MDPI - Publisher of Open Access Journals

Open AccessArticle Tick Haller’s Organ, a New Paradigm for Arthropod Olfaction: How Ticks Differ from Insects

by Ann L. Carr, Robert D. Mitchell III, Anirudh Dhammi, Brooke W. Bissinger, Daniel E. Sonenshine and R. Michael Roe

Int. J. Mol. Sci. 2017, 18(7), 1563; doi:10.3390/ijms18071563

Received: 24 May 2017 / Revised: 13 July 2017 / Accepted: 14 July 2017 / Published: 18 July 2017

Viewed by 313 | PDF Full-text (2109 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

Ticks are the vector of many human and animal diseases; and host detection is critical to this process. Ticks have a unique sensory structure located exclusively on the 1st pairs of legs; the fore-tarsal Haller’s organ, not found in any other animals, presumed

[...] Read more.

Ticks are the vector of many human and animal diseases; and host detection is critical to this process. Ticks have a unique sensory structure located exclusively on the 1st pairs of legs; the fore-tarsal Haller’s organ, not found in any other animals, presumed to function like the insect antennae in chemosensation but morphologically very different. The mechanism of tick chemoreception is unknown. Utilizing next-generation sequencing and comparative transcriptomics between the 1st and 4th legs (the latter without the Haller’s organ), we characterized 1st leg specific and putative Haller’s organ specific transcripts from adult American dog ticks, Dermacentor variabilis. The analysis suggested that the Haller’s organ is involved in olfaction, not gustation. No known odorant binding proteins like those found in insects, chemosensory lipocalins or typical insect olfactory mechanisms were identified; with the transcriptomic data only supporting a possible olfactory G-protein coupled receptor (GPCR) signal cascade unique to the Haller’s organ. Each component of the olfactory GPCR signal cascade was identified and characterized. The expression of GPCR, G_αo and β-arrestin transcripts identified exclusively in the 1st leg transcriptome, and putatively Haller’s organ specific, were examined in unfed and blood-fed adult female and male D. variabilis. Blood feeding to repletion in adult females down-regulated the expression of all three chemosensory transcripts in females but not in males; consistent with differences in post-feeding tick behavior between sexes and an expected reduced chemosensory function in females as they leave the host. Data are presented for the first time of the potential hormonal regulation of tick chemosensation; behavioral assays confirmed the role of the Haller’s organ in N,N-diethyl-meta-toluamide (DEET) repellency but showed no role for the Haller’s organ in host attachment. Further research is needed to understand the potential role of the GPCR cascade in olfaction. Full article

(This article belongs to the Special Issue Molecular Entomology of Insects of Economic Importance)

► Figures

Open AccessCommunication Optical Tracking and Digital Quantification of Beating Behavior in Bioengineered Human Cardiac Organoids

by Mahesh Devarasetty, Steven Forsythe, Thomas D. Shupe, Shay Soker, Colin E. Bishop, Anthony Atala and Aleksander Skardal

Biosensors 2017, 7(3), 24; doi:10.3390/bios7030024

Received: 15 March 2017 / Revised: 9 June 2017 / Accepted: 17 June 2017 / Published: 23 June 2017

Viewed by 534 | PDF Full-text (2602 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

Organoid and organ-on-a-chip technologies are rapidly advancing towards deployment for drug and toxicology screening applications. Liver and cardiac toxicities account for the majority of drug candidate failures in human trials. Liver toxicity generally produces liver cell death, while cardiac toxicity causes adverse changes

[...] Read more.

Organoid and organ-on-a-chip technologies are rapidly advancing towards deployment for drug and toxicology screening applications. Liver and cardiac toxicities account for the majority of drug candidate failures in human trials. Liver toxicity generally produces liver cell death, while cardiac toxicity causes adverse changes in heart beat kinetics. In traditional 2D cultures, beating kinetics can be measured by electrode arrays, but in some 3D constructs, quantifying beating kinetics can be more challenging. For example, real time measurements of calcium flux or contractile forces are possible, yet rather complex. In this communication article, we demonstrate a simple sensing system based on software code that optically analyzes video capture files of beating cardiac organoids, translates these files in representations of moving pixels, and quantifies pixel movement activity over time to generate beat kinetic plots. We demonstrate this system using bioengineered cardiac organoids under baseline and drug conditions. This technology offers a non-invasive, low-cost, and incredibly simple method for tracking and quantifying beating behavior in cardiac organoids and organ-on-a-chip systems for drug and toxicology screening. Full article

(This article belongs to the Special Issue Advances in Optical, RF, Microwave and Wireless BioSensing for Health, Environment and Agriculture)

► Figures

Figure 1

Open AccessReview Microtechnology-Based Multi-Organ Models

by Seung Hwan Lee and Jong Hwan Sung

Bioengineering 2017, 4(2), 46; doi:10.3390/bioengineering4020046

Received: 19 March 2017 / Revised: 17 May 2017 / Accepted: 18 May 2017 / Published: 21 May 2017

Viewed by 756 | PDF Full-text (2340 KB) | HTML Full-text | XML Full-text

Abstract

Drugs affect the human body through absorption, distribution, metabolism, and elimination (ADME) processes. Due to their importance, the ADME processes need to be studied to determine the efficacy and side effects of drugs. Various in vitro model systems have been developed and used

[...] Read more.

Drugs affect the human body through absorption, distribution, metabolism, and elimination (ADME) processes. Due to their importance, the ADME processes need to be studied to determine the efficacy and side effects of drugs. Various in vitro model systems have been developed and used to realize the ADME processes. However, conventional model systems have failed to simulate the ADME processes because they are different from in vivo, which has resulted in a high attrition rate of drugs and a decrease in the productivity of new drug development. Recently, a microtechnology-based in vitro system called “organ-on-a-chip” has been gaining attention, with more realistic cell behavior and physiological reactions, capable of better simulating the in vivo environment. Furthermore, multi-organ-on-a-chip models that can provide information on the interaction between the organs have been developed. The ultimate goal is the development of a “body-on-a-chip”, which can act as a whole body model. In this review, we introduce and summarize the current progress in the development of multi-organ models as a foundation for the development of body-on-a-chip. Full article

(This article belongs to the Special Issue Human Organs-on-Chips for In Vitro Disease Models)

► Figures

Open AccessReview The Role of Microfluidics for Organ on Chip Simulations

by Aziz Ur Rehman Aziz, Chunyang Geng, Mengjie Fu, Xiaohui Yu, Kairong Qin and Bo Liu

Bioengineering 2017, 4(2), 39; doi:10.3390/bioengineering4020039

Received: 24 March 2017 / Revised: 1 May 2017 / Accepted: 2 May 2017 / Published: 4 May 2017

Viewed by 783 | PDF Full-text (2020 KB) | HTML Full-text | XML Full-text

Abstract

A multichannel three-dimensional chip of a microfluidic cell culture which enables the simulation of organs is called an “organ on a chip” (OC). With the integration of many other technologies, OCs have been mimicking organs, substituting animal models, and diminishing the time and

[...] Read more.

A multichannel three-dimensional chip of a microfluidic cell culture which enables the simulation of organs is called an “organ on a chip” (OC). With the integration of many other technologies, OCs have been mimicking organs, substituting animal models, and diminishing the time and cost of experiments which is better than the preceding conventional in vitro models, which make them imperative tools for finding functional properties, pathological states, and developmental studies of organs. In this review, recent progress regarding microfluidic devices and their applications in cell cultures is discussed to explain the advantages and limitations of these systems. Microfluidics is not a solution but only an approach to create a controlled environment, however, other supporting technologies are needed, depending upon what is intended to be achieved. Microfluidic platforms can be integrated with additional technologies to enhance the organ on chip simulations. Besides, new directions and areas are mentioned for interested researchers in this field, and future challenges regarding the simulation of OCs are also discussed, which will make microfluidics more accurate and beneficial for biological applications. Full article

(This article belongs to the Special Issue Human Organs-on-Chips for In Vitro Disease Models)

► Figures

Figure 1

Open AccessReview High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

by Dong-Mei Zhang, Rui-Qing Jiao and Ling-Dong Kong

Nutrients 2017, 9(4), 335; doi:10.3390/nu9040335

Received: 6 February 2017 / Revised: 15 March 2017 / Accepted: 24 March 2017 / Published: 29 March 2017

Viewed by 1201 | PDF Full-text (650 KB) | HTML Full-text | XML Full-text

Abstract

High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free

[...] Read more.

High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption. Full article

(This article belongs to the Special Issue Dietary Fructose and Glucose: The Multifacetted Aspects of their Metabolism and Implication for Human Health)

► Figures

Figure 1

Open AccessHypothesis Increased Dicarbonyl Stress as a Novel Mechanism of Multi-Organ Failure in Critical Illness

by Bas C. T. van Bussel, Marcel C. G. van de Poll, Casper G. Schalkwijk and Dennis C. J. J. Bergmans

Int. J. Mol. Sci. 2017, 18(2), 346; doi:10.3390/ijms18020346

Received: 26 November 2016 / Revised: 16 January 2017 / Accepted: 3 February 2017 / Published: 7 February 2017

Viewed by 424 | PDF Full-text (449 KB) | HTML Full-text | XML Full-text

Abstract

Molecular pathological pathways leading to multi-organ failure in critical illness are progressively being unravelled. However, attempts to modulate these pathways have not yet improved the clinical outcome. Therefore, new targetable mechanisms should be investigated. We hypothesize that increased dicarbonyl stress is such a

[...] Read more.

Molecular pathological pathways leading to multi-organ failure in critical illness are progressively being unravelled. However, attempts to modulate these pathways have not yet improved the clinical outcome. Therefore, new targetable mechanisms should be investigated. We hypothesize that increased dicarbonyl stress is such a mechanism. Dicarbonyl stress is the accumulation of dicarbonyl metabolites (i.e., methylglyoxal, glyoxal, and 3-deoxyglucosone) that damages intracellular proteins, modifies extracellular matrix proteins, and alters plasma proteins. Increased dicarbonyl stress has been shown to impair the renal, cardiovascular, and central nervous system function, and possibly also the hepatic and respiratory function. In addition to hyperglycaemia, hypoxia and inflammation can cause increased dicarbonyl stress, and these conditions are prevalent in critical illness. Hypoxia and inflammation have been shown to drive the rapid intracellular accumulation of reactive dicarbonyls, i.e., through reduced glyoxalase-1 activity, which is the key enzyme in the dicarbonyl detoxification enzyme system. In critical illness, hypoxia and inflammation, with or without hyperglycaemia, could thus increase dicarbonyl stress in a way that might contribute to multi-organ failure. Thus, we hypothesize that increased dicarbonyl stress in critical illness, such as sepsis and major trauma, contributes to the development of multi-organ failure. This mechanism has the potential for new therapeutic intervention in critical care. Full article

(This article belongs to the Special Issue Glyoxalase System)

► Figures

Figure 1

Open AccessReview 3D Printing of Organs-On-Chips

by Hee-Gyeong Yi, Hyungseok Lee and Dong-Woo Cho

Bioengineering 2017, 4(1), 10; doi:10.3390/bioengineering4010010

Received: 29 November 2016 / Revised: 14 January 2017 / Accepted: 20 January 2017 / Published: 25 January 2017

Cited by 2 | Viewed by 1360 | PDF Full-text (2452 KB) | HTML Full-text | XML Full-text

Abstract

Organ-on-a-chip engineering aims to create artificial living organs that mimic the complex and physiological responses of real organs, in order to test drugs by precisely manipulating the cells and their microenvironments. To achieve this, the artificial organs should to be microfabricated with an

[...] Read more.

