Molecular Medicine Reports (Mol Med Rep)

Publisher: Spandidos Publications

Current impact factor: 1.55

Impact Factor Rankings

2016 Impact Factor Available summer 2017
2014 / 2015 Impact Factor 1.554
2013 Impact Factor 1.484
2012 Impact Factor 1.17
2011 Impact Factor 0.418
2010 Impact Factor 0.307
2009 Impact Factor 0.22
2008 Impact Factor 0

Impact factor over time

Impact factor
Year

Additional details

5-year impact 1.49
Cited half-life 2.40
Immediacy index 0.28
Eigenfactor 0.01
Article influence 0.32
Website Molecular Medicine Reports website
ISSN 1791-2997
OCLC 248467032
Material type Periodical, Internet resource
Document type Journal / Magazine / Newspaper, Internet Resource

Publisher details

Spandidos Publications

  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Conditions
    • Publisher's version/PDF must be used
    • On Institutional Repository or Funder's repository
    • Must link to publisher version
    • Published source must be acknowledged with full citation
    • Publisher will automatically deposit authors post-print in PubMed Central or Europe PMC after 6 months or 12 months as required by funding agency
    • Reviewed 07 July 2014
  • Classification
    white

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: The typical progression of oral cancer is from hyperplastic epithelial lesions through dysplasia to invasive carcinoma. It is important to investigate malignant oral cancer progression and development in order to determine useful approaches of prevention of dysplastic lesions. The present study aimed to gain insights into the underlying molecular mechanism of oral carcinogenesis by establishing a rat model of oral carcinogenesis using 4‑nitroquinoline 1‑oxide. Subsequently, transcription profile analysis using an integrating microarray was performed. The dynamic gene expression changes of the six stages of rat oral carcinogenesis (normal, mild epithelial dysplasia, moderate dysplasia, severe dysplasia, carcinoma in situ and oral squamous cell carcinomas) were analyzed using component plane presentations (CPP)‑self‑organizing map (SOM). Six genes were verified by quantitative polymerase chain reaction, immunohistochemistry and succinate dehydrogenase (SDH) activity assay kit. Numerous differentially expressed genes (DEGs) were identified during rat oral carcinogenesis. CPP‑SOM determined that these DEGs were primarily enriched during cell cycle, apoptosis, inflammatory response and tricarboxylic acid cycle, indicating the coordinated regulation of molecular networks. In addition, the expression of specific DEGs, such as janus kinase 3, cyclin‑dependent kinase A‑1, B‑cell chronic lymphocytic leukaemia/lymphoma 2‑like 2, nuclear factor‑κB, tumor necrosis factor receptor superfamily member 1A, cyclin D1 and SDH were identified to have high concordance with the results from microarray data. The current study demonstrated that oral carcinogenesis is a multi‑step and multi‑gene process, with a distinct pattern alteration along a continuum of malignant transformation. In addition, this comprehensive investigation provided a theoretical basis for the understanding of the molecular alterations associated with oral carcinogenesis.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: An array of specific and non‑specific molecules, which are expressed in the testis, have been demonstrated to be responsible for testicular function. Our previous study revealed that dermatopontin (DPT) is expressed in Sertoli cells of the testis, however, its roles in testicular function remains somewhat elusive. In the present study, CdCl2‑ and busulfan‑induced testicular dysfunction models were used to investigate the implications of DPT expression for testicular function. The mRNA and protein expression levels of DPT were detected using reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. A negative correlation was observed between testicular damage and the expression of DPT, which suggested that an increase in DPT expression may be a marker for testicular dysfunction. This result was corroborated by the finding that transgenic mice exhibiting Sertoli cell‑specific overexpression of DPT exhibited damage to their testicular morphology. Additionally, DPT overexpression in the testis affected the expression levels of claudin‑11 and zonula occludens‑1, which indicated that DPT may affect testicular function by affecting the integrity of the blood‑testis barrier (BTB). In conclusion, the present study provided evidence to suggest that DPT may be indicative of mouse testicular dysfunction, since increased expression may be associated with damage to the BTB.