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1.
Eur Rev Med Pharmacol Sci ; 26(13): 4614-4624, 2022 07.
Article in English | MEDLINE | ID: mdl-35856351

ABSTRACT

OBJECTIVE: Synthetic hydroxyapatite (HA) and its related materials have made great progress in basic research and clinical application in spinal repair and reconstruction. However, the effect of HA and its composites used in spinal fusion still remained controversial. This meta-analysis aimed at evaluating the efficacy and safety of HA compared with autologous bone. MATERIALS AND METHODS: A systematic search in PubMed, MEDLINE, China National Knowledge Internet, EMBASE, and the Cochrane Library was conducted for relevant studies from inception until May 2021. Studies investigating the application of HA and its related composites in spinal fusion were selected for analysis. RESULTS: The operation time of patients treated with artificial bone containing HA was less than that of patients with autologous bone (p = 0.02). The amount of operative blood loss in patients in the HA group was less than that in the autograft group (p = 0.007). Patients treated with autologous bone got a more significant advantage in fusion rate at 6 months (p = 0.009). Nevertheless, there was no significant difference in the fusion rate between patients in the two groups at 12 months or no less than 24 months postoperatively (p = 0.24; p = 0.87). Compared to the autograft group, the HA group significantly decreased postoperative adverse events (p = 0.03). Furthermore, there was no significant difference in the Oswestry Disability Index (p = 1.00) nor the Visual Analogue Scale score (p = 0.94) between the two groups. CONCLUSIONS: This meta-analysis suggests that the clinical application of HA and its related composite materials in spinal reconstruction is comparable to that of autologous bone, with satisfactory efficacy and safety.


Subject(s)
Durapatite , Spinal Fusion , Bone Transplantation , Durapatite/adverse effects , Humans , Lumbar Vertebrae/surgery , Spine , Treatment Outcome
2.
Eur Rev Med Pharmacol Sci ; 25(9): 3460-3469, 2021 05.
Article in English | MEDLINE | ID: mdl-34002819

ABSTRACT

OBJECTIVE: This study aims to explore the correlation between N-acetyltransferase 2 (NAT2) expression in colorectal cancer (CRC) tissues and the progression and prognosis of CRC. Through in vitro and in vivo experiments, the biological functions of NAT2 in the occurrence and development of CRC were explored. PATIENTS AND METHODS: Immunohistochemical (IHC) staining, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot were used to detect the difference of NAT2 expression in CRC tissues and normal tissues. The role of NAT2 in the cell proliferation, apoptosis, migration, invasion, and tumorigenesis and development of CRC was analyzed by cell counting kit-8 (CCK-8), colony formation, flow cytometry, transwell cell invasion, wound-healing assays and construction of nude mouse xenograft model. The correlation between the expression level of NAT2, and the overall survival and clinicopathological characteristics of CRC patients were statistically analyzed to preliminarily determine the clinical significance of NAT2 in the diagnosis and prognosis of CRC. RESULTS: The expression level of NAT2 was notably upregulated in CRC. NAT2 knockdown inhibited the proliferation, migration, invasion and in vivo tumor formation of CRC cells, and promoted cell apoptosis. High NAT2 expression was associated with TNM stage, differentiation degree, tumor size, distant metastasis, lymph node metastasis and poor prognosis in CRC patients. CONCLUSIONS: This study showed that the expression level of NAT2 in CRC tissues was increased and closely related to the metastasis and prognosis of CRC. In addition, NAT2 can be used as a new prognostic biomarker and therapeutic target for CRC.


Subject(s)
Arylamine N-Acetyltransferase/metabolism , Colorectal Neoplasms/metabolism , Arylamine N-Acetyltransferase/deficiency , Arylamine N-Acetyltransferase/genetics , Cell Proliferation , Cells, Cultured , Colorectal Neoplasms/pathology , Humans
3.
Cancer Radiother ; 25(4): 323-329, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33446419

