Osteogenic CpG Oligodeoxynucleotide, iSN40, Inhibits Osteoclastogenesis in a TLR9-Dependent Manner.

A CpG oligodeoxynucleotide (CpG-ODN), iSN40, was originally identified as promoting the mineralization and differentiation of osteoblasts, independent of Toll-like receptor 9 (TLR9). Since CpG ODNs are often recognized by TLR9 and inhibit osteoclastogenesis, this study investigated the TLR9 dependence and anti-osteoclastogenic effect of iSN40 to validate its potential as an osteoporosis drug. The murine monocyte/macrophage cell line RAW264.

Development of the 12-Base Short Dimeric Myogenetic Oligodeoxynucleotide That Induces Myogenic Differentiation.

A myogenetic oligodeoxynucleotide (myoDN), iSN04 (5'-AGA TTA GGG TGA GGG TGA-3'), is a single-stranded 18-base telomeric DNA that serves as an anti-nucleolin aptamer and induces myogenic differentiation, which is expected to be a nucleic acid drug for the prevention of disease-associated muscle wasting. To improve the drug efficacy and synthesis cost of myoDN, shortening the sequence while maintaining its structure-based function is a major challenge. Here, we report the novel 12-base non-telomeric myoDN, iMyo01 (5'-TTG GGT GGG GAA-3'), which has comparable myogenic activity to iSN04.

Exploring the Role of Desmoplastic Physical Stroma in Pancreatic Cancer Progression Using a Three-Dimensional Collagen Matrix Model.

Pancreatic ductal adenocarcinoma (PDAC) is a refractory tumor with a poor prognosis, and its complex microenvironment is characterized by a fibrous interstitial matrix surrounding PDAC cells. Type I collagen is a major component of this interstitial matrix. Abundant type I collagen promotes its deposition and cross-linking to form a rigid and dense physical barrier, which limits drug penetration and immune cell infiltration and provides drug resistance and metabolic adaptations.

Functional engineering of human iPSC-derived parasympathetic neurons enhances responsiveness to gastrointestinal hormones.

Food-derived biological signals are transmitted to the brain via peripheral nerves through the paracrine activity of gastrointestinal (GI) hormones. The signal transduction circuit of the brain-gut axis has been analyzed in animals; however, species-related differences and animal welfare concerns necessitate investigation using in vitro human experimental models. Here, we focused on the receptors of five GI hormones (CCK, GLP1, GLP2, PYY, and serotonin (5-HT)), and established human induced pluripotent stem cell (iPSC) lines that functionally expressed each receptor.

Myogenetic Oligodeoxynucleotide Induces Myocardial Differentiation of Murine Pluripotent Stem Cells.

An 18-base myogenetic oligodeoxynucleotide (myoDN), iSN04, acts as an anti-nucleolin aptamer and induces myogenic differentiation of skeletal muscle myoblasts. This study investigated the effect of iSN04 on murine embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). In the undifferentiated state, iSN04 inhibited the proliferation of ESCs and iPSCs but did not affect the expression of pluripotent markers.

Decoding Metabolic Symbiosis between Pancreatic Cancer Cells and Cancer-Associated Fibroblasts Using Cultured Tumor Microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a poor prognosis, largely due to its unique tumor microenvironment (TME) and dense fibrotic stroma. Cancer-associated fibroblasts (CAFs) play a crucial role in promoting tumor growth and metastasis, contributing to the metabolic adaptation of PDAC cells. However, the metabolic interactions between PDAC cells and CAFs are not well-understood.

Myogenetic Oligodeoxynucleotides as Anti-Nucleolin Aptamers Inhibit the Growth of Embryonal Rhabdomyosarcoma Cells.

Embryonal rhabdomyosarcoma (ERMS) is the muscle-derived tumor retaining myogenic ability. iSN04 and AS1411, which are myogenetic oligodeoxynucleotides (myoDNs) serving as anti-nucleolin aptamers, have been reported to inhibit the proliferation and induce the differentiation of myoblasts. The present study investigated the effects of iSN04 and AS1411 in vitro on the growth of multiple patient-derived ERMS cell lines, ERMS1, KYM1, and RD.

