Review Articles

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J. G. Hengstler
Leibniz Research Centre for Working Environment and Human Factors
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B. C. Behera, Pune, India
T. Chen, Stanford, CA/USA
E. Corsini, Milan, Italy
P. Diel, Cologne, Germany
C. Esser, Duesseldorf, Germany
P. B. Farmer, Leicester/UK
S. Hammad, South Valley/Egypt
P. Jennings, Innsbruck, Austria
M. Lotti, Bonn, Germany / Padova, Italy
P. Micke, Uppsala, Sweden
A. N. Misra, Ranchi, Jharkhand State, India
B. Ponugoti, Pennsylvania, PA/USA
C. Pope, Stillwater, OK/USA
K. Renganathan, Johnstown, PA/USA
S. D. Ray, Fort Wayne, IN/USA
M. Schwarz, Tuebingen, Germany
J. Timmer, Freiburg, Germany
H. van Steeg, Bilthoven, The Netherlands
A. Winterpacht, Erlangen, Germany
Y. Zhou, New Haven, CT/USA

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Managing editor/EXCLI Journal
Leibniz Research Centre for Working Environment and Human Factors
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Now showing 1 - 16 of 16

A review of environmental and occupational exposure to xylene and its health concerns
(2015-11-23) Niaz, Kamal; Bahadar, Haji; Maqbool, Faheem; Abdollahi, Mohammad
Xylene is a cyclic hydrocarbon, and an environmental pollutant. It is also used in dyes, paints, polishes, medical technology and different industries as a solvent. Xylene easily vaporizes and divides by sunlight into other harmless chemicals. The aim of the present review is to collect the evidence of the xylene toxicity, related to non-cancerous health hazards, as well as to provide possible effective measurement to minimize its risk ratio. For current study a bibliographic search of more than 250 peer-reviewed papers in scientific data including PubMed, and Google Scholar about xylene was done. But approximately 130 peer-reviewed papers relevant to xylene were included (Figure 1). All scientific data was reviewed with key words of “xylene toxicity”, “xylene toxic health effects”, “environmental volatile organic compounds”, “human exposure to xylene”, “xylene poisoning in laboratory workers”, “effects of xylene along with other hydrocarbons”, “neurotoxicity of selected hydrocarbons”, and “toxic effects of particular xylene isomers in animals”. According to these studies, xylene is released into the atmosphere as fugitive emissions from petrochemical industries, fire, cigarette, from different vehicles. Short term exposure to mixed xylene or their individual isomers result in irritation of the nose, eyes and throat subsequently leading toward neurological, gastrointestinal and reproductive harmful effects. In addition long term exposure to xylene may cause hazardous effects on respiratory system, central nervous system, cardiovascular system, and renal system. The health concerns of xylene are well documented in animals and human. It is important to improve health policies, launch xylene related health and toxicity awareness campaigns, to get rid of its dangerous outcomes. Chronic diseases have become a threat to human globally, with special prominence in regions, where xylene is used with other chemicals (benzene, toluene etc.) especially in petroleum and rubber industry. The mechanism of toxicity and interactions with endocrine system should be followed up which is the main threat to human health.
Regulatory RNAs controlling vascular (dys)function by affecting TGF-ß family signalling
(2015-07-10) Kurakula, Kondababu; Goumans, Marie-Jose; ten Dijke, Peter
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Over the last few years, microRNAs (miRNAs) have emerged as master regulators of gene expression in cardiovascular biology and di¬sease. miRNAs are small endogenous non-coding RNAs that usually bind to 3′ untranslated region (UTR) of their target mRNAs and inhibit mRNA stability or translation of their target genes. miRNAs play a dynamic role in the pathophysiology of many CVDs through their effects on target mRNAs in vascular cells. Recently, numerous miRNAs have been implicated in the regulation of the transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) signalling pathway which plays crucial roles in diverse biological processes, and is involved in pathogenesis of many diseases including CVD. This review gives an overview of current literature on the role of miRNAs targeting TGF-β/BMP signalling in vascular cells, including endothelial cells and smooth muscle cells. We also provide insight into how this miRNA-mediated regulation of TGF-β/BMP signalling might be used to harness CVD.