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: An endoscopic examination is currently the most reliable method for monitoring disease activity in patients with inflammatory bowel disease (IBD). However, endoscopic evaluations are unable to detect mucosal inflammation at the earliest stages. The present study aimed to evaluate the molecular profiles of inflamed and unaffected colon mucosa from patients with mild Crohn's disease (CD) and ulcerative colitis (UC), in order to identify a more sensitive method for monitoring mucosal impairment. Patients were recruited and colon biopsies from the inflamed and the normal‑appearing mucosa of patients with mild IBD were obtained by colonoscopy. Gene expression analysis was performed using microarrays, after which Gene Ontology and clustering were performed using bioinformatics. In addition, the levels of inflammatory cytokines were analyzed by reverse transcription‑quantitative polymerase chain reaction. A total of 620 genes in the inflamed and 210 genes in the unaffected colon mucosa with at least a 3‑fold change, as compared with healthy controls, were detected in patients with mild CD, and 339 genes in the inflamed and 483 genes in the unaffected colon mucosa were detected in patients with mild UC. Heat mapping demonstrated a similarity in the gene alteration patterns, and altered transcripts overlapped, between the inflamed and unaffected colon mucosa. Interferon‑γ and interleukin‑17 mRNA levels were comparably elevated in the inflamed and unaffected colon mucosa from patients with IBD. Marked gene expression alterations were detected in the inflamed and unaffected colon mucosa from patients with mild IBD, and these showed marked similarity and overlap between the two groups. The results of the present study suggested that inflammation was not limited to the endoscopic lesions and that gene expression profiling may be considered a sensitive tool for monitoring mucosal inflammation, predicting relapses and optimizing therapeutic strategies for patients with IBD.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: Previous studies have highlighted that the transforming growth factor‑β1 (TGF‑β1) pathway may be activated by hypoxic conditions. TGF‑β1 also participates in the regulation of proliferation, differentiation, migration and apoptosis of various cell types. Furthermore, TGF‑β1 has been reported to participate in the regulation of the progression of pulmonary arterial hypertension (PAH). However, the effect of TGF‑β1 on pulmonary arterial smooth muscle cells (PASMCs) and the corresponding molecular mechanisms remain unclear. The present study aimed to determine whether TGF‑β1 protects against cell apoptosis in PASMCs, and identify the underlying molecular mechanisms. Western blotting, MTT and lactate dehydrogenase activity assays were performed, and the activity of caspase‑3 and caspase‑9 was detected in order to investigate the hypothesis. It was determined that TGF‑β1 may facilitate cell growth in a dose‑dependent manner in serum‑starved PASMCs. Furthermore, it was observed that apoptosis in serum‑starved PASMCs was inhibited by TGF‑β1 via regulation of the expression levels of mitochondrial membrane proteins. Additionally, the phosphatidylinositol 3‑kinase/protein kinase B (PI3K/Akt) pathway was found to be activated by TGF‑β1 in PASMCs, while the inhibition of PI3K/Akt signaling also prevented the apoptosis‑limiting effects of TGF‑β1. These observations suggest that TGF‑β1 protects PASMCs from apoptosis and contributes to pulmonary vascular medial thickening via the PI3K/Akt pathway.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: MicroRNAs (miRs), a class of non‑coding RNAs 18‑25 nucleotides in length, generally serve suppressive role in the regulation of gene expression via directly binding to the 3'‑untranslated region (UTR) of their target mRNA. Previous studies have identified several miRs to be involved in thermal injury repair. However, the role of miR let‑7b during the recovery of thermal injury, in addition to the underlying mechanisms, has not previously been studied. In the present study, the expression of let‑7b was observed to be significantly increased in skin tissue shortly following thermal injury, however, gradually reduced during the recovery of thermal injury. Notably, similar findings were observed in heat‑denatured skin fibroblasts. Furthermore, collagen, type I, alpha 1 (COL1A1) and collagen, type I, alpha 2 (COL1A2), which are associated with the synthesis of type I collagen, were identified as two targets of let‑7b in skin fibroblasts. The overexpression of let‑7b was observed to upregulate the protein expression levels of COL1A1 and COL1A2, while knockdown of let‑7b reduced the levels of COL1A1 and COL1A2 in skin fibroblasts. Furthermore, COL1A1 and COL1A2 were significantly downregulated shortly following thermal injury, while gradually upregulated during healing, in heat‑damaged skin tissue and skin fibroblasts, with the expression profiles opposite to that of let‑7b. Taken together, this suggests that the downregulation of let‑7b in heat‑damaged dermis promotes the synthesis of type I collagen and thus aids in burn wound repair.