ABSTRACT

PURPOSE: To identify the valuable predictors of grade≥2 radiation pneumonitis (RP) in patient treated with radiotherapy after pneumonectomy for non-small cell lung cancer (NSCLC); and to construct a nomogram predicting the incidence of grade≥2 RP in such patients. PATIENTS AND METHODS: We reviewed 82 patients with NSCLC received radiotherapy after pneumonectomy from 2008 to 2018. The endpoint was grade≥2 RP. Univariate and multivariate regression analysis were conducted to evaluate significant factors of grade≥2 RP. Receiver operating characteristic (ROC) curve was used to establish optimal cutoff values and the nomogram was built to make the predictive model visualized. Descriptive analysis was performed on 5 patients with grade 3 RP. RESULTS: A total of 22(26.8%) patients developed grade 2 RP and 5(6.1%) patients were grade 3 RP. V5, V10, V20, V30, MLD, PTV, and PTV/TLV were associated with the occurrence of grade≥2 RP in univariate analysis, while none of the clinical factors was significant; V5(OR,1.213;95%CI,1.099-1.339; P<0.001) and V20(OR,1.435;95%CI,1.166-1.765; P=0.001) were the independent significant predictors by multivariate analysis and were included in the nomogram. The ROC analysis for the cutoff values for predicting grade≥2 RP were V5>23% (AUC=0.819, sensitivity:0.701, specificity:0.832) and V20>8% (AUC=0.812, sensitivity:0.683, specificity:0.811). Additionally, grade≥3 RP did not occur when V5<30%, V20<13% and MLD<751.2cGy, respectively. CONCLUSIONS: Our study showed that V5 and V20 were independent predictors for grade≥2 RP in NSCLC patients receiving radiotherapy after pneumonectomy. Grade 3 RP did not occur whenV5<30%, V20<13% and MLD<751.2cGy, respectively. In addition, patient underwent right pneumonectomy may have a lower tolerance to radiation compared to left pneumonectomy.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Radiation Pneumonitis/etiology , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Lung Neoplasms/surgery , Male , Middle Aged , Nomograms , Pneumonectomy , Postoperative Care , ROC Curve , Radiation Pneumonitis/epidemiology , Radiation Pneumonitis/pathology , Regression Analysis , Retrospective Studies , Sensitivity and Specificity , Tumor Burden
4.
Anim Genet ; 52(1): 78-89, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33301219

ABSTRACT

DNA methylation was one of the earliest discovered epigenetic modifications in vertebrates, and is an important epigenetic mechanism involved in the expression of genes in many biological processes, including muscle growth and development. Its effects on economically important traits are evidenced in reported differences in meat quality traits between Chinese indigenous pig breeds (Wannanhua pig) and Western commercial pig breeds (Yorkshire pig), and this presents a unique model for analyzing the effects of DNA methylation on these traits. In the present study, a whole genome DNA methylation analysis was performed on the two breeds using methylated DNA immunoprecipitation. GO functional enrichment and pathway enrichment analyses identified differentially methylated genes primarily associated with fatty acid metabolism, biological processes of muscle development and signaling pathways related to muscle development and pork quality. Differentially methylated genes were verified by sodium pyrosequencing, and the results were consistent with the sequencing results. The results of the integrative analysis between DNA methylation and gene expression revealed that the DNA methylation levels showed a significantly negative correlation with gene expression levels around the transcription start site of genes. In total, 41 genes were both differentially expressed and methylated; these genes were related to fat metabolism, lipid metabolism and skeletal muscle development. This study could help further explore the molecular mechanisms and phenotypic differences in pig growth and development among different breeds.


Subject(s)
DNA Methylation , Epigenesis, Genetic , Muscle, Skeletal/metabolism , Swine/genetics , Animals , Breeding , Female , Genetic Association Studies , Lipid Metabolism/genetics , Muscle Development/genetics , Pork Meat , Signal Transduction , Transcriptome
5.
Eur Rev Med Pharmacol Sci ; 23(23): 10226-10233, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31841176

ABSTRACT

OBJECTIVE: Ovarian cancer is the most common fatal gynecologic malignancy in females all over the world. Recently, long noncoding RNAs (lncRNAs) have been reported to exert pivotal functions in tumorigenesis. In this research, lncRNA SNHG14 was studied to identify its role in the metastasis of ovarian cancer. PATIENTS AND METHODS: SNHG14 expression was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in ovarian cancer specimens. Functional assays including wound healing assay, transwell assay, and Matrigel assay were performed to detect the effect of SNHG14 on the migration and invasion of ovarian cancer cells. In addition, the underlying mechanism was further explored through qRT-PCR and Western blot assay. RESULTS: SNHG14 level was dramatically higher in ovarian cancer specimens. Moreover, cell migration and invasion were significantly attenuated via the inhibition of SNHG14, while enhanced via the SNHG14 overexpression. Besides, the expression of DGCR8 mRNA and protein was markedly downregulated after the knockdown of SNHG14, while upregulated after SNHG14 overexpression. Furthermore, the expression level of DGCR8 was increased in cancer tissues and positively related to the expression of SNHG14 in ovarian cancer tissues. CONCLUSIONS: In summary, SNHG14 could enhance cell migration and invasion via upregulating DGCR8 in ovarian cancer.


