Identification of CD109 in the extracellular vesicles derived from ovarian cancer stem-like cells.

Ovarian cancer is the deadliest gynecological cancer because it has few early symptoms and metastasizes to the surrounding organs at advanced stages. Cancer stem cells (CSCs), a subpopulation of cells with acquired drug resistance, contribute to the recurrence and poor prognosis of ovarian cancer. CD109, a cell surface glycoprotein, has been reported to be a marker of CSCs; however, it remains unclear whether CD109 is secreted by CSCs.

Synergistic combination of RAD51-SCR7 improves CRISPR-Cas9 genome editing efficiency by preventing R-loop accumulation.

CRISPR-Cas9 has emerged as a powerful tool for genome editing. However, Cas9 genome editing faces challenges, including low efficiency and off-target effects. Here, we report that combined treatment with RAD51, a key factor in homologous recombination, and SCR7, a DNA ligase IV small-molecule inhibitor, enhances CRISPR-Cas9-mediated genome-editing efficiency in human embryonic kidney 293T and human induced pluripotent stem cells, as confirmed by cyro- transmission electron microscopy and functional analyses.

Multi-proteomic analyses of 5xFAD mice reveal new molecular signatures of early-stage Alzheimer's disease.

An early diagnosis of Alzheimer's disease is crucial as treatment efficacy is limited to the early stages. However, the current diagnostic methods are limited to mid or later stages of disease development owing to the limitations of clinical examinations and amyloid plaque imaging. Therefore, this study aimed to identify molecular signatures including blood plasma extracellular vesicle biomarker proteins associated with Alzheimer's disease to aid early-stage diagnosis.

Comparative Phosphoproteomics of Neuro-2a Cells under Insulin Resistance Reveals New Molecular Signatures of Alzheimer's Disease.

Insulin in the brain is a well-known critical factor in neuro-development and regulation of adult neurogenesis in the hippocampus. The abnormality of brain insulin signaling is associated with the aging process and altered brain plasticity, and could promote neurodegeneration in the late stage of Alzheimer's disease (AD). The precise molecular mechanism of the relationship between insulin resistance and AD remains unclear.

Stimulation of the Migration and Expansion of Adult Mouse Neural Stem Cells by the FPR2-Specific Peptide WKYMVm.

Neural stem cells (NSCs) are multipotent cells capable of self-renewal and differentiation into different nervous system cells. Mouse NSCs (mNSCs) are useful tools for studying neurogenesis and the therapeutic applications of neurodegenerative diseases in mammals. Formyl peptide receptor 2 (FPR2), expressed in the central nervous system and brain, is involved in the migration and differentiation of murine embryonic-derived NSCs.

Application of Proteomics in Cancer: Recent Trends and Approaches for Biomarkers Discovery.

Proteomics has become an important field in molecular sciences, as it provides valuable information on the identity, expression levels, and modification of proteins. For example, cancer proteomics unraveled key information in mechanistic studies on tumor growth and metastasis, which has contributed to the identification of clinically applicable biomarkers as well as therapeutic targets. Several cancer proteome databases have been established and are being shared worldwide.

Emodin induces collagen type I synthesis in Hs27 human dermal fibroblasts.

Fibrillar collagen and elastic fibers are the main components of the dermal extracellular matrix (ECM), which confers mechanical strength and resilience to the skin. In particular, type I collagen produced by fibroblasts is the most abundant collagen that determines the general strength of the ECM, thereby contributing to the prevesntion of the skin-aging process. Although the natural anthraquinone derivative emodin (1,3,8-trihydroxy-6-methylanthraquinone) exerts numerous beneficial effects, including antiviral, anticancer, anti-inflammatory and wound-healing effects in diverse cells, the effect of emodin on collagen expression or skin aging is not fully understood.

Coadministration of endothelial and smooth muscle cells derived from human induced pluripotent stem cells as a therapy for critical limb ischemia.

Critical limb ischemia is a condition in which tissue necrosis occurs due to arterial occlusion, resulting in limb amputation in severe cases. Both endothelial cells (ECs) and vascular smooth muscle cells (SMCs) are needed for the regeneration of peripheral arteries in ischemic tissues. However, it is difficult to isolate and cultivate primary EC and SMC from patients for therapeutic angiogenesis.

