International Journal of Molecular Medicine Impact Factor & Information

Publisher: Panepistēmio tēs Krētēs, Spandidos Publications

Current impact factor: 2.09

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 2.088
2013 Impact Factor 1.88
2012 Impact Factor 1.957
2011 Impact Factor 1.573
2010 Impact Factor 1.814
2009 Impact Factor 1.98
2008 Impact Factor 1.88
2007 Impact Factor 1.847
2006 Impact Factor 1.854
2005 Impact Factor 2.09
2004 Impact Factor 3.19
2003 Impact Factor 1.94
2002 Impact Factor 2.063
2001 Impact Factor 1.689
2000 Impact Factor 1.899
1999 Impact Factor 1.058
1998 Impact Factor

Impact factor over time

Impact factor

Additional details

5-year impact 2.01
Cited half-life 5.60
Immediacy index 0.44
Eigenfactor 0.01
Article influence 0.48
Website International Journal of Molecular Medicine website
Other titles International journal of molecular medicine (Online)
ISSN 1107-3756
OCLC 53915595
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

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

Publications in this journal

  • International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2418

  • International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2415

  • International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2413

  • International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2417

  • International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2416

  • International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2412
  • [Show abstract] [Hide abstract]
    ABSTRACT: Orexins are a class of peptides which have a potent influence on a broad variety of cancer cells. Autophagy is closely associated with tumors; however, its function is not yet completely understood. In this study, we aimed to determine whether orexin A induces autophagy in HCT‑116 human colon cancer cells and to elucidate the molecular mechanisms involved. For this purpose, HCT‑116 cells were treated with orexin A, and cell viability was then measured by MTT assay, and apoptosis was determined by flow cytometry. The expression levels of autophagy‑related proteins were measured by western blot analysis. Quantitative analysis of autophagy following acridine orange (AO) staining was performed using fluorescence microscopy, and cellular morphology was observed under a transmission electron microscope. In addition, the HCT‑116 cells were treated with the extracellular signal‑regulated kinase (ERK) inhibitor, U0126, or the autophagy inhibitor, chloroquine, in combination with orexin A in order to examine the activation of ERK. We found that orexin A significantly inhibited the viability of the HCT‑116 cells. Both autophagy and apoptosis were activated during the orexin A‑induced death of HCT‑116 cells. When the HCT‑116 cells were treated with orexin A for 24 h, an accumulation of punctate microtubule-associated protein-1 light chain 3 (LC3) and an increase in LC3‑Ⅱ protein levels were also detected, indicating the activation of autophagy. Moreover, orexin A upregulated ERK phosphorylation; however, U0126 or chloroquine abrogated ERK phosphorylation and decreased autophagy, compared to treatment with orexin A alone. Therefore, our findings demonstratedm that orexin A induced autophagy through the ERK pathway in HCT‑116 human colon cancer cells. The inhibition of autophagy may thus prove to be an effective strategy for enhancing the antitumor potential of orexin A as a treatment for colon cancer.
    International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2409
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    ABSTRACT: The one gene-one enzyme hypothesis, first introduced by Beadle and Tatum in the 1940s and based on their genetic analysis and observation of phenotype changes in Neurospora crassa challenged by various experimental conditions, has witnessed significant advances in recent decades. Much of our understanding of the association between genes and their phenotype expression has benefited from the completion of the human genome project, and has shown continual transformation guided by the effort directed at the annotation and characterization of human genes. Similarly, the idea of one drug‑one primary disease indication that traditionally has been the benchmark for the labeling and usage of drugs has also undergone evident progressive refinements; in recent years the science and practice of pharmaceutical development has notable success in the strategy of drug repurposing. Drug repurposing is an innovative approach where, instead of de novo synthesis and discovery of new drugs with novel indications, drug candidates with the desired usage are identified by a process of re‑profiling using an open‑source database or knowledge of known or failed drugs already in existence. In the present study, the repurposing drug strategy employing open‑access data portal drug‑target interactome (DTome) is applied to the uncovering of new clinical usage for probenecid.
    International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2411

