Molecular medicine reports最新文献

Chronic kidney disease (CKD)‑associated cardiac injury is a common complication in patients with CKD. Indole‑3 acetic acid (IAA) is a uremic toxin that injures the cardiovascular system. Saikosaponin A (SSA) protects against pressure overload‑induced cardiac fibrosis. However, the role and molecular mechanisms of IAA and SSA in CKD‑associated cardiac injury remain unclear. The present study investigated the effects of IAA and SSA on CKD‑associated cardiac injury in neonatal mouse cardiomyocytes and a mouse model of CKD. The expression of tripartite motif‑containing protein 16 (Trim16), receptor interacting protein kinase 2 (RIP2) and phosphorylated‑p38 were assessed using western blotting. The ubiquitination of RIP2 was measured by coimmunoprecipitation, and mouse cardiac structure and function were evaluated using hematoxylin and eosin staining and echocardiography. The results demonstrated that, SSA inhibited IAA‑induced cardiomyocyte hypertrophy, upregulated Trim16 expression, downregulated RIP2 expression and decreased p38 phosphorylation. Furthermore, Trim16 mediated SSA‑induced degradation of RIP2 by ubiquitination. In a mouse model of IAA‑induced CKD‑associated cardiac injury, SSA upregulated the protein expression levels of Trim16 and downregulated those of RIP2. Moreover, SSA alleviated heart hypertrophy and diastolic dysfunction in IAA‑treated mice. Taken together, these results suggest that SSA is a protective agent against IAA‑induced CKD‑associated cardiac injury and that Trim16‑mediated ubiquitination‑related degradation of RIP2 and p38 phosphorylation may contribute to the development of CKD‑associated cardiac injury.

Diabetic liver injury (DLI) can result in several diseases of the liver, including steatohepatitis, liver fibrosis, cirrhosis, and liver cancer. Low‑dose ionizing radiation (LDIR) has hormetic effects in normal/disease conditions. However, whether LDIR has a beneficial effect on DLI has not been assessed previously. MicroRNA (miR)‑155 and its target gene suppressor of cytokine signaling 1 (SOCS1) play critical roles in modulating hepatic proliferation, apoptosis, and immunity. However, whether a miR‑155‑SOCS1 axis is involved in high glucose (HG) induced hepatic damage remains to be determined. In the present study, mouse hepatocyte AML12 cells were treated with 30 mM glucose (HG), 75 mGy X‑ray (LDIR), or HG plus LDIR. The expression levels of miR‑155 and SOCS1 were determined by reverse transcription‑quantitative PCR and western blotting. Additionally, apoptosis was measured using flow cytometry. The release of inflammatory factors, including TNF‑α, IL‑1β, IL‑6, IL‑10, and IFN‑γ, after HG and/or LDIR treatment was detected by ELISA. The results showed that HG may induce hepatic apoptosis by upregulating the levels of miR‑155 and downregulating the levels of SOCS1. HG also stimulated the secretion of TNF‑α, IL‑1β, IL‑6, and IL‑10. However, LDIR blocked the HG‑induced activation of a miR‑155‑SOCS1 axis and suppressed the release of inflammatory factors. These results indicated that a miR‑155‑SOCS1 axis plays a role in HG‑induced liver injury, and LDIR may exert a hepatoprotective effect by regulating the miR‑155‑SOCS1 axis.

Erectile dysfunction (ED) is a prevalent disease that causes sexual dysfunction in males. Inflammation‑induced endothelial dysfunction is a fundamental pathophysiological symptom of ED, which is impacted by cell death. Pyroptosis is a type of programmed cell death mediated by the inflammasome that was discovered in inflammatory disorders. The activation of nucleotide‑binding oligomerization domain‑like receptors, particularly downstream inflammatory factors, such as IL‑1β and IL‑18, is indicative of caspase‑dependent pyroptosis. Although the underlying mechanisms of pyroptosis have been investigated in several disorders, the role of pyroptosis in ED remains to be fully elucidated. At present, studies on pyroptosis have focused on improving the understanding of ED pathogenesis and promoting the development of novel therapeutic options. The present review article aimed to discuss the literature surrounding the mechanisms underlying pyroptosis, and summarize the role of pyroptosis in the development and progression of inflammation‑mediated ED.

