Modeling RET-Rearranged Non-Small Cell Lung Cancer (NSCLC): Generation of Lung Progenitor Cells (LPCs) from Patient-Derived Induced Pluripotent Stem Cells (iPSCs).

REarranged during Transfection (RET) oncogenic rearrangements can occur in 1-2% of lung adenocarcinomas. While RET-driven NSCLC models have been developed using various approaches, no model based on patient-derived induced pluripotent stem cells (iPSCs) has yet been described. Patient-derived iPSCs hold great promise for disease modeling and drug screening.

A novel berberine derivative targeting adipocyte differentiation to alleviate TNF-α-induced inflammatory effects and insulin resistance in OP9 cells.

Inflammation and insulin resistance play important roles in the development and progression of type 2 diabetes mellitus. The enhancement of adipocyte differentiation can improve insulin sensitivity by increasing glucose uptake, improving insulin signaling, and reducing inflammation. However, only a few adipogenic agents have shown clinical success in patients with type 2 diabetes mellitus.

Novel bone Morphogenetic Protein (BMP)-2/4 Consensus Peptide (BCP) for the Osteogenic Differentiation of C2C12 Cells.

Background: Despite the promising clinical potential of bone morphogenetic protein (BMP)-related therapies for bone formation, their side effects warrant the need for alternative therapeutic peptides. BMP family members can aid in bone repair; however, peptides derived from BMP2/ 4 have not yet been investigated.

Methods: In this study, three candidates BMP2/4 consensus peptide (BCP) 1, 2, and 3 were identified and their ability to induce osteogenesis in C2C12 cells was analyzed.

Single cell transcriptomics reveals reduced stress response in stem cells manipulated using localized electric fields.

Membrane disruption using Bulk Electroporation (BEP) is a widely used non-viral method for delivering biomolecules into cells. Recently, its microfluidic counterpart, Localized Electroporation (LEP), has been successfully used for several applications ranging from for therapeutic purposes to from live cells for temporal analysis. However, the side effects of these processes on gene expression, that can affect the physiology of sensitive stem cells are not well understood.

Ca entry through reverse Na+/Ca exchanger in NCI-H716, glucagon-like peptide-1 secreting cells.

Glucagon like peptide-1 (GLP-1) released from enteroendocine L-cells in the intestine has incretin effects due to its ability to amplify glucose-dependent insulin secretion. Promotion of an endogenous release of GLP-1 is one of therapeutic targets for type 2 diabetes mellitus. Although the secretion of GLP-1 in response to nutrient or neural stimuli can be triggered by cytosolic Ca elevation, the stimulus-secretion pathway is not completely understood yet.

Heme oxygenase-1 gene delivery for altering high mobility group box-1 protein in pancreatic islet.

Pancreatic islet transplantation is a promising strategy for the treatment of type I diabetes. High-mobility group box-1 (HMGB1), highly expressed in islet cells, is a potent immune stimulator in immune rejection. Heme oxygenase-1 (HO1) gene therapy can modulate the release of HMGB1 by altering intracellular molecules for successful cell transplantation.

Effects of solvent osmolarity and viscosity on cartilage energy dissipation under high-frequency loading.

Articular cartilage is a spatially heterogeneous, dissipative biological hydrogel with a high fluid volume fraction. Although energy dissipation is important in the context of delaying cartilage damage, the dynamic behavior of articular cartilage equilibrated in media of varied osmolarity and viscosity is not widely understood. This study investigated the mechanical behaviors of cartilage when equilibrated to media of varying osmolarity and viscosity.

Detection of Hematopoietic Stem Cell Transcriptome in Human Fetal Kidneys and Kidney Organoids Derived From Human Induced Pluripotent Stem Cells.

Background: In mammalians, hematopoietic stem cells (HSCs) arise in the dorsal aorta from the hemogenic endothelium, followed by their migration to the fetal liver and to the bone marrow. In zebrafish, the kidney is the site of primary hematopoiesis. In humans, the presence of HSCs in the fetal or adult kidney has not been established.

Asarylaldehyde enhances osteogenic differentiation of human periodontal ligament stem cells through the ERK/p38 MAPK signaling pathway.

Periodontitis is an inflammatory disease that affects tooth-supporting tissues. Chronic inflammation can progress to periodontitis, which results in loss of alveolar bone. Asarylaldehyde is a potential substance for bone metabolism present in natural compounds.

Embryonic Program Activated during Blast Crisis of Chronic Myelogenous Leukemia (CML) Implicates a TCF7L2 and MYC Cooperative Chromatin Binding.

Chronic myeloid leukemia (CML) is characterized by an inherent genetic instability, which contributes to the progression of the disease towards an accelerated phase (AP) and blast crisis (BC). Several cytogenetic and genomic alterations have been reported in the progression towards BC, but the precise molecular mechanisms of this event are undetermined. Transcription Factor 7 like 2 (TFC7L2) is a member of the TCF family of proteins that are known to activate WNT target genes such as Cyclin D1.

Synergistic stimulating effect of 2-hydroxymelatonin and BMP-4 on osteogenic differentiation in vitro.