  • International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2410
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    ABSTRACT: The majority of p53 mutations, which are responsible for gain of oncogenic function, are missense mutations in hotspot codons. However, in our previous study, we demonstrated that a deletion spanning codons 127-133 in the p53 gene (designated as del p53) was detected in doxorubicin-resistant MCF-7 cell lines following various induction processes. In the present study, we aimed to investigate the role of del p53 and its association with the proliferation, metastasis and drug resistance of MCF-7 cells. The MCF-7/del p53 cell line is a representative of the del p53 stably expressed clones which were constructed by transfection of the del p53-containing construct into MCF-7/wt cells. Markers of multidrug resistance (MDR), epithelial-mesenchymal transition (EMT) and stem cell-like properties were examined in the MCF-7/del p53 cells. The results revealed that the MCF-7/del p53 cells expressed full-length p53 and del p53 mRNA and protein, as well as P-glycoprotein (P-gp). The MCF-7/del p53 cells acquired resistance to doxorubicin with increased P-gp efflux function. Using a transient expression assay, the mdr1 promoter was found to be significantly activated by external or integrated del p53 (P<0.001). The inhibition of nuclear factor (NF)-κB by cyclosporine sensitized the MCF-7/del p53 cells to doxorubicin toxicity. In addition, the morphological characteristics of the MCF-7/del p53 and MCF-7/adr were similar. EMT was observed in the MCF-7/del p53 cells as demonstrated by the presence of the mesenchymal markers, Slug and vimentin, and the decrease in the epithelial marker, cadherin 1, type 1, E-cadherin (CDH1), as well as an enhanced migration ability (P<0.001). Furthermore, the number of cells expressing the cancer stem cell-like marker, CD44, increased, accompanied by mammosphere formation. Taken together, these findings indicate that the expression of del p53 in MCF-7/del p53 cells enables the cells to partially acquire doxorubicin resistance characteristics of the MCF-7/adr cells. Thus, del p53 may be an important factor in non-invasive MCF-7 cells, activating NF-κB signaling and the mdr1 promoter and partially attributing to EMT; the cells thus acquire stem cell‑like properties, which facilitates drug resistance. Therefore, the 21-bp deletion of p53 may prove to be a therapeutic strategy with which to prevent cancer cells from acquiring resistance to drugs.
    International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2406
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    ABSTRACT: With the increase in life expectancy, there is also growing interest in anti-aging treatments and technologies. The development of anti-aging functional drugs for the skin, and foods from natural sources, may offer solutions to this global matter. Aging involves structural, functional and biochemical changes that occur throughout cells and bodily tissues; the amount of hormones secreted from of all human organs, including the skin, decreases over time. Matrix metalloproteinase (MMP) genes (MMP-1 and -8) play an important role in the aging of skin fibroblasts. For example, an increased MMP expression causes accelerated aging and the degradation of skin elasticity-related genes. In the present study, we examined the anti-wrinkle effects of tuna heart extract which are mediated through the inhibition of MMPs in skin cells. Generally, tuna contains high concentrations of selenium and antioxidants, which serve to remove free radicals, and is known to delay skin and body aging. In addition, unsaturated fatty acids in tuna help to maintain the natural glossy look of skin, and increase skin elasticity, providing moisture for dry skin. A recent study confirmed the various bio-effects of boiled tuna extract and muscle. However, bioactivity studies using tuna heart are limited. Thus, in the present study, we obtained extracts and fractions of tuna heart, and examined their effects on Hs27 human fibroblast proliferation using an MTS assay. In addition, we measured procollagen type 1 levels and elastase activity, and performed β-galactosidase staining. We then measured the expression levels of phosphatidylinositol 3-kinase/Akt and MMP-related genes by western blot analysis and RT-PCR. Our results revealed that tuna heart extract decreased MMP expression by upregulating tissue inhibitors of metalloproteinase-1 (TIMP-1) and decreasing elastase activity, thus exerting anti-aging and anti-wrinkle effects by increasing collagen synthesis and promoting skin fibroblast proliferation. Thus, our data suggest that tuna heart (TH)-H2O fractions exert anti-wrinkle effects on Hs27 cells.
    International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2407
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    ABSTRACT: Pulmonary vascular remodeling is a significant pathological feature of hypoxia-induced pulmonary hypertension (HPH), while pulmonary artery smooth muscle cell (PASMC) proliferation plays a leading role in pulmonary vascular remodeling. Spermine (Sp), a polyamine, plays a critical role in periodic cell proliferation and apoptosis. The present study was conducted to observe the association between hypoxia-induced PASMC proliferation and polyamine metabolism, and to explore the effects of exogenous Sp on PASMC poliferation and the related mechanisms. In the present study, PASMCs were cultured with cobalt chloride (CoCl2) to establish a hypoxia model, and Sp at various final concentrations (0.1, 1, 10 and 100 µM) was added to the medium of PASMCs 40 min prior to the induction of hypoxia. Cell proliferation was measured by 3-(4,5-dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay, cell counting kit-8 assay and 5-bromo‑2'‑deoxyuridine (BrdU) incorporation assay. Cell cycle progression was determined by flow cytometry, and the protein expression levels of spermidine/spermine N1-acetyltransferase (SSAT; the key enzyme in the terminal degradation of polyamine), ornithine decarboxylase (ODC; the key enzyme of polyamine biosynthesis), cyclin D1 and p27 were measured by western blot analysis. The results revealed that the proliferation of the PASMCs cultured with CoCl2 at 50 µM for 24 h markedly increased. The expression of ODC was decreased and the expression of SSAT was increased in the cells under hypoxic conditions. Exogenous Sp at concentrations of 1 and 10 µM significantly inhibited hypoxia-induced PASMC proliferation, leading to cell cycle arrest at the G1/G0 phase. In addition, Sp decreased cyclin D1 expression, increased p27 expression, and suppressed the phosphorylation of extracellular signal‑regulated kinase 1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT); however, the above-metioned parameters were not markedly affected by Sp at concentrations of 0.1 or 100 µM. These results suggest that hypoxia disrupts polyamine metabolism, and Sp at concentrations of 1 and 10 µM inhibits the increase in human PASMC proliferation caused by chemically-induced hypoxia via the suppression of the ERK1/2- and PI3K/AKT-associated pathways. This study thus offer new insight into the prevention and treatment of HPH.