Mesenchymal Stem Cell-Mediated Therapy of Peripheral Artery Disease Is Stimulated by a Lamin A-Progerin Binding Inhibitor.

Objective: Human adipose tissue-derived mesenchymal stem cells (ASCs) have been reported to promote angiogenesis and tissue repair. However, poor survival and engraftment efficiency of transplanted ASCs are the major bottlenecks for therapeutic application. The present study aims to improve the therapeutic efficacy of ASCs for peripheral artery diseases.

- and -Induced Vascular Progenitor Cells Enhance Functional Recovery in Ischemic Vascular Disease Model-Brief Report.

Objective: Vascular progenitor cells (VPCs), which are able to differentiate into both endothelial cells and smooth muscle cells, have the potential for treatment of ischemic diseases. Generated by pluripotent stem cells, VPCs carry the risk of tumorigenicity in clinical application. This issue could be resolved by direct lineage conversion, the induction of functional cells from another lineage by using only lineage-restricted transcription factors.

Formyl Peptide Receptor 2 Activation Ameliorates Dermal Fibrosis and Inflammation in Bleomycin-Induced Scleroderma.

Systemic sclerosis is a profibrotic autoimmune disease mediated by the dysregulation of extracellular matrix synthesis. Formyl peptide receptor 2 (Fpr2) is a G protein-coupled receptor that modulates inflammation and host defense by regulating the activation of inflammatory cells, such as macrophages. However, the role of Fpr2 in the development and therapy of scleroderma is still unclear.

Role of stem cell mobilization in the treatment of ischemic diseases.

Stem cell mobilization plays important roles in the treatment of severe ischemic diseases, including myocardial infarction, limb ischemia, ischemic stroke, and acute kidney injury. Stem cell mobilization refers to the egress of heterogeneous stem cells residing in the bone marrow into the peripheral blood. In the clinic, granulocyte colony-stimulating factor (G-CSF) is the drug most commonly used to induce stem cell mobilization.

Recent advances in stem cell therapeutics and tissue engineering strategies.

Background: Tissue regeneration includes delivering specific types of cells or cell products to injured tissues or organs for restoration of tissue and organ function. Stem cell therapy has drawn considerable attention since transplantation of stem cells can overcome the limitations of autologous transplantation of patient's tissues; however, it is not perfect for treating diseases. To overcome the hurdles associated with stem cell therapy, tissue engineering techniques have been developed.

Role of CXCR2 in the Ac-PGP-Induced Mobilization of Circulating Angiogenic Cells and its Therapeutic Implications.

Circulating angiogenic cells (CACs) have been implicated in the repair of ischemic tissues, and their mobilization from bone marrow is known to be regulated by the activations of chemokine receptors, including CXCR2 and CXCR4. This study was conducted to investigate the role of N-acetylated proline-glycine-proline (Ac-PGP; a collagen-derived chemotactic tripeptide) on CAC mobilization and its therapeutic potential for the treatment of peripheral artery diseases. Ac-PGP was administered daily to a murine hind limb ischemia model, and the effects of Ac-PGP on blood perfusion and CAC mobilization (Sca1 Flk1 cells) into peripheral blood were assessed.

TRRAP stimulates the tumorigenic potential of ovarian cancer stem cells.

Ovarian cancer is the most fatal gynecological malignancy in women and identification of new therapeutic targets is essential for the continued development of therapy for ovarian cancer. TRRAP (transformation/transcription domain-associated protein) is an adaptor protein and a component of histone acetyltransferase complex. The present study was undertaken to investigate the roles played by TRRAP in the proliferation and tumorigenicity of ovarian cancer stem cells.

Atrial natriuretic peptide accelerates human endothelial progenitor cell-stimulated cutaneous wound healing and angiogenesis.

Atrial natriuretic peptide (ANP) is a powerful vasodilating peptide secreted by cardiac muscle cells, and endothelial progenitor cells (EPCs) have been reported to stimulate cutaneous wound healing by mediating angiogenesis. To determine whether ANP can promote the EPC-mediated repair of injured tissues, we examined the effects of ANP on the angiogenic properties of EPCs and on cutaneous wound healing. In vitro, ANP treatment enhanced the migration, proliferation, and endothelial tube-forming abilities of EPCs.

