Abstract:
:Previous genome-wide association studies have demonstrated that single nucleotide polymorphisms in T‑box (TBX)5 are associated with increased susceptibility to atrial fibrillation (AF), and a recent study has causally linked a TBX5 mutation to atypical Holt-Oram syndrome and paroxysmal AF. However, the prevalence and spectrum of TBX5 mutations in patients with AF remain to be elucidated. In the present study, a cohort of 190 unrelated patients with idiopathic AF were prospectively recruited, with 400 unrelated healthy individuals recruited as controls. The coding exons and flanking introns of the TBX5 gene were sequenced in the participants. The functional characteristics of the mutant TBX5 were delineated in contrast with its wild‑type counterpart using a dual‑luciferase reporter assay system. As a result, a novel heterozygous TBX5 mutation, p.P132S, was identified in an index patient with AF, with a mutational prevalence of ~0.53%. Genetic analysis of the proband's family showed that the mutation co‑segregated with AF, and was transmitted in an autosomal dominant pattern. The missense mutation was absent in the 800 control chromosomes, and the altered amino acid was completely evolutionarily conserved across species. Functional analyses revealed that the mutant TBX5 had significantly reduced transcriptional activity. Furthermore, the mutation markedly decreased the synergistic activation between TBX5 and NK2 homeobox 5, another transcription factor which has been causatively linked to AF. The present study was the first, to the best of our knowledge, to report on the association between a TBX5 loss‑of‑function mutation and increased susceptibility to AF. These results provide novel insight into the molecular mechanism underpinning AF, and have potential implications in the development of novel prophylactic and therapeutic strategies for AF, the most common form of sustained cardiac arrhythmia.
journal_name
Mol Med Repjournal_title
Molecular medicine reportsauthors
Guo DF,Li RG,Yuan F,Shi HY,Hou XM,Qu XK,Xu YJ,Zhang M,Liu X,Jiang JQ,Yang YQ,Qiu XBdoi
10.3892/mmr.2016.5043subject
Has Abstractpub_date
2016-05-01 00:00:00pages
4349-56issue
5eissn
1791-2997issn
1791-3004journal_volume
13pub_type
临床试验,杂志文章,多中心研究abstract::Portal hypertension (PHT) is one of the most severe consequences of liver cirrhosis. Carvedilol is a first‑line pharmacological treatment of PHT. However, the antifibrogenic effects of carvedilol on liver cirrhosis and the intrinsic mechanisms underlying these effects have not been thoroughly investigated. The present...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2019.10401
更新日期:2019-08-01 00:00:00
abstract::LL‑37 is the only known member of the cathelicidin family of antimicrobial peptides in humans. In addition to its broad spectrum of antimicrobial activities, LL‑37 may modulate various inflammatory reactions. The authors previously revealed that LL‑37 improves the survival of a murine cecal ligation and puncture (CLP)...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.7267
更新日期:2017-10-01 00:00:00
abstract::Family with sequence similarity 172, member A (FAM172A), was cloned from human aortic tissues and confirmed in our previous study in 2009, however, its functions remain to be fully elucidated. In our previous studies, the protein expression of FAM172A in human aortic smooth muscle cells was found to be upregulated by ...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2015.4548
更新日期:2016-01-01 00:00:00
abstract::Pseudomonas aeruginosa continues to be a predominant cause of infections with high intrinsic resistance to antibiotics, resulting in treatment failure. P. aeruginosa is the leading cause of respiratory infections among cystic fibrosis (CF) patients. Resistance to carbapenem antibiotics among P. aeruginosa has been rep...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2014.2685
更新日期:2015-01-01 00:00:00
abstract::Endothelial cell injury caused by reactive oxygen species (ROS) plays a critical role in the pathogenesis of atherosclerosis. Therefore, phytochemicals or antioxidants that inhibit the production of ROS have clinical value for the treatment of atherosclerosis. Rhein is one of the most important active components of rh...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2012.793
更新日期:2012-05-01 00:00:00
abstract::The generation of β‑amyloid protein (Aβ) is considered a key step in the pathogenesis of Alzheimer's disease (AD) and the regulation of its production is an important therapeutic strategy. It was hypothesized in the present study that Nogo‑A may be involved in AD and may regulate the generation of Aβ. Nogo‑A is known ...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2021.11827
更新日期:2021-03-01 00:00:00