2-Hydroxymelatonin is a metabolite produced when melatonin 2-hydroxylase catalyzes melatonin. Recent studies have reported the important roles of melatonin in bone metabolism. However, the roles of 2-hydroxymelatonin in bone metabolism remains poorly understood.

A novel neuronal organoid model mimicking glioblastoma (GBM) features from induced pluripotent stem cells (iPSC).

Background: Current experimental models using either human or mouse cell lines, are not representative of the complex features of GBM. In particular, there is no model to study patient-derived iPSCs to generate a GBM model. Overexpression of c-met gene is one of the molecular features of GBM leading to increased signaling via STAT3 phosphorylation.

iPSC-Derived Embryoid Bodies as Models of c--Mutated Hereditary Papillary Renal Cell Carcinoma.

Hereditary cancers with cancer-predisposing mutations represent unique models of human oncogenesis, as a driving oncogenic event is present in germline. Currently, there are no satisfactory models to study these malignancies. We report the generation of IPSC from the somatic cells of a patient with hereditary c-mutated papillary renal cell carcinoma (PRCC).

Modeling malignancies using induced pluripotent stem cells: from chronic myeloid leukemia to hereditary cancers.

Over the last decade, the possibility of reprogramming malignant cells to a pluripotent state has been achieved in several hematological malignancies, including myeloproliferative neoplasms, myelodysplastic syndromes, and chronic myeloid leukemia (CML). It has been shown that it is readily possible to generate induced pluripotent stem cells (iPSCs) from several types of primary CML cells and to generate progenitors and differentiated cells with variable efficiency. Although these experiments have brought some new insights in the understanding of CML pathophysiology, the ultimate goal of generating induced leukemic stem cells (LSCs) with long-term multilineage potential has not yet been demonstrated.

A randomized controlled clinical study of periodontal tissue regeneration using an extracellular matrix-based resorbable membrane in combination with a collagenated bovine bone graft in intrabony defects.

Purpose: The purpose of this study was to investigate the feasibility of regenerative therapy with a collagenated bone graft and resorbable membrane in intrabony defects, and to evaluate the effects of the novel extracellular matrix (ECM)-based membrane clinically and radiologically.

Methods: Periodontal tissue regeneration procedure was performed using an ECM-based resorbable membrane in combination with a collagenated bovine bone graft in intrabony defects around the teeth and implants. A novel extracellular matrix membrane (NEM) and a widely-used membrane (WEM) were randomly applied to the test group and the control group, respectively.

Effects of the fibrous topography-mediated macrophage phenotype transition on the recruitment of mesenchymal stem cells: An in vivo study.

Host responses to a biomaterial critically influence its in vivo performance. Biomaterial architectures that can recruit endogenous host stem cells could be beneficial in tissue regeneration or integration. Here, we report that the fibrous topography of biomaterials promotes the recruitment of host mesenchymal stem cells (MSCs) by facilitating the macrophage phenotype transition from M1-to-M2.

Comparative, randomized, double-blind clinical study of alveolar ridge preservation using an extracellular matrix-based dental resorbable membrane in the extraction socket.

Purpose: The aim of this study was to radiographically and clinically compare the effect of extracellular matrix (ECM) membranes on dimensional alterations following a ridge preservation procedure.

Methods: One of 2 different ECM membranes was applied during a ridge preservation procedure. A widely used ECM membrane (WEM; Bio-Gide, Geistlich Biomaterials, Wolhusen, Switzerland) was applied in the treatment group and a newly developed ECM membrane (NEM; Lyso-Gide, Oscotec Inc.

Effect of Extracellular Matrix Membrane on Bone Formation in a Rabbit Tibial Defect Model.

Absorbable extracellular matrix (ECM) membrane has recently been used as a barrier membrane (BM) in guided tissue regeneration (GTR) and guided bone regeneration (GBR). Absorbable BMs are mostly based on collagen, which is more biocompatible than synthetic materials. However, implanted absorbable BMs can be rapidly degraded by enzymes in vivo.

Endometrial stromal sarcoma presented as an incidental lung mass with multiple pulmonary nodules.

Low-grade endometrial stromal sarcoma (ESS) is an uncommon gynecologic malignancy of mesodermal origin. Pulmonary metastasis of low-grade ESS can occur years and decades after the treatment of the primary disease. Low-grade ESS is frequently mistaken as benign uterine neoplasm like uterine leiomyoma, which can potentially lead to a misdiagnosis.

In situ formation and collagen-alginate composite encapsulation of pancreatic islet spheroids.

In this study, we suggest in situ islet spheroid formation and encapsulation on a single platform without replating as a method for producing mono-disperse spheroids and minimizing damage to spheroids during encapsulation. Using this approach, the size of spheroid can be controlled by modulating the size of the concave well. Here, we used 300 μm concave wells to reduce spheroid size and thereby eliminating the central necrosis caused by large volume.

MRI of transplanted surface-labeled pancreatic islets with heparinized superparamagnetic iron oxide nanoparticles.

Transplantation of insulin-secreting pancreatic islets can provide real-time regulation of blood glucose in patients with type 1 diabetes mellitus. Currently, noninvasive and repetitive monitoring of islet engraftment and function is an emerging and promising modality for successful islet transplantation. Here we report a new technique for highly sensitive in vivo magnetic resonance (MR) imaging of transplanted pancreatic islets.