3D cell printing of in vitro stabilized skin model and in vivo pre-vascularized skin patch using tissue-specific extracellular matrix bioink: A step towards advanced skin tissue engineering.

3D cell-printing technique has been under spotlight as an appealing biofabrication platform due to its ability to precisely pattern living cells in pre-defined spatial locations. In skin tissue engineering, a major remaining challenge is to seek for a suitable source of bioink capable of supporting and stimulating printed cells for tissue development. However, current bioinks for skin printing rely on homogeneous biomaterials, which has several shortcomings such as insufficient mechanical properties and recapitulation of microenvironment.

Trib2 regulates the pluripotency of embryonic stem cells and enhances reprogramming efficiency.

Embryonic stem (ES) cells are pluripotent cells characterized by self-renewability and differentiation potential. Induced pluripotent stem (iPS) cells are ES cell-equivalent cells derived from somatic cells by the introduction of core reprogramming factors. ES and iPS cells are important sources for understanding basic biology and for generating therapeutic cells for clinical applications.

Identification of a novel angiogenic peptide from periostin.

Angiogenic peptides have therapeutic potential for the treatment of chronic ischemic diseases. Periostin, an extracellular matrix protein expressed in injured tissues, promotes angiogenesis and tissue repair. We previously reported that in vivo administration of both recombinant full-length protein and the first FAS I domain of periostin alleviated peripheral artery occlusive disease by stimulating the migration of humane endothelial colony forming cells (ECFCs) and subsequent angiogenesis.

Role of Krüppel-Like Factor 4 in the Maintenance of Chemoresistance of Anaplastic Thyroid Cancer.

Background: Anaplastic thyroid cancer (ATC) has a very poor prognosis due to its aggressive nature and resistance to conventional treatment. Radiotherapy and chemotherapy are not fully effective because of the undifferentiated phenotype and enhanced drug resistance of ATC. The objective of this study was to evaluate the involvement of Krüppel-like factor 4 (KLF4), a stemness-associated transcription factor, in the undifferentiated phenotype and drug resistance of ATC.

Role of TAZ in Lysophosphatidic Acid-Induced Migration and Proliferation of Human Adipose-Derived Mesenchymal Stem Cells.

Transcriptional co-activator with a PDZ-binding motif (TAZ) is an important factor in lysophosphatidic acid (LPA)-induced promotion of migration and proliferation of human mesenchymal stem cells (MSCs). The expression of TAZ significantly increased at 6 h after LPA treatment, and TAZ knockdown inhibited the LPA-induced migration and proliferation of MSCs. In addition, embryonic fibroblasts from TAZ knockout mice exhibited the reduction in LPA-induced migration and proliferation.

The anti-microbial peptide SR-0379 stimulates human endothelial progenitor cell-mediated repair of peripheral artery diseases.

Ischemia is a serious disease, characterized by an inadequate blood supply to an organ or part of the body. In the present study, we evaluated the effects of the anti-microbial peptide SR-0379 on the stem cell-mediated therapy of ischemic diseases. The migratory and tube-forming abilities of human endothelial progenitor cells (EPCs) were enhanced by treatment with SR-0379 in vitro.

N-Acetylated Proline-Glycine-Proline Accelerates Cutaneous Wound Healing and Neovascularization by Human Endothelial Progenitor Cells.

Human endothelial progenitor cells (hEPCs) are promising therapeutic resources for wound repair through stimulating neovascularization. However, the hEPCs-based cell therapy has been hampered by poor engraftment of transplanted cells. In this study, we explored the effects of N-acetylated Proline-Glycine-Proline (Ac-PGP), a degradation product of collagen, on hEPC-mediated cutaneous wound healing and neovascularization.

Phospholipid End-Capped Bioreducible Polyurea Micelles as a Potential Platform for Intracellular Drug Delivery of Doxorubicin in Tumor Cells.

Bioreducible polymeric nanocarriers bearing disulfide bonds have been widely used for intracellular therapeutic delivery, since they are quickly sliced or reduced in the reductive milieu of cytosol. Incorporation of hydrophobic phospholipid analogues to polymers improves the biocompatibility by reducing the protein adsorption and platelet adhesion on the cell membranes. In this study, we have developed a series of bioreducible polyureas (PUs) bearing disulfide linkages in their backbone and phospholipid moieties in their chain ends.