International Journal of Molecular Medicine

Peng, Xiafeng; Wang, Shixin; Chen, Hongwu; Chen, Minglong

doi: N/Apmid: N/A

Ischemic heart disease (IHD) is a prevalent cardiovascular disease characterized by the formation, progression and rupture of atherosclerotic plaque. The Notch signaling pathway is a key mechanism facilitating intercellular coordination. An increasing number of studies have revealed the significance of Notch signaling, particularly as regards Notch1. Of note, the existence of aberrant Notch1 signaling in IHD is universal, suggesting clinical significance. Thus, the present review summarizes the implications of Notch1 signaling in endothelial cells, vascular smooth muscle cells and macrophages in association with the development of IHD. The present review also examined the effects of Notch1 signaling on various remodeling stages of IHD consisting of reendothelialization, neovascularization, and myocardial fibrosis. Moreover, the participation of Notch1 signaling in conventional reperfusion treatments and cardiac regeneration therapies is discussed. On the whole, the present review aims to outline Notch1 signaling as a novel target which may be used to enhance the treatment efficacy for patients with IHD.

Vazgiourakis, Vassilios; Zervou, Maria; Papageorgiou, Louis; Chaniotis, Dimitrios; Spandidos, Demetrios; Vlachakis, Dimitrios; Eliopoulos, Elias; Goulielmos, George

doi: N/Apmid: N/A

Cardiovascular disease (CVD) comprises a broad spectrum of pathological conditions that affect the heart or blood vessels, including sequelae that arise from damaged vasculature in other organs of the body, such as the brain, kidneys or eyes. Atherosclerosis is a chronic inflammatory disease of the arterial intima and is the primary cause of coronary artery disease, peripheral vascular disease, heart attack, stroke and renal pathology. It represents a leading cause of mortality worldwide and the loss of human productivity that is marked by an altered immune response. Endometriosis is a heritable, heterogeneous, common gynecological condition influenced by multiple genetic, epigenetic and environmental factors, affecting up to 10% of the female population of childbearing age, causing pain and infertility; it is characterized by the ectopic growth of endometrial tissue outside the uterine cavity. Of note, epidemiological data obtained thus far have suggested a link between endometriosis and the risk of developing CVD. The similarities observed in specific molecular and cellular pathways of endometriosis and CVD may be partially explained by a shared genetic background. The present review presents and discusses the shared genetic factors which have been reported to be associated with the development of both disorders.

Wang, Yunshan; Liu, Xiaoyan; Zheng, Hui; Wang, Qin; An, Li; Wei, Guangwei

doi: N/Apmid: N/A

Subsequently to the publication of the above article, and a Corrigendum that was published with the intention of rectifying the issue of overlapping data panels showing cell migration and invasion assay data in Fig. 8 (DOI: 10.3892/mmr.2018.9415; published online on September 24, 2017), it was drawn to the Editors' attention by a concerned reader that certain of the data shown for the epithelial‑mesenchymal transition experiments in Fig. 2B, western blotting data in Fig. 6 and scratch‑wound assay data shown in Fig. 7A were strikingly similar to data appearing in different form in other articles by different authors at different research institutes, which had already been published elsewhere prior to this paper's submission to International Journal of Molecular Medicine. In addition, several other instances of overlapping data panels were identified in Fig. 8. Owing to the fact that a substantial number of contentious data included in this paper had already been published elsewhere prior to its submission to International Journal of Molecular Medicine, 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. [International Journal of Molecular Medicine 40: 1114‑1124, 2017; DOI: 10.3892/ijmm.2017.3118]