abstract::PTEN acts as a phosphatidylinositol phosphatase with a possible role in the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. Mutations in PTEN are frequent and their presence is associated with poor prognosis in breast cancer, which is the most common type of non-cutaneous malignancy in females. Delivery of the tumor...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2015.3509
更新日期:2015-07-01 00:00:00
abstract::In order to investigate the pathogenic targets and associated biological process of Alzheimer's disease in the present study, mRNA expression profiles (GSE28146) and microRNA (miRNA) expression profiles (GSE16759) were downloaded from the Gene Expression Omnibus database. In GSE28146, eight control samples, and Alzhei...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2016.5828
更新日期:2016-11-01 00:00:00
abstract::The present study aimed to reveal the potential genes associated with the pathogenesis of intervertebral disc degeneration (IDD) by analyzing microarray data using bioinformatics. Gene expression profiles of two regions of the intervertebral disc were compared between patients with IDD and controls. GSE70362 containin...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.7741
更新日期:2017-12-01 00:00:00
abstract::Despite advances in the treatment of T‑cell acute lymphoblastic leukemia (T‑ALL), the outcome of T‑ALL treatment remains unsatisfactory, therefore, more effective treatment is urgently required. The present study examined the cytotoxicities of bortezomib in combination with daunorubicin against human Jurkat and Molt‑4...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.6554
更新日期:2017-07-01 00:00:00
abstract::Triptolide is known to exert anti-inflammatory and immunomodulatory activities; however, its impact on intestinal fibrosis has not been previously examined. Based on our previous studies of the suppressive activity of triptolide on human colonic subepithelial myofibroblasts and the therapeutic efficacy of triptolide i...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2015.3582
更新日期:2015-08-01 00:00:00
abstract::Prostate cancer (PCa) poses a high risk to older men and it is the second most common type of male malignant tumor in western developed countries. Additionally, there is a lack of effective therapies for PCa at advanced stages. Novel treatment strategies such as adenovirus‑mediated gene therapy and virotherapy involve...
journal_title:Molecular medicine reports
pub_type: 杂志文章,评审
doi:10.3892/mmr.2017.7487
更新日期:2017-11-01 00:00:00
abstract::The mechanisms underlying myricetin-induced cancer cell apoptosis remain to be elucidated. Certain previous studies have shown that myricetin induces apoptosis through the mitochondrial pathway. Apoptosis, however, can also be induced by other classical pathways, including endoplasmic reticulum (ER) stress and DNA dou...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2016.4763
更新日期:2016-03-01 00:00:00
abstract::Y‑box binding protein‑1 (YB‑1) has been identified as an oncoprotein in various malignancies. The aim of this study was to investigate the biological role of YB‑1 and its association with epithelial‑to‑mesenchymal transition (EMT) in colorectal cancer (CRC). The expression of YB‑1 and three EMT‑related proteins (E‑cad...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2014.2545
更新日期:2014-11-01 00:00:00
abstract::Lung cancer is a leading cause of cancer-associated mortality worldwide. The cisplatin (DDP)‑based chemotherapy remains the foundation of treatment for the majority of patients affected by advanced non‑small cell lung cancer (NSCLC). However, DDP‑resistance limits the clinical utility of this drug in patients with adv...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.8301
更新日期:2018-03-01 00:00:00
abstract::Cnidium monnieri (L.) Cusson is a frequently used traditional Chinese medicine that treats gynecological diseases and carbuncles. However, the mechanism of action of C. monnieri remains to be fully elucidated. The present study examined the cell cycle arrest and apoptotic effects resulting from ethanol extract of C. m...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.8183
更新日期:2018-02-01 00:00:00
abstract::It has previously been demonstrated that phosphatidylinositol-3-kinase (PI3K)/Akt and cleaved caspase-3 serve critical roles in the apoptosis of cardiac myocytes following ischemia/reperfusion injury. Epigallocatechin-3-gallate (EGCG), the predominant catechin component of green tea, has been reported to have potentia...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2015.3603
更新日期:2015-08-01 00:00:00
abstract::Current studies have highlighted long non‑coding RNAs (lncRNAs) as critical regulators in various cancers, including colorectal cancer (CRC). By utilizing publicly available data from The Cancer Genome Atlas dataset, MLK7 antisense RNA 1 (MLK7‑AS1) was identified as a novel lncRNA that correlated with CRC progression....
