLR is an independent prognostic factor for OS and PFS in CCA patients after radical resection, including patients requiring adjuvant therapy.
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http://dx.doi.org/10.1155/2019/8506967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369483PMC
January 2019

Combining multi-dimensional data to identify a key signature (gene and miRNA) of cisplatin-resistant gastric cancer.

J Cell Biochem 2018 08 25;119(8):6997-7008. Epub 2018 Apr 25.

Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, P. R. China.

Gastric cancer (GC) is one of the most lethal malignant tumors; the resistance of this type of tumor is the main source of GC treatment failure. In this study, we used bioinformatics analysis to verify differences in resistant GCs and identify an effective method for reversing drug resistance in GC. Microarray data [gene and microRNA (miRNA)] were analyzed using GEO2R software, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied to further enrich the genetic data. miRNA-gene interactions were determined using Cytoscape (v.3.5.1). Online software was used to analyze protein interactions and predict network structure. The Cancer Genome Atlas (TCGA) database was used to verify the expression levels of genes in GC resistance. miR-604 expression levels were verified by real-time PCR in GC cell lines. We screened 3981 GC resistance-associated genes and 244 miRNAs using bioinformatics methods. Six hub genes were identified and verified in the TCGA database, including five up-regulated genes, POLR2L, POLR2C, POLR2F, APRT, and LMAN2, and a down-regulated gene, NFKB2. The up-regulated genes POLR2L, POLR2C, APRT, and LMAN2 interact with miR-604; therefore, we focused on miR-604, which has low expression in drug-resistant GC. The results of this study indicate that through bioinformatics technologies, we have determined the hub genes and hub miRNAs related to drug resistance in GC. Among them, miR-604 could become a new indicator in the diagnosis of drug-resistant GC and may be used to investigate the pathogenesis of resistance in GC.
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http://dx.doi.org/10.1002/jcb.26908DOI Listing
August 2018

Prognostic Value of Combination of Pretreatment Red Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio in Patients with Gastric Cancer.

Gastroenterol Res Pract 2018 14;2018:8042838. Epub 2018 Feb 14.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Aims: Gastric cancer (GC) is often diagnosed at an advanced stage; inexpensive and valid biomarkers for GC are still unavailable. We aimed to evaluate the prognosis of the combination of pretreatment red cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR) in patients with GC.

Methods: A retrospective analysis from 103 GC patients who were diagnosed at our institution from 2012 to 2016 was performed. Both pretreatment RDW and NLR were calculated based on the recommended cutoff values of 13.4% and 2.755, respectively. Combined values of RDW and NLR (RDW + NLR) stratified patients into a score of 0 (RDW ≤ 13.4% and NLR ≤ 2.755), a score of 1 (RDW > 13.4% or NLR > 2.755), and a score of 2 (RDW > 13.4% and NLR > 2.755). Prognostic significances for overall survival (OS) and progression-free survival (PFS) were assessed.

Results: Pretreatment RDW + NLR was a significantly independent prognostic factor for OS and PFS. Moreover, high RDW + NLR was strongly related to age, tumor location, TNM stage, CA125, and CA199. In a subgroup analysis for patients with advanced gastric cancer (AGC), we observed that the level of RDW + NLR was markedly associated with OS and PFS.

Conclusion: Pretreatment RDW + NLR is a simple, inexpensive, and valid prognostic system to predict the survival in patients with GC, especially AGC.
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http://dx.doi.org/10.1155/2018/8042838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832175PMC
February 2018

Apoptin-derived peptide reverses cisplatin resistance in gastric cancer through the PI3K-AKT signaling pathway.

Cancer Med 2018 04 9;7(4):1369-1383. Epub 2018 Mar 9.

Department of Biochemistry and Molecular Biology, Harbin Medical University, Daqing Campus, Daqing, Heilongjiang, 163319, China.

The prognosis of gastric cancer (GC) remains poor due to clinical drug resistance, and novel drugs are urgently needed. Apoptin-derived peptide (AdP) is an antitumor polypeptide constructed in our laboratory that has been used to combat cisplatin (CDDP) resistance in GC cells. MTT and colony-formation assays and Hoechst 33342 staining were used to measure the cytotoxicity of CDDP and AdP in GC cells. Cell apoptosis was measured using an Annexin-V-FITC/PI dual staining assay. Western blot analysis was conducted to detect the expression of proteins in the PI3K/AKT signaling pathway and resistance-related markers. AdP exerted a specific cytotoxic effect on GC cells and CDDP-resistant GC cells in a concentration- and time-dependent manner. AdP also suppressed cell invasion and migration. Additionally, AdP inhibited the expression of p85, AKT, p-p85, p-AKT, multidrug resistance 1 (MDR1), and aryl hydrocarbon nuclear translocator (ARNT) in the PI3K/AKT/ARNT signaling pathway, which promoted apoptosis and necrosis in GC cells. AdP promoted apoptosis in CDDP-resistant GC cells by suppressing the PI3K/AKT/ARNT signaling pathway and might be considered a candidate agent for the clinical treatment of cisplatin-resistant GC.
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http://dx.doi.org/10.1002/cam4.1380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911602PMC
April 2018

A peptide derived from apoptin inhibits glioma growth.