Organ-on-a-chip engineering aims to create artificial living organs that mimic the complex and physiological responses of real organs, in order to test drugs by precisely manipulating the cells and their microenvironments. To achieve this, the artificial organs should to be microfabricated with an extracellular matrix (ECM) and various types of cells, and should recapitulate morphogenesis, cell differentiation, and functions according to the native organ. A promising strategy is 3D printing, which precisely controls the spatial distribution and layer-by-layer assembly of cells, ECMs, and other biomaterials. Owing to this unique advantage, integration of 3D printing into organ-on-a-chip engineering can facilitate the creation of micro-organs with heterogeneity, a desired 3D cellular arrangement, tissue-specific functions, or even cyclic movement within a microfluidic device. Moreover, fully 3D-printed organs-on-chips more easily incorporate other mechanical and electrical components with the chips, and can be commercialized via automated massive production. Herein, we discuss the recent advances and the potential of 3D cell-printing technology in engineering organs-on-chips, and provides the future perspectives of this technology to establish the highly reliable and useful drug-screening platforms. Full article

(This article belongs to the Special Issue Human Organs-on-Chips for In Vitro Disease Models)

► Figures

Open AccessCorrection Correction: 3D Bioprinting Technologies for Hard Tissue and Organ Engineering. Materials 2016, 9, 802

by Xiaohong Wang, Qiang Ao, Xiaohong Tian, Jun Fan, Yujun Wei, Weijian Hou, Hao Tong and Shuling Bai

Materials 2016, 9(11), 911; doi:10.3390/ma9110911

Received: 7 November 2016 / Revised: 7 November 2016 / Accepted: 8 November 2016 / Published: 10 November 2016

Viewed by 522 | PDF Full-text (142 KB) | HTML Full-text | XML Full-text

Abstract

n/a Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

Open AccessArticle Epistemic Communities, Human Rights, and the Global Diffusion of Legislation against the Organ Trade

by Fikresus Amahazion

Soc. Sci. 2016, 5(4), 69; doi:10.3390/socsci5040069

Received: 11 August 2016 / Revised: 30 September 2016 / Accepted: 19 October 2016 / Published: 27 October 2016

Viewed by 799 | PDF Full-text (640 KB) | HTML Full-text | XML Full-text

Abstract

Over the past several decades, over 100 countries have passed legislation banning commercial organ transplantation. What explains this rapid, global diffusion of laws? Based on qualitative data from in-depth interviews, historical analysis, and secondary sources, this paper explores the role played by the

[...] Read more.

Over the past several decades, over 100 countries have passed legislation banning commercial organ transplantation. What explains this rapid, global diffusion of laws? Based on qualitative data from in-depth interviews, historical analysis, and secondary sources, this paper explores the role played by the medical epistemic community and human rights in the global spread of laws against the organ trade. In addition to shaping, guiding, and influencing norms and approaches to transplantation, the epistemic community has been instrumental in the development of various resolutions, policy initiatives, recommended practices, statements, legislation, and model laws. Moreover, the epistemic community helped position the organ trade as an issue of societal and global importance, and it persistently encouraged states to undertake actions, such as implementing legislation, to combat the organ trade. Critically, the epistemic community’s efforts against the organ trade incorporated the concepts of human rights, integrity, and dignity, which had diffused globally and become institutionalized in the period after WWII. Full article

► Figures

Figure 1

Open AccessArticle Organ-Specific Gene Expression Changes in the Fetal Liver and Placenta in Response to Maternal Folate Depletion

by Jill A. McKay, Long Xie, Michiel Adriaens, Chris T. Evelo, Dianne Ford and John C. Mathers

Nutrients 2016, 8(10), 661; doi:10.3390/nu8100661

Received: 22 August 2016 / Revised: 13 October 2016 / Accepted: 14 October 2016 / Published: 22 October 2016

Abstract

Growing evidence supports the hypothesis that the in utero environment can have profound implications for fetal development and later life offspring health. Current theory suggests conditions experienced in utero prepare, or “programme”, the fetus for its anticipated post-natal environment. The mechanisms responsible for

[...] Read more.

Growing evidence supports the hypothesis that the in utero environment can have profound implications for fetal development and later life offspring health. Current theory suggests conditions experienced in utero prepare, or “programme”, the fetus for its anticipated post-natal environment. The mechanisms responsible for these programming events are poorly understood but are likely to involve gene expression changes. Folate is essential for normal fetal development and inadequate maternal folate supply during pregnancy has long term adverse effects for offspring. We tested the hypothesis that folate depletion during pregnancy alters offspring programming through altered gene expression. Female C57BL/6J mice were fed diets containing 2 mg or 0.4 mg folic acid/kg for 4 weeks before mating and throughout pregnancy. At 17.5 day gestation, genome-wide gene expression was measured in male fetal livers and placentas. In the fetal liver, 989 genes were expressed differentially (555 up-regulated, 434 down-regulated) in response to maternal folate depletion, with 460 genes expressed differentially (250 up-regulated, 255 down-regulated) in the placenta. Only 25 differentially expressed genes were common between organs. Maternal folate intake during pregnancy influences fetal gene expression in a highly organ specific manner which may reflect organ-specific functions. Full article

(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism)

► Figures

Figure 1

Open AccessArticle Microscopic Visualisation of Zoonotic Arbovirus Replication in Tick Cell and Organ Cultures Using Semliki Forest Virus Reporter Systems

by Lesley Bell-Sakyi, Sabine Weisheit, Claudia Rückert, Gerald Barry, John Fazakerley and Rennos Fragkoudis

Vet. Sci. 2016, 3(4), 28; doi:10.3390/vetsci3040028

Received: 28 July 2016 / Revised: 9 September 2016 / Accepted: 22 September 2016 / Published: 29 September 2016

Viewed by 654 | PDF Full-text (7739 KB) | HTML Full-text | XML Full-text

Abstract

Ticks are vectors and reservoirs of many arboviruses pathogenic for humans or domestic animals; in addition, during bloodfeeding they can acquire and harbour pathogenic arboviruses normally transmitted by other arthropods such as mosquitoes. Tick cell and organ cultures provide convenient tools for propagation

[...] Read more.

Ticks are vectors and reservoirs of many arboviruses pathogenic for humans or domestic animals; in addition, during bloodfeeding they can acquire and harbour pathogenic arboviruses normally transmitted by other arthropods such as mosquitoes. Tick cell and organ cultures provide convenient tools for propagation and study of arboviruses, both tick-borne and insect-borne, enabling elucidation of virus-tick cell interaction and yielding insight into the mechanisms behind vector competence and reservoir potential for different arbovirus species. The mosquito-borne zoonotic alphavirus Semliki Forest virus (SFV), which replicates well in tick cells, has been isolated from Rhipicephalus, Hyalomma, and Amblyomma spp. ticks removed from mammalian hosts in East Africa; however nothing is known about any possible role of ticks in SFV epidemiology. Here we present a light and electron microscopic study of SFV infecting cell lines and organ cultures derived from African Rhipicephalus spp. ticks. As well as demonstrating the applicability of these culture systems for studying virus-vector interactions, we provide preliminary evidence to support the hypothesis that SFV is not normally transmitted by ticks because the virus does not infect midgut cells. Full article

(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)

► Figures

Figure 1

Open AccessReview 3D Bioprinting Technologies for Hard Tissue and Organ Engineering

by Xiaohong Wang, Qiang Ao, Xiaohong Tian, Jun Fan, Yujun Wei, Weijian Hou, Hao Tong and Shuling Bai

Materials 2016, 9(10), 802; doi:10.3390/ma9100802

Received: 31 July 2016 / Revised: 19 September 2016 / Accepted: 22 September 2016 / Published: 27 September 2016

Abstract

Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over

[...] Read more.

Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especially for hard organ regeneration, a series of new theories, strategies and protocols have been proposed. Some of the technologies have been applied in medical therapies with some successes. Each of the technologies has pros and cons in hard tissue and organ engineering. In this review, we summarize the advantages and disadvantages of the historical available innovative 3D bioprinting technologies for used as special tools for hard tissue and organ engineering. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

► Figures

Figure 1

Open AccessArticle An Inflammatory Nucleus Pulposus Tissue Culture Model to Test Molecular Regenerative Therapies: Validation with Epigallocatechin 3-Gallate

by Olga Krupkova, Marian Hlavna, Julie Amir Tahmasseb, Joel Zvick, Dominik Kunz, Keita Ito, Stephen J. Ferguson and Karin Wuertz-Kozak

Int. J. Mol. Sci. 2016, 17(10), 1640; doi:10.3390/ijms17101640

Received: 23 July 2016 / Revised: 15 September 2016 / Accepted: 19 September 2016 / Published: 27 September 2016

Viewed by 726 | PDF Full-text (6323 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

Organ cultures are practical tools to investigate regenerative strategies for the intervertebral disc. However, most existing organ culture systems induce severe tissue degradation with only limited representation of the in vivo processes. The objective of this study was to develop a space- and

[...] Read more.

Organ cultures are practical tools to investigate regenerative strategies for the intervertebral disc. However, most existing organ culture systems induce severe tissue degradation with only limited representation of the in vivo processes. The objective of this study was to develop a space- and cost-efficient tissue culture model, which represents degenerative processes of the nucleus pulposus (NP). Intact bovine NPs were cultured in a previously developed system using Dyneema jackets. Degenerative changes in the NP tissue were induced either by the direct injection of chondroitinase ABC (1–20 U/mL) or by the diffusion of interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) (both 100 ng/mL) from the culture media. Extracellular matrix composition (collagens, proteoglycans, water, and DNA) and the expression of inflammatory and catabolic genes were analyzed. The anti-inflammatory and anti-catabolic compound epigallocatechin 3-gallate (EGCG, 10 µM) was employed to assess the relevance of the degenerative NP model. Although a single injection of chondroitinase ABC reduced the proteoglycan content in the NPs, it did not activate cellular responses. On the other hand, IL-1β and TNF-α significantly increased the mRNA expression of inflammatory mediators IL-6, IL-8, inducible nitric oxide synthase (iNOS), prostaglandin-endoperoxide synthase 2 (PTGS2) and matrix metalloproteinases (MMP1, MMP3, and MMP13). The cytokine-induced gene expression in the NPs was ameliorated with EGCG. This study provides a proof of concept that inflammatory NP cultures, with appropriate containment, can be useful for the discovery and evaluation of molecular therapeutic strategies against early degenerative disc disease. Full article

(This article belongs to the Special Issue Natural Anti-Inflammatory Agents)

► Figures

Open AccessReview Microfluidic-Based Multi-Organ Platforms for Drug Discovery

by Ahmad Rezaei Kolahchi, Nima Khadem Mohtaram, Hassan Pezeshgi Modarres, Mohammad Hossein Mohammadi, Armin Geraili, Parya Jafari, Mohsen Akbari and Amir Sanati-Nezhad

Micromachines 2016, 7(9), 162; doi:10.3390/mi7090162

Received: 24 May 2016 / Revised: 23 August 2016 / Accepted: 24 August 2016 / Published: 8 September 2016

Viewed by 1328 | PDF Full-text (2089 KB) | HTML Full-text | XML Full-text

Abstract

Development of predictive multi-organ models before implementing costly clinical trials is central for screening the toxicity, efficacy, and side effects of new therapeutic agents. Despite significant efforts that have been recently made to develop biomimetic in vitro tissue models, the clinical application of

[...] Read more.