Tripartite motif‑containing 14 (TRIM14) is an E3 ubiquitin ligase that primarily participates in the natural immune response and in tumour development via ubiquitination. However, the role of TRIM14 in cardiac hypertrophy is not currently clear. The present study examined the role of TRIM14 in cardiac hypertrophy and its potential molecular mechanism. TRIM14 was overexpressed in neonatal rat cardiomyocytes using adenovirus and cardiomyocyte hypertrophy was induced using phenylephrine (PE). Cardiomyocyte hypertrophy was assessed by measuring cardiomyocyte surface area and markers of hypertrophy. In addition, TRIM14‑transgenic (TRIM14‑TG) mice were created and cardiac hypertrophy was induced using transverse aortic constriction (TAC). Cardiac function, heart weight‑to‑body weight ratio (HW/BW), cardiomyocyte cross‑sectional area, cardiac fibrosis and hypertrophic markers were further examined. The expression of AKT signalling pathway‑related proteins was detected. TRIM14 overexpression in cardiomyocytes promoted PE‑induced increases in cardiomyocyte surface area and hypertrophic markers. TRIM14‑TG mice developed worse cardiac function, greater HW/BW, cross‑sectional area and cardiac fibrosis, and higher levels of hypertrophic markers in response to TAC. TRIM14 overexpression also increased the phosphorylation levels of AKT, GSK‑3β, mTOR and p70S6K in vivo and in vitro. To the best our knowledge, the present study was the first to reveal that overexpression of TRIM14 aggravated cardiac hypertrophy in vivo and in vitro, which may be related to activation of the AKT signalling pathway.

Cardiovascular disease (CVD) is a common chronic clinical condition and is the main cause of death in humans worldwide. Understanding the genetic and molecular mechanisms involved in the development of CVD is essential to develop effective prevention strategies and therapeutic measures. An increasing number of CVD‑related genetic studies have been conducted, including those on the potential roles of microRNAs (miRs). These studies have demonstrated that miR‑378 is involved in the pathological processes of CVD, including those of myocardial infarction, heart failure and coronary heart disease. Despite the potential importance of miR‑378 CVD, a comprehensive summary of the related literature is lacking. Thus, the present review aimed to summarize the findings of previous studies on the roles and mechanisms of miR‑378 in a variety of CVDs and provide an up‑to date basis for further r research targeting the prevention and treatment of CVDs.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Hoechst staining data shown in Fig. 4E were strikingly similar to data appearing in different form in another article by different authors at a different research institute; moreover, an unexpectedly high degree of similarity was noted with the data featured in a couple of different data panels showing the results of apoptosis experiments in Fig. 4D. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 2113‑2120, 2018; DOI: 10.3892/mmr.2017.8145].

Lung injury is one of the common extra‑articular lesions in rheumatoid arthritis (RA). Due to its insidious onset and no obvious clinical symptoms, it can be easily dismissed in the early stage of diagnosis, which is one of the reasons that leads to a decline of the quality of life and subsequent death of patients with RA. However, its pathogenesis is still unclear and there is a lack of effective therapeutic targets. In the present study, tandem mass tag‑labeled proteomics was used to research the lung tissue proteins in RA model (adjuvant arthritis, AA) rats that had secondary lung injury. The aim of the present study was to identify the differentially expressed proteins related to RA‑lung injury, determine their potential role in the pathogenesis of RA‑lung injury and provide potential targets for clinical treatment. Lung tissue samples were collected from AA‑lung injury and normal rats. The differentially expressed proteins (DEPs) were identified by tandem mass spectrometry. Bioinformatic analysis was used to assess the biological processes and signaling pathways associated with these DEPs. A total of 310 DEPs were found, of which 244 were upregulated and 66 were downregulated. KEGG anlysis showed that 'fatty acid degradation', 'fatty acid metabolism', 'fatty acid elongation', 'complement and coagulation cascades', 'peroxisome proliferator‑activated receptor signaling pathway' and 'hypoxia‑inducible factor signaling pathway' were significantly upregulated in the lung tissues of AA‑lung injury. Immunofluorescence staining confirmed the increased expression of clusterin, serine protease inhibitors and complement 1qc in lung tissue of rats with AA lung injury. In the present study, the results revealed the significance of certain DEPs (for example, C9, C1qc and Clu) in the occurrence and development of RA‑lung injury and provided support through experiments to identify potential biomarkers for the early diagnosis and prevention of RA‑lung injury.