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2018.9702
更新日期:2019-02-01 00:00:00
abstract::Sulforaphane (SFN) is a naturally occurring chemopreventive agent, which effectively inhibits proliferation of HepG2 human hepatocellular carcinoma cells via mitochondria‑mediated apoptosis. Endoplasmic reticulum stress is considered the most important cause of cell apoptosis; therefore, the present study aimed to det...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2016.6016
更新日期:2017-01-01 00:00:00
abstract::The purpose of the present study was to examine the effects of myricetin on reducing cerebral ischemia injury in a rat model. A rat model of permanent middle cerebral artery occlusion (pMCAO) was used in the present study. Rats were randomized into the following five groups: Sham, model, low‑myricetin (1 mg/kg), mediu...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.8212
更新日期:2018-02-01 00:00:00
abstract::The present study aimed to determine the intracellular localization of Cpn0425 in Chlamydophila pneumoniae-infected cells. The recombinant plasmid pGEX-6p/Cpn0425 was transformed into E.coli Bl21 cells to express the fusion protein. Following purification with glutathione S-transfer...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2012.1083
更新日期:2012-12-01 00:00:00
abstract::The splicing factor is important in cancer development, modulation numerous tumor suppressors and oncogenes, and regulation of multiple signaling pathways. Splicing factor 2/alternative splicing factor (SF2/ASF) is a proto‑oncogene, which has been implicated in the development of hepatocellular carcinoma. However, the...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2015.3851
更新日期:2015-09-01 00:00:00
abstract::Embryonic stem (ES) cells are pluripotent stem cells derived from a developmental stage of pre‑implanted embryos. The present study investigated the effect of female sex steroid hormones on the characteristics of human ES cells by using a feeder‑free culture protocol. In a feeder‑free condition without sex hormones, h...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.6672
更新日期:2017-07-01 00:00:00
abstract::Subsequent to the publication of the above paper, the authors have realized that there were errors in Fig. 1 on page 902; essentially, the experimental data described as being 'Preterm' and 'Infected preterm' should have been labelled as 'Full‑term without labor' and 'Preterm', respectively. Note that these errors in ...
journal_title:Molecular medicine reports
pub_type: 杂志文章,已发布勘误
doi:10.3892/mmr.2018.8572
更新日期:2018-04-01 00:00:00
abstract::MicroRNAs (miRNAs) are important regulators of a variety of biological processes and their dysregulation is closely related to cancer formation and progression. Therefore, examination of aberrantly expressed miRNAs in oral squamous cell carcinoma (OSCC) may provide important clues for the diagnosis and treatment of pa...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2018.9292
更新日期:2018-09-01 00:00:00
abstract::Curcumin is characterized by anti‑inflammatory, anti‑oxidative, antiviral, antifibrotic, anticoagulation and glucose regulatory functions. However, whether it is protective in diabetes mellitus‑associated cerebral infarction remains to be fully elucidated. In the present study, it was demonstrated for the first time, ...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.8085
更新日期:2018-01-01 00:00:00
abstract::Trefoil factor 3 (TFF3) serves an important role in intestinal mucosal damage and healing, and contributes to the pathogenesis and treatment of inflammatory bowel disease (IBD). The aim of the present study was to determine the association between TFF3 and microRNA‑7‑5p (miR‑7‑5p) in IBD. Tissue immunohistochemistry w...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.6730
更新日期:2017-08-01 00:00:00
abstract::Benign thyroid nodules are among the most common endocrine disorders. Recent advances in diagnostic imaging and pathology have significantly contributed to better risk stratification of thyroid nodules. However, current treatment options, beyond surgical approaches are limited. The following placebo-controlled study p...
journal_title:Molecular medicine reports
pub_type: 临床试验,杂志文章
doi:10.3892/mmr.2019.10453
更新日期:2019-09-01 00:00:00
abstract::Oxyresveratrol (ORES) is a natural phenolic compound with multiple biological functions including antioxidation, anti‑inflammation and neuroprotection; however, the inhibitory effect of ORES on osteosarcoma remains largely unknown. The present study aimed to determine the effects of ORES on osteosarcoma cell Saos‑2. C...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2020.11591
更新日期:2020-12-01 00:00:00
abstract::The present study aimed to identify any association between bone morphogenetic protein‑7 (BMP‑7) and the expression of the transcriptional co‑repressor Ski‑related novel protein N (SnoN), in addition to alterations in tubulointerstitial fibrosis, during the development and progression of diabetic nephropathy (DN). Str...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.7025
更新日期:2017-09-01 00:00:00