    International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2408
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    ABSTRACT: Drowning is a cause of accidental mortality. However, survival may result in acute lung injury. The aim of the present study was to evaluate the effects of 3,5,4'-tri-O-acetylresveratrol (AC-Res) on acute lung injury (ALI) induced by seawater inhalation in rats. ALI models were established by the tracheal instillation of artificial seawater with or without 50 mg/kg AC-Res pretreatment for 7 days. Lung samples from different groups were harvested 4 h after the model was established. Histological changes, blood vessel permeability, inflammatory factor secretion and expression states of the nuclear factor-κB (NF-κB) and inducible NOS (i-NOS) pathway were assessed to evaluate seawater‑induced lung injury and the protective effects of acetylated resveratrol. The results showed that seawater inspiration led to physiological structure changes and an increased permeability of blood vessels. In addition, seawater stimulation enhanced the expression levels of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-1 β (IL-1β) secretion in vitro and in vivo. Notably, seawater inhalation increased NF-κB and i-NOS expression in lungs and cells. On the other hand, pretreatment of AC-Res inhibited the abnormal expression of the NF-κB and i-NOS pathways, followed by decreased NO, TNF-α and IL-1β secretion, protein and cell content in bronchoalveolar lavage fluid (BALF) and Evans blue, protein and cell infiltration from blood vessels into lung tissues. The results therefore suggest that AC-Res attenuated seawater inhalation induced‑ALI by interfering with the NF-κB and i-NOS pathways.
    International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2403
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    ABSTRACT: The aim of this study was to identify the mechanisms through which dielectric-barrier discharge plasma damages human keratinocytes (HaCaT cells) through the induction of oxidative stress. For this purpose, the cells were exposed to surface dielectric-barrier discharge plasma in 70% oxygen and 30% argon. We noted that cell viability was decreased following exposure of the cells to plasma in a time-dependent manner, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The levels of intracellular reactive oxygen species (ROS) were determined using 2',7'-dichlorodihydrofluorescein diacetate and dihydroethidium was used to monitor superoxide anion production. Plasma induced the generation of ROS, including superoxide anions, hydrogen peroxide and hydroxyl radicals. N-acetyl cysteine, which is an antioxidant, prevented the decrease in cell viability caused by exposure to plasma. ROS generated by exposure to plasma resulted in damage to various cellular components, including lipid membrane peroxidation, DNA breaks and protein carbonylation, which was detected by measuring the levels of 8-isoprostane and diphenyl-1-pyrenylphosphine assay, comet assay and protein carbonyl formation. These results suggest that plasma exerts cytotoxic effects by causing oxidative stress-induced damage to cellular components.
    International Journal of Molecular Medicine 11/2015; DOI:10.3892/ijmm.2015.2405
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    ABSTRACT: The α-Gal epitope (Galα1,3Galα1,4GlcNAc‑R) is ubiquitously presented in non-primate mammals, marsupials and New World Monkeys, but it is absent in humans, apes and Old World monkeys. However, the anti-Gal antibody (~1% of immunoglobulins) is naturally generated in human, and is found as the immunoglobulin G (IgG), IgM and IgA isotypes. Owing to the specific binding of the anti‑Gal antibody with the α‑Gal epitope, humans have a distinct anti‑α‑gal reactivity, which is responsible for hyperacute rejection of organs transplanted from α‑gal donors. In addition, the α1,3 galactosyltransferases (α1,3GT) can catalyze the synthesis of the α‑Gal epitope. Therefore, the α1,3GT gene, which encodes the α1,3GT, is developed profoundly. The distributions of the α‑Gal epitope and anti‑Gal antibody, and the activation of α1,3GT, reveal that the enzyme of α1,3GT in ancestral primates is ineffective. Comparison of the nucleotide sequence of the human α1,3‑GT pseudogene to the corresponding different species sequence, and according to the evolutionary tree of different species, the results of evolutionary inactivation of the α1,3GT gene in ancestral primates attribute to the mutations under a stronger selective pressure. However, on the basis of the structure, the mechanism and the specificity of the α‑Gal epitope and anti‑Gal antibody, they can be applied to clinical exploitation. Knocking out the α1,3GT gene will eliminate the xenoantigen, Gal(α1,3)Gal, so that the transplantation of α1,3GT gene knockout pig organ into human becomes a potential clinically acceptable treatment for solving the problem of organ shortage. By contrast, the α‑Gal epitope expressed through the application of chemical, biochemical and genetic engineering can be exploited for the clinical use. Targeting anti‑Gal‑mediated autologous tumor vaccines, which express α‑Gal epitope to antigen‑presenting cells, would increase their immunogenicity and elicit an immune response, which will be potent enough to eradicate the residual tumor cells. For tumor vaccines, the way of increasing immunogenicity of certain viral vaccines, including flu vaccines and human immunodeficiency virus vaccines, can also be used in the elderly. Recently, α‑Gal epitope nanoparticles have been applied to accelerate wound healing and further directions on regeneration of internally injured tissues.
    International Journal of Molecular Medicine 10/2015; DOI:10.3892/ijmm.2015.2397