Identification of a Novel Osteogenetic Oligodeoxynucleotide (osteoDN) That Promotes Osteoblast Differentiation in a TLR9-Independent Manner.

Dysfunction of bone-forming cells, osteoblasts, is one of the causes of osteoporosis. Accumulating evidence has indicated that oligodeoxynucleotides (ODNs) designed from genome sequences have the potential to regulate osteogenic cell fate. Such osteogenetic ODNs (osteoDNs) targeting and activating osteoblasts can be the candidates of nucleic acid drugs for osteoporosis.

Myogenetic oligodeoxynucleotide complexed with berberine promotes differentiation of chicken myoblasts.

Myoblasts are myogenic precursors that develop into myotubes during muscle formation. Improving efficiency of myoblast differentiation is important for advancing meat production by domestic animals. We recently identified novel oligodeoxynucleotides (ODNs) termed myogenetic ODNs (myoDNs) that promote the differentiation of mammalian myoblasts.

Transcription of Endogenous Retrovirus Group K Members and Their Neighboring Genes in Chicken Skeletal Muscle Myoblasts.

Skeletal muscle myoblasts are myogenic precursor cells that generate myofibers during muscle development and growth. We recently reported that broiler myoblasts, compared to layer myoblasts, proliferate and differentiate more actively and promptly into myocytes, which corresponds well with the muscle phenotype of broilers. Furthermore, RNA sequencing (RNA-seq) revealed that numerous genes are differentially expressed between layer and broiler myoblasts during myogenic differentiation.

Identification of the Myogenetic Oligodeoxynucleotides (myoDNs) That Promote Differentiation of Skeletal Muscle Myoblasts by Targeting Nucleolin.

Herein we report that the 18-base telomeric oligodeoxynucleotides (ODNs) designed from the GG genome promote differentiation of skeletal muscle myoblasts which are myogenic precursor cells. We termed these myogenetic ODNs (myoDNs). The activity of one of the myoDNs, iSN04, was independent of Toll-like receptors, but dependent on its conformational state.

Distinct cell proliferation, myogenic differentiation, and gene expression in skeletal muscle myoblasts of layer and broiler chickens.

Myoblasts play a central role during skeletal muscle formation and growth. Precise understanding of myoblast properties is thus indispensable for meat production. Herein, we report the cellular characteristics and gene expression profiles of primary-cultured myoblasts of layer and broiler chickens.

Berberine and palmatine inhibit the growth of human rhabdomyosarcoma cells.

A natural isoquinoline alkaloid, berberine, has been known to exhibit anti-tumor activity in various cancer cells inducing cell cycle arrest. However, it has not been investigated whether berberine and its analogs inhibit the growth of rhabdomyosarcoma (RMS), which is the most frequent soft tissue tumor in children. The present study examined the anti-tumor effects of berberine and palmatine on expansions of three human embryonal RMS cell lines; ERMS1, KYM1, and RD.

Toll-like receptor ligand-dependent inflammatory responses in chick skeletal muscle myoblasts.

Toll-like receptors (TLRs) are a group of sensory receptors which are capable of recognizing a microbial invasion and activating innate immune system responses, including inflammatory responses, in both immune and non-immune cells. However, TLR functions in chick myoblasts, which are myogenic precursor cells contributing to skeletal muscle development and growth, have not been studied. Here, we report the expression patterns of TLR genes as well as TLR ligand-dependent transcriptions of interleukin (IL) genes in primary-cultured chick myoblasts.

Autonomous xenogenic cell fusion of murine and chick skeletal muscle myoblasts.

Cell-cell fusion has been a great technology to generate valuable hybrid cells and organisms such as hybridomas. In this study, skeletal muscle myoblasts were utilized to establish a novel method for autonomous xenogenic cell fusion. Myoblasts are mononuclear myogenic precursor cells and fuse mutually to form multinuclear myotubes.