Plants with potential use on obesity and its complications
(2015-07-09) Gamboa-Gómez, Claudia I.; Rocha-Guzmán, Nuria E.; Gallegos-Infante, J. Alberto; Moreno-Jiménez, Martha R.; Vázquez-Cabral, Blanca D.; González-Laredo, Rubén F.
Obesity is the most prevalent nutritional disease and a growing public health problem worldwide. This disease is a causal component of the metabolic syndrome related with abnormalities, including hyperglycemia, dyslipidemia, hypertension, inflammation, among others. There are anti-obesity drugs, affecting the fundamental processes of the weight regulation; however they have shown serious side effects, which outweigh their beneficial effects. Most recent studies on the treatment of obesity and its complications have focused on the potential role of different plants preparation that can exert a positive effect on the mechanisms involved in this pathology. For instance, anti-obesity effects of green tea and its isolated active principles have been reported in both in vitro (cell cultures) and in vivo (animal models) that possess healthy effects, decreasing adipose tissue through reduction of adipocytes differentiation and proliferation. A positive effect in lipid profile, and lipid and carbohydrates metabolisms were demonstrated as well. In addition, anti-inflammatory and antioxidant activities were studied. However, the consumption of green tea and its products is not that common in Western countries, where other plants with similar bioactivity predominate; nevertheless, the effect extension has not been analyzed in depth, despite of their potential as alternative treatment for obesity. In this review the anti-obesity potential and reported mechanisms of action of diverse plants such as: Camellia sinensis, Hibiscus sabdariffa, Hypericum perforatum, Persea americana, Phaseolus vulgaris, Capsicum annuum, Rosmarinus officinalis, Ilex paraguariensis, Citrus paradisi, Citrus limon, Punica granatum, Aloe vera, Taraxacum officinale and Arachis hypogaea is summarized. We consider the potential of these plants as natural alternative treatments of some metabolic alterations associated with obesity.
Experimental procedures to identify and validate specific mRNA targets of miRNAs
(2015-07-02) Elton, Terry S.; Yalowich, Jack C.
Functionally matured microRNAs (miRNAs) are small single-stranded non-coding RNA molecules which are emerging as important post-transcriptional regulators of gene expression and consequently are central players in many physiological and pathological processes. Since the biological roles of individual miRNAs will be dictated by the mRNAs that they regulate, the identification and validation of miRNA/mRNA target interactions is critical for our understanding of the regulatory networks governing biological processes. We promulgate the combined use of prediction algorithms, the examination of curated databases of experimentally supported miRNA/mRNA interactions, manual sequence inspection of cataloged miRNA binding sites in specific target mRNAs, and review of the published literature as a reliable practice for identifying and prioritizing biologically important miRNA/mRNA target pairs. Once a preferred miRNA/mRNA target pair has been selected, we propose that the authenticity of a functional miRNA/mRNA target pair be validated by fulfilling four well-defined experimental criteria. This review summarizes our current knowledge of miRNA biology, miRNA/mRNA target prediction algorithms, validated miRNA/mRNA target data bases, and outlines several experimental methods by which miRNA/mRNA targets can be authenticated. In addition, a case study of human endoglin is presented as an example of the utilization of these methodologies.
Role of anti-diabetic drugs as therapeutic agents in Alzheimer's disease
(2015-05-19) Rizvi, Syed Mohd. Danish; Shaikh, Sibhghatulla; Waseem, Shah Mohammad Abbas; Shakil, Shazi; Abuzenadah, Adel M.; Biswas, Deboshree; Tabrez, Shams; Ashraf, Ghulam Md.; Kamal, Mohammad Amjad
Recent data have suggested a strong possible link between Type 2 Diabetes Mellitus and Alzheimer’s disease (AD), although exact mechanisms linking the two are still a matter of research and debate. Interestingly, both are diseases with high incidence and prevalence in later years of life. The link appears so strong that some scientists use Alzheimer’s and Type 3 Diabetes interchangeably. In depth study of recent data suggests that the anti diabetic drugs not only have possible role in treatment of Alzheimer’s but may also arrest the declining cognitive functions associated with it. The present review gives an insight into the possible links, existing therapeutics and clinical trials of anti diabetic drugs in patients suffering from AD primarily or as co-morbidity. It may be concluded that the possible beneficial effects and usefulness of the current anti diabetic drugs in AD cannot be neglected and further research is required to achieve positive results. Currently, several drug trials are in progress to give conclusive evidence based data.