  • International Journal of Molecular Medicine 10/2015; in press.
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    ABSTRACT: Polysialic acid (PSA) is highly expressed during embryonic development, but barely expressed during postnatal development, and may be 're-expressed' in cancer tissues. In this study, motility and migration assays were performed to compare the changes in cell behavior between non-malignant and maligant cells. Next, the expression levels of PSA were evaluated in 4 human and mouse normal breast or breast cancer (BC) cell lines using 1,2-diamino-4,5-methylenedioxybenzene-labeling HPLC technology, as well as in human clinical BC tissue samples. PSA expression was significantly higher in malignant cells (where it appeared to facilitate cell migration and motility) than in non-malignant cells. Enhanced PSA expression levels were also observed during epithelial-mesenchymal transition (EMT), a leading cause of cancer cell metastasis, which was induced in the NMuMG and MCF10A cells by treatment with transforming growth factor-β1 (TGF-β1). An increased PSA expression also correlated with the disease stage in the patients with BC (P<0.0001). Using RT-qPCR, we found that polysialyltransferase ST8SiaIV (PST) and polysialyltransferase ST8SiaII (STX), which are responsible for PSA synthesis, were differently expressed in the tested BC samples. However, PST, but not STX, was re-expressed in 14 out of 20 clinical BC samples. The findings of the present study indicate that the pathophysiology of BC involves the aberrant regulation of PSA expression and PST gene expression.
    International Journal of Molecular Medicine 10/2015; DOI:10.3892/ijmm.2015.2395
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    ABSTRACT: Mutations in matrilin-3 are associated with common skeletal diseases, such as hand osteoarthritis (HOA), as well as rare chondrodysplasias, such as multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). In the present study, we constructed the mutations R116W [at the von Willebrand factor, type A (vWFA) domain], T298M [at the first epidermal growth factor (EGF) domain] and C299S (at the first EGF domain), according to the mouse sequence, which are associated with human MED, HOA and SEMD, respectively, by overlap extension PCR and inserted them into an expression vector (pcDNA3.1/v5-His). We transfected these contructs into the COS-1 or MCT cells, and the results revealed that the HOA-related matrilin-3 mutation (T298M) leads to a high expression level of growth arrest DNA damage-inducible gene 153 (GADD153, also known as CHOP; an endoplasmic reticulum stress marker), as shown by western blot analysis and does not significantly affect protein secretion, as shown by immunofluorescence staining; however, osteochondroplasia, i.e., MED-related (R116W) and SEMD-related (C299S) mutations lead to both high levels of GADD153 expression and protein trafficking into the cytoplasm and form multiple vacuoles in cells, which in turn leads to insufficient protein secretion.
    International Journal of Molecular Medicine 10/2015; 36(6). DOI:10.3892/ijmm.2015.2377