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: The present study aimed to determine the effect of microRNA (miR)‑210 on osteoarthritis (OA). The expression levels of miR‑210, type I and X collagen (COL1A1 and COL10A1) and matrix metallopeptidase 13 (MMP13) in OA and normal chondrocytes were determined using reverse transcription‑quantitative polymerase chain reaction analysis. The OA chondrocytes were transfected with an miRNA precursor for miR‑210 or a negative control. After 3, 7, 14 and 21 days, the expression levels of miR‑210 were examined, the proliferation of the OA chondrocytes were determined using an XTT assay and the protein levels of Ki67 and HIF‑3α were analyzed by Western blotting. After 21 days, the mRNA and protein levels of COL1A1, COL10A1 and MMP13 were analyzed. Th present study demonstrated that the expression levels of miR‑210 and COL1A1 were lower, and the expression levels of COL10A1 and MMP13 were higher in the OA chondrocytes, compared with the levels of expression in the normal chondrocytes. Overexpression of miR‑210 significantly promoted the proliferation of OA chondrocytes and induced the protein expression of Ki67. In addition, miR‑210 overexpression markedly increased the expression of COL1A1 expression, but decreased the expression levels of COL10A1 and MMP13. A luciferase reporter assay confirmed the direct interaction between miR‑210 and hypoxia‑inducible factor (HIF)‑3α. miR‑210 did not alter the mRNA expression of HIF‑3α, however, it suppressed the protein expression of HIF‑3α. Additionally, HIF‑3α knockdown significantly promoted OA chondrocyte proliferation and increased the mRNA levels of COL1A1, whereas it decreased the mRNA levels of COL10A1 and MMP13. The results of the present study suggested that miR‑210 may be a negative regulator of the progression of OA, which increases chondrocyte proliferation and prompts extracellular matrix deposition by directly targeting HIF‑3α.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: Forkhead box M1 (FOXM1) is a characteristic proliferation‑associated transcription factor, which is overexpressed in various types of human cancer. The aim of the present study was to determine the expression of FOXM1 in a large collection of colorectal cancer (CRC) samples. Between March 2012 and January 2014, 96 patients with histologically diagnosed CRC were recruited into the current study. Using immunohistochemistry, reverse transcription‑quantitative polymerase chain reaction and western blotting, mRNA and protein expression levels of FOXM1 in CRC tissue samples were determined. The function of FOXM1 in the CRC cells was evaluated by small interfering RNA‑mediated depletion of FOXM1, followed by analyses of cell proliferation and invasion. High levels of staining for FOXM1 were observed in significantly more CRC tissue samples: 85.42% (82/96) of CRC tissue samples compared with 18.75% (18/96) of adjacent normal mucosa tissue samples. Silencing FOXM1 inhibited the proliferation of LoVo cells, which express a relatively high level of FOXM1, and the invasion and migration of LoVo cells were also markedly suppressed. The data from the present study suggested that the pathogenesis of human CRC may be mediated by FOXM1, and that FOXM1 inhibition may provide a promising therapeutic strategy for CRC.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: Patients with essential hypertension undergo endothelial dysfunction, particularly in the conduit arteries. Cilostazol, a type III phosphodiesterase inhibitor, serves a role in the inhibition of platelet aggregation and it is widely used in the treatment of peripheral vascular diseases. Previous studies have suggested that cilostazol suppresses endothelial dysfunction; however, it remains unknown whether cilostazol protects the endothelial function in essential hypertension. The aim of the present study was to investigate whether, and how, cilostazol suppresses angiotensin II (angII)‑induced endothelial dysfunction. Human umbilical vein endothelial cells (HUVECs) and Sprague Dawley rats were exposed to angII and treated with cilostazol. Endothelial cell apoptosis and function, nitric oxide and superoxide production, phosphorylation (p) of Akt, and caspase‑3 protein expression levels were investigated. AngII exposure resulted in the apoptosis of endothelial cells in vitro and in vivo. In vitro, cilostazol significantly suppressed the angII‑induced apoptosis of HUVECs; however, this effect was reduced in the presence of LY294002, a phosphoinositide 3 kinase (PI3K) inhibitor. Furthermore, cilostazol suppressed the angII‑induced p‑Akt downregulation and cleaved caspase‑3 upregulation. These effects were also alleviated by LY294002. In vivo, cilostazol suppressed the angII‑induced endothelial cell apoptosis and dysfunction. Cilostazol was also demonstrated to partially reduced the angII‑induced increase in superoxide production. The results of the present study suggested that cilostazol suppresses endothelial apoptosis and dysfunction by modulating the PI3K/Akt pathway.