Osmoregulation in zebrafish: ion transport mechanisms and functional regulation
(2015-05-11) Guh, Ying-Jey; Lin, Chia-Hao; Hwang, Pung-Pung
Fish, like mammals, have to maintain their body fluid ionic and osmotic homeostasis through sophisticated iono-/osmoregulation mechanisms, which are conducted mainly by ionocytes of the gill (the skin in embryonic stages), instead of the renal tubular cells in mammals. Given the advantages in terms of genetic database availability and manipulation, zebrafish is an emerging model for research into regulatory and integrative physiology. At least five types of ionocytes, HR, NaR, NCC, SLC26, and KS cells, have been identified to carry out Na+ uptake/H+ secretion/NH4+ excretion, Ca2+ uptake, Na+/Cl- uptake, K+ secretion, and Cl- uptake/HCO3- secretion, respectively, through distinct sets of transporters. Several hormones, namely isotocin, prolactin, cortisol, stanniocalcin-1, calcitonin, endothelin-1, vitamin D, parathyorid hormone 1, catecholamines, and the renin-angiotensin-system, have been demonstrated to positively or negatively regulate ion transport through specific receptors at different ionocytes stages, at either the transcriptional/translational or posttranslational level. The knowledge obtained using zebrafish answered many long-term contentious or unknown issues in the field of fish iono-/osmoregulation. The homology of ion transport pathways and hormone systems also means that the zebrafish model informs studies on mammals or other animal species, thereby providing insights into related fields.
A systematic review of the cardiotoxicity of methadone
(2015-05-05) Alinejad, Samira; Kazemi, Toba; Zamani, Nasim; Hoffman, Robert S.; Mehrpour, Omid
Methadone is one of the most popular synthetic opioids in the world with some favorable properties making it useful both in the treatment of moderate to severe pain and for opioid addiction. Increased use of methadone has resulted in an increased prevalence of its toxicity, one aspect of which is cardiotoxicity. In this paper, we review the effects of methadone on the heart as well as cardiac concerns in some special situations such as pregnancy and childhood. Methods: We searched for the terms methadone, toxicity, poisoning, cardiotoxicity, heart, dysrhythmia, arrhythmia, QT interval prolongation, torsade de pointes, and Electrocardiogram (ECG) in bibliographical databases including TUMS digital library, PubMed, Scopus, and Google Scholar. This review includes relevant articles published between 2000 and 2013. The main cardiac effects of methadone include prolongation of QT interval and torsade de pointes. Other effects include changes in QT dispersion, pathological U waves, Taku-Tsubo syndrome (stress cardiomyopathy), Brugada-like syndrome, and coronary artery diseases. The aim of this paper is to inform physicians and health care staff about these adverse effects. Effectiveness of methadone in the treatment of pain and addiction should be weighed against these adverse effects and physicians should consider the ways to lessen such undesirable effects. This article presents some recommendations to prevent heart toxicity in methadone users.
