RANKL Is a Downstream Mediator for Insulin-Induced Osteoblastic Differentiation of Vascular Smooth Muscle Cells

Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation

Mechanisms underlying electro-mechanical dysfunction in the Zucker diabetic fatty rat heart: a model of obesity and type 2 diabetes

Diabetes mellitus (DM) is a major and worsening global health problem, currently affecting over 450 million people and reducing their quality of life. Type 2 diabetes mellitus (T2DM) accounts for more than 90% of DM and the global epidemic of obesity, which largely explains the dramatic increase in the incidence and prevalence of T2DM in the past 20 years. Obesity is a major risk factor for DM which is a major cause of morbidity and mortality in diabetic patients. The electro-mechanical function of the heart is frequently compromised in diabetic patients. The aim of this review is to discuss the pathophysiology of electro-mechanical dysfunction in the diabetic heart and in particular, the Zucker diabetic fatty (ZDF) rat heart, a well-studied model of T2DM and obesity

Penerapan Standar Akuntansi Keuangan Entitas Mikro Kecil Dan Menengah Pada Usaha Mikro Kecil Dan Menengah (Studi Kasus Pada Umkm Terdaftar Di Kecamatan Trenggalek)

Penelitian ini merupakan jenis penelitian deskriptif kualitatif yang bertujuan untuk mengetahui penerapan Standar Akuntansi Keuangn Entitas Mikro Kecil Menengah oleh pelaku Usaha Mikro Kecil Menengah (SAK EMKM) yang terdaftar di Kecamatan Trenggalek, menganalisis hambatan yang dihadapi pelaku UMKM dalam menerapkan SAK EMKM, serta memberikan alternatif solusi atas hambatan yang dihadapi. Subjek penelitian dalam penelitian ini yaitu pelaku UMKM yang telah terdaftar pada Kecamatan Trenggalek. Terdapat 22 data yang diperoleh peneliti dengan metode wawancara terstruktur dan kuesioner terhadap 22 pelaku usaha. Hasil analisis menunjukkan bahwa tidak adanya pelaku UMKM yang menerapkan SAK EMKM dalam pencatatan akuntansi usahanya, namun sebagian kecil pelaku UMKM melakukan pencatatan akuntansi. Hambatan yang dialami pelaku UMKM yaitu belum adanya sosialisasi akuntansi, minimnya penggunaan software akuntansi, dan rendahnya kesadaran dalam memperbaiki pencatatan akuntansi pada usahanya. Alternatif solusi yang diberikan yaitu dilakukannya sosialisasi akuntansi serta sosialisasi dan pengenalan software akuntansi

Multidisciplinary approach to the management of pulmonary embolism patients: the pulmonary embolism response team (PERT)

Christopher W Root,1 David M Dudzinski,2 Bishoy Zakhary,3 Oren A Friedman,4 Akhilesh K Sista,5 James M Horowitz6 1Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Division of Cardiology, Department of Internal Medicine, Massachusetts General Hospital, Boston, MA, USA; 3Department of Internal Medicine, Oregon Health & Science University, Portland, OR, USA; 4Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 5Division of Vascular and Interventional Radiology, Department of Radiology, NYU Langone Health, New York, NY, USA; 6Leon H. Charney Division of Cardiology, Department of Medicine, NYU Langone Health, New York, NY, USA Abstract: Pulmonary embolism (PE) is a potentially fatal disease with a broad range of treatment options that spans multiple specialties. The rapid evolution and expansion of novel therapies to treat PE make it a disease process that is well suited to a multidisciplinary approach. In order to facilitate a rapid, robust response to the diagnosis of PE, some hospitals have established multidisciplinary pulmonary embolism response teams (PERTs). The PERT model is based on existing multidisciplinary teams such as heart teams and rapid response teams. A PERT is composed of clinicians from the range of specialties involved in the treatment of PE, including pulmonology critical care, interventional radiology, cardiology, and cardiothoracic surgery among others. A PERT is a 24/7 consult service that is able to provide expert advice on the initial management of PE patients and convene in real time to develop a consensus treatment plan specifically tailored to the needs of a particular patient and consistent with the capabilities of the institution. In this review, we discuss the rationale for establishing a PERT and its potential benefits. We discuss considerations in forming a PERT and present case studies of several PERTs currently in operation at different institutions. We also discuss potential difficulties in forming a PERT and review evidence that has been generated by some of the PERTs that have been in operation the longest. Keywords: pulmonary embolism, pulmonary embolism response team, thrombosis, thrombolysis, venous thromboembolis