Development of predictive multi-organ models before implementing costly clinical trials is central for screening the toxicity, efficacy, and side effects of new therapeutic agents. Despite significant efforts that have been recently made to develop biomimetic in vitro tissue models, the clinical application of such platforms is still far from reality. Recent advances in physiologically-based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling, micro- and nanotechnology, and in silico modeling have enabled single- and multi-organ platforms for investigation of new chemical agents and tissue-tissue interactions. This review provides an overview of the principles of designing microfluidic-based organ-on-chip models for drug testing and highlights current state-of-the-art in developing predictive multi-organ models for studying the cross-talk of interconnected organs. We further discuss the challenges associated with establishing a predictive body-on-chip (BOC) model such as the scaling, cell types, the common medium, and principles of the study design for characterizing the interaction of drugs with multiple targets. Full article

(This article belongs to the Special Issue Microfluidic Bioreactors and Organ-on-Chip Devices for Drug Screening and Disease Modeling)

► Figures

Open AccessReview Treatment of HEV Infection in Patients with a Solid-Organ Transplant and Chronic Hepatitis

by Nassim Kamar, Sébastien Lhomme, Florence Abravanel, Olivier Marion, Jean-Marie Peron, Laurent Alric and Jacques Izopet

Viruses 2016, 8(8), 222; doi:10.3390/v8080222

Received: 28 June 2016 / Revised: 30 July 2016 / Accepted: 9 August 2016 / Published: 15 August 2016

Cited by 4 | Viewed by 733 | PDF Full-text (667 KB) | HTML Full-text | XML Full-text

Abstract

Hepatitis E virus (HEV) infection can cause hepatic and extra-hepatic manifestations. Treatment of HEV infection has been thoroughly studied in solid-organ-transplant patients who have developed a chronic HEV infection. In this review, we report on our current knowledge regarding treatment of HEV infection.

[...] Read more.

Hepatitis E virus (HEV) infection can cause hepatic and extra-hepatic manifestations. Treatment of HEV infection has been thoroughly studied in solid-organ-transplant patients who have developed a chronic HEV infection. In this review, we report on our current knowledge regarding treatment of HEV infection. Full article

(This article belongs to the Special Issue Recent Progress in Hepatitis E Virus Research)

► Figures

Figure 1

Open AccessReview Circulating Organ-Specific MicroRNAs Serve as Biomarkers in Organ-Specific Diseases: Implications for Organ Allo- and Xeno-Transplantation

by Ming Zhou, Hidetaka Hara, Yifan Dai, Lisha Mou, David K. C. Cooper, Changyou Wu and Zhiming Cai

Int. J. Mol. Sci. 2016, 17(8), 1232; doi:10.3390/ijms17081232

Received: 26 May 2016 / Revised: 25 July 2016 / Accepted: 26 July 2016 / Published: 1 August 2016

Cited by 3 | Viewed by 878 | PDF Full-text (1284 KB) | HTML Full-text | XML Full-text

Abstract

Different cell types possess different miRNA expression profiles, and cell/tissue/organ-specific miRNAs (or profiles) indicate different diseases. Circulating miRNA is either actively secreted by living cells or passively released during cell death. Circulating cell/tissue/organ-specific miRNA may serve as a non-invasive biomarker for allo- or

[...] Read more.

Different cell types possess different miRNA expression profiles, and cell/tissue/organ-specific miRNAs (or profiles) indicate different diseases. Circulating miRNA is either actively secreted by living cells or passively released during cell death. Circulating cell/tissue/organ-specific miRNA may serve as a non-invasive biomarker for allo- or xeno-transplantation to monitor organ survival and immune rejection. In this review, we summarize the proof of concept that circulating organ-specific miRNAs serve as non-invasive biomarkers for a wide spectrum of clinical organ-specific manifestations such as liver-related disease, heart-related disease, kidney-related disease, and lung-related disease. Furthermore, we summarize how circulating organ-specific miRNAs may have advantages over conventional methods for monitoring immune rejection in organ transplantation. Finally, we discuss the implications and challenges of applying miRNA to monitor organ survival and immune rejection in allo- or xeno-transplantation. Full article

(This article belongs to the Special Issue Biomarkers in Drug-Induced Organ Injury)

► Figures

Open AccessReview Organ-Tumor-on-a-Chip for Chemosensitivity Assay: A Critical Review

by Navid Kashaninejad, Mohammad Reza Nikmaneshi, Hajar Moghadas, Amir Kiyoumarsi Oskouei, Milad Rismanian, Maryam Barisam, Mohammad Said Saidi and Bahar Firoozabadi

Micromachines 2016, 7(8), 130; doi:10.3390/mi7080130

Received: 11 May 2016 / Revised: 22 June 2016 / Accepted: 18 July 2016 / Published: 28 July 2016

Cited by 2 | Viewed by 1155 | PDF Full-text (4096 KB) | HTML Full-text | XML Full-text

Abstract

With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis

[...] Read more.

With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system) make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D) nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate the efficacy of anticancer drugs are integrated on the same chip. In this article, we critically review the cutting edge advances in this field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1) Lung; (2) Bone marrow; (3) Brain; (4) Breast; (5) Urinary system (kidney, bladder and prostate); (6) Intestine; and (7) Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heart–liver–intestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET) of anticancer drugs and more realistically recapitulate tumor in vivo-like microenvironment. Full article

(This article belongs to the Special Issue Microfluidic Bioreactors and Organ-on-Chip Devices for Drug Screening and Disease Modeling)

► Figures

Open AccessReview Mimicking the Kidney: A Key Role in Organ-on-Chip Development

by Roberto Paoli and Josep Samitier

Micromachines 2016, 7(7), 126; doi:10.3390/mi7070126

Received: 28 April 2016 / Revised: 11 July 2016 / Accepted: 13 July 2016 / Published: 20 July 2016

Viewed by 880 | PDF Full-text (3508 KB) | HTML Full-text | XML Full-text

Abstract

Pharmaceutical drug screening and research into diseases call for significant improvement in the effectiveness of current in vitro models. Better models would reduce the likelihood of costly failures at later drug development stages, while limiting or possibly even avoiding the use of animal

[...] Read more.

Pharmaceutical drug screening and research into diseases call for significant improvement in the effectiveness of current in vitro models. Better models would reduce the likelihood of costly failures at later drug development stages, while limiting or possibly even avoiding the use of animal models. In this regard, promising advances have recently been made by the so-called “organ-on-chip” (OOC) technology. By combining cell culture with microfluidics, biomedical researchers have started to develop microengineered models of the functional units of human organs. With the capacity to mimic physiological microenvironments and vascular perfusion, OOC devices allow the reproduction of tissue- and organ-level functions. When considering drug testing, nephrotoxicity is a major cause of attrition during pre-clinical, clinical, and post-approval stages. Renal toxicity accounts for 19% of total dropouts during phase III drug evaluation—more than half the drugs abandoned because of safety concerns. Mimicking the functional unit of the kidney, namely the nephron, is therefore a crucial objective. Here we provide an extensive review of the studies focused on the development of a nephron-on-chip device. Full article

(This article belongs to the Special Issue Microfluidic Bioreactors and Organ-on-Chip Devices for Drug Screening and Disease Modeling)

► Figures

Open AccessArticle Cytostretch, an Organ-on-Chip Platform

by Nikolas Gaio, Berend van Meer, William Quirós Solano, Lambert Bergers, Anja van de Stolpe, Christine Mummery, Pasqualina M. Sarro and Ronald Dekker

Micromachines 2016, 7(7), 120; doi:10.3390/mi7070120

Received: 10 May 2016 / Revised: 30 June 2016 / Accepted: 7 July 2016 / Published: 14 July 2016

Cited by 4 | Viewed by 622 | PDF Full-text (8270 KB) | HTML Full-text | XML Full-text

Abstract

Organ-on-Chips (OOCs) are micro-fabricated devices which are used to culture cells in order to mimic functional units of human organs. The devices are designed to simulate the physiological environment of tissues in vivo. Cells in some types of OOCs can be stimulated in

[...] Read more.

Organ-on-Chips (OOCs) are micro-fabricated devices which are used to culture cells in order to mimic functional units of human organs. The devices are designed to simulate the physiological environment of tissues in vivo. Cells in some types of OOCs can be stimulated in situ by electrical and/or mechanical actuators. These actuations can mimic physiological conditions in real tissue and may include fluid or air flow, or cyclic stretch and strain as they occur in the lung and heart. These conditions similarly affect cultured cells and may influence their ability to respond appropriately to physiological or pathological stimuli. To date, most focus has been on devices specifically designed to culture just one functional unit of a specific organ: lung alveoli, kidney nephrons or blood vessels, for example. In contrast, the modular Cytostretch membrane platform described here allows OOCs to be customized to different OOC applications. The platform utilizes silicon-based micro-fabrication techniques that allow low-cost, high-volume manufacturing. We describe the platform concept and its modules developed to date. Membrane variants include membranes with (i) through-membrane pores that allow biological signaling molecules to pass between two different tissue compartments; (ii) a stretchable micro-electrode array for electrical monitoring and stimulation; (iii) micro-patterning to promote cell alignment; and (iv) strain gauges to measure changes in substrate stress. This paper presents the fabrication and the proof of functionality for each module of the Cytostretch membrane. The assessment of each additional module demonstrate that a wide range of OOCs can be achieved. Full article

(This article belongs to the Special Issue Microfluidic Bioreactors and Organ-on-Chip Devices for Drug Screening and Disease Modeling)

► Figures

Open AccessReview Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension

by Natalia Muñoz-Durango, Cristóbal A. Fuentes, Andrés E. Castillo, Luis Martín González-Gómez, Andrea Vecchiola, Carlos E. Fardella and Alexis M. Kalergis

Int. J. Mol. Sci. 2016, 17(7), 797; doi:10.3390/ijms17070797

Received: 24 March 2016 / Revised: 2 May 2016 / Accepted: 10 May 2016 / Published: 23 June 2016

Cited by 7 | Viewed by 1254 | PDF Full-text (906 KB) | HTML Full-text | XML Full-text

Abstract

Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control

[...] Read more.

Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. Full article

(This article belongs to the Special Issue Molecular Research on Hypertension)

Open AccessArticle Feasibility of Multiple Examinations Using ⁶⁸Ga-Labelled Collagelin Analogues: Organ Distribution in Rat for Extrapolation to Human Organ and Whole-Body Radiation Dosimetry

by Irina Velikyan, Ulrika Rosenström, Thomas N. Bulenga, Olof Eriksson and Gunnar Antoni

Pharmaceuticals 2016, 9(2), 31; doi:10.3390/ph9020031

Received: 20 April 2016 / Revised: 30 May 2016 / Accepted: 1 June 2016 / Published: 6 June 2016

Viewed by 851 | PDF Full-text (1008 KB) | HTML Full-text | XML Full-text

Abstract

Objectives: Fibrosis is involved in many chronic diseases. It affects the functionality of vital organs, such as liver, lung, heart and kidney. Two novel imaging agents for positron emission tomography (PET) imaging of fibrosis have previously pre-clinically demonstrated promising target binding and

[...] Read more.

