Biphasic insulin Aspart 30 vs. NPH plus regular human insulin in type 2 diabetes patients; a cost-effectiveness study

Background: The aim of this study was to compare the efficacy, safety, costs, and cost-effectiveness of biphasic insulin aspart 30 (BIAsp 30) with NPH plus regular human insulin (NPH/Reg) in patients with type 2 diabetes mellitus (T2DM). Methods: It was a Single-center, parallel-group, randomized, clinical trial (Trial Registration: NCT01889095). One hundred and seventy four T2DM patients with poorly controlled diabetes (HbA1c � 8 (63.9 mmol/mol)) were randomly assigned to trial arms (BIAsp 30 and NPH/Reg) and were followed up for 48 weeks. BIAsp 30 was started at an initial dose of 0.2-0.6 IU/Kg in two divided doses and was titrated according to the glycemic status of the patient. Similarly, NPH/Reg insulin was initiated at a dose of 0.2-0.6 IU/Kg with a 2:1 ratio and was subsequently titrated. Level of glycemic control, hypoglycemic events, direct and indirect costs, quality adjusted life year (QALY) and incremental cost-effectiveness ratio have been assessed. Results: HbA1c, Fasting plasma glucose (FPG), and two-hour post-prandial glucose (PPG) were improved in both groups during the study (P < 0.05 for all analyses). Lower frequencies of minor, major, and nocturnal hypoglycemic episodes were observed with BIAsp 30 (P < 0.05). Additionally, BIAsp 30 was associated with less weight gain and also higher QALYs (P < 0.05). Total medical and non-medical costs were significantly lower with BIAsp 30 as compared with NPH/Reg (930.55 ± 81.43 USD vs. 1101.24 ± 165.49 USD, P = 0.004). Moreover, BIAsp 30 showed lower ICER as a dominant alternative. Conclusions: Despite being more expensive, BIAsp 30 offers the same glycemic control as to NPH/Reg dose-dependently and also appears to cause fewer hypoglycemic events and to be more cost-effective in Iranian patients with type 2 diabetes. © 2016 The Author(s)

A developed asymmetric mulitlevel inverter with lower number of components

In this paper, a new configuration for symmetrical and asymmetrical multilevel inverters is proposed. In asymmetric mode, different algorithms are suggested in order to determine the magnitudes of DC voltage sources. The merit of this topology to the conventional symmetric and asymmetric inverters is verified by the provided comparisons. This topology uses a lower number of power electronic devices such as switches, IGBTs, diodes, related gate driver circuits and DC voltage sources. Owing the lower amount of requirements, it has lower total costs and needs less installation area. Also the control strategy has less complexity. The proposed converter can generate all the desired output voltage levels with positive and negative values. To confirm the practicability of the proposed inverter, simulation and experimental results are provided which are in good agreements

The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model

Abstract Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma. A Piggybac vector encoding IP-10 was employed to transfect hADSC ex vivo. Expression and bioactivity of the transgenic protein from hADSCs expressing IP-10 were confirmed prior to in vivo studies. Our results indicated that hADSCs expressing IP-10 could inhibit the growth of B16F10 melanoma cells and significantly prolonged survival. Immunohistochemistry analysis, TUNEL assay and western blot analysis indicated that hADSCs expressing IP-10 inhibited tumor cell growth, hindered tumor infiltration of Tregs, restricted angiogenesis and significantly prolonged survival. In conclusion, our results demonstrated that targeting metastatic tumor sites by hADSC expressing IP-10 could reduce melanoma tumor growth and lung metastasis. Keywords: Melanoma Metastasis Human adipose derived mesenchymal stem cells CXCL1

Exosome-mediated delivery of functionally active miRNA-142-3p inhibitor reduces tumorigenicity of breast cancer in vitro and in vivo

Zahra Naseri,1 Reza Kazemi Oskuee,2 Mahmoud Reza Jaafari,3,4 Mehdi Forouzandeh Moghadam5 1Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 2Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 3Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; 4Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; 5Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Background: Exosomes, widely recognized natural nanovesicles, represent one of the recently discovered modes of intercellular communication due to their ability to transmit crucial cellular information that can be engineered to have robust delivery and targeting capacity. MiR-142-3p, one of the upregulated microRNAs (miRNAs) in many types of breast cancer, activates the canonical Wnt signaling pathway and transactivates the miR-150 expression, and results in the hyperproliferation of cancer cells in vitro and mammary glands in vivo.Materials and methods: In this study, we exploited the exosomes isolated from bone marrow-derived mesenchymal stem cells (MSCs-Exo) to deliver LNA (locked nucleic acid)-modified anti-miR-142-3p oligonucleotides to suppress the expression level of miR-142-3p and miR-150 in 4T1 and TUBO breast cancer cell lines.Results: The in vitro results showed that the MSCs-Exo can efficiently deliver anti-miR-142-3p to reduce the miR-142-3p and miR-150 levels and increase the transcription of the regulatory target genes, APC and P2X7R. We also evaluated in vivo distribution of the MSCs-Exo in tumor-bearing mice. The in vivo result indicated that MSCs-Exo can penetrate the tumor site and are suitable nanovehicles to deliver the inhibitory oligonucleotides into the tumor tissues to downregulate the expression levels of miR-142-3p and miR-150.Conclusion: We showed that MSCs-derived exosomes could be used as a feasible nanovehicle to deliver drug molecules like LNA-anti-miR-142-3p in both in vitro and in vivo studies. Keywords: MSCs-derived exosomes, tumor tropism, Wnt/&beta;-catenin signaling pathway, breast cancer, LNA-antimiR-142-3p&nbsp