Subject(s)
Ovarian Neoplasms/physiopathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/physiology , RNA-Binding Proteins/biosynthesis , Cell Line, Tumor , Cell Movement , Cell Proliferation , Down-Regulation , Female , Gene Expression Regulation, Neoplastic/physiology , Gene Knockdown Techniques , Humans , Ovarian Neoplasms/metabolism , RNA, Long Noncoding/antagonists & inhibitors , RNA, Long Noncoding/biosynthesis , Transfection , Up-Regulation
6.
Food Funct ; 10(8): 4792-4801, 2019 Aug 01.
Article in English | MEDLINE | ID: mdl-31314026

ABSTRACT

The immunoregulatory effect of a novel Craterellus cornucopioides polysaccharide (CCP) with a triple-helix structure on immunosuppressive BALB/c mice models was investigated; moreover, the immune response of BALB/c mice models in the preventive and therapeutic treatment groups treated with CCP was explored, and its molecular mechanism was elucidated. It was found that the BALB/c mice models in the preventive groups treated with CCP (120 and 240 mg kg-1 d-1) had better immunoregulatory activity. The spleen and thymus weight indices of the BALB/c mice models were significantly increased, and the histopathological analysis indicated a protective function of CCP against the immunosuppression induced by cyclophosphamide (CTX). Moreover, CCP displayed definite and clear synergistic effects on the T- or B-lymphocyte proliferation induced by ConA or LPS, respectively, promoted the natural killer (NK) cell activity and significantly increased phagocytic activity to activate peritoneal macrophages in immunosuppressive mice. The western blot and quantitative real-time polymerase chain reaction (qRT-PCR) results provided comprehensive evidence that CCP could upregulate the protein expression of the G-protein-coupled cell membrane receptor TLR4 and the production of its downstream protein kinases (TRAF6, TK1, p-IKKα/ß and NF-κB p50); this, in turn, enhanced the production of cytokines (IL-2, IL-6, TNF-α and IFN-α) through both preventive and therapeutic treatments via regulation of the TLR4-NFκB pathway in the peritoneal macrophage of immunosuppressive mice.


Subject(s)
Agaricales/chemistry , Immune System Diseases/drug therapy , Immunologic Factors/administration & dosage , NF-kappa B/immunology , Polysaccharides/administration & dosage , Toll-Like Receptor 4/immunology , Animals , Female , Humans , Immune System Diseases/genetics , Immune System Diseases/immunology , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Immunosuppression Therapy , Interleukin-6 , Killer Cells, Natural/immunology , Macrophages, Peritoneal/immunology , Mice , Mice, Inbred BALB C , NF-kappa B/genetics , Polysaccharides/chemistry , Polysaccharides/isolation & purification , TNF Receptor-Associated Factor 6/genetics , TNF Receptor-Associated Factor 6/immunology , Toll-Like Receptor 4/genetics , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
7.
Int J Biol Macromol ; 126: 796-804, 2019 Apr 01.
Article in English | MEDLINE | ID: mdl-30594621

ABSTRACT

In the study, a new triple-helix polysaccharide with favorable stability was purified from C. cornucopioides. Its structural characterization, stability and solution behavior were investigated by the GC-MS, periodate oxidation-smith degradation, FT-IR, 1D and 2D NMR spectroscopy, methylation analysis, Scanning electron microscope, Congo-red, CD, TGA and DSC analysis. The results showed that Craterellus cornucopioide polysaccharide (CCP) possessed the molecular weight of 1.97 × 103 kDa, is mainly composed of mannose (48.73%), galactose (17.37%), glucose (15.97%) and xylose (17.93%), respectively. It was a heteroglycan with (1 → 3)­linked­ß­d­Manp­(1 → 6)­linked α­d­Galp backbone distributed by (1 → 4)­linked­α­d­Xylp­t­α­d­Manp and t­ß­d­Glup units at O-6. The result of TGA and DSC assay indicated that CCP has a favorable thermal stability. MTT and Scanning electro microscopy (SEM) assay showed that CCP could significantly improve the proliferation activity and induce cells activation of RAW264.7 in a certain range of concentrations and period.


Subject(s)
Chemical Phenomena , Immunologic Factors/chemistry , Immunologic Factors/pharmacology , Macrophages/cytology , Polysaccharides/chemistry , Polysaccharides/pharmacology , Agaricales , Animals , Calorimetry, Differential Scanning , Carbon-13 Magnetic Resonance Spectroscopy , Cell Proliferation/drug effects , Cell Shape/drug effects , Circular Dichroism , Congo Red , Macrophages/drug effects , Methylation , Mice , Microscopy, Atomic Force , Molecular Conformation , Molecular Weight , Polysaccharides/isolation & purification , Proton Magnetic Resonance Spectroscopy , RAW 264.7 Cells , Solutions , Spectroscopy, Fourier Transform Infrared , Thermogravimetry
8.
Eur Rev Med Pharmacol Sci ; 22(16): 5091-5097, 2018 08.
Article in English | MEDLINE | ID: mdl-30178827