Persimmon (Diospyros kaki) fruit: hidden phytochemicals and health claims
(2015-05-04) Butt, Masood Sadiq; Sultan, M. Tauseef; Aziz, Mahwish; Naz, Ambreen; Ahmed, Waqas; Kumar, Naresh; Imran, Muhammad
Currently, nutrition and health linkages focused on emerging strategy of diet based regimen to combat various physiological threats including cardiovascular disorders, oxidative stress, diabetes mellitus, etc. In this context, consumption of fruits and vegetables is gaining considerable importance as safeguard to maintain human health. Likewise, their phytochemicals and bioactive molecules are also becoming popular as promising demulcent against various ailments. The current review is an effort to sum up information regarding persimmon fruit with special reference to its phytochemistry and associated health claims. Accordingly, the role of its certain bioactive molecules like proanthocyanidin, carotenoids, tannins, ﬂavonoids, anthocyanidin, catechin, etc. is highlighted. Owing to rich phytochemistry, persimmon and its products are considered effective in mitigating oxidative damage induced by reactive oxygen species (ROS). The antioxidant potential is too responsible for anti-malignant and anti-melanogenic perspectives of persimmon functional ingredients. Additionally, they are effectual in soothing lifestyle related disparities e.g. cardiovascular disorders and diabetes mellitus. There are proven facts that pharmacological application of persimmon or its functional ingredients like proanthocyanidin may helps against hyperlipidemia and hyperglycemia. Nevertheless, astringent taste and diospyrobezoars formation are creating lacuna to prop up its vitality. In toto, persimmon and its components hold potential as one of effective modules in diet based therapy; however, integrated research and meta-analysis are still required to enhance meticulousness.
Data- and knowledge-based modeling of gene regulatory networks: an update
(2015-03-02) Linde, Jörg; Schulze, Sylvie; Henkel, Sebastian G.; Guthke, Reinhard
Gene regulatory network inference is a systems biology approach which predicts interactions between genes with the help of high-throughput data. In this review, we present current and updated network inference methods focusing on novel techniques for data acquisition, network inference assessment, network inference for interacting species and the integration of prior knowledge. After the advance of Next-Generation-Sequencing of cDNAs derived from RNA samples (RNA-Seq) we discuss in detail its application to network inference. Furthermore, we present progress for large-scale or even full-genomic network inference as well as for small-scale condensed network inference and review advances in the evaluation of network inference methods by crowdsourcing. Finally, we reflect the current availability of data and prior knowledge sources and give an outlook for the inference of gene regulatory networks that reflect interacting species, in particular pathogen-host interactions.
A review on biological and chemical diversity in Berberis (Berberidaceae)
(2015-02-20) Srivastava, Sharad; Srivastava, Manjoosha; Misra, Ankita; Pandey, Garima; Rawat, AKS
Berberis is an important genus and well known in the Indian as well as European systems of traditional medicine. It is used since ancient times for curing eye disease, fever, jaundice, rheumatism, vomiting during pregnancy, kidney and gall balder stones and various other ailments due to the presence of biologically active alkaloid berberine. Action of the root extracts of few species are believed to be as powerful as quinine in the treatment of malarial fever. A plethora of literature pertaining to the taxonomy, biology, chemistry, traditional and ethnic uses of Berberis in different countries and indigenous cultures was collected by both offline (library, journals, textbooks etc.) and online mode (electronic search of available databases). In addition to this, books on traditional medicine and ethno pharmacological knowledge were also referred to extract ancient uses of Berberis in different traditional medicine systems. Most of the folklore, traditional and ethno botanical claims about Berberis species were validated by broad spectrum in vitro and vivo pharmacological studies. The present article summarizes its usage in eye and liver disorder, fever, kidney and gall stones along with anticancer activity. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations.
Deep sea as a source of novel-anticancer drugs
(2015-02-10) Russo, Patrizia; Del Bufalo, Alessandra; Fini, Massimo
The deep-sea habitat is a source of very potent marine-derived agents that may inhibit the growth of human cancer cells “in vitro” and “in vivo”. Salinosporamide-A, Marizomib, by Salinispora species is a proteasome inhibitor with promising anticancer activity (Phase I/II trials). Different deep-sea-derived drugs are under preclinical evaluation. Cancer is a complex disease that may be represented by network medicine. A simple consequence is the change of the concept of target entity from a single protein to a whole molecular pathway and or cellular network. Deep-sea-derived drugs fit well to this new concept.