Objectives: Fibrosis is involved in many chronic diseases. It affects the functionality of vital organs, such as liver, lung, heart and kidney. Two novel imaging agents for positron emission tomography (PET) imaging of fibrosis have previously pre-clinically demonstrated promising target binding and organ distribution characteristics. However, the relevant disease monitoring in the clinical setup would require multiple repetitive examinations per year. Thus, it is of paramount importance to investigate the absorbed doses and total effective doses and thus, the potential maximum number of examinations per year. Methods: Two cyclic peptide (c[CPGRVMHGLHLGDDEGPC]) analogues coupled via an ethylene glycol linker (EG₂) to either 2-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7-triazonan-1-yl)acetic acid (NO2A-Col) or 4-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7-triazacyclononan-1-yl)-5-(tert-butoxy)-5-oxopentanoic acid (NODAGA-Col) were labelled with ⁶⁸Ga. The resulting agents, [⁶⁸Ga]Ga-NO2A-Col and [⁶⁸Ga]Ga-NODAGA-Col, were administered in the tail vein of male and female Sprague–Dawley rats (N = 24). An ex vivo organ distribution study was performed at the 5-, 10-, 20-, 40-, 60- and 120-min time points. The resulting data were extrapolated for the estimation of human organ and total body absorbed and total effective doses using Organ Level Internal Dose Assessment Code software (OLINDA/EXM 1.1) assuming a similar organ distribution pattern between the species. Time-integrated radioactivity in each organ was calculated by trapezoidal integration followed by a single-exponential fit to the data points extrapolated to infinity. The resulting values were used for the residence time calculation. Results: Ex vivo organ distribution data revealed fast blood clearance and washout from most of the organs. Although the highest organ absorbed dose was found for kidneys (0.1 mGy/MBq), this organ was not the dose-limiting one and would allow for the administration of over 1460 MBq per year for both [⁶⁸Ga]Ga-NO2A-Col and [⁶⁸Ga]Ga-NODAGA-Col. The total effective dose was the limiting parameter with 0.0155/0.0156 (female/male) mSv/MBq and 0.0164/0.0158 (female/male) mSv/MBq, respectively, for [⁶⁸Ga]Ga-NO2A-Col and [⁶⁸Ga]Ga-NODAGA-Col. This corresponded to the total amount of radioactivity that could be administered per year of 643 and 621 MBq before reaching the annual limit of 10 mSv. Thus, up to six examinations would be possible. The residence time and organ absorbed doses in liver and spleen were higher for [⁶⁸Ga]Ga-NODAGA-Col as compared to [⁶⁸Ga]Ga-NO2A-Col. Conclusion: The limiting parameter for the administered dose was the total effective dose that would allow for at least six examinations per year that might be sufficient for adequate disease monitoring in longitudinal studies and a routine clinical setup. Full article

(This article belongs to the Special Issue New Challenges in Radiochemistry)

Open AccessReview Biodegradable Polymers and Stem Cells for Bioprinting

by Meijuan Lei and Xiaohong Wang

Molecules 2016, 21(5), 539; doi:10.3390/molecules21050539

Received: 16 March 2016 / Revised: 12 April 2016 / Accepted: 13 April 2016 / Published: 29 April 2016

Cited by 7 | Viewed by 1851 | PDF Full-text (1797 KB) | HTML Full-text | XML Full-text

Abstract

It is imperative to develop organ manufacturing technologies based on the high organ failure mortality and serious donor shortage problems. As an emerging and promising technology, bioprinting has attracted more and more attention with its super precision, easy reproduction, fast manipulation and advantages

[...] Read more.

It is imperative to develop organ manufacturing technologies based on the high organ failure mortality and serious donor shortage problems. As an emerging and promising technology, bioprinting has attracted more and more attention with its super precision, easy reproduction, fast manipulation and advantages in many hot research areas, such as tissue engineering, organ manufacturing, and drug screening. Basically, bioprinting technology consists of inkjet bioprinting, laser-based bioprinting and extrusion-based bioprinting techniques. Biodegradable polymers and stem cells are common printing inks. In the printed constructs, biodegradable polymers are usually used as support scaffolds, while stem cells can be engaged to differentiate into different cell/tissue types. The integration of biodegradable polymers and stem cells with the bioprinting techniques has provided huge opportunities for modern science and technologies, including tissue repair, organ transplantation and energy metabolism. Full article

(This article belongs to the Special Issue Biomaterials and Bioprinting)

Open AccessArticle Is There a Chronic Elevation in Organ-Tissue Sleeping Metabolic Rate in Very Fit Runners?

by Taishi Midorikawa, Shigeho Tanaka, Takafumi Ando, Chiaki Tanaka, Konishi Masayuki, Megumi Ohta, Suguru Torii and Shizuo Sakamoto

Nutrients 2016, 8(4), 196; doi:10.3390/nu8040196

Received: 28 November 2015 / Revised: 15 February 2016 / Accepted: 22 March 2016 / Published: 2 April 2016

Viewed by 968 | PDF Full-text (925 KB) | HTML Full-text | XML Full-text

Abstract

It is unclear whether the resting metabolic rate of individual organ-tissue in adults with high aerobic fitness is higher than that in untrained adults; in fact, this topic has been debated for years using a two-component model. To address this issue, in the

[...] Read more.

It is unclear whether the resting metabolic rate of individual organ-tissue in adults with high aerobic fitness is higher than that in untrained adults; in fact, this topic has been debated for years using a two-component model. To address this issue, in the present study, we examined the relationship between the measured sleeping energy expenditure (EE) by using an indirect human calorimeter (IHC) and the calculated resting EE (REE) from organ-tissue mass using magnetic resonance imaging, along with the assumed metabolic rate constants in healthy adults. Seventeen healthy male long-distance runners were recruited and grouped according to the median \(\dot{\text{V}}\)O₂peak: very fit group (>60 mL/min/kg; n = 8) and fit group (<60 mL/min/kg; n = 9). Participants performed a graded exercise test for determining \(\dot{\text{V}}\)O₂peak; X-ray absorptiometry and magnetic resonance imaging were used to determine organ-tissue mass, and IHC was used to determine sleeping EE. The calculated REE was estimated as the sum of individual organ-tissue masses multiplied by their metabolic rate constants. No significant difference was observed in the measured sleeping EE, calculated REE, and their difference, as well as in the slopes and intercepts of the two regression lines between the groups. Moreover, no significant correlation between \(\dot{\text{V}}\)O₂peak and the difference in measured sleeping EE and calculated REE was observed for all subjects. Thus, aerobic endurance training does not result in a chronic elevation in the organ-tissue metabolic rate in cases with \(\dot{\text{V}}\)O₂peak of approximately 60 mL/min/kg. Full article

(This article belongs to the Special Issue Anthropometry, Body Composition and Resting Energy Expenditure in Healthy Populations)

Open AccessReview Severe Dermatophytosis and Acquired or Innate Immunodeficiency: A Review

by Claire Rouzaud, Roderick Hay, Olivier Chosidow, Nicolas Dupin, Anne Puel, Olivier Lortholary and Fanny Lanternier

J. Fungi 2016, 2(1), 4; doi:10.3390/jof2010004

Received: 21 October 2015 / Revised: 16 November 2015 / Accepted: 14 December 2015 / Published: 31 December 2015

Cited by 5 | Viewed by 973 | PDF Full-text (1597 KB) | HTML Full-text | XML Full-text

Abstract

Dermatophytes are keratinophilic fungi responsible for benign and common forms of infection worldwide. However, they can lead to rare and severe diseases in immunocompromised patients. Severe forms include extensive and/or invasive dermatophytosis, i.e., deep dermatophytosis and Majocchi’s granuloma. They are reported in

[...] Read more.

Dermatophytes are keratinophilic fungi responsible for benign and common forms of infection worldwide. However, they can lead to rare and severe diseases in immunocompromised patients. Severe forms include extensive and/or invasive dermatophytosis, i.e., deep dermatophytosis and Majocchi’s granuloma. They are reported in immunocompromised hosts with primary (autosomal recessive CARD9 deficiency) or acquired (solid organ transplantation, autoimmune diseases requiring immunosuppressive treatments, HIV infection) immunodeficiencies. The clinical manifestations of the infection are not specific. Lymph node and organ involvement may also occur. Diagnosis requires both mycological and histological findings. There is no consensus on treatment. Systemic antifungal agents such as terbinafine and azoles (itraconazole or posaconazole) are effective. However, long-term outcome and treatment management depend on the site and extent of the infection and the nature of the underlying immunodeficiency. Full article

(This article belongs to the Special Issue Cutaneous Fungal Diseases)

Open AccessReview Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering

by Ana Rubina Perestrelo, Ana C. P. Águas, Alberto Rainer and Giancarlo Forte

Sensors 2015, 15(12), 31142-31170; doi:10.3390/s151229848

Received: 22 September 2015 / Revised: 16 November 2015 / Accepted: 4 December 2015 / Published: 10 December 2015

Cited by 19 | Viewed by 1767 | PDF Full-text (549 KB) | HTML Full-text | XML Full-text

Abstract

Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery,

[...] Read more.

Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called “organ-on-a-chip” technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field. Full article

(This article belongs to the Special Issue Novel Biomaterials and Sensors for Tissue Engineering)

Open AccessReview Pneumocystis Pneumonia in Solid-Organ Transplant Recipients

by Xavier Iriart, Marine Le Bouar, Nassim Kamar and Antoine Berry

J. Fungi 2015, 1(3), 293-331; doi:10.3390/jof1030293

Received: 17 June 2015 / Revised: 1 September 2015 / Accepted: 2 September 2015 / Published: 28 September 2015

Viewed by 835 | PDF Full-text (266 KB) | HTML Full-text | XML Full-text

Abstract

Pneumocystis pneumonia (PCP) is well known and described in AIDS patients. Due to the increasing use of cytotoxic and immunosuppressive therapies, the incidence of this infection has dramatically increased in the last years in patients with other predisposing immunodeficiencies and remains an important

[...] Read more.

Pneumocystis pneumonia (PCP) is well known and described in AIDS patients. Due to the increasing use of cytotoxic and immunosuppressive therapies, the incidence of this infection has dramatically increased in the last years in patients with other predisposing immunodeficiencies and remains an important cause of morbidity and mortality in solid-organ transplant (SOT) recipients. PCP in HIV-negative patients, such as SOT patients, harbors some specificity compared to AIDS patients, which could change the medical management of these patients. This article summarizes the current knowledge on the epidemiology, risk factors, clinical manifestations, diagnoses, prevention, and treatment of Pneumocystis pneumonia in solid-organ transplant recipients, with a particular focus on the changes caused by the use of post-transplantation prophylaxis. Full article

(This article belongs to the Special Issue Fungal Infections in Transplant Recipients)

Open AccessReview Diagnostic Modalities for Invasive Mould Infections among Hematopoietic Stem Cell Transplant and Solid Organ Recipients: Performance Characteristics and Practical Roles in the Clinic

by Ghady Haidar, Bonnie A. Falcione and M. Hong Nguyen

J. Fungi 2015, 1(2), 252-276; doi:10.3390/jof1020252

Received: 6 June 2015 / Revised: 28 August 2015 / Accepted: 31 August 2015 / Published: 10 September 2015

Cited by 1 | Viewed by 853 | PDF Full-text (740 KB) | HTML Full-text | XML Full-text

Abstract

The morbidity and mortality of hematopoietic stem cell and solid organ transplant patients with invasive fungal infections (IFIs) remain high despite an increase in the number of effective antifungal agents. Early diagnosis leading to timely administration of antifungal therapy has been linked to

[...] Read more.