Significant advancements have been achieved in the area of molecular targeted therapy for lung adenocarcinoma (LUAD). However, the complex molecular patterns and high heterogeneity of LUAD confine the efficacy of these therapies to a specific subset of patients; therefore, it is necessary to explore novel targets for LUAD treatment. The expression levels of anillin (ANLN) in LUAD were analyzed using the Gene Expression Profiling Interactive Analysis database. Furthermore, the association between ANLN gene expression and patient survival outcomes was evaluated using the Kaplan‑Meier Plotter. Subsequently, small interfering RNA (siRNA) transfection was performed to knock down ANLN in A549 and H1299 cell lines, after which, TUNEL, colony formation and Transwell assays were conducted to assess cell death, colony formation and migration, respectively. Additionally, western blot analysis was performed to analyze the expression levels of caspase‑1, interleukin (IL)‑18 (IL‑18), IL‑1β, NLR family pyrin domain‑containing 3 (NLRP3), apoptosis‑associated speck‑like protein containing a CARD domain (ASC) and cleaved gasdermin D (GSDMD) following ANLN knockdown. The results revealed that ANLN mRNA expression was significantly increased in LUAD tissues compared with adjacent normal samples. Furthermore, the expression levels of ANLN displayed an increasing trend with advancing clinical stage. Furthermore, patients with high ANLN expression levels exhibited poor overall survival rates compared with those with low ANLN expression levels. Subsequent ANLN knockdown experiments indicated elevated cell death rate, and reduced colony formation and migration in both A549 and H1299 cells. Additionally, ANLN knockdown resulted in increased protein expression levels of pyroptosis‑associated molecules, including caspase‑1, NLRP3, cleaved‑GSDMD, IL‑1β, ASC and IL‑18 in both A549 and H1299 cells. In conclusion, ANLN represents an important gene and a promising therapeutic target for LUAD. Its potential as a therapeutic target makes it an interesting candidate for further exploration in the development of novel treatment strategies for LUAD.

The Na/K‑ATPase/Src complex is reportedly able to affect reactive oxygen species (ROS) amplification. However, it has remained elusive whether NADPH oxidases (NOXs) are involved in this oxidant amplification loop in renal fibrosis. To test this hypothesis, interactions between oxidative features and Na/K‑ATPase/Src activation were examined in a mouse model of unilateral urethral obstruction (UUO)‑induced experimental renal fibrosis. Both 1‑tert‑butyl‑3‑(4‑chlorophenyl)‑1H‑pyrazolo[3,4‑d]pyrimidin‑4‑amine (PP2) and apocynin significantly attenuated the development of UUO‑induced renal fibrosis. Apocynin administration attenuated the expression of NOXs and oxidative markers (e.g., nuclear factor erythroid 2‑related factor 2, heme oxygenase‑1,4‑hydroxynonenal and 3‑nitrotyrosine); it also partially restored Na/K‑ATPase expression and inhibited the activation of the Src/ERK cascade. Furthermore, administration of PP2 after UUO induction partially reversed the upregulation of NOX2, NOX4 and oxidative markers, while inhibiting the activation of the Src/ERK cascade. Complementary experiments in LLC‑PK1 cells corroborated the in vivo observations. Inhibition of NOX2 by RNA interference attenuated ouabain‑induced oxidative stress, ERK activation and E‑cadherin downregulation. Thus, it is indicated that NOXs are major contributors to ROS production in the Na/K‑ATPase/Src/ROS oxidative amplification loop, which is involved in renal fibrosis. The disruption of this vicious feed‑forward loop between NOXs/ROS and redox‑regulated Na/K‑ATPase/Src may have therapeutic applicability for renal fibrosis disorders.

Adipose tissue‑derived mesenchymal stem cells (ADMSCs) differentiate into cardiomyocytes and may be an ideal cell source for myocardial regenerative medicine. Ghrelin is a gastric‑secreted peptide hormone involved in the multilineage differentiation of MSCs. To the best of our knowledge, however, the role and potential downstream regulatory mechanism of ghrelin in cardiomyocyte differentiation of ADMSCs is still unknown. The mRNA and protein levels were measured by reverse transcription‑quantitative PCR and western blotting. Immunofluorescence staining was used to show the expression and cellular localization of cardiomyocyte markers and β‑catenin. RNA sequencing was used to explore the differentially expressed genes (DEGs) that regulated by ghrelin. The present study found that ghrelin promoted cardiomyocyte differentiation of ADMSCs in a concentration‑dependent manner, as shown by increased levels of cardiomyocyte markers GATA binding protein 4, α‑myosin heavy chain (α‑MHC), ISL LIM homeobox 1, NK2 homeobox 5 and troponin T2, cardiac type. Ghrelin increased β‑catenin accumulation in nucleus and decreased the protein expression of secreted frizzled‑related protein 4 (SFRP4), an inhibitor of Wnt signaling. RNA sequencing was used to determine the DEGs regulated by ghrelin. Functional enrichment showed that DEGs were more enriched in cardiomyocyte differentiation‑associated terms and Wnt pathways. Dead‑box helicase 17 (DDX17), an upregulated DEG, showed enhanced mRNA and protein expression levels following ghrelin addition. Overexpression of DDX17 promoted protein expression of cardiac‑specific markers and β‑catenin and enhanced the fluorescence intensity of α‑MHC and β‑catenin. DDX17 upregulation inhibited protein expression of SFRP4. Rescue assay confirmed that the addition of SFRP4 partially reversed ghrelin‑enhanced protein levels of cardiac‑specific markers and the fluorescence intensity of α‑MHC. In conclusion, ghrelin promoted cardiomyocyte differentiation of ADMSCs by DDX17‑mediated regulation of the SFRP4/Wnt/β‑catenin axis.