NeoPep S: A New Generation of AIMP1-derived Peptide (AdP) Effects on Wound Healing In Vivo.

BACKGROUND/AIM: The skin plays an important role in protecting the body from mechanical damage, microbial infection, ultraviolet radiation, and extreme temperatures. Many products as well as ongoing studies have focused on skin injury and repair; however, unlimited challenges are still being faced. Furthermore, the drugs that are currently on the market are not adequate to meet the increasing medical needs. This study aimed to discover whether our new product can efficiently promote wound repair and skin restoration. MATERIALS AND METHODS: in this study, we applied a new AIMP1-derived peptide (AdP), NeoPep S, administered in two dose types (1 ppm and 3 ppm), and determined their effect on skin wound repair in rat models. Cell proliferation and inflammatory responses were assessed using immunofluorescence (IF) staining and ELISA assay. RESULTS: As expected, our results showed more rapid and satisfactory progress in wound closure upon treatment with NeoPep S 3 ppm than with NeoPep S 1 ppm. The 3 ppm peptide derived from AIMP1 protein, harmoniously interacted with the wound to promote re-epithelialization and collagen regeneration, as well as the down-regulation of several types of cytokines and chemokines, such as TNF-α, IL-6, IL-8, IL-lß, MCP-1, and F4/80. Moreover, it was demonstrated to promote fibroblast proliferation, migration, and differentiation by TGF-ßl and TGF-ß3 modulation, as well as nitrite and reactive oxygen species scavenging. CONCLUSION: The novel peptide NeoPep S 3 ppm showed high effectiveness and safety in wound healing.

FAM72, Glioblastoma Multiforme (GBM) and Beyond.

Neural stem cells (NSCs) offer great potential for regenerative medicine due to their excellent ability to differentiate into various specialized cell types of the brain. In the central nervous system (CNS), NSC renewal and differentiation are under strict control by the regulation of the pivotal SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2)-Family with sequence similarity 72 (FAM72) master gene (i.e., |-SRGAP2-FAM72-|) via a divergent gene transcription activation mechanism. If the gene transcription control unit (i.e., the intergenic region of the two sub-gene units, SRGAP2 and FAM72) gets out of control, NSCs may transform into cancer stem cells and generate brain tumor cells responsible for brain cancer such as glioblastoma multiforme (GBM). Here, we discuss the surveillance of this |-SRGAP2-FAM72-| master gene and its role in GBM, and also in light of FAM72 for diagnosing various types of cancers outside of the CNS.

A Novel Divergent Gene Transcription Paradigm-the Decisive, Brain-Specific, Neural |-Srgap2-Fam72a-| Master Gene Paradigm.

Brain development and repair largely depend on neural stem cells (NSCs). Here, we suggest that two genes, i.e., Srgap2 (SLIT-ROBO Rho GTPase-activating protein 2) and Fam72a (family with sequence similarity to 72, member A), constitute a single, NSC-specific, |-Srgap2-Fam72a-| master gene pair co-existing in reciprocal functional dependency. This gene pair has a dual, commonly used, intergenic region (IGR) promotor, which is a prerequisite in controlling human brain plasticity. We applied fluorescence cellular microscopy and fluorescence-activated cell sorting (FACS) to assess rat |-Srgap2-Fam72a-| master gene IGR promotor activity upon stimulation with two contrary growth factors: nerve growth factor (Ngf, a differentiation growth factor) and epidermal growth factor (Egf, a mitotic growth factor). We found that Ngf and Egf acted on the same IGR gene promotor element of the |-Srgap2-Fam72a-| master gene to mediate cell differentiation and proliferation, respectively. Ngf mediated Srgap2 expression and neuronal survival and differentiation while Egf activated Fam72a transcription and cell proliferation. Our data provide new insights into the specific regulation of the |-Srgap2-Fam72a-| master gene with its dual IGR promotor that controls two reverse-oriented functional-dependent genes located on opposite DNA strands. This structure represents a novel paradigm for controlling transcription of divergent genes in regulating NSC gene expression. This paradigm may allow for novel therapeutic approaches to restore or improve higher cognitive functions and cure cancers.

Brain plasticity, cognitive functions and neural stem cells: a pivotal role for the brain-specific neural master gene |-SRGAP2-FAM72-|.

Due to an aging society with an increased dementia-induced threat to higher cognitive functions, it has become imperative to understand the molecular and cellular events controlling the memory and learning processes in the brain. Here, we suggest that the novel master gene pair |-SRGAP2-FAM72-| (SLIT-ROBO Rho GTPase activating the protein 2, family with sequence similarity to 72) reveals a new dogma for the regulation of neural stem cell (NSC) gene expression and is a distinctive player in the control of human brain plasticity. Insight into the specific regulation of the brain-specific neural master gene |-SRGAP2-FAM72-| may essentially contribute to novel therapeutic approaches to restore or improve higher cognitive functions.

Cognitive Functions: Human vs. Animal - 4:1 Advantage |-FAM72-SRGAP2-|.

With the advent of computational genomics, an intensive search is underway for unique biomarkers for Homo sapiens that could be used to differentiate taxa within the Hominoidea, in particular to distinguish Homo from the apes (Pan, Gorilla, Pongo, and Hylobates) and species or subspecies within the genus Homo (H. sapiens, H. heidelbergensis, H. neanderthalensis, H. erectus, and the Denisovans). Here, we suggest that the |-FAM72-SRGAP2-| (family with sequence similarity 72/SLIT-ROBO Rho GTPase activating protein 2) gene pair is a unique molecular biomarker for the genus Homo that could also help to place Australopithecus at its most appropriate place within the phylogenetic tree and may explain the distinctive higher brain cognitive functions of humans.