The morbidity and mortality of hematopoietic stem cell and solid organ transplant patients with invasive fungal infections (IFIs) remain high despite an increase in the number of effective antifungal agents. Early diagnosis leading to timely administration of antifungal therapy has been linked to better outcomes. Unfortunately, the diagnosis of IFIs remains challenging. The current gold standard for diagnosis is a combination of histopathology and culture, for which the sensitivity is <50%. Over the past two decades, a plethora of non-culture-based antigen and molecular assays have been developed and clinically validated. In this article, we will review the performance of the current commercially available non-cultural diagnostics and discuss their practical roles in the clinic. Full article

(This article belongs to the Special Issue Fungal Infections in Transplant Recipients)

Open AccessArticle Bioengineered Lacrimal Gland Organ Regeneration in Vivo

by Masatoshi Hirayama, Kazuo Tsubota and Takashi Tsuji

J. Funct. Biomater. 2015, 6(3), 634-649; doi:10.3390/jfb6030634

Received: 27 June 2015 / Revised: 18 July 2015 / Accepted: 23 July 2015 / Published: 30 July 2015

Cited by 6 | Viewed by 1835 | PDF Full-text (823 KB) | HTML Full-text | XML Full-text

Abstract

The lacrimal gland plays an important role in maintaining a homeostatic environment for healthy ocular surfaces via tear secretion. Dry eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye disorders and causes ocular discomfort, significant visual

[...] Read more.

The lacrimal gland plays an important role in maintaining a homeostatic environment for healthy ocular surfaces via tear secretion. Dry eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye disorders and causes ocular discomfort, significant visual disturbances, and a reduced quality of life. Current therapies for dry eye disease, including artificial tear eye drops, are transient and palliative. The lacrimal gland, which consists of acini, ducts, and myoepithelial cells, develops from its organ germ via reciprocal epithelial-mesenchymal interactions during embryogenesis. Lacrimal tissue stem cells have been identified for use in regenerative therapeutic approaches aimed at restoring lacrimal gland functions. Fully functional organ replacement, such as for tooth and hair follicles, has also been developed via a novel three-dimensional stem cell manipulation, designated the Organ Germ Method, as a next-generation regenerative medicine. Recently, we successfully developed fully functional bioengineered lacrimal gland replacements after transplanting a bioengineered organ germ using this method. This study represented a significant advance in potential lacrimal gland organ replacement as a novel regenerative therapy for dry eye disease. In this review, we will summarize recent progress in lacrimal regeneration research and the development of bioengineered lacrimal gland organ replacement therapy. Full article

(This article belongs to the Special Issue Ocular Tissue Engineering) Printed Edition available

Open AccessReview Histoplasmosis and Blastomycosis in Solid Organ Transplant Recipients

by Carol A. Kauffman and Marisa H. Miceli

J. Fungi 2015, 1(2), 94-106; doi:10.3390/jof1020094

Received: 29 May 2015 / Revised: 17 June 2015 / Accepted: 18 June 2015 / Published: 30 June 2015

Cited by 1 | Viewed by 846 | PDF Full-text (662 KB) | HTML Full-text | XML Full-text

Abstract

Histoplasmosis and blastomycosis are geographically restricted dimorphic fungi that cause infection after the conidia produced in the mold phase are inhaled into the lungs. In the lungs, at 37 °C, these organisms undergo transformation into the yeast phase. In transplant recipients, infection can

[...] Read more.

Histoplasmosis and blastomycosis are geographically restricted dimorphic fungi that cause infection after the conidia produced in the mold phase are inhaled into the lungs. In the lungs, at 37 °C, these organisms undergo transformation into the yeast phase. In transplant recipients, infection can occur by exposure to the mold in the environment, by reactivation of infection that had occurred previously and had been controlled by the host until immunosuppressive medications were given post-transplantation, and finally by transmission from the donor organ in the case of histoplasmosis. In transplant recipients, disseminated infection is common, and pulmonary infection is more likely to be severe than in a non-immunosuppressed person. Diagnosis has been improved, allowing earlier treatment, with the use of rapid antigen tests performed on serum and urine. Initial treatment, for all but the mildest cases of acute pulmonary histoplasmosis, should be with a lipid formulation of amphotericin B. After clinical improvement has occurred, step-down therapy with itraconazole is recommended for a total of 12 months for most transplant recipients, but some patients will require long-term suppressive therapy to prevent relapse of disease. Full article

(This article belongs to the Special Issue Fungal Infections in Transplant Recipients)

Open AccessArticle Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity

by Karolina A.P. Wijnands, Dennis M. Meesters, Kevin W.Y. van Barneveld, Ruben G.J. Visschers, Jacob J. Briedé, Benjamin Vandendriessche, Hans M.H. van Eijk, Babs A.F.M. Bessems, Nadine van den Hoven, Christian J.H. von Wintersdorff, Peter Brouckaert, Nicole D. Bouvy, Wouter H. Lamers, Anje Cauwels and Martijn Poeze

Nutrients 2015, 7(7), 5217-5238; doi:10.3390/nu7075217

Received: 12 May 2015 / Revised: 15 May 2015 / Accepted: 18 June 2015 / Published: 29 June 2015

Abstract

Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative.

[...] Read more.

Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues. Full article

Open AccessReview Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients

by Ramya Chockalingam, Christopher Downing and Stephen K. Tyring

J. Clin. Med. 2015, 4(6), 1229-1239; doi:10.3390/jcm4061229

Received: 9 May 2015 / Revised: 27 May 2015 / Accepted: 28 May 2015 / Published: 3 June 2015

Cited by 13 | Viewed by 1526 | PDF Full-text (111 KB) | HTML Full-text | XML Full-text

Abstract

Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC) are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent

[...] Read more.

Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC) are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent years, human papillomaviruses (HPV) of the beta genus have been implicated in the pathogenesis of post-transplant SCCs. The underlying mechanism of carcinogenesis has been attributed to the E6 and E7 proteins of HPV. Specific immunosuppressive medications, such as the calcineurin inhibitors and azathioprine, are associated with a higher incidence of post-transplant SCCs compared to other immunosuppressive agents. Compared to other immunosuppressives, mTOR inhibitors and mycophenolate mofetil have been associated with a decreased risk of developing post-transplant non-melanoma skin cancers. As a result, they may represent ideal immunosuppressive medications in organ transplant recipients. Treatment options for post-transplant SCCs include surgical excision, Mohs micrographic surgery, systemic retinoid therapy, adjunct topical therapy, electrodessication and curettage, and radiation therapy. This review will discuss the epidemiology, risk factors, and management options of post-transplant SCCs. In addition, the underlying mechanisms of beta-HPV mediated carcinogenesis will be discussed. Full article

(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)

Open AccessArticle Technical Efficiency and Organ Transplant Performance: A Mixed-Method Approach

by Carmen de-Pablos-Heredero, Carlos Fernández-Renedo and Jose-Amelio Medina-Merodio

Int. J. Environ. Res. Public Health 2015, 12(5), 4869-4888; doi:10.3390/ijerph120504869

Received: 24 January 2015 / Revised: 9 April 2015 / Accepted: 23 April 2015 / Published: 5 May 2015

Viewed by 1110 | PDF Full-text (456 KB) | HTML Full-text | XML Full-text

Abstract

Mixed methods research is interesting to understand complex processes. Organ transplants are complex processes in need of improved final performance in times of budgetary restrictions. As the main objective a mixed method approach is used in this article to quantify the technical efficiency

[...] Read more.

Mixed methods research is interesting to understand complex processes. Organ transplants are complex processes in need of improved final performance in times of budgetary restrictions. As the main objective a mixed method approach is used in this article to quantify the technical efficiency and the excellence achieved in organ transplant systems and to prove the influence of organizational structures and internal processes in the observed technical efficiency. The results show that it is possible to implement mechanisms for the measurement of the different components by making use of quantitative and qualitative methodologies. The analysis show a positive relationship between the levels related to the Baldrige indicators and the observed technical efficiency in the donation and transplant units of the 11 analyzed hospitals. Therefore it is possible to conclude that high levels in the Baldrige indexes are a necessary condition to reach an increased level of the service offered. Full article

Open AccessArticle Effects of Mechanical Stretching on the Morphology and Cytoskeleton of Vaginal Fibroblasts from Women with Pelvic Organ Prolapse

by Sumei Wang, Zhenyu Zhang, Dongyuan Lü and Qiuxiang Xu

Int. J. Mol. Sci. 2015, 16(5), 9406-9419; doi:10.3390/ijms16059406

Received: 12 October 2014 / Revised: 4 March 2015 / Accepted: 8 April 2015 / Published: 27 April 2015

Cited by 4 | Viewed by 1514 | PDF Full-text (5167 KB) | HTML Full-text | XML Full-text

Abstract

Mechanical load and postmenopausal hypoestrogen are risk factors for pelvic organ prolapse (POP). In this study, we applied a 0.1-Hz uniaxial cyclic mechanical stretching (CS) with 10% elongation and 10⁻⁸ M 17-β-estradiol to vaginal fibroblasts isolated from postmenopausal women with or without

[...] Read more.

Mechanical load and postmenopausal hypoestrogen are risk factors for pelvic organ prolapse (POP). In this study, we applied a 0.1-Hz uniaxial cyclic mechanical stretching (CS) with 10% elongation and 10⁻⁸ M 17-β-estradiol to vaginal fibroblasts isolated from postmenopausal women with or without POP to investigate the effects of CS and estrogen on cell morphology and cytoskeletons of normal and POP fibroblasts. Under static culture condition, POP fibroblasts exhibited lower cell circularity and higher relative fluorescence intensities (RFIs) of F-actin, α-tubulin and vimentin. When cultured with CS, all fibroblasts grew perpendicular to the force and exhibited a decreased cell projection area, cell circularity and increased cell length/width ratio; normal fibroblasts exhibited increased RFIs of all three types of cytoskeleton, and POP fibroblasts exhibited a decreased RFI of F-actin and no significant differences of α-tubulin and vimentin. After being cultured with 17-β-estradiol and CS, normal fibroblasts no longer exhibited significant changes in the cell projection area and the RFIs of F-actin and α-tubulin; POP fibroblasts exhibited no significant changes in cell circularity, length/width ratio and F-actin even with the increased RFIs of α-tubulin and vimentin. These findings suggest that POP fibroblasts have greater sensitivity to and lower tolerance for mechanical stretching, and estrogen can improve the prognosis. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

► Figures

Open AccessArticle Accuracy Analysis of a Multi-View Stereo Approach for Phenotyping of Tomato Plants at the Organ Level

by Johann Christian Rose, Stefan Paulus and Heiner Kuhlmann

Sensors 2015, 15(5), 9651-9665; doi:10.3390/s150509651

Received: 18 December 2014 / Revised: 14 April 2015 / Accepted: 20 April 2015 / Published: 24 April 2015

Cited by 10 | Viewed by 1524 | PDF Full-text (10766 KB) | HTML Full-text | XML Full-text

Abstract

Accessing a plant’s 3D geometry has become of significant importance for phenotyping during the last few years. Close-up laser scanning is an established method to acquire 3D plant shapes in real time with high detail, but it is stationary and has high investment

[...] Read more.