Neutrophil biology
(2015-02-10) Kobayashi, Yoshiro
Neutrophil extracellular traps (NETs) are involved in bacterial killing as well as autoimmunity, because NETs contain proteases, bactericidal peptides, DNA and ribonucleoprotein. NETs are formed via a novel type of cell death called NETosis. NETosis is distinct from apoptosis, but it resembles necrosis in that both membranes are not intact so that they allow intracellular proteins to leak outside of the cells. Removal of NETs and neutrophils undergoing NETosis by phagocytes and its subsequent response are not completely clarified, as compared with the response after removal of either apoptotic or necrotic neutrophils by phagocytes. How neutrophil density in peripheral blood is kept within a certain range is important for health and disease. Although the studies on severe congenital neutropenia and benign ethnic neutropenia have provided unbiased views on it, the studies are rather limited to human neutropenia, and mice with a mutation of mouse counterpart gene often fail to exhibit neutropenia. Degranulation plays a critical role in bactericidal action. The recent studies revealed that it is also involved in immunomodulation, pain control and estrous cycle control. N1 and N2 are representative of neutrophil subpopulations. The dichotomy holds true in patients or mice with severe trauma or cancer, providing the basis of differential roles of neutrophils in diseases.
MicroRNAs in endometrial cancer
(2015-02-02) Yanokura, Megumi; Banno, Kouji; Iida, Miho; Irie, Haruko; Umene, Kiyoko; Masuda, Kenta; Kobayashi, Yusuke; Tominaga, Eiichiro; Aoki, Daisuke
Endometrial cancer is a common malignant gynecological tumor, but there are few biomarkers that are useful for early and accurate diagnosis and few treatments other than surgery. However, use of microRNAs (miRNAs) that induces gene downregulation in cells may permit effective and minimally invasive diagnosis and treatment. In endometrial cancer cells, expression levels of miRNAs including miR-185, miR-210 and miR-423 are upregulated and those of miR-let7e, miR-30c and miR-221 are downregulated compared to normal tissues, and these miRNAs are involved in carcinogenesis, invasion and metastasis. miRNAs with expression changes such as miR-181b, miR-324-3p and miR-518b may be used as prognostic biomarkers and transfection of miR-152 may inhibit cancer growth. However, most current studies of miRNAs are at a basic level and further work is needed to establish clinical applications targeting miRNAs.
Molecular mechanisms of etoposide
(2015-01-19) Montecucco, Alessandra; Zanetta, Francesca; Biamonti, Giuseppe
Etoposide derives from podophyllotoxin, a toxin found in the American Mayapple. It was first synthesized in 1966 and approved for cancer therapy in 1983 by the U.S. Food and Drug Administration (Hande, 1998). Starting from 1980s several studies demonstrated that etoposide targets DNA topoisomerase II activities thus leading to the production of DNA breaks and eliciting a response that affects several aspects of cell metabolisms. In this review we will focus on molecular mechanisms that account for the biological effect of etoposide.
Heat shock protein 90 targeting therapy
(2015-01-06) Tatokoro, Manabu; Koga, Fumitaka; Yoshida, Soichiro; Kihara, Kazunori
Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone that plays a role in stabilizing and activating more than 200 client proteins. It is required for the stability and function of numerous oncogenic signaling proteins that determine the hallmarks of cancer. Since the initial discovery of the first Hsp90 inhibitor in the 1970s, multiple phase II and III clinical trials of several Hsp90 inhibitors have been undertaken. This review provides an overview of the current status on clinical trials of Hsp90 inhibitors and future perspectives on novel anticancer strategies using Hsp90 inhibitors.
Advances in hepatic stem/progenitor cell biology
(2015-01-06) Verhulst, Stefaan; Best, Jan; van Grunsven, Leo A.; Dollé, Laurent
The liver is famous for its strong regenerative capacity, employing different modes of regeneration according to type and extent of injury. Mature liver cells are able to proliferate in order to replace the damaged tissue allowing the recovery of the parenchymal function. In more severe scenarios hepatocytes are believed to arise also from a facultative liver progenitor cell compartment. In human, severe acute liver failure and liver cirrhosis are also both important clinical targets in which regeneration is impaired, where the role of this stem cell compartment seems more convincing. In animal models, the current state of ambiguity regarding the identity and role of liver progenitor cells in liver physiology dampens the enthusiasm for the potential use of these cells in regenerative medicine. The aim of this review is to give the basics of liver progenitor cell biology and discuss recent results vis-à-vis their identity and contribution to liver