oa Editorial

After a decade of successful journey, Current Molecular Medicine welcomes its prospective growth in a new decade. In marching into the second year of my editorship, great efforts are continuously devoted to publication of high quality research articles dealing with mechanisms and therapies of various human diseases. In this issue, a total of 9 research articles have been selected. Article one is by Das's group reporting KLF2-mediated transcriptional regulation of arthritis via modulation of monocyte differentiation and function. These authors have previously demonstrated that Kruppel-like factor 2 (KLF2) inhibits proinflammatory activation of monocytes. In the current study, they show that significantly greater numbers of inflammatory subset of CD11b'F4/80'Ly6C' monocytes were recruited to the inflammatory sites in KLF2 hemizygous mice compared to the wild type littermate controls. In parallel, inflammatory mediators, MCP-1, Cox-2 and PAI-1 were significantly up-regulated in bone marrow-derived monocytes isolated from KLF2 hemizygous mice, in comparison to wild-type controls. Furthermore, they found that monocytes isolated from KLF2 hemizygous mice contained more matured and differentiated cells towards osteoclastic lineage, potentially contributing to the severity of cartilage and bone damage in induced arthritic mice. The severity of arthritis was also associated with enhanced expression of HSP60, HSP90 and MMP13, but attenuated expression of pPTEN, p21, p38 and HSP25/27 in bone marrow cells of arthritic KLF2 hemizygous mice compared to wild type littermate controls. These data provide new insights and evidences of KLF2-mediated transcriptional regulation of arthritis. The generation of functional neural progenitor cells (NPCs) independent of donor brain tissue and embryonic tissues is of great therapeutic interest with regard to regenerative medicine and the possible treatment of neurodegenerative disorders. Traditionally, NPCs are derived through the differentiation of embryonic stem cells (ESCs) and Induced pluripotent stem cells (iPSCs). However, the induction of NPCs from ESCs and iPSCs is a complicated process that increases the risk of neoplasia and undesired cell types. This process can be circumvented through the direct conversion of somatic cells from one cell type to another by ectopic expression of specifically defined transcription factors. Using gene expression profiling and parental cells from E/Nestin:EGFP transgenic mice as a monitoring system, Zheng's group in article 2, tested nine factors with the potential to directly convert fibroblasts into NPCs. They found that five of these factors can directly convert adult dermal fibroblasts into NPC-like cells (iNPCs), and the resulting iNPCs possessed similar properties as primary NPCs including proliferation, self-renewal and differentiation. Significantly, iNPCs also exhibit chemotactic properties similar to those of primary NPCs. Their results provide an important alternative strategy to generate iNPCs for cell replacement therapy of neurodegenerative diseases. Intraneuronal accumulation of abnormal phosphorylated tau (p-tau) is a molecular pathology in many neurodegenerative tauopathies, including Alzheimer's disease (AD) and frontotemporal dementia with parkinsonism-linked to chromosome 17 (FTDP-17). However, the underlying mechanism remains unclear. In article 3, Shen's group showed an inverse relationship between endoplasmic reticulum membrane ubiquitin ligase (E3) Hrd1 expression and p-tau accumulation in the hippocampal neurons of AD, and proposed that Hrd1 may be a negative regulator of p-tau. This study provides important insight into the molecular mechanisms of human tauopathies. Cancer metastasis is the main cause of mortality. How metastatic cells arising from primary tumors and targeting to specific organs remain largely unknown. One of the cytokine receptors, cysteine x cysteine (CXC) chemokine receptor 4 (CXCR4), initially linked with leukocyte trafficking, is found overexpressed in various tumors and mediates homing of tumor cells to distant sites expressing its cognate ligand CXCL12. Thus, identification of CXCR4 inhibitors has great potential to abrogate tumor metastasis. In article 4, the study by Liu and Pang's group demonstrated that xanthohumol (XN), a prenylflavonoid derived from the female flowers of the hops plant (Humulus lupulus. L), suppressed CXCR4 expression in various cancer cell types in a concentration- and time-dependent manner. They demonstrated that XN abolished cell invasion induced by CXCL12 in both breast and colon cancer cells. Mechanistically, XN could block endogenous activation of nuclear factor kappa B, a key transcription factor regulating the expression of CXCR4 in cancer cells. Together, their results suggested that XN, as a novel inhibitor of CXCR4, could be a promising therapeutic agent contributed to cancer treatment.....