Accessing a plant’s 3D geometry has become of significant importance for phenotyping during the last few years. Close-up laser scanning is an established method to acquire 3D plant shapes in real time with high detail, but it is stationary and has high investment costs. 3D reconstruction from images using structure from motion (SfM) and multi-view stereo (MVS) is a flexible cost-effective method, but requires post-processing procedures. The aim of this study is to evaluate the potential measuring accuracy of an SfM- and MVS-based photogrammetric method for the task of organ-level plant phenotyping. For this, reference data are provided by a high-accuracy close-up laser scanner. Using both methods, point clouds of several tomato plants were reconstructed at six following days. The parameters leaf area, main stem height and convex hull of the complete plant were extracted from the 3D point clouds and compared to the reference data regarding accuracy and correlation. These parameters were chosen regarding the demands of current phenotyping scenarios. The study shows that the photogrammetric approach is highly suitable for the presented monitoring scenario, yielding high correlations to the reference measurements. This cost-effective 3D reconstruction method depicts an alternative to an expensive laser scanner in the studied scenarios with potential for automated procedures. Full article

(This article belongs to the Section Physical Sensors)

Open AccessArticle Analysis of the Science and Technology Narrative within Organ Donation and Transplantation Coverage in Canadian Newspapers

by Jennifer Cheung and Gregor Wolbring

Technologies 2015, 3(2), 74-93; doi:10.3390/technologies3020074

Received: 8 September 2014 / Revised: 2 March 2015 / Accepted: 2 April 2015 / Published: 9 April 2015

Cited by 1 | Viewed by 1685 | PDF Full-text (365 KB) | HTML Full-text | XML Full-text

Abstract

Organ failure is one cause of death. Advancements in scientific research and technological development made organ transplantation possible and continue to find better ways to substitute failed organs with other organs of biological origin or artificial organs. Media, including newspapers, are one source

[...] Read more.

Organ failure is one cause of death. Advancements in scientific research and technological development made organ transplantation possible and continue to find better ways to substitute failed organs with other organs of biological origin or artificial organs. Media, including newspapers, are one source of information for the public. The purpose of this study was to examine to what extent and how science and technology research and development are covered in the organ transplantation and organ donation (ODOT) coverage of n = 300 Canadian newspapers, including the two Canadian newspapers with national reach (The Globe and Mail, National Post). The study generated qualitative and quantitative data addressing the following issues: (1) which scientific and technological developments are mentioned in the ODOT coverage; and (2) what issues are mentioned in the coverage of scientific and technological advancements linked to ODOT. We found little to no coverage of many technological and scientific advancements evident in academic and grey literature covering ODOT, and we found little engagement with social and ethical issues already raised about these advancements in the literature. The only area we found to be covered to a broader extent was xenotransplantation, although the coverage stopped after 2002. We argue that the newspaper coverage of ODOT under reports scientific and technological advancements related to ODOT and the issues these advancements might raise. Full article

Open AccessReview Pathogenesis of Target Organ Damage in Hypertension: Role of Mitochondrial Oxidative Stress

by Speranza Rubattu, Beniamino Pagliaro, Giorgia Pierelli, Caterina Santolamazza, Sara Di Castro, Silvia Mennuni and Massimo Volpe

Int. J. Mol. Sci. 2015, 16(1), 823-839; doi:10.3390/ijms16010823

Received: 18 November 2014 / Accepted: 26 December 2014 / Published: 31 December 2014

Cited by 29 | Viewed by 2869 | PDF Full-text (1201 KB) | HTML Full-text | XML Full-text

Abstract

Hypertension causes target organ damage (TOD) that involves vasculature, heart, brain and kidneys. Complex biochemical, hormonal and hemodynamic mechanisms are involved in the pathogenesis of TOD. Common to all these processes is an increased bioavailability of reactive oxygen species (ROS). Both in vitro

[...] Read more.

Hypertension causes target organ damage (TOD) that involves vasculature, heart, brain and kidneys. Complex biochemical, hormonal and hemodynamic mechanisms are involved in the pathogenesis of TOD. Common to all these processes is an increased bioavailability of reactive oxygen species (ROS). Both in vitro and in vivo studies explored the role of mitochondrial oxidative stress as a mechanism involved in the pathogenesis of TOD in hypertension, especially focusing on atherosclerosis, heart disease, renal failure, cerebrovascular disease. Both dysfunction of mitochondrial proteins, such as uncoupling protein-2 (UCP2), superoxide dismutase (SOD) 2, peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), calcium channels, and the interaction between mitochondria and other sources of ROS, such as NADPH oxidase, play an important role in the development of endothelial dysfunction, cardiac hypertrophy, renal and cerebral damage in hypertension. Commonly used anti-hypertensive drugs have shown protective effects against mitochondrial-dependent oxidative stress. Notably, few mitochondrial proteins can be considered therapeutic targets on their own. In fact, antioxidant therapies specifically targeted at mitochondria represent promising strategies to reduce mitochondrial dysfunction and related hypertensive TOD. In the present article, we discuss the role of mitochondrial oxidative stress as a contributing factor to hypertensive TOD development. We also provide an overview of mitochondria-based treatment strategies that may reveal useful to prevent TOD and reduce its progression. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)

Open AccessArticle The Liturgical Use of the Organ in the Sixteenth Century: the Judgments of Cajetan and the Dominican Order

by Michael O'Connor

Religions 2014, 5(3), 751-766; doi:10.3390/rel5030751

Received: 10 June 2014 / Revised: 3 July 2014 / Accepted: 10 July 2014 / Published: 13 August 2014

Viewed by 1172 | PDF Full-text (123 KB) | HTML Full-text | XML Full-text

Abstract

This paper explores the liturgical use of the organ in the sixteenth century according to the judgments of Tommaso de Vio, Cajetan (1469–1534) and the Dominicans. In particular, it asks the question: In worship, is solo organ music capable of conveying a specific

[...] Read more.

This paper explores the liturgical use of the organ in the sixteenth century according to the judgments of Tommaso de Vio, Cajetan (1469–1534) and the Dominicans. In particular, it asks the question: In worship, is solo organ music capable of conveying a specific meaning or a particular text (as seemed to be expected in alternatim practice)? The Dominican sources show an increasingly skeptical attitude, with a consequent tendency to limit the organ’s role in worship. The implication of this study is that organ alternatim did not fall out of favor (with the Dominicans at least) because it failed to carry out the job it was given in the fourteenth and fifteenth centuries, but because it could not do the new job is was given in the sixteenth century. Organ alternatim made sense in a gothic worldview, but less so under the influence of renaissance humanism. While these Dominicans accepted the use of the organ, they did so with great concern at the potential influx of secular music into worship, since secular melodies and rhythms, even without their original words, bring multiple inappropriate associations. To remedy this, various strategies were used to harness instrumental music to text. Full article

(This article belongs to the Special Issue Music and Spirituality) Printed Edition available

Open AccessArticle Diurnal Profiles of Melatonin Synthesis-Related Indoles, Catecholamines and Their Metabolites in the Duck Pineal Organ

by Bogdan Lewczuk, Natalia Ziółkowska, Magdalena Prusik and Barbara Przybylska-Gornowicz

Int. J. Mol. Sci. 2014, 15(7), 12604-12630; doi:10.3390/ijms150712604

Received: 5 June 2014 / Revised: 1 July 2014 / Accepted: 3 July 2014 / Published: 16 July 2014

Cited by 4 | Viewed by 1617 | PDF Full-text (2687 KB) | HTML Full-text | XML Full-text

Abstract

This study characterizes the diurnal profiles of ten melatonin synthesis-related indoles, the quantitative relations between these compounds, and daily variations in the contents of catecholamines and their metabolites in the domestic duck pineal organ. Fourteen-week-old birds, which were reared under a 12L:12D cycle,

[...] Read more.

This study characterizes the diurnal profiles of ten melatonin synthesis-related indoles, the quantitative relations between these compounds, and daily variations in the contents of catecholamines and their metabolites in the domestic duck pineal organ. Fourteen-week-old birds, which were reared under a 12L:12D cycle, were killed at two-hour intervals. The indole contents were measured using HPLC with fluorescence detection, whereas the levels of catecholamines and their metabolites were measured using HPLC with electrochemical detection. All indole contents, except for tryptophan, showed significant diurnal variations. The 5-hydroxytryptophan level was approximately two-fold higher during the scotophase than during the photophase. The serotonin content increased during the first half of the photophase, remained elevated for approximately 10 h and then rapidly decreased in the middle of the scotophase. N-acetylserotonin showed the most prominent changes, with a more than 15-fold increase at night. The melatonin cycle demonstrated only an approximately 5-fold difference between the peak and nadir. The 5-methoxytryptamine content was markedly elevated during the scotophase. The 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid and 5-methoxytryptophol profiles were analogous to the serotonin rhythm. The norepinephrine and dopamine contents showed no significant changes. The DOPA, DOPAC and homovanillic acid levels were higher during the scotophase than during the photophase. Vanillylmandelic acid showed the opposite rhythm, with an elevated level during the daytime. Full article

(This article belongs to the Special Issue Advances in the Research of Melatonin 2014)

► Figures

Open AccessArticle Biological Effects of Clinically Relevant CoCr Nanoparticles in the Dura Mater: An Organ Culture Study

by Iraklis Papageorgiou, Thomas Abberton, Martin Fuller, Joanne L. Tipper, John Fisher and Eileen Ingham

Nanomaterials 2014, 4(2), 485-504; doi:10.3390/nano4020485

Received: 29 March 2014 / Revised: 9 May 2014 / Accepted: 26 May 2014 / Published: 16 June 2014

Cited by 2 | Viewed by 1498 | PDF Full-text (4191 KB) | HTML Full-text | XML Full-text

Abstract

Medical interventions for the treatment of spinal disc degeneration include total disc replacement and fusion devices. There are, however, concerns regarding the generation of wear particles by these devices, the majority of which are in the nanometre sized range with the potential to

[...] Read more.

Medical interventions for the treatment of spinal disc degeneration include total disc replacement and fusion devices. There are, however, concerns regarding the generation of wear particles by these devices, the majority of which are in the nanometre sized range with the potential to cause adverse biological effects in the surrounding tissues. The aims of this study were to develop an organ culture model of the porcine dura mater and to investigate the biological effects of CoCr nanoparticles in this model. A range of histological techniques were used to analyse the structure of the tissue in the organ culture. The biological effects of the CoCr wear particles and the subsequent structural changes were assessed using tissue viability assays, cytokine assays, histology, immunohistochemistry, and TEM imaging. The physiological structure of the dura mater remained unchanged during the seven days of in vitro culture. There was no significant loss of cell viability. After exposure of the organ culture to CoCr nanoparticles, there was significant loosening of the epithelial layer, as well as the underlying collagen matrix. TEM imaging confirmed these structural alterations. These structural alterations were attributed to the production of MMP-1, -3, -9, -13, and TIMP-1. ELISA analysis revealed that there was significant release of cytokines including IL-8, IL-6, TNF-α, ECP and also the matrix protein, tenascin-C. This study suggested that CoCr nanoparticles did not cause cytotoxicity in the dura mater but they caused significant alterations to its structural integrity that could lead to significant secondary effects due to nanoparticle penetration, such as inflammation to the local neural tissue. Full article

(This article belongs to the Special Issue Nanotoxicology)

► Figures

Open AccessReview The Power and the Promise of Cell Reprogramming: Personalized Autologous Body Organ and Cell Transplantation

by Ana Belen Alvarez Palomo, Michaela Lucas, Rodney J. Dilley, Samuel McLenachan, Fred Kuanfu Chen, Jordi Requena, Marti Farrera Sal, Andrew Lucas, Inaki Alvarez, Dolores Jaraquemada and Michael J. Edel

J. Clin. Med. 2014, 3(2), 373-387; doi:10.3390/jcm3020373

Received: 14 January 2014 / Revised: 17 February 2014 / Accepted: 19 February 2014 / Published: 4 April 2014

Viewed by 1769 | PDF Full-text (241 KB) | HTML Full-text | XML Full-text

Abstract

Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) or direct reprogramming to desired cell types are powerful and new in vitro methods for the study of human disease, cell replacement therapy, and drug development. Both methods to reprogram cells are unconstrained by

[...] Read more.

Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) or direct reprogramming to desired cell types are powerful and new in vitro methods for the study of human disease, cell replacement therapy, and drug development. Both methods to reprogram cells are unconstrained by the ethical and social questions raised by embryonic stem cells. iPSC technology promises to enable personalized autologous cell therapy and has the potential to revolutionize cell replacement therapy and regenerative medicine. Potential applications of iPSC technology are rapidly increasing in ambition from discrete cell replacement applications to the iPSC assisted bioengineering of body organs for personalized autologous body organ transplant. Recent work has demonstrated that the generation of organs from iPSCs is a future possibility. The development of embryonic-like organ structures bioengineered from iPSCs has been achieved, such as an early brain structure (cerebral organoids), bone, optic vesicle-like structures (eye), cardiac muscle tissue (heart), primitive pancreas islet cells, a tooth-like structure (teeth), and functional liver buds (liver). Thus, iPSC technology offers, in the future, the powerful and unique possibility to make body organs for transplantation removing the need for organ donation and immune suppressing drugs. Whilst it is clear that iPSCs are rapidly becoming the lead cell type for research into cell replacement therapy and body organ transplantation strategies in humans, it is not known whether (1) such transplants will stimulate host immune responses; and (2) whether this technology will be capable of the bioengineering of a complete and fully functional human organ. This review will not focus on reprogramming to iPSCs, of which a plethora of reviews can be found, but instead focus on the latest developments in direct reprogramming of cells, the bioengineering of body organs from iPSCs, and an analysis of the immune response induced by iPSC-derived cells and tissues. Full article

(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)

Open AccessReview Increased Circulatory Asymmetric Dimethylarginine and Multiple Organ Failure: Bile Duct Ligation in Rat as a Model

by Jiunn-Ming Sheen, Yu-Chieh Chen, You-Lin Tain and Li-Tung Huang

Int. J. Mol. Sci. 2014, 15(3), 3989-4006; doi:10.3390/ijms15033989

Received: 5 December 2013 / Revised: 4 February 2014 / Accepted: 26 February 2014 / Published: 5 March 2014

Cited by 9 | Viewed by 1885 | PDF Full-text (343 KB) | HTML Full-text | XML Full-text

Abstract

Bile duct ligation (BDL)-treated rats exhibit cholestasis, increased systemic oxidative stress, and liver fibrosis, which ultimately lead to liver cirrhosis. Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of nitric oxide synthase that can decrease the synthesis of nitric oxide. BDL rats have higher

[...] Read more.

Bile duct ligation (BDL)-treated rats exhibit cholestasis, increased systemic oxidative stress, and liver fibrosis, which ultimately lead to liver cirrhosis. Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of nitric oxide synthase that can decrease the synthesis of nitric oxide. BDL rats have higher plasma and hepatic ADMA levels, which may be due to increased hepatic protein arginine methyltransferase-1 and decreased dimethylarginine dimethylaminohydrolase expression. BDL rats also exhibit renal and brain damage characterized by increased tissue ADMA concentrations. The increased plasma ADMA levels and multiple organ damages seen here are also observed following multiple organ failures associated with critical illness. This review discusses the dysregulation of ADMA in major organs in BDL rats and the role of increased ADMA in multiple organ damages. Full article

(This article belongs to the Special Issue ADMA and Nitrergic System)

Open AccessArticle Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis

by Tanya L. Poshusta, Nagaaki Katoh, Morie A. Gertz, Angela Dispenzieri and Marina Ramirez-Alvarado

Int. J. Mol. Sci. 2013, 14(11), 22604-22617; doi:10.3390/ijms141122604

Received: 1 October 2013 / Revised: 25 October 2013 / Accepted: 4 November 2013 / Published: 15 November 2013

Cited by 13 | Viewed by 1868 | PDF Full-text (677 KB) | HTML Full-text | XML Full-text

Abstract

Light chain (AL) amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatments. AL amyloidosis patients

[...] Read more.

Light chain (AL) amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatments. AL amyloidosis patients who achieve hematological complete response (CR) do not necessarily achieve organ response regardless of the treatment they received. In order to investigate the possible correlation between amyloid formation kinetics and organ response, we selected AL amyloidosis patients from the trial with kidney involvement and CR after treatment. Six patients were selected and their monoclonal immunoglobulin light chains were characterized. The proteins showed differences in their stability and their kinetics of amyloid formation. A correlation was detected at pH 7.4, showing that less stable proteins are more likely to form amyloid fibrils. AL-T03 is too unstable to form amyloid fibrils at pH 7.4. This protein was found in the only patient in the study that had organ response, suggesting that partially folded species are required for amyloid formation to occur in AL amyloidosis. Full article

(This article belongs to the collection Protein Folding)

Open AccessReview Calcidiol Deficiency in End-Stage Organ Failure and after Solid Organ Transplantation: Status quo

by Ursula Thiem, Bartosz Olbramski and Kyra Borchhardt

Nutrients 2013, 5(7), 2352-2371; doi:10.3390/nu5072352

Received: 7 May 2013 / Revised: 13 June 2013 / Accepted: 14 June 2013 / Published: 1 July 2013

Viewed by 2227 | PDF Full-text (438 KB) | HTML Full-text | XML Full-text

Abstract

Among patients with organ failure, vitamin D deficiency is extremely common and frequently does not resolve after transplantation. This review crystallizes and summarizes existing data on the status quo of vitamin D deficiency in patients with organ failure and in solid organ transplant

[...] Read more.

Among patients with organ failure, vitamin D deficiency is extremely common and frequently does not resolve after transplantation. This review crystallizes and summarizes existing data on the status quo of vitamin D deficiency in patients with organ failure and in solid organ transplant recipients. Interventional studies evaluating different treatment strategies, as well as current clinical practice guidelines and recommendations on the management of low vitamin D status in these patients are also discussed. Full article

(This article belongs to the Special Issue Vitamin D and Human Health) Printed Edition available

Open AccessReview Homeotic Genes and the ABCDE Model for Floral Organ Formation in Wheat

by Koji Murai

Plants 2013, 2(3), 379-395; doi:10.3390/plants2030379

Received: 19 April 2013 / Revised: 2 June 2013 / Accepted: 18 June 2013 / Published: 25 June 2013

Cited by 6 | Viewed by 2655 | PDF Full-text (615 KB) | HTML Full-text | XML Full-text

Abstract

Floral organ formation has been the subject of intensive study for over 20 years, particularly in the model dicot species Arabidopsis thaliana. These studies have led to the establishment of a general model for the development of floral organs in higher plants,

[...] Read more.

Floral organ formation has been the subject of intensive study for over 20 years, particularly in the model dicot species Arabidopsis thaliana. These studies have led to the establishment of a general model for the development of floral organs in higher plants, the so-called ABCDE model, in which floral whorl-specific combinations of class A, B, C, D, or E genes specify floral organ identity. In Arabidopsis, class A, B, C, D, E genes encode MADS-box transcription factors except for the class A gene APETALA2. Mutation of these genes induces floral organ homeosis. In this review, I focus on the roles of these homeotic genes in bread wheat (Triticum aestivum), particularly with respect to the ABCDE model. Pistillody, the homeotic transformation of stamens into pistil-like structures, occurs in cytoplasmic substitution (alloplasmic) wheat lines that have the cytoplasm of the related wild species Aegilops crassa. This phenomenon is a valuable tool for analysis of the wheat ABCDE model. Using an alloplasmic line, the wheat ortholog of DROOPING LEAF (TaDL), a member of the YABBY gene family, has been shown to regulate pistil specification. Here, I describe the current understanding of the ABCDE model for floral organ formation in wheat. Full article

(This article belongs to the Special Issue Developmental Biology and Biotechnology of Plant Sexual Reproduction)

Open AccessArticle Gonadotropins Activate Oncogenic Pathways to Enhance Proliferation in Normal Mouse Ovarian Surface Epithelium

by Tyvette S. Hilliard, Dimple A. Modi and Joanna E. Burdette

Int. J. Mol. Sci. 2013, 14(3), 4762-4782; doi:10.3390/ijms14034762

Received: 31 January 2013 / Revised: 21 February 2013 / Accepted: 25 February 2013 / Published: 28 February 2013

Cited by 14 | Viewed by 2204 | PDF Full-text (1830 KB) | HTML Full-text | XML Full-text

Abstract

Ovarian cancer is the most lethal gynecological malignancy affecting American women. The gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), have been implicated as growth factors in ovarian cancer. In the present study, pathways activated by FSH and LH in normal ovarian

[...] Read more.

Ovarian cancer is the most lethal gynecological malignancy affecting American women. The gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), have been implicated as growth factors in ovarian cancer. In the present study, pathways activated by FSH and LH in normal ovarian surface epithelium (OSE) grown in their microenvironment were investigated. Gonadotropins increased proliferation in both three-dimensional (3D) ovarian organ culture and in a two-dimensional (2D) normal mouse cell line. A mouse cancer pathway qPCR array using mRNA collected from 3D organ cultures identified Akt as a transcriptionally upregulated target following stimulation with FSH, LH and the combination of FSH and LH. Activation of additional pathways, such as Birc5, Cdk2, Cdk4, and Cdkn2a identified in the 3D organ cultures, were validated by western blot using the 2D cell line. Akt and epidermal growth factor receptor (EGFR) inhibitors blocked gonadotropin-induced cell proliferation in 3D organ and 2D cell culture. OSE isolated from 3D organ cultures stimulated with LH or hydrogen peroxide initiated growth in soft agar. Hydrogen peroxide stimulated colonies were further enhanced when supplemented with FSH. LH colony formation and FSH promotion were blocked by Akt and EGFR inhibitors. These data suggest that the gonadotropins stimulate some of the same proliferative pathways in normal OSE that are activated in ovarian cancers. Full article

(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)

Open AccessArticle Assessing Organ Doses from Paediatric CT Scans—A Novel Approach for an Epidemiology Study (the EPI-CT Study)

by Isabelle Thierry-Chef, Jérémie Dabin, Eva G. Friberg, Johannes Hermen, Tore S. Istad, Andreas Jahnen, Lucian Krille, Choonsik Lee, Carlo Maccia, Arvid Nordenskjöld, Hilde M. Olerud, Kaddour Rani, Jean-Luc Rehel, Steven L. Simon, Lara Struelens and Ausrele Kesminiene

Int. J. Environ. Res. Public Health 2013, 10(2), 717-728; doi:10.3390/ijerph10020717

Received: 4 December 2012 / Revised: 30 January 2013 / Accepted: 31 January 2013 / Published: 18 February 2013

Cited by 21 | Viewed by 2198 | PDF Full-text (418 KB) | HTML Full-text | XML Full-text

Abstract

The increasing worldwide use of paediatric computed tomography (CT) has led to increasing concerns regarding the subsequent effects of exposure to radiation. In response to this concern, the international EPI-CT project was developed to study the risk of cancer in a large multi-country

[...] Read more.

