Latrophilin-2 Deletion in Cardiomyocyte Disrupts Cell Junction, Leading to D-CMP.

Background: Latrophilin-2 (Lphn2), an adhesive GPCR (G protein-coupled receptor), was found to be a specific marker of cardiac progenitors during the differentiation of pluripotent stem cells into cardiomyocytes or during embryonic heart development in our previous studies. Its role in adult heart physiology, however, remains unclear.

Methods: The embryonic lethality resulting from deletion necessitates the establishment of cardiomyocyte-specific, tamoxifen-inducible knockout mice, which was achieved by crossing mice with mice having MerCreMer (tamoxifen-inducible Cre [Cyclization recombinase] recombinase) under the α-myosin heavy chain promoter.

SOX17-mediated LPAR4 expression plays a pivotal role in cardiac development and regeneration after myocardial infarction.

Lysophosphatidic acid receptor 4 (LPAR4) exhibits transient expression at the cardiac progenitor stage during pluripotent stem cell (PSC)-derived cardiac differentiation. Using RNA sequencing, promoter analyses, and a loss-of-function study in human PSCs, we discovered that SRY-box transcription factor 17 (SOX17) is an essential upstream factor of LPAR4 during cardiac differentiation. We conducted mouse embryo analyses to further verify our human PSC in vitro findings and confirmed the transient and sequential expression of SOX17 and LPAR4 during in vivo cardiac development.

A subset of macrophages and monocytes in the mouse bone marrow express atypical chemokine receptor 1.

Duffy antigen receptor for chemokines (DARC)/CD234, also known as atypical chemokine receptor 1 (ACKR1), is a seven-transmembrane domain protein expressed on erythrocytes, vascular endothelium, and a subset of epithelial cells (Peiper et al., 1995). Previously, we reported that ACKR1 was expressed in bone marrow macrophages.

Cardiovascular Regeneration via Stem Cells and Direct Reprogramming: A Review.

Cardiovascular disease (CVD) is the leading causes of morbidity and death globally. In particular, a heart failure remains a major problem that contributes to global mortality. Considerable advancements have been made in conventional pharmacological therapies and coronary intervention surgery for cardiac disorder treatment.

The G Protein-Coupled Receptor Latrophilin-2, A Marker for Heart Development, Induces Myocardial Repair After Infarction.

Discovering cell-surface markers based on a comprehensive understanding of development is utilized to isolate a particular cell type with high purity for therapeutic purposes. Given that latrophilin-2 (Lphn2) substantially contributes to cardiac differentiation, we examined whether Lphn2 regulates functional significance in heart development and repair. We performed whole-mount immunostaining followed by clearing technique of embryo, RNA sequencing related to Lphn2-knockout (KO) embryo, and in vivo functional analyses of Lphn2+ cells using echocardiography.

Adhesion GPCR Latrophilin-2 Specifies Cardiac Lineage Commitment through CDK5, Src, and P38MAPK.

Identifying lineage-specific markers is pivotal for understanding developmental processes and developing cell therapies. Here, we investigated the functioning of a cardiomyogenic cell-surface marker, latrophilin-2 (LPHN2), an adhesion G-protein-coupled receptor, in cardiac differentiation. LPHN2 was selectively expressed in cardiac progenitor cells (CPCs) and cardiomyocytes (CMCs) during mouse and human pluripotent stem cell (PSC) differentiation; cell sorting with an anti-LPHN2 antibody promoted the isolation of populations highly enriched in CPCs and CMCs.

Lysophosphatidic Acid Receptor 4 Is Transiently Expressed during Cardiac Differentiation and Critical for Repair of the Damaged Heart.

Efficient differentiation of pluripotent stem cells (PSCs) into cardiac cells is essential for the development of new therapeutic modalities to repair damaged heart tissue. We identified a novel cell surface marker, the G protein-coupled receptor lysophosphatidic acid receptor 4 (LPAR4), specific to cardiac progenitor cells (CPCs) and determined its functional significance and therapeutic potential. During in vitro differentiation of mouse and human PSCs toward cardiac lineage, LPAR4 expression peaked after 3-7 days of differentiation in cardiac progenitors and then declined.