ABSTRACT

OBJECTIVE: The aim of this study was to detect the expression of RBM5-AS1 during fracture healing, and to explore its possible mechanism. MATERIALS AND METHODS: A mice tibia fracture model was constructed in this study. Mice in the control group and experimental group were sham-operated on the left tibia and were operated in the right tibia, respectively. The tibia bones of both groups were obtained at 4 d, 8 d, 12 d, 16 d, 20 d, and 24 d after the operation. Quantitative polymerase chain reaction (qPCR) was used to detect the expression of RBM5-AS1 in tibiae. After interfering with the expression of RBM5-AS1 in bone cells, Cell Counting Kit-8 (CCK-8) was used to detect cell proliferation ability, and flow cytometry was applied to detect apoptosis. Western blot was used to measure the protein expression of beta-catenin and RBM5 after down-regulating RBM5-AS1. Finally, beta-catenin was interfered in osteoblasts to explore the relationship between RBM5-AS1 and beta-catenin. RESULTS: Compared with the control group, the expression of RBM5-AS1 in the experimental group was significantly increased on the 4 d, 8 d, 12 d, and 16 d after fracture surgery. However, no statistical difference was observed on the 20 d and 24 d between the two groups. After interfering with RBM5-AS1, the apoptosis of chondrocytes and osteoblasts was significantly increased in both mouse and human cells, while the expression of beta-catenin was strikingly decreased. Further up-regulation of beta-catenin could reduce the apoptosis of bone cells. The expression of RBM5, which was a natural antisense transcript of RBM5-AS1, was increased after down-regulating RBM5-AS1. CONCLUSIONS: RBM5-AS1 can inhibit the apoptosis of bone cells by promoting the expression of beta-catenin and can be used as a biomarker for fracture healing.


Subject(s)
Fracture Healing/physiology , Fractures, Bone/metabolism , Osteoblasts/metabolism , RNA-Binding Proteins/biosynthesis , Tibia/metabolism , beta Catenin/biosynthesis , Animals , Apoptosis/physiology , Biomarkers/metabolism , Cells, Cultured , Fractures, Bone/genetics , Male , Mice , RNA-Binding Proteins/genetics , Tibia/injuries , Up-Regulation/physiology , beta Catenin/genetics
9.
Eur Rev Med Pharmacol Sci ; 22(13): 4128-4137, 2018 07.
Article in English | MEDLINE | ID: mdl-30024601

ABSTRACT

OBJECTIVE: Gastric carcinoma (GC) is a common cancer with heavy mortality and poor outcome at advanced stages and metastasis. Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be an oncogene in GC recently. However, the underlying mechanism is far from understood. We aimed to explore the role of NEAT1 in GC as well as the underlying mechanisms. PATIENTS AND METHODS: The expression of NEAT1 in clinical human GC tissues and GC cell lines were assessed by quantitative reverse transcription PCR. Then, NEAT1 was non-physiologically expressed in GC cells (SGC-7901 and MKN45 cells), followed by estimation of cell viability, migration, invasion, apoptosis, activation of the phosphatidylinositol-3-kinase (PI3K)/AKT and glycogen synthase kinase 3ß (GSK3ß) pathways, and microRNA (miR)-17 level. Moreover, the effects of miR-17 inhibition on cell viability, migration, and activation of the PI3K/AKT and GSK3ß pathways in GC cells overexpressing NEAT1 were also explored. RESULTS: NEAT1 was up-regulated in GC tissues and cell lines. Then, cell viability and migration of GC cells were markedly increased by NEAT1 overexpression, while the cell invasion and apoptosis were unchanged. The phosphorylated level of PI3K, AKT, and GSK3ß were increased by NEAT1 overexpression. Subsequently, we found miR-17 level was positively correlated with NEAT1 expression, and NEAT1 functions through up-regulating miR-17. CONCLUSIONS: NEAT1 was up-regulated in GC tissues and cell lines. Its overexpression enhanced cell viability and migration through up-regulating miR-17, along with activation of the PI3K/AKT and GSK3ß pathways.


Subject(s)
Apoptosis/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Stomach Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Glycogen Synthase Kinase 3 beta/genetics , Humans , Male , Middle Aged , Phosphatidylinositol 3-Kinases/metabolism , Up-Regulation
10.
Eur Rev Med Pharmacol Sci ; 22(6): 1549-1553, 2018 03.
Article in English | MEDLINE | ID: mdl-29630096

ABSTRACT

OBJECTIVE: Polycystic ovary syndrome (PCOS) causes ovulation disorder and infertility in female patients. This study recruited PCOS patients and adopted testosterone therapy to analyze its effect on expression of nuclear peroxisome proliferation activated receptor γ (PPARγ), and cytochrome P450 aromatase (P450arom) in ovary granular cells of patients. PATIENTS AND METHODS: PCOS and non-PCOS patients were treated with testosterone at 1.0 nmol/L, 10 nmol/L. qRT-PCR was used to detect the expressions of PPARγ and P450arom while Western blot was performed for the evaluation of protein expression. RESULTS: In the experimental group, the level of PPARγ mRNA was significantly elevated whilst the expression of P450arom was statistically decreased (p < 0.05). The treatment of 10 nmol/l testosterone significantly elevated PPARγ mRNA and protein expression, and decreased P450arom expression (p < 0.05). The level of PPARγ was positively correlated with testosterone concentration, and was negatively correlated with P450arom expression (p < 0.05). CONCLUSIONS: Testosterone causes hyperandrogenism microenvironment of PCOS patients, with a correlated increase of PPARγ and reduction of P450arom.