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: The Wnt/β‑catenin signaling pathway has been reported to regulate cisplatin resistance in several types of cancer cell. The present study aimed to investigate the role and underlying mechanism of Wnt/β‑catenin signaling in cisplatin resistance of lung adenocarcinoma cells. Wild‑type and cisplatin‑resistant A549 human lung adenocarcinoma cells (A549/WT and A549/CDDP, respectively) were cultured in vitro and exposed to different cisplatin concentrations. Cells were incubated with 10 mM lithium chloride (LiCl) to activate β‑catenin signaling. Cell proliferation was determined using the MTS assay. Cell apoptosis was evaluated using Annexin V/propidium iodide double staining, followed by flow cytometry. β‑catenin was knocked down using small interfering RNA (siRNA). The intracellular distribution of β‑catenin was determined by immunocytochemistry, and the mRNA and protein expressions of target genes were examined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. β‑catenin and B‑cell lymphoma‑extra large (Bcl‑xl) were significantly upregulated in A549/CDDP cells compared with A549/WT cells (P<0.05). LiCl reduced the sensitivity of A549/WT cells to cisplatin (P<0.01); and upregulated, increased phosphorylation (P<0.05) and enhanced nuclear translocation of β‑catenin. LiCl also significantly elevated the mRNA and protein expression levels of Bcl‑xl (P<0.05). Notably, silencing of β‑catenin with siRNA decreased the mRNA and protein expression of Bcl‑xl, and sensitized A549/WT cells to cisplatin (P<0.01). The findings of the current study suggest that upregulation of β‑catenin signaling may contribute to cisplatin resistance in lung adenocarcinoma cells by upregulating Bcl‑xl. Therefore, molecular targeting of Wnt/β‑catenin signaling may sensitize lung cancer cells to cisplatin.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: The present study aimed to explore the function of miR‑34b promoter methylation in cell proliferation in children's acute leukemia. Quantitative PCR and methylation‑specific PCR were performed to measure the levels of miR‑34b and its promoter methylation in normal cells, eight leukemia cell lines as well as primary leukemic cells isolated from patients newly diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and mixed lymphocytic lymphoma. miR‑34b levels in leukemia cell lines and primary leukemic cells were significantly lower than those in normal cells. The miR‑34b promoter was found to be methylated in all leukemia cell lines, 24 of 31 ALL patients and 8 of 19 AML patients, but not in the 23 normal controls. miR‑34b expression and methylation of its promoter were not associated with most clinical parameters assessed; however, miR‑34b levels in prednisone‑sensitive ALL were significantly different from those in insensitive ALL. A cell counting kit‑8 assay showed that transfection of miR‑34b mimics into K562 cells inhibited their proliferation. Furthermore, treatment with the demethylating agent 5‑aza‑2‑deoxycytidine significantly enhanced miR‑34b expression levels and decreased the methylation status of its promoter in HL‑60 and K562 cells. In conclusion, the results of the present study indicated that in pediatric leukemia cells and leukemia cell lines, the expression of miR‑34b is inhibited by methylation of its promoter, which impairs the restraining effects of miR‑34b on cell proliferation. It was also indicated that the expression of miR‑34b in ALL patients may affect their response to early treatments.