The MicroRNA-92a/Sp1/MyoD Axis Regulates Hypoxic Stimulation of Myogenic Lineage Differentiation in Mouse Embryonic Stem Cells.

Hypoxic microenvironments exist in developing embryonic tissues and determine stem cell fate. We previously demonstrated that hypoxic priming plays roles in lineage commitment of embryonic stem cells. In the present study, we found that hypoxia-primed embryoid bodies (Hyp-EBs) efficiently differentiate into the myogenic lineage, resulting in the induction of the myogenic marker MyoD, which was not mediated by hypoxia-inducible factor 1α (HIF1α) or HIF2α, but rather by Sp1 induction and binding to the MyoD promoter.

Identification of Adult Mesodermal Progenitor Cells and Hierarchy in Atherosclerotic Vascular Calcification.

The nature of calcifying progenitor cells remains elusive. In this study, we investigated the developmental hierarchy and dynamics of progenitor cells. In vitro and in vivo reconstitution assays demonstrated that Sca-1+/PDGFRα- cells in the bone marrow (BM) are the ancestors of Sca-1+/PDGFRα+ cells.

Identification of the early and late responder genes during the generation of induced pluripotent stem cells from mouse fibroblasts.

Background: The generation of induced pluripotent stem cell (iPSC), a substitute for embryonic stem cell (ESC), requires the proper orchestration of a transcription program at the chromatin level. Our recent approach for the induction of pluripotent stem cells from fibroblasts using protein extracts from mouse ESCs could overcome the potential tumorigenicity risks associated with random retroviral integration. Here, we examine the epigenetic modifications and the transcriptome of two types of iPSC and of partially reprogrammed iPSCs (iPSCp) generated independently from adult cardiac and skin fibroblasts to assess any perturbations of the transcription program during reprogramming.

Dipeptidyl Peptidase-4 Inhibitor Increases Vascular Leakage in Retina through VE-cadherin Phosphorylation.

The inhibitors of CD26 (dipeptidyl peptidase-4; DPP4) have been widely prescribed to control glucose level in diabetic patients. DPP4-inhibitors, however, accumulate stromal cell-derived factor-1α (SDF-1α), a well-known inducer of vascular leakage and angiogenesis both of which are fundamental pathophysiology of diabetic retinopathy. The aim of this study was to investigate the effects of DPP4-inhibitors on vascular permeability and diabetic retinopathy.

Seborrheic dermatitis treatment with stellate ganglion block: a case report.

Seborrheic dermatitis is a chronic recurrent inflammatory disorder presumed to be caused by increased sebaceous gland secretion, metabolic changes in the cutaneous microflora, and changes in the host immune function. Stellate ganglion block (SGB) is known to increase the blood flow rate without altering the blood pressure, heart rate, or cardiac output, to stabilize hypertonic conditions of the sympathetic nerves, and to affect the endocrine and immune systems. It is used in the differential diagnosis and treatment of autonomic nervous system disorders of the head, neck, and upper limbs.

Endotracheal intubation using i-gel® and lightwand in a patient with difficult airway: a case report.

This case report involves tracheal intubation using i-gel® in combination with a lightwand in a patient with a difficult airway, classified as Cormack-Lehane grade 3. I-gel® was used during anesthesia induction to properly maintain ventilation. The authors have previously reported successful tracheal intubation on a patient with a difficult airway through the use of i-gel® and a fiberoptic bronchoscope.

Role of Zscan4 in secondary murine iPSC derivation mediated by protein extracts of ESC or iPSC.

Previously, we found that the delivery of mouse ES (mES) cell-derived proteins to adult fibroblasts enables the full reprogramming of these cells, converting them to mouse pluripotent stem cells (protein-iPS cells) without transduction of defined factors. During reprogramming, global gene expression and epigenetic status such as DNA methylation and histone modifications convert from somatic to ES-equivalent status. mES cell extract-derived iPS cells are biologically and functionally indistinguishable from mES cells in its potential in differentiation both in vitro and in vivo.