Subject(s)
Aromatase/metabolism , Gene Expression Regulation/drug effects , PPAR gamma/metabolism , Polycystic Ovary Syndrome/pathology , Testosterone/pharmacology , Adult , Aromatase/genetics , Cells, Cultured , Female , Humans , Ovary/cytology , Ovary/drug effects , Ovary/metabolism , PPAR gamma/genetics , Polycystic Ovary Syndrome/metabolism
11.
Oncogenesis ; 6(10): e387, 2017 Oct 09.
Article in English | MEDLINE | ID: mdl-28991259

ABSTRACT

Aberrant activation of nuclear factor-κB (NF-κB) has been observed in a wide range of human cancers and is thought to promote tumorigenesis and metastasis. As a central component of NF-κB pathway, p65 protein level is tightly regulated and could be subjected to proteasome degradation. Here we demonstrated that p65 can bind to HSC70 with four consensus recognition motif in its RHD domain and be constitutively transported to the lysosome membrane to bind with lysosome-associated membrane protein type 2A and degraded within the lysosome in two epithelial cell lines, proposing that p65 can be degraded by chaperone-mediated autophagy (CMA). Of great importance, there is a decreased CMA activity together with impaired degradation of p65 in a process of epithelial-mesenchymal transition (EMT). The resulted accumulation of p65 leads to higher NF-κB activity and contributes to the progression and maintenance of the EMT program. Taken together, our results define a novel regulatory mechanism for the important transcription factor p65, and these findings would shed new light on the inhibition of EMT, as well as metastasis of cancer cells.

12.
Eur Rev Med Pharmacol Sci ; 21(8): 1932-1937, 2017 04.
Article in English | MEDLINE | ID: mdl-28485783

ABSTRACT

OBJECTIVE: To discuss the influence of screening and intervention of hyperthyroidism on pregnancy outcome. PATIENTS AND METHODS: The clinical data of 122 pregnant women who had been confirmed with hyperthyroidism from April 2012 to July 2014 in the Weifang People's Hospital were analyzed retrospectively (25 untreated, 97 treated). 60 with normal pregnancy check were randomly selected as control group. The pregnancy outcomes of the two groups of patients were analyzed. RESULTS: Among 10,427 pregnant women, 122 of them were diagnosed with hyperthyroidism, the prevalence of hyperthyroidism and subclinical hyperthyroidism were 0.44% and 0.73%. The occurrence of adverse maternal, obstetric complication, and adverse perinatal infant of the untreated group was higher than that of the treated group, and the inter-group differences were of statistically significance (p<0.05). However, the comparison of treated group and control group showed that there was no statistical significance in occurrences of adverse maternal, obstetric complication, and adverse perinatal infant (p>0.05). CONCLUSIONS: Timely screening for gestational thyroid disease and actively intervention treatment can significantly improve the outcome of pregnancy.


Subject(s)
Hyperthyroidism/diagnosis , Pregnancy Complications/diagnosis , Adult , Female , Humans , Hyperthyroidism/complications , Hyperthyroidism/therapy , Infant, Newborn , Pregnancy , Pregnancy Complications/therapy , Pregnancy Outcome , Retrospective Studies
13.
Eur Rev Med Pharmacol Sci ; 21(9): 2114-2129, 2017 05.
Article in English | MEDLINE | ID: mdl-28537673

ABSTRACT

OBJECTIVE: The goal of our study was to identify the regulatory mechanisms of gene expression mediated by miRNAs and DNA methylation in colon adenocarcinoma (COAD). MATERIALS AND METHODS: The miRNAs and mRNAs expression and DNA methylation data of COAD and adjacent normal tissues were obtained from The Cancer Genome Atlas (TCGA) database. Based on the differentially expressed miRNAs and mRNAs, miRNA-mRNA pairs were obtained by correlation analysis and prediction algorithms. Finally, COAD-specific miRNA-mRNA regulatory network was generated. Additionally, the biological functions of miRNA targets were further revealed by GO and KEGG enrichment analysis. Besides, the correlation analysis between gene expression and DNA methylation was also performed after differential analysis. RESULTS: We identified 55 differentially expressed miRNAs and 1291 differentially expressed mRNAs in COAD compared with adjacent normal tissues. We observed a global miRNA up-regulation in tumors. A total of 58 miRNA-mRNA pairs were not only predicted by algorithms but also negatively correlated. The increased expression of has-mir-141, -19a, -20a 19b-1, 19b-2, 16, 590 and -335 were closely associated with the carcinogenesis of COAD. Functional enrichment analysis showed that the miRNA targets were significantly enriched in pancreatic secretion, salivary secretion, gastric acid secretion and bile secretion. Regarding the regulatory role of DNA methylation, we identified 11 genes whose expressions were negatively correlated with DNA methylation level. Among those genes, MSX1 and KRT7 were down-regulated and hypermethylated in COAD compared with adjacent normal tissues. CONCLUSIONS: These eight miRNAs (has-mir-141, -19a, -20a 19b-1, 19b-2, 16, 590 and -335) and two genes (MSX1 and KRT7) may play a role in the process of COAD. These findings highlighted the potential regulatory mechanisms of miRNA and DNA methylation on mRNA expression in COAD carcinogenesis.