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: Cancer‑associated fibroblasts (CAFs), key components of the tumor stroma, can regulate tumorigenesis by altering the tumor microenvironment in variety of ways to promote angiogenesis, recruit inflammatory immune cells and remodel the extracellular matrix. Using a murine xenograft model of colon carcinoma, the present study observed that oxaliplatin increased the accumulation of CAFs and stimulated the production of cytokines associated with CAFs. When oxaliplatin was combined with the small‑molecule dipeptidyl peptidase inhibitor PT‑100, which inhibits CAFs by targeting fibroblast activation protein (FAP), the accumulation of CAFs was markedly reduced, xenograft tumor growth was significantly suppressed and the survival of the mice increased, compared to those of mice treated with oxaliplatin or PT‑100 alone. Furthermore, the xenograft tumor tissues of mice treated with oxaliplatin and PT‑100 contained lower numbers of tumor‑associated macrophages and dendritic cells, expressed lower levels of cytokines associated with CAFs and had a lower density of CD31+ endothelial cells. The present study demonstrated that pharmacological inhibition of CAFs improved the response to chemotherapy, reduced the recruitment of immune tumor‑promoting cells and inhibited angiogenesis. Combining chemotherapy with agents which target CAFs may represent a novel strategy for improving the efficacy of chemotherapy and reducing chemoresistance.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: The clinical application of natural products derived from traditional Chinese medicine has gained attention in cancer chemotherapeutics. Echinacoside (ECH), one of the phenylethanoids, isolated from the stems of Cistanches salsa (a Chinese herbal medicine) has tissue‑protective and anti‑apoptotic effects on the central nervous system. However, it remains largely elusive whether ECH possesses tumor suppressive activity. In the present study, it was demonstrated that ECH can markedly inhibit the proliferation of pancreatic adenocarcinoma cells by inducing the production of reactive oxygen species and the perturbation of mitochondrial membrane potential and thus triggering apoptosis. Furthermore, it was elucidated that ECH represses tumor cell growth through modulating MAPK activity. In conclusion, this study reveals an novel function of ECH in preventing cancer development, and implies that the usage of ECH could be a potential chemotherapeutic strategy for cancer.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: The expression levels of microRNA‑21 (miR‑21) are increased in a number of types of solid tumors. However, the association between miR‑21 expression and clinical features of patients with gastric carcinoma, and gastric cancer proliferation, invasion and migration remains to be elucidated. The present study investigated the effect of miR‑21 on the clinical features, proliferation, invasion and migration of gastric cancer and the underlying mechanisms associated with Noxa. Reverse transcription quantitative polymerase chain reaction (RT‑qPCR) was performed to detect the expression levels of miR‑21 and Noxa in samples of gastric cancer tissue and matched, adjacent, non‑tumor tissue. The association between miR‑21 expression and the clinical features of patients with gastric carcinoma, as well as the correlation between the mRNA and protein expression levels of miR‑21 and Noxa were analyzed. SGC‑7901 gastric cancer cells were cultured in vitro and transfected with an miR‑21 mimic. The effect of miR‑21 upregulation on proliferation and the cell cycle was determined using the MTT assay and flow cytometry. In addition, migration and invasion of SGC‑7901 cells were observed using the Transwell assay. The target gene of miR‑21 was identified using bioinformatics software and a dual luciferase reporting system. The effect of miR‑21 upregulation on Noxa expression levels in SGC‑7901 cells was also analyzed by RT‑qPCR and western blotting. Increased levels of miR‑21 expression and decreased levels of Noxa expression were observed in gastric cancer tissue samples when compared with the adjacent non‑tumor tissue samples. An increased miR‑21 expression level was identified as a risk factor for advanced stage gastric cancer, lymph node metastasis and larger primary tumors. Furthermore, the overexpression of miR‑21 inhibited Noxa expression levels in SGC‑7901 cells. Therefore, high levels of miR‑21 expression may induce gastric cancer migration and invasion via the downregulation of Noxa expression.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: Acquired resistance to epidermal growth factor inhibitors has been reported to be associated with cross‑resistance to radiation. Paris Saponins (PSs) exert a wide range of pharmacological activities, including cell apoptosis induction, multidrug resistance inhibition, angiogenesis inhibition and tumor cell migration by modulating various signaling pathways. The present study aimed to investigate the radiosensitization effects of PSII, PSVI and PSVII in a gefitinib‑resistant PC‑9‑ZD lung adenocarcinoma cell line, and the possible mechanism underlying their function. A clonogenic assay was performed to determine the effects of PS radiosensitization on the PC‑9‑ZD cell line. The cell cycle was analyzed by flow cytometry, and cell apoptosis