The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG I...

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Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.

Petri nets, as a graphical and mathematical tool, provide a uniform environment for modelling, formal analysis, and design of discrete event systems. The main objective of this paper is to introduce the fundamental concepts of Petri nets to researchers and practitioners, both from academia and industry, who are involved in the work in the areas of modelling and analysis of industrial types of systems, as well as those who may potentially be involved in these areas. The paper begins with an overview of applications of Petri nets, mostly industrial ones. Then, it proceeds with a description of Petri nets, properties, and analysis methods. The discussion of properties is put in the context of industrial applications. The analysis methods are illustrated using an example of a simple robotic assembly system. The performance analysis, using Petri nets, is discussed for deterministic and stochastic Petri nets. The presented techniques are illustrated by examples representing simple production systems. In addition, the paper introduces high-level Petri nets, fuzzy Petri nets, and temporal Petri nets. This is done in the context of application prospects. The paper also briefly discusses some of the reasons restricting the use of Petri nets, mostly, to academic institutions. >

/pdf/petri-nets-and-industrial-applications-a-tutorial-2z7do95d63.pdf

Petri nets and industrial applications: A tutorial

Multitargeting by curcumin as revealed by molecular interaction studies

Objective External fistulas represent a disabling manifestation of Crohn9s disease with a difficult curability and a high relapse rate despite a large therapeutic armamentarium. Stem cell therapy is a novel and promising approach for treatment of chronic inflammatory conditions. We therefore investigated the feasibility, safety and efficacy of serial intrafistular injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in the treatment of fistulising Crohn9s disease. Patients and methods We enrolled 12 consecutive outpatients (eight males, median age 32 years) refractory to or unsuitable for current available therapies. MSCs were isolated from bone marrow and expanded ex vivo to be used for both therapeutic and experimental purposes. Ten patients (two refused) received intrafistular MSC injections (median 4) scheduled every 4 weeks, and were monitored by surgical, MRI and endoscopic evaluation for 12 months afterwards. The feasibility of obtaining at least 50×10 6 MSCs from each patient, the appearance of adverse events, and the efficacy in terms of fistula healing and reduction of both Crohn9s disease and perianal disease activity indexes were evaluated. In addition, the percentage of both mucosal and circulating regulatory T cells expressing FoxP3, and the ability of MSCs to influence mucosal T cell apoptosis were investigated. Results MSC expansion was successful in all cases; sustained complete closure (seven cases) or incomplete closure (three cases) of fistula tracks with a parallel reduction of Crohn9s disease and perianal disease activity indexes (p Conclusions Locally injected MSCs represent a feasible, safe and beneficial therapy in refractory fistulising Crohn9s disease.

https://gut.bmj.com/content/gutjnl/60/6/788.full.pdf

Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease

The premature-ageing disease Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by constitutive production of progerin, a mutant form of the nuclear architectural protein lamin A1,2. Progerin is also expressed sporadically in wild-type cells and has been linked to physiological ageing3. Cells from HGPS patients exhibit extensive nuclear defects, including abnormal chromatin structure4,5 and increased DNA damage6. At the organismal level, HGPS affects several tissues, particularly those of mesenchymal origin7. How the cellular defects of HGPS cells lead to the organismal defects has been unclear. Here, we provide evidence that progerin interferes with the function of human mesenchymal stem cells (hMSCs). We find that expression of progerin activates major downstream effectors of the Notch signalling pathway. Induction of progerin in hMSCs changes their molecular identity and differentiation potential. Our results support a model in which accelerated ageing in HGPS patients, and possibly also physiological ageing, is the result of adult stem cell dysfunction and progressive deterioration of tissue functions.

http://www.med.upenn.edu/timm/documents/LaminAStemCells.pdf

Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing

This paper overviews our present understanding of the fundamentals behind Electrolytic Plasma Technology (EPT) in view of the experimental results and theoretical predictions. EPT is an effective surface engineering tool that combines cleaning and coating of metals. During EPT processing, DC voltage is applied to the electrodes in the aqueous electrolyte, which produces plasma at the surface of the work piece. Thermal, chemical, electrical and mechanical effects imparted by EPT to the work piece create unique surface characteristics. The mechanism and metallurgical aspects of the effects are discussed in detail. EPT is under development for industrial applications in specific processes and is being explored for other potential commercial applications. Both of the aspects are presented. The experimental and industrial tests to date demonstrate that EPT is an emerging surface engineering technique with economical commercial applications in the field of surface engineering.