Subject(s)
Adenocarcinoma/genetics , Colonic Neoplasms/genetics , MicroRNAs/genetics , RNA, Messenger/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Humans
14.
Oncogenesis ; 6(2): e298, 2017 Feb 20.
Article in English | MEDLINE | ID: mdl-28218735

ABSTRACT

Aurora kinase A (AURKA) has been implicated in the regulation of cell cycle progression, mitosis and a key number of oncogenic signaling pathways in various malignancies. However, little is known about its role in gastric cancer prognosis and genotoxic resistance. Here we found that AURKA was highly overexpressed in gastric cancer and inversely correlated with disease prognosis. Overexpression of AURKA exacerbated gastric cancer drug resistance through upregulating the expression of the anti-apoptotic protein Survivin. Conversely, we demonstrated that AURKA depletion caused a decrease in Survivin protein levels by increasing its ubiquitylation and degradation. Mass spectrometric analysis revealed that upon AURKA depletion, Survivin bound to the FBXL7 E3 ubiquitin ligase, which induced ubiquitin-proteasome degradation of Survivin. In addition, we showed that AURKA regulated FBXL7 both at the levels of transcription and translation. Moreover, proteomic analysis of nuclear AURKA-interacting proteins identified Forkhead box protein P1 (FOXP1). We next showed that AURKA was required for FBXL7 transcription and that AURKA negatively regulated FOXP1-mediated FBXL7 expression. The physiological relevance of the regulation of Survivin by AURKA through the FOXP1-FBXL7 axis was further underscored by the significant positive correlations between AURKA and Survivin expression in gastric cancer patient samples. Moreover, the AURKA depletion or kinase inhibition-induced apoptotic cell death could be reversed by Survivin ectopic overexpression, further supporting that AURKA regulated Survivin to enhance drug resistance. In agreement, inhibition of AURKA synergistically enhanced the cytotoxic effect of DNA-damaging agents in cancer cells by suppressing Survivin expression. Taken together, our data suggest that AURKA restricts Survivin ubiquitylation and degradation in gastric cancer to promote drug resistance and hence the AURKA-Survivin axis can be targeted to promote the efficacy of DNA-damaging agents in gastric cancer.

15.
Oncogene ; 36(3): 304-317, 2017 01 19.
Article in English | MEDLINE | ID: mdl-27345399

ABSTRACT

Aberrant p62 overexpression has been implicated in breast cancer development. Here, we found that p62 expression was elevated in breast cancer stem cells (BCSCs), including CD44+CD24- fractions, mammospheres, ALDH1+ populations and side population cells. Indeed, short-hairpin RNA (shRNA)-mediated knockdown of p62 impaired breast cancer cells from self-renewing under anchorage-independent conditions, whereas ectopic overexpression of p62 enhanced the self-renewal ability of breast cancer cells in vitro. Genetic depletion of p62 robustly inhibited tumor-initiating frequencies, as well as growth rates of BCSC-derived tumor xenografts in immunodeficient mice. Consistently, immunohistochemical analysis of clinical breast tumor tissues showed that high p62 expression levels were linked to poorer clinical outcome. Further gene expression profiling analysis revealed that p62 was positively correlated with MYC expression level, which mediated the function of p62 in promoting breast cancer stem-like properties. MYC mRNA level was reduced upon p62 deletion by siRNA and increased with p62 overexpression in breast cancer cells, suggesting that p62 positively regulated MYC mRNA. Interestingly, p62 did not transactivate MYC promoter. Instead, p62 delayed the degradation of MYC mRNA by repressing the expression of let-7a and let-7b, thus promoting MYC mRNA stabilization at the post-transcriptional level. Consistently, let-7a and let-7b mimics attenuated p62-mediated MYC mRNA stabilization. Together, these findings unveiled a previously unappreciated role of p62 in the regulation of BCSCs, assigning p62 as a promising therapeutic target for breast cancer treatments.


