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Alzheimer's disease (AD) is the most common type of neurological disorder that results from brain cell death; however, not all brain regions are simultaneously affected to the same extent. Despite single biomarkers for AD having been determined on a genome‑wide scale, the differential co‑expression in gene pairs between regions and interactions with other types of cellular molecules, particularly non‑coding (nc)RNAs, are often overlooked in studies investigating the underlying mechanisms associated with AD. In the present study, based on 1,548 samples obtained from a cohort of 90 patients with AD spanning 19 brain regions, a gene‑pair based method was established for the classification of 19 brain regions into seven different groups, including marked disparate groupings of six single regions and a cluster of another 13 regions as revealed by principal component analysis (PCA). To further investigate the different underlying mechanisms associated with each group, five highly interconnected functional modules of the protein‑protein interaction network were demonstrated to characterize the seven region groups containing six single groups and 13 clustered regions based on 4,731 gene‑pairs. Genes in two of the functional modules exhibited a strong association with pathways associated with the nervous system, including cholinergic synapses, circadian entrainment and dopaminergic synapses. Notably, following integration of these two modules with a ncRNA‑mediated network, one module demonstrated a strong association with micro (mi)RNAs, which were revealed to interact with numerous long non‑coding (lnc)RNAs associated with AD, such as metastasis associated lung adenocarcinoma transcript 1 and taurine upregulated 1. This suggested that mRNAs and lncRNAs may represent competing endogenous RNAs for binding with miRNAs. Thus, these results indicated that the ncRNA‑mediated gene regulatory module detected by the established gene pair‑based method may further the understanding of underlying mechanisms associated with AD as well as aid the development of novel therapeutic strategies for the treatment of patients with AD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Psoriasis is a multifactorial disease and the mechanisms involved in its pathogenesis remain to be elucidated. FOS-like antigen 1 (Fra-1) is a proto-oncogene. It is a negative inhibitor of activator protein-1 activity and possesses transforming activity. The effect of and possible mechanisms underlying Fra-1 in psoriasis remain to be elucidated. In the present study, western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) techniques were used to identify differentially expressed Fra-1 in psoriatic and in normal control tissues. Compared with the control samples, the expression of normalized Fra-1 genes in psoriasis was 12.6 times higher. Western blot analysis was used to assess the protein levels of Fra-1. The results demonstrated that the protein expression of Fra-1 was high in tissues affected by psoriasis. This also corresponded with the results of RT-qPCR. Fra-1-stable expressing HaCaT/Fra-1 or control HaCaT/vector cell lines were then generated to elucidate the function of Fra-1 in the growth of HaCaT cells. The results demonstrated that Fra-1 promoted the growth of HaCaT cells in vitro by arresting the cell cycle and inhibiting cell apoptosis. These results suggested that Fra-1 may be important in psoriasis. [ABSTRACT FROM AUTHOR]