Zheng, Yaguo; Ma, Hong; Yan, Yufeng; Ye, Peng; Yu, Wande; Lin, Song; Chen, Shao-Liang

doi: N/Apmid: N/A

Filamin A (FLNA) is a high molecular weight cytoskeleton protein important for cell locomotion. A relationship between FLNA mutations and pulmonary arterial hypertension (PAH) has previously been reported; however, the detailed mechanism remains unclear. The present study aimed to explore the role of FLNA in vascular smooth muscle cells during the development of PAH. Smooth muscle cell (SMC)‑specific FLNA‑deficient mice were generated and the mice were then exposed to hypoxia for 28 days to build the mouse model of PAH. Human pulmonary arterial smooth muscle cells (PASMCs) were also cultured and transfected with FLNA small interfering RNA or overexpression plasmids to investigate the effects of FLNA on PASMC proliferation and migration. Notably, compared with control individuals, the expression levels of FLNA were increased in lung tissues from patients with PAH, and it was obviously expressed in the PASMCs of pulmonary arterioles. FLNA deficiency in SMCs attenuated hypoxia‑induced pulmonary hypertension and pulmonary vascular remodeling. In vitro studies suggested that absence of FLNA impaired PASMC proliferation and migration, and produced lower levels of phosphorylated (p)‑PAK‑1 and RAC1 activity. However, FLNA overexpression promoted PASMC proliferation and migration, and increased the expression levels of p‑PAK‑1 and RAC1 activity. The present study highlights the role of FLNA in pulmonary vascular remodeling; therefore, it could serve as a potential target for the treatment of PAH.

Fan, Cong; Wang, Yunshan; Liu, Ziming; Sun, Ying; Wang, Xiuwen; Wei, Guangwei; Wei, Junmin

doi: N/Apmid: N/A

Following the publication of this paper, it was drawn to the Editor's attention by concerned readers that several of the cellular images shown in Figs. 6A and 8A, the scratch‑wound assay images shown in Fig. 5A, the western blotting data in Figs. 2C and 7A and the Matrigel invasion assays in Fig. 5C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to International Journal of Molecular Medicine, 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. [International Journal of Molecular Medicine 36: 204‑214, 2015; DOI: 10.3892/ijmm.2015.2217]

Dong, Wei; Li, Wenyan; Zhang, Shaojin; Zeng, Xian; Qin, Qi; Fan, Huifeng; Tang, Zhonghui; Wu, Xia; Lu, Gen; Dong, Wei; Li, Wenyan; Zhang, Shaojin; Zeng, Xian; Qin, Qi; Fan, Huifeng; Tang, Zhonghui; Wu, Xia;

Zheng, Liming; Zhang, Li; Zheng, Yi; An, Jiaxing; Wen, Guorong; Jin, Hai; Tuo, Biguang

doi: N/Apmid: N/A

Besides causing severe acute respiratory syndrome (SARS), SARS‑coronavirus 2 (SARS‑CoV‑2) also harms the digestive system. Given the appearance of numerous cases of SARS‑CoV‑2, it has been demonstrated that SARS‑CoV‑2 is able to harm target organs such as the gastrointestinal tract, liver and pancreas, and either worsen the condition of patients with basic digestive illnesses or make their prognosis poor. According to several previously published studies, angiotensin‑converting enzyme II (ACE2) and transmembrane serine protease II (TMPRSS2) are expressed either singly or in combination in the digestive system and in other regions of the human body. In order to change the viral conformation, create a fusion hole and release viral RNA into the host cell for replication and transcription, SARS‑CoV‑2 is capable of binding to these two proteins through the spike protein on its surface. As a result, the body experiences an immune reaction and an inflammatory reaction, which may lead to nausea, diarrhea, abdominal pain and even gastrointestinal bleeding, elevated levels of liver enzymes, acute liver injury, pancreatitis and other serious lesions. In order to provide possible strategies for the clinical diagnosis and treatment of digestive system diseases during the COVID‑19 pandemic, the molecular structure of SARS‑CoV‑2 and the mechanism via which SARS‑CoV‑2 enters the human body through ACE2 and TMPRSS2 were discussed in the present review, and the clinical manifestations of SARS‑CoV‑2 infection in the digestive system were also summarized. Finally, the expression characteristics of ACE2 and TMPRSS2 in the main target organs of the digestive system were described.