Oncotarget 2017 May;8(19):31119-31132

Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, Daqing, P.R. China.

Glioblastoma (GBM) is associated with poor prognosis due to its resistance to surgery, irradiation, and conventional chemotherapy. Thus, efficient therapeutic approaches for the treatment of GBM are urgently needed. HSP70 is an antiapoptotic protein that participates in the inhibition of both mitochondrial and membrane receptor apoptosis pathways and is highly expressed in glioma tissues. Here, we investigated a derivative of apoptin; specifically, a chicken anemia viral protein with selective toxicity toward cancer cells that can inhibit hyperactive molecules, including HSP70. Our earlier studies demonstrated that apoptin directly binds to the promoter of HSP70 and inhibits HSP70 transcription, which contributes to HSP70 downregulation. This study provides the first demonstration of the therapeutic potential of an apoptin-derived peptide for the treatment of GBM by identifying the minimal region of the apoptin domain required for interaction with the heat-shock element (HSE). This apoptin-derived peptide (ADP) inhibits glioma cell proliferation and tumor growth as well as exhibits an increased ability to promote apoptosis in GBM cells compared with rapamycin and temozolomide. ADP treatment inhibited xenograft tumor growth and increased the overall health and survival of nude mice implanted with GBM cells. These effects were measured in tumors obtained from cell lines and were observed in both intracranial and subcutaneous xenografts. In conclusion, we provide the first demonstration that ADP has therapeutic potential for the treatment of human GBM. Specifically, this study suggests that ADP is a potent candidate for drug development based on its favorable toxicity and pharmacokinetic profiles as well as its time- and cost-saving benefits.
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http://dx.doi.org/10.18632/oncotarget.16094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458194PMC
May 2017

Gene delivery of apoptin-derived peptide using an adeno-associated virus vector inhibits glioma and prolongs animal survival.

Biochem Biophys Res Commun 2017 01 3;482(3):506-513. Epub 2017 Feb 3.

Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, 163319, PR China. Electronic address:

Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of the secreted HSP70-targeted peptide APOPTIN derived from Apoptin to GBM tumors. We applied this therapy to GBM models using human U87MG glioma cells and GBM xenograft models in mice. In U87MG and U251MG cells, conditioned medium from AAV2-apoptin-derived peptide (ADP)-expressing cells induced 83% and 78% cell death. In mice bearing intracranial U87MG tumors treated with AAV2-ADP, treatment resulted in a significant decrease in tumor growth and longer survival in mice bearing orthotopic invasive GBM brain tumors. These data indicate that ssAAV2-ADP injection in the left hemisphere effectively prevented ipsilateral tumor growth but was insufficient to prevent distal tumor growth in the contralateral hemisphere. However, the systemic route is the most effective approach for treating widely dispersed tumors. In summary, systemic delivery of AAV2-ADP is an attractive approach for invasive GBM treatment.
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http://dx.doi.org/10.1016/j.bbrc.2016.10.059DOI Listing
January 2017

Different Risk Indictors of Diabetic Nephropathy in Transforming Growth Factor-beta1 T869C CC/CT Genotype and TT Genotype.

Iran J Public Health 2016 Jun;45(6):761-7

Dept. of Endocrinology of Hangzhou Red Cross Hospital, Hangzhou, China.

Background: Transforming growth factor-beta 1(TGF-β1) T869C (rs1800470, the same below) gene polymorphism is notably relative with the development of Diabetic Nephropathy (DN), and CC/CT genotype diabetic have higher frequency of than TT genotype diabetic. To find out individual risk factors in the two genotypes especially in susceptible genotype could provide more efficient and targeted prevention.

Methods: This was a prospective cohort study. A total of 251 type 2 diabetes mellitus (T2DM) patients [53.4% male, 56(52-67) years] were enrolled in this cohort study. Multiple concerned factors were collected and the relationship of these risk factors and development of DN were evaluated by Cox regression analysis. Hazard ratios of development of DN were calculated by Kaplan-Meier curves and the Cox proportional hazards model for CC/CT genotype versus TT genotype patients.

Results: TGF-β1 T869C gene polymorphism was an independent predictor of DN in T2DM patients (HR, 2.08; 95%CI, 1.18-3.66; P=0.012). Hyperlipemia (HR, 1.91; 95%CI, 1.19-3.08; P=0.007), age (HR, 0.95; 95%CI, 0.93-0.98; P=0.001) and smoking status (HR, 2.36; 95%CI, 1.07-5.21; P=0.033) were risk indictors of the development of DN in CC/CT genotype patients. HbA1c (HR, 2.8; 95%CI, 1.07-7.30; P=0.036), hypertension (HR, 7.46; 95%CI, 1.38-40.29; P=0.02), and hyperlipemia (HR, 12.33; 95%CI, 1.05-145.39; P=0.046) were risk indictors for the development of DN in TT genotype patients.

Conclusion: TGF-β1 T869C gene polymorphism was an independent predictor of DN for T2DM patients and CC/CT genotype had higher susceptibility to DN. CC/CT genotype and TT genotype patients had different risk indictors of DN.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026831PMC
June 2016
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