Subject(s)
Breast Neoplasms/pathology , MicroRNAs/genetics , Neoplastic Stem Cells/pathology , Proto-Oncogene Proteins c-myc/genetics , RNA, Messenger/genetics , Sequestosome-1 Protein/metabolism , Animals , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , MCF-7 Cells , Mice , Middle Aged , Neoplasm Transplantation , Neoplastic Stem Cells/metabolism , Prognosis , RNA Stability , RNA, Messenger/chemistry , Sequestosome-1 Protein/genetics , Up-Regulation
16.
Eur Rev Med Pharmacol Sci ; 20(22): 4756-4760, 2016 11.
Article in English | MEDLINE | ID: mdl-27906445

ABSTRACT

OBJECTIVE: We conduct this study to investigate the expression level of miR-210 in elderly patients with COPD combined with ischemic stroke and analyzed its application value as a sensitive diagnostic indicator. PATIENTS AND METHODS: 50 cases of elderly patients with COPD combined with ischemic stroke were selected as group A, 50 cases of elderly patients with COPD were selected as group B, 50 cases of elderly patients with ischemic stroke were selected as group C, and 50 cases of healthy volunteers as group D. Real-time PCR assay for quantification was used to detect the expression level of miR-210 in peripheral blood and receiver operating curve (ROC) was used to analyze the diagnostic sensitivity and accuracy. RESULTS: MiR-210 level of group A was the lowest, followed by group B and group C; group D had the highest levels. The difference was statistically significant (p<0.05). MiR-210 levels decreased with an increasing decline degree of lung function and the difference was statistically significant (p<0.05). After miR-210 diagnosis, COPD sensitivity was 85.6%, the specificity was 72.6%, accuracy (AUC) was 0.821, and 95% CI 0.632-0.924. CONCLUSIONS: The down-regulation of MiR-210 expression in the COPD combined with ischemic stroke can be regarded as a sensitive index in diagnosis of COPD and ischemic stroke.


Subject(s)
Biomarkers/blood , MicroRNAs/metabolism , Pulmonary Disease, Chronic Obstructive/genetics , Stroke/genetics , Aged , Down-Regulation , Humans , ROC Curve
17.
Anim Genet ; 47(3): 324-33, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27038141

ABSTRACT

Western commercial pig breeds have been intensively selected, resulting in a sizeable, rapid and efficient accretion of muscle but a reduction in meat quality. When compared with Western commercial pig breeds, Chinese indigenous pig breeds exhibited slower growth rates and reduced lean meat content but superior perceived meat quality. To study the factors that determine meat quality, we examined piglets of one Western commercial breed (Yorkshire) and one Chinese indigenous breed (Wannanhua) and sequenced the longissimus dorsi muscle using RNA-sequencing (RNA-seq). We analyzed their transcriptomes, focusing on identifying candidate genes that may influence porcine muscle growth, meat quality and adipose deposition. Gene Ontology functional enrichment and pathway enrichment analyses identified differentially expressed genes (DEGs) primarily associated with glycolytic metabolism, biological processes of muscle development and signaling pathways related to fatty acid metabolism, growth and carcass traits. This finding suggests that the DEGs may play important roles in determining meat quality traits. Quantitative real-time reverse transcription polymerase chain reaction confirmed the differential expression of 12 selected DEG. This study identified a number of novel candidate genes for porcine meat quality and carcass traits that merit further investigation to elucidate the molecular mechanisms responsible for muscle growth and fat deposition.


Subject(s)
Breeding , Meat/analysis , Muscle Development/genetics , Sus scrofa/genetics , Adipose Tissue/physiology , Animals , Female , Gene Ontology , Lipid Metabolism/genetics , Muscle, Skeletal/physiology , Real-Time Polymerase Chain Reaction , Sequence Analysis, RNA , Transcriptome
18.
Dis Esophagus ; 29(4): 392-9, 2016 May.
Article in English | MEDLINE | ID: mdl-25715747

ABSTRACT

Esophagitis is the second most common gastrointestinal manifestation of cytomegalovirus (CMV) infection after colitis. CMV esophagitis has been reported in patients who have undergone transplantation, are on long-term renal dialysis, or who have the human immunodeficiency virus infection. This study aimed to investigate the clinical characteristics and manifestations of CMV esophagitis in patients who underwent diagnostic endoscopy. A total of 16 patients with histologically proven CMV infection were identified from 1539 patients with esophageal ulcers and analyzed retrospectively (January 2006 to December 2013). Patients' personal data (age, smoking, and alcohol consumption), underlying systemic diseases (diabetes mellitus, end-stage renal disease, and chronic obstructive pulmonary disease), malignancy, indication for esophagogastroduodenoscopy, endoscopic characteristics, and diagnostic methods (pathological or serological findings) were collected for further analysis. Among the patients with CMV esophagitis, the mean age was 59.94 years (range, 23-84 years). The male : female ratio was 1.67:1. Odynophagia and epigastralgia were common symptoms. Of the 16 patients, 3 (18.75%) were infected with the human immunodeficiency virus and 9 (56.25%) had an underlying malignancy, including lung cancer (6 patients), esophageal cancer (2 patients), gastric cancer (1 patient), ampulla of Vater cancer (1 patient), and lymphoma (1 patient). Six of the 9 patients (66.7%) with malignancy had been administered concurrent chemoradiotherapy (CCRT). In this study, patients with malignancy who had been administered CCRT were at increased risk for CMV esophagitis, which had not been reported before in the literature. CMV esophagitis should be considered as a potential treatment-related complication of CCRT.