was analyzed with Annexin V/propidium iodide and Hoechst staining. Protein expression levels were detected by western blotting. The results of the present study revealed a significant increase in PC‑9‑ZD cell line radiosensitivity following treatment with PSs. PSs induced G2/M cell cycle phase arrest and apoptosis of the irradiated PC‑9‑ZD cells. Notably, the expression levels of B cell lymphoma 2 (Bcl‑2) were downregulated, and those of caspase‑3, Bcl‑2‑associated X protein (Bax) and p21/Waf1/Cip1 were upregulated following treatment with PSs. The present results demonstrated that PSs induced radiosensitivity in gefitinib‑resistant cells by inducing G2/M phase arrest and by enhancing the apoptotic response via the modulation of caspase‑3, Bax, Bcl‑2 and p21/Waf1/Cip1 expression.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: Mutations in the human ether‑à‑go‑go‑related gene (hERG) are responsible for long‑QT syndrome (LQTS) type 2 (LQT2). In the present study, a heterozygous missense mutation (A561V) linked to LQT2, syncope and epilepsy was identified in the S5/pore region of the hERG protein. The mutation, A561V, was prepared and subcloned into hERG‑pcDNA3.0. Mutant plasmids were co‑transfected into HEK‑293 cells, which stably express wild‑type (WT) hERG, in order to mimic a heterozygous genotype, and the whole‑cell current was recorded using a patch‑clamp technique. Confocal microscopy was performed to evaluate the membrane distribution of the hERG channel protein using a green fluorescent protein tagged to the N‑terminus of hERG. A561V‑hERG decreased the amplitude of the WT‑hERG currents in a concentration‑dependent manner. In addition, A561V‑hERG resulted in alterations to activation, inactivation and recovery from inactivation in the hERG protein channels. Further evaluation of hERG membrane localization indicated that the A561V‑hERG mutant protein was unable to travel to the plasma membrane, which resulted in a trafficking‑deficient WT‑hERG protein. In conclusion, A561V‑hERG exerts a potent dominant‑negative effect on WT‑hERG channels, resulting in decreased hERG currents and impairment of hERG membrane localization. This may partially elucidate the clinical manifestations of LQTS patients who carry the A561V mutation.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: Hepatoblastoma is the most common type of malignant liver tumor in children. While outcomes have been greatly improved in the past decades, the treatment of advanced hepatoblastoma has remained challenging. Enhancer of zeste homologue 2 (EZH2), a member of the polycomb group regulators of gene activity, is amplified and overexpressed in a variety of cancers. However, the role of EZH2 in hepatoblastoma has remained to be fully elucidated. The purpose of the present study was to investigate the expression patterns of EZH2 in hepatoblastoma cells and to assess the anti‑cancer effects of EZH2 depletion. Western blot analysis revealed that EZH2 expression was significantly higher in hepatoblastoma specimens compared with that in peri‑tumor tissues, while p27 was reduced in hepatoblastoma. Suppression of EHZ2 using lentiviral small hairpin RNA inhibited hepatoblastoma cell proliferation, induced cell cycle arrest in G1 phase and enhanced the expression of G1/S‑phase checkpoint protein p27. These results suggested that EZH2 may represent a potential diagnostic marker and therapeutic target for the treatment of hepatoblastoma.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: Alterations to the expression L‑type calcium channels (LTCCs) and Kv4.3 potassium channels form the possible basis of atrial electrical remodeling during rapid pacing. The mitogen‑activated protein kinase (MAPK) pathway is affected by increases in cytoplasmic Ca2+, and therefore represents an attractive candidate for the regulation and mediation of Ca2+‑induced ion channel remodeling. The present study aimed to investigate alterations to the ion channel‑MAPK axis, and to determine its influence on ion channel remodeling during atrial fibrillation. Rat atrial myocytes were isolated, cultured, and in vitro rapid pacing was established. Intracellular Ca2+ signals were monitored using the Fluo‑3/AM Ca2+ indicator. Verapamil, PD98058 and SB203580 were added to the culture medium of various groups at specific time‑points. The mRNA expression levels of LTCC‑α1c and Kv4.3 potassium channels were detected by reverse transcription‑polymerase chain reaction. Western blotting was performed to determine the expression levels of channel and signaling proteins. The results demonstrated that fast pacing significantly increased the intracellular Ca2+ concentration in atrial myocytes, whereas treatment with verapamil markedly inhibited this increase. In addition, verapamil significantly antagonized the rapid pacing‑induced activation of extracellular signal‑regulated kinase (ERK) and p38MAPK. These results indicated that the MAPK pathway may have an important role in the opening of LTCCs, and alterations to MAPK molecule expression could affect the expression and remodeling of ion channels.