oa Editorial (A Significant Step Towards New Altitude)

In marking its 11th anniversary, Current Molecular Medicine is undergoing significant change in its contents. Starting from this issue, CMM is going to publish research articles with exciting and important new discoveries. In the present issue, seven articles dealing with mechanisms of various human diseases are published. The first article was contributed by Tang et al., authors of previous articles published in PNAS, etc., who illustrated an important development in the treatment of inflammatory diseases. Abnormal and prolonged inflammatory reaction is related to a variety of disorders such as immune system disorders, atherosclerosis, arthritis, heart disease and cancer. Previous studies have revealed the existence of a link between inflammatory diseases and elevated levels of Tumor Necrosis Factor alpha (TNF-α). Therefore, modulation of TNF-α expression is important in the regulation of inflammatory disorders. In the present study, the authors demonstrated that a transcription factor named LPS-induced TNF factor (LITAF) significantly induces TNF-α production. Furthermore, they found that p53 and its synthetic peptide 162-motif specifically downregulate LITAF/TNF-α gene expression in human cells in vitro. The 162-motif, when delivered into cells and organs, reduces serum TNF-α level in mice and prevents TNF-α-induced lung lesions and endotoxic shock. These results highlight the regulation of LITAF/TNF-α by p53 and its short peptide 162-motif and pave the way for pharmacotherapeutic approaches in the treatment of inflammatory diseases. The second article was contributed by Rull et al., authors of previous articles published in J. Proteome Res., etc., who provided strong evidence for the plausible role of the combined assessment of defense against oxidative stress and inflammation in the evaluation of peripheral arterial diseases such as atherosclerosis. Generalized atherosclerosis is likely in symptomatic peripheral arterial diseases (PAD), affecting a large portion of arteries in the low extremities. To search for the potential indicator of disease state and/or susceptibility, the authors proposed a novel approach based on a putative role between paraoxonase-1 and monocyte chemoattractant protein- 1/chemokine ligand-2. These results help to establish clinical criteria for the diagnosis of symptomatic peripheral arterial diseases. The third article was contributed by Mitchell et al., authors of previous articles published in Oncogene, etc., who elegantly demonstrated that GEFT, a Rho family guanine nucleotide exchange factor can regulate differentiation of lens epithelial cells. This regulation occurs through a Rac1-dependent mechanism. Previously this group demonstrated that GEFT regulates differentiation of hippocampal neurons and neuro2a neuroblastoma cells. Here the authors provided the first evidence to show that GEFT regulates the localization of Rac1 to modulate expression of multiple genes of the crystallin families and thus controls differentiation of the ocular lens. These results shed new light to the functional mechanisms of GEFT in regulating cell differentiation. The 4th article was contributed by Wu group, authors of previous articles published in Proteomics, etc., who explored the possible molecular mechanism mediating viral infection-triggered congenital cardiovascular diseases during the perinatal period using microarray analysis. These authors found that 99 genes display differential expressions during viral infection of the ECV304 cells by Rubella virus, human Cytomegalovirus and Herpes Simplex virus. The present study suggested a possible common molecular mechanism how viral infection might result in congenital cardiovascular diseases. The 5th article was contributed by Xiao group, authors of previous articles published in Cancer Research, etc., who explored the role of adipocytes in regulating osteoblast differentiation during bone aging. Using direct and indirect culture modes, the authors revealed presence of the crosstalk between adipocytes and osteoblasts through secretory factors in the medium. After comparative analysis of gene expression in the conditioned osteoblasts and adipocytes, the authors suggested that the adipocytes derived from bone mesenchymal stem cells may regulate osteoblast differentiation in the aged bone through TGFβ mediated cranonical Wnt signaling pathway. The 6th article was contributed by Wu group, authors of previous articles published in Plos One, etc., who explored the role of docosahexaenoic acid (DHA) in sensitizing brain tumor cells to etoposide-induced apoptosis. These authors demonstrated that when combined, DHA and etopside markedly suppress expression of the genes involved in DNA damage repair, cell proliferation, survival, invasion, and angiogenesis and suggested that it may be beneficial for combined therapy on brain tumors with the anticancer drugs DHA and etoposide. These articles, out of questions, will contribute to important aspects of the novel mechanisms for various human diseases as well as important information for the development of new therapeutic strategies for these diseases.