Wang, Wei; Liu, Da; Yang, Liyun; Chen, Lixia; Miao, Mengdan; Liu, Yongsheng; Yin, Yajuan; Wei, Mei; Liu, Gang; An, Yonghui; Zheng, Mingqi

doi: N/Apmid: N/A

Compound Kushen injection (CKI) is a type of traditional Chinese medicine that has previously been studied for the treatment of various types of cancer. Previous studies have reported that CKI regulates cell apoptosis by downregulating the PI3K/Akt pathway. The present study aimed to determine whether CKI alleviates heart failure (HF) by attenuating cardiomyocyte apoptosis via the inhibition of the PI3K/Akt pathway. Angiotensin II (Ang II) was used to elicit HF, and osmotic minipumps with either Ang II (2 µg/kg/day) or phosphate‑buffered saline (PBS; 200 µl) were subcutaneously implanted into 6‑week‑old male C57BL/6 mice for 3 weeks. In addition, PBS or CKI (25 mg/kg/day) were subcutaneously infused once a day for 3 weeks. Echocardiography was used to examine hemodynamics. The myocardial injury biomarkers, cardiac troponin I and N‑terminal (NT)‑pro hormone B‑type natriuretic peptide, were assessed using enzyme‑linked immunosorbent assay. Transmission electron microscopy was used to determine the morphology of the myocardium. The rate of apoptosis was detected using TUNEL staining and flow cytometry (FCM), and the expression levels of apoptosis‑related proteins were measured using western blot (WB) analysis. Moreover, H9C2 cells were treated with CKI (2 mg/ml) or LY294002 (an inhibitor of the PI3K/Akt pathway; 25 µmol/l) in combination with Ang II (1 µmol/l) for 48 h. Cell Counting Kit‑8 assay, FCM and WB analysis were performed in the H9C2 cells to examine cell viability, cell cycle distribution and representative signaling proteins. It was found that CKI promoted healthy cardiac function, reduced myocardial structural damage and reduced the rate of cardiomyocyte apoptosis. CKI markedly attenuated the expression of apoptosis‑related proteins in the PI3K/Akt pathway. The results of the in vitro experiments indicated that CKI promoted cardiomyocyte proliferation and inhibited apoptosis, similar to LY294002. On the whole, the present study demonstrates that CKI reduces cardiomyocyte apoptosis, promotes healthy cardiac function and attenuates Ang II‑mediated HF. These ameliorative effects may be associated with the inhibition of the PI3K/Akt pathway.

Zhang, Jian-Zheng; Liu, Zhi; Liu, Jia; Ren, Ji-Xin; Sun, Tian-Sheng

doi: N/Apmid: N/A

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that several of the western blotting images shown in Fig. 4 on p. 822 were strikingly similar to data which had appeared in Fig. 5A of the following paper: Fan J, Frey RS and Malik AB: TLR4 signaling induces TLR2 expression in endothelial cells via neutrophil NADPH oxidase. J Clin Invest 112: 1235‑1243, 2003. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to International Journal of Molecular Medicine, 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. [International Journal of Molecular Medicine 33: 817‑824, 2014; DOI: 10.3892/ijmm.2014.1650]

Wang, Ying; Sun, Zhen; Zang, Guangyao; Zhang, Lili; Wang, Zhongqun

doi: N/Apmid: N/A

Diabetes mellitus (DM) is a metabolic disorder, which if not managed properly, can lead to serious health problems over time and impose significant financial burden on the patient, their family and society as a whole. The study of this disease and the underlying biological mechanism is gaining momentum. Multiple pieces of conclusive evidence show that ceramides are involved in the occurrence and development of diabetes. The present review focuses on the function of ceramides, a type of sphingolipid signaling molecule, to provide a brief description of ceramides and their metabolism, discuss the significant roles of ceramides in the healthy skin barrier, and speculate on the potential involvement of ceramides in the pathogenesis and development of diabetic foot ulcers (DFUs). Understanding these aspects of this disease more thoroughly is crucial to establish how ceramides contribute to the etiology of diabetic foot infections and identify possible therapeutic targets for the treatment of DFUs.