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: Alzheimer's disease (AD) is the most common form of dementia among the aging population. It is pathologically characterized by synaptic impairment, accumulation of neurofibrillary tangles and amyloid‑β (Aβ) deposition. MicroRNA‑26b (miR‑26b) has been observed to be upregulated in the human temporal cortex in AD, however, the function of miR‑26b has not been verified. Reverse transcription‑quantitative polymerase chain reaction was conducted to investigate the expression levels of miR‑26b in a double transgenic mouse model of AD. Following transfection of miR‑26b or an miR‑26b inhibitor, western blot analysis, enzyme‑linked immunosorbent assay and luciferase assays were performed. The present study demonstrated that the expression levels of miR‑26b were upregulated in a double transgenic mouse model of AD. It was also demonstrated that upregulation of miR‑26b in N2a/APP cells downregulated the insulin‑like growth factor 1 (IGF‑1) protein expression level and promoted Aβ production, whereas inhibition of miR‑26b in N2a/APP cells upregulated the IGF‑1 protein level and suppressed Aβ production. Furthermore, miR‑26b target sites in IGF‑1 were confirmed using a luciferase assay in HEK293 cells. The present study may be useful in the development of effective therapeutic strategies against AD.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: The present study aimed to explore the molecular mechanisms associated with intervertebral disc degeneration (IDD) induced by tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β. The microarray dataset no. GSE42611 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between four experimental nucleus pulposus samples and four control nucleus pulposus samples were analyzed. Subsequently, Gene Ontology (GO) and pathway enrichment analyses of DEGs were performed, followed by protein‑protein interaction (PPI) network construction and prediction of a regulatory network of transcription factor (TFs). Finally, the transcriptional regulatory network was integrated into the PPI network to analyze the network modules. A total of 246 upregulated and 290 downregulated DEGs were identified. The upregulated DEGs were mainly associated with GO terms linked with inflammatory response and apoptotic pathways, while the downregulated DEGs were mainly associated with GO terms linked with cell adhesion and pathways of extracellular matrix ‑ receptor interaction. In the PPI network, IL6, COL1A1, NFKB1 and HIF1A were hub genes, and in addition, NFKB1 and HIF1A were TFs. Pathways of apoptosis and extracellular matrix ‑ receptor interaction may have important roles in IDD progression. IL6, COL1A1 and the TFs NFKB1 and HIF1A may be used as biomarkers for IDD diagnosis and treatment.
    No preview · Article · Feb 2016 · Molecular Medicine Reports
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    ABSTRACT: The extensive skin defects induced by severe burns are dangerous and can be fatal. Currently, the most common therapy is tangential excision to remove the necrotic or denatured areas of skin, followed by skin grafting. Xenogeneic dermal substitutes, such as porcine acellular dermal matrix (ADM), are typically used to cover the burn wounds, and may accelerate wound healing. It is assumed that burned skin that still maintains partial biological activity may be recycled to construct an autologous acellular dermal matrix, termed 'deep‑degree burned dermal matrix (DDBDM)'. In theory, DDBDM may avoid the histoincompatibility issues associated with foreign or xenogeneic dermal matrices, and reduce therapy costs by making full use of discarded skin. In the present study, the collagens within prepared DDBDM were thickened, disorganized and partially fractured, however, they still maintained their reticular structure and tensile strength (P<0.01). Through microarray analysis of the cytokines present in ADM and DDBDM, it was determined that the DDBDM did not produce excessive levels of harmful burn toxins. Following 4 weeks of subcutaneous implantation, ADM and DDBDM were incompletely degraded and maintained good integrity. No significant inflammatory reaction or rejection were observed, which indicated that ADM and DDBDM have good histocompatibility. Therefore, DDBDM may be a useful material for the treatment of deep‑degree burns.
    No preview · Article · Feb 2016 · Molecular Medicine Reports