Activated platelet supernatant can augment the angiogenic potential of human peripheral blood stem cells mobilized from bone marrow by G-CSF.

Platelets not only play a role in hemostasis, but they also promote angiogenesis and tissue recovery by releasing various cytokines and making an angiogenic milieu. Here, we examined autologous 'activated platelet supernatant (APS)' as a priming agent for stem cells; thereby enhance their pro-angiogenic potential and efficacy of stem cell-based therapy for ischemic diseases. The mobilized peripheral blood stem cells ((mob)PBSCs) were isolated from healthy volunteers after subcutaneous injection of granulocyte-colony stimulating factor.

Successful resuscitation of cardiac arrest caused by CO2 embolism with intra-aortic injection of epinephrine during off-pump coronary bypass surgery -a case report-.

Although compressed gas (CO2) blowers have been used safely to aid accurate grafting during off-pump coronary bypass surgery, hemodynamic collapse due to gas embolism into the right coronary artery may occur. Supportive measures to facilitate gas clearance by increasing the coronary perfusion pressure have been reported to be successful in restoring hemodynamic stability. However, right ventricular dysfunction and atrioventricular nodal ischemia may hinder effective systemic delivery of the vasoactive medications, even when performing resuscitative measures such as direct cardiac massage.

Magnetic bionanoparticle enhances homing of endothelial progenitor cells in mouse hindlimb ischemia.

Background And Objectives: Poor homing efficiency is one of the major limitations of current stem cell therapy. Magnetic bionanoparticles (MPs) obtained from Magnetospirillum sp. AMB-1 have a lipid bilayer membrane and ferromagnetic properties.

The effect-site concentration of propofol producing respiratory depression during spinal anesthesia.

Background: Propofol is used worldwide for its sedative effective; nonetheless, has the serious side effect of respiratory depression. An increased blood concentration of propofol is well known to be associated with increased respiratory depression. However, there are no studies of the effect site concentration inducing respiratory depression.

Post-operative nausea and vomiting after gynecologic laparoscopic surgery: comparison between propofol and sevoflurane.

Background: We compared the incidence and degree of post-operative nausea and vomiting (PONV) in patients who received general anesthesia with propofol or sevoflurane using the Rhodes index of nausea, vomiting, and retching (RINVR) to assess the degree of PONV quantitatively and objectively during the post-anesthetic period.

Methods: We performed a prospective study involving 38 patients who underwent gynecologic laparoscopic surgery in our hospital between September 2008 and August 2009. Nineteen patients were anesthetized with propofol during the entire anesthetic period and the other 19 patients received 2.

Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation.

The concept of reprogramming of somatic cells has opened a new era in regenerative medicine. Transduction of defined factors has successfully achieved pluripotency. However, during the generation process of induced pluripotent stem (iPS) cells, genetic manipulation of certain factors may cause tumorigenicity, which limits further application.

Priming with angiopoietin-1 augments the vasculogenic potential of the peripheral blood stem cells mobilized with granulocyte colony-stimulating factor through a novel Tie2/Ets-1 pathway.

Background: The low engraftment rate of stem/progenitor cells infused via the intracoronary route to the ischemic myocardium is one of the most important factors limiting the efficacy of cell therapy. We investigated the concept of priming peripheral blood stem cells enriched by granulocyte colony-stimulating factor mobilization and apheresis ((mob)PBSCs) with angiopoietin-1 (Ang1), to enhance the engraftment into the ischemic tissue and neovasculogenic potential.

Methods And Results: The expression of Tie2, the Ang1 receptor, was significantly higher in (mob)PBSCs than naïve peripheral blood mononuclear cells (19.

Rhabdomyolysis following posterior lumbar interbody fusion in prone position: report 2 cases: Two cases report.

The spine surgery performed in the prone position could cause severe complications such as visual acuity impairment, spinal infarct and rhabdomyolysis. When treating rhabdomyolysis, it is important to prevent acute renal failure from accompanying rhabdomyolysis due to the poor prognosis. We have experienced two cases of rhabdomyolysis after spine surgery where dark urine was present during spine surgery under general anesthesia.