Subject(s)
Chemoradiotherapy/adverse effects , Cytomegalovirus Infections , Esophagitis , HIV Infections/epidemiology , Neoplasms , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/physiopathology , Endoscopy, Digestive System/methods , Esophagitis/diagnosis , Esophagitis/epidemiology , Esophagitis/physiopathology , Esophagitis/virology , Female , Humans , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/therapy , Retrospective Studies , Risk Factors , Symptom Assessment/methods , Taiwan/epidemiology
19.
Osteoporos Int ; 27(1): 57-63, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26126579

ABSTRACT

UNLABELLED: This is the first study to investigate the association between the use of selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) and the risk of fractures using a nationwide representative cohort of ethnic Chinese. Current use of SSRI/SNRI and the co-morbidity, especially osteoporosis and history of falling, play an important role in the increased risk of fractures. INTRODUCTION: This nested case-control study examines the association between the timing, intensity, and individual components of serotonergic antidepressant (including SSRIs and SNRIs) use and the risk of all-cause fracture. METHODS: Using the 2002-2011 Taiwan National Health Insurance Research Database, we identified patients who received at least three prescriptions of antidepressants between January 1st 2002 and December 31st 2010 as our study cohort. In the study cohort, we identify 8250 patients who had first admission for fracture and 33,000 matched controls (1:4, matched by age, sex, and cohort entry date). Multivariate conditional logistic regression was used to estimate the association between the use of serotonergic antidepressants and the risk of fracture. RESULTS: Current users of serotonergic antidepressants were associated with an increased risk of fracture (adjusted odds ratio (aOR) 1.16 [95 % confidence interval 1.07-1.25]). Furthermore, a higher risk of fractures was found in patients with osteoporosis (aOR 3.05 [2.73-3.42]) or a history of falling (aOR 6.13 [3.41-11.0]). The risks of fracture between SSRI and SNRI users were comparable. CONCLUSION: Current use of SSRI/SNRI is associated with an increased risk of all caused fractures. Additionally, the co-morbidity, especially osteoporosis and a history of falling, plays an important role in the risk of fractures.


Subject(s)
Antidepressive Agents/adverse effects , Osteoporotic Fractures/chemically induced , Selective Serotonin Reuptake Inhibitors/adverse effects , Serotonin and Noradrenaline Reuptake Inhibitors/adverse effects , Accidental Falls/statistics & numerical data , Adult , Aged , Case-Control Studies , Comorbidity , Databases, Factual , Drug Utilization/statistics & numerical data , Female , Humans , Male , Middle Aged , Osteoporotic Fractures/epidemiology , Risk Assessment/methods , Taiwan/epidemiology
20.
Andrology ; 3(4): 717-22, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26097073

ABSTRACT

The aim of this study was to investigate the relationship between the etiology of the couples and risk of fertilization failure (FF) in conventional in vitro fertilization (IVF) cycles and the effect of rescue intracytoplasmic sperm injection (ICSI) technique to offspring. A total of 2542 IVF cycles were divided into four groups according to infertile etiology: Group A - primary infertility with normal semen parameters; Group B - secondary infertility with oligoasthenozoospermia; Group C - primary infertility with oligoasthenozoospermia; and Group D - secondary infertility with normal semen parameters. The results showed that there were significant differences in incidence of FF among Group A (16.8%), Group B (20.9%), Group C (48.7%), and Group D (0.9%) (p < 0.001). Logistic regression models demonstrated that primary infertility (OR: 10.898, 95% CI: 4.651-25.583, p < 0.001) and oligoasthenozoospermia (OR: 12.215, 95% CI: 5.903-25.276, p < 0.001) were independent risk factors for FF. There were no significant differences in main outcomes between conventional ICSI and rescue ICSI. In conclusion, the patients with primary infertility and oligoasthenozoospermia might be at higher risk of FF. The rescue ICSI technique is safe and helpful for IVF cycles of FF.


Subject(s)
Fertilization in Vitro/statistics & numerical data , Infertility, Male , Adult , Female , Humans , Male , Pregnancy , Pregnancy Rate , Retrospective Studies , Treatment Failure
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