The increasing worldwide use of paediatric computed tomography (CT) has led to increasing concerns regarding the subsequent effects of exposure to radiation. In response to this concern, the international EPI-CT project was developed to study the risk of cancer in a large multi-country cohort. In radiation epidemiology, accurate estimates of organ-specific doses are essential. In EPI-CT, data collection is split into two time periods—before and after introduction of the Picture Archiving Communication System (PACS) introduced in the 1990s. Prior to PACS, only sparse information about scanner settings is available from radiology departments. Hence, a multi-level approach was developed to retrieve information from a questionnaire, surveys, scientific publications, and expert interviews. For the years after PACS was introduced, scanner settings will be extracted from Digital Imaging and Communications in Medicine (DICOM) headers, a protocol for storing medical imaging data. Radiation fields and X-ray interactions within the body will be simulated using phantoms of various ages and Monte-Carlo-based radiation transport calculations. Individual organ doses will be estimated for each child using an accepted calculation strategy, scanner settings, and the radiation transport calculations. Comprehensive analyses of missing and uncertain dosimetry data will be conducted to provide uncertainty distributions of doses. Full article

Open AccessArticle Entropy Stress and Scaling of Vital Organs over Life Span Based on Allometric Laws

by Kalyan Annamalai and Carlos Silva

Entropy 2012, 14(12), 2550-2577; doi:10.3390/e14122550

Received: 28 September 2012 / Revised: 22 November 2012 / Accepted: 26 November 2012 / Published: 12 December 2012

Cited by 6 | Viewed by 2194 | PDF Full-text (746 KB) | HTML Full-text | XML Full-text

Abstract

Abstract: Past theories on total lifetime energy expenditures and entropy generation in biological systems (BS) dealt with whole systems, but the recent literature suggests that the total metabolic rate of a BS,q̇_body (W) is a sum of product of specific metabolic rate

[...] Read more.

Abstract: Past theories on total lifetime energy expenditures and entropy generation in biological systems (BS) dealt with whole systems, but the recent literature suggests that the total metabolic rate of a BS,q̇_body (W) is a sum of product of specific metabolic rate q̇_k,m (W/kg of organ k) of each vital life organ, k {k = brain, heart, kidney and liver, or abbreviated as BHKL, and rest of the organ mass (R)} and mass of each organ k (mk). Using this hypothesis, Kleiber’s law on metabolic rate of BS (q̇_body) for animals of different sizes was validated. In this work, a similar procedure is adopted in estimating total entropy generation rate of whole human body (σ̇_body, W/K) as a sum of product of specific entropy generation rate for each organ, σ̇_k,m (W/{K kg of organ k·}) and the organ mass at any given age (t). Further integrating over life span for each organ (tlife), the lifetime specific entropy generated by organ k, σ_k,m,life (J of organ k/ {K kg organ k}) is calculated. Then lifetime entropy generation of unit body mass, σ_body,M,life (J/{K kg body mass·}) is calculated as a sum of the corresponding values contributed by all vital organs to unit body mass and verified with previously published literature. The higher the σ_k,m,life , the higher the entropy stress level (which is a measure of energy released by unit organ mass of k as heat) and the irreversibility within the organ, resulting in faster degradation of organ and the consequent health problems for the whole BS. In order to estimate σ̇_k (W/K of organ k), data on energy release rate (q̇) is needed over lifetime for each organ. While the Adequate Macronutrients Distribution Range (AMDR)/Adequate Intake (AI) publication can be used in estimating the energy intake of whole body vs. age for the human body, the energy expenditure data is not available at organ level. Hence the σ_k,m,life was computed using existing allometric laws developed for the metabolism of the organs, the relation between the mk of organ and body mass mB, and the body mass growth data mB(t) over the lifetime. Based on the values of σ_{k, m, life,} the organs were ranked from highest to lowest entropy generation and the heart is found to be the most entropy-stressed organ. The entropy stress levels of the other organs are then normalized to the entropy stress level (NESH) of the heart. The NESH values for organs are as follows: Heart: 1.0, Kidney: 0.92, Brain: 0.46, Liver: 0.41, Rest of BS: 0.027. If normalized to rest of body (R), NESR, heart: 37, Kidney: 34, Brain: 17, Liver: 15, Rest of BS: 1.0; so heart will fail first followed by kidney and other organs in order. Supporting data is provided. Full article

► Figures

Figure 1

Open AccessArticle Proteomic Analysis of the Organ of Corti Using Nanoscale Liquid Chromatography Coupled with Tandem Mass Spectrometry

by Hong Peng, Miao Liu, Jason Pecka, Kirk W. Beisel and Shi-Jian Ding

Int. J. Mol. Sci. 2012, 13(7), 8171-8188; doi:10.3390/ijms13078171

Received: 27 April 2012 / Revised: 5 June 2012 / Accepted: 25 June 2012 / Published: 2 July 2012

Abstract

The organ of Corti (OC) in the cochlea plays an essential role in auditory signal transduction in the inner ear. For its minute size and trace amount of proteins, the identification of the molecules in pathophysiologic processes in the bone-encapsulated OC requires both

[...] Read more.

The organ of Corti (OC) in the cochlea plays an essential role in auditory signal transduction in the inner ear. For its minute size and trace amount of proteins, the identification of the molecules in pathophysiologic processes in the bone-encapsulated OC requires both delicate separation and a highly sensitive analytical tool. Previously, we reported the development of a high resolution metal-free nanoscale liquid chromatography system for highly sensitive phosphoproteomic analysis. Here this system was coupled with a LTQ-Orbitrap XL mass spectrometer to investigate the OC proteome from normal hearing FVB/N male mice. A total of 628 proteins were identified from six replicates of single LC-MS/MS analysis, with a false discovery rate of 1% using the decoy database approach by the OMSSA search engine. This is currently the largest proteome dataset for the OC. A total of 11 proteins, including cochlin, myosin VI, and myosin IX, were identified that when defective are associated with hearing impairment or loss. This study demonstrated the effectiveness of our nanoLC-MS/MS platform for sensitive identification of hearing loss-associated proteins from minute amount of tissue samples. Full article

(This article belongs to the collection Advances in Proteomic Research)

Open AccessArticle The Biology of Autoimmune Response in the Scurfy Mice that Lack the CD4⁺Foxp3⁺ Regulatory T-Cells

by Shyr-Te Ju, Rahul Sharma, Felicia Gaskin, John T. Kung and Shu Man Fu

Biology 2012, 1(1), 18-42; doi:10.3390/biology1010018

Received: 2 March 2012 / Revised: 22 March 2012 / Accepted: 26 March 2012 / Published: 4 April 2012

Cited by 1 | Viewed by 2367 | PDF Full-text (866 KB) | HTML Full-text | XML Full-text

Abstract

Due to a mutation in the Foxp3 transcription factor, Scurfy mice lack regulatory T-cells that maintain self-tolerance of the immune system. They develop multi-organ inflammation (MOI) and die around four weeks old. The affected organs are skin, tail, lungs and liver. In humans,

[...] Read more.

Due to a mutation in the Foxp3 transcription factor, Scurfy mice lack regulatory T-cells that maintain self-tolerance of the immune system. They develop multi-organ inflammation (MOI) and die around four weeks old. The affected organs are skin, tail, lungs and liver. In humans, endocrine and gastrointestinal inflammation are also observed, hence the disease is termed IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome. The three week period of fatal MOI offers a useful autoimmune model in which the controls by genetics, T-cell subsets, cytokines, and effector mechanisms could be efficiently investigated. In this report, we will review published work, summarize our recent studies of Scurfy double mutants lacking specific autoimmune-related genes, discuss the cellular and cytokine controls by these genes on MOI, the organ-specificities of the MOI controlled by environments, and the effector mechanisms regulated by specific Th cytokines, including several newly identified control mechanisms for organ-specific autoimmune response. Full article

(This article belongs to the Special Issue Feature Papers)

Open AccessArticle High-Density Real-Time PCR-Based in Vivo Toxicogenomic Screen to Predict Organ-Specific Toxicity

by Gabriella Fabian, Nora Farago, Liliana Z. Feher, Lajos I. Nagy, Sandor Kulin, Klara Kitajka, Tamas Bito, Vilmos Tubak, Robert L. Katona, Laszlo Tiszlavicz and Laszlo G. Puskas

Int. J. Mol. Sci. 2011, 12(9), 6116-6134; doi:10.3390/ijms12096116

Received: 29 April 2011 / Revised: 24 August 2011 / Accepted: 5 September 2011 / Published: 19 September 2011

Abstract

Toxicogenomics, based on the temporal effects of drugs on gene expression, is able to predict toxic effects earlier than traditional technologies by analyzing changes in genomic biomarkers that could precede subsequent protein translation and initiation of histological organ damage. In the present study

[...] Read more.

Toxicogenomics, based on the temporal effects of drugs on gene expression, is able to predict toxic effects earlier than traditional technologies by analyzing changes in genomic biomarkers that could precede subsequent protein translation and initiation of histological organ damage. In the present study our objective was to extend in vivo toxicogenomic screening from analyzing one or a few tissues to multiple organs, including heart, kidney, brain, liver and spleen. Nanocapillary quantitative real-time PCR (QRT-PCR) was used in the study, due to its higher throughput, sensitivity and reproducibility, and larger dynamic range compared to DNA microarray technologies. Based on previous data, 56 gene markers were selected coding for proteins with different functions, such as proteins for acute phase response, inflammation, oxidative stress, metabolic processes, heat-shock response, cell cycle/apoptosis regulation and enzymes which are involved in detoxification. Some of the marker genes are specific to certain organs, and some of them are general indicators of toxicity in multiple organs. Utility of the nanocapillary QRT-PCR platform was demonstrated by screening different references, as well as discovery of drug-like compounds for their gene expression profiles in different organs of treated mice in an acute experiment. For each compound, 896 QRT-PCR were done: four organs were used from each of the treated four animals to monitor the relative expression of 56 genes. Based on expression data of the discovery gene set of toxicology biomarkers the cardio- and nephrotoxicity of doxorubicin and sulfasalazin, the hepato- and nephrotoxicity of rotenone, dihydrocoumarin and aniline, and the liver toxicity of 2,4-diaminotoluene could be confirmed. The acute heart and kidney toxicity of the active metabolite SN-38 from its less toxic prodrug, irinotecan could be differentiated, and two novel gene markers for hormone replacement therapy were identified, namely fabp4 and pparg, which were down-regulated by estradiol treatment. Full article

(This article belongs to the Special Issue Toxicogenomics)

► Figures

MDPI Contact

Advanced Search

Search Results

MDPI Contact

Advanced Search

Search Results

Years

Subjects

Journals

Article Types

Countries