Electrolytic plasma technology: Science and engineering—An overview

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Introduction

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Mesenchymal stem cells and its characteristics

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Experimental/preclinical MSC-based studies


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MSC transplantation

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Genetically modified MSC-based therapy

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MSC-based protein therapy

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Tissue engineering using MSCs




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Clinical studies

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Challenges and future prospects





Mesenchymal stem cells (MSCs), adherent fibroblastoid cells, present in bone marrow and many other tissues can be easily isolated and expanded in vitro. They are capable of differentiating into different cell types such as osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial cells and neuronal cells. Such immense plasticity coupled with their ability to modulate the activity of immune cells makes them attractive for stem cell-based therapy aimed at treating previously incurable disorders. Preclinical studies have reported successful use of MSCs for delivering therapeutic proteins and repairing defects in a variety of disease models. These studies highlighted the in vivo potential of MSCs and their ability to home to injury sites and modify the microenvironment by secreting paracrine factors to augment tissue repair. Their therapeutic applicability has been widened by genetic modification to enhance differentiation and tissue targeting, and use in tissue engineering. Clinical trials for diseases such as osteogenesis imperfecta, graft-versus-host disease and myocardial infarction have shown some promise, demonstrating the safe use of both allogeneic and autologous cells. However, lack of knowledge of MSC behaviour and responses in vitro and in vivo force the need for basic and animal studies before heading to the clinic. Contrasting reports on immunomodulatory functions and tumorigenicity along with issues such as mode of cell delivery, lack of specific marker, low survival and engraftment require urgent attention to harness the potential of MSC-based therapy in the near future.

Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine.

Mesenchymal stem cells (MSCs) represent an adherent, fibroblast-like population present not only in the bone marrow, but in a number of tissues, including blood, adipose tissue, muscle, and dermis. Their extensive proliferation and transdifferentiation potential makes them best suited for tissue engineering applications. Identification of growth factors and signaling pathways involved in self-renewal and differentiation is important for designing strategies to overcome replicative senescence and attain directed differentiation. Wnt, bone morphogenetic protein (BMP), and Notch pathways have been implicated to play key roles in self-renewal and differentiation of hematopoietic, intestinal, and epidermal stem cells. They are also involved in regulating MSC differentiation. However, MSC self-renewal has not received much attention, with Nucleostemin being the only recently identified proliferation molecule. Although immortalization using viral oncogenes and telomerase has been achieved, transformation in long-term cultures is a potential risk. Understanding of the mechanisms governing osteogenic differentiation of MSCs is expanding with the recent identification of two major transcription factors, Osterix and Runx2. Enhanced expansion as well as osteogenic differentiation of MSCs can be attained using a combinatorial approach involving co-expression of proliferation and differentiation genes. However, a thorough understanding of the molecular mechanism is necessary for enhancing the self-renewal ability and osteogenic potential in vitro.

Mesenchymal Stem Cells: Molecular Targets for Tissue Engineering

A fuzzy Petri net for knowledge representation and reasoning

CD34 is highly glycosylated surface antigen of enormous clinical utility in the identification, enumeration, and purification of engraftable lymphohematopoietic progenitors for transplantation. However, recently its importance in the specific marking of most immature hematopoietic stem/progenitor cells have been questioned by addressing long-term reconstitution capability of CD34(-) hematopoietic cellular fractions. These controversies have stimulated a demand for elucidation of the structure, function, and molecular interactions of CD34 to define exactly its biological significance in clinical regimens. There is accumulating data showing the participation of CD34 in adhesion or perhaps homing of lymphohematopoietic progenitors. On the other hand, CD34 has been demonstrated to down-regulate cytokine-induced differentiation and proliferation of CD34(+) cells. Studies in CD34 knockout mice revealed normal hematopoiesis but a profound delay in hematopoietic reconstitution after sublethal irradiation of the mice. In short, CD34 expression is likely to represent a specific state of hematopoietic development that may have altered adhering properties with expanding and differentiating capabilities in both in vitro and in vivo conditions. This article focuses on the adhesive properties of CD34 and its potential role in homing, which are likely to mimic lymphocyte homing to the inflammatory sites.

Pallavi Gupta

Papers

Electrolytic plasma technology: Science and engineering—An overview

Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine.

Mesenchymal Stem Cells: Molecular Targets for Tissue Engineering

A fuzzy Petri net for knowledge representation and reasoning

Hematopoietic stem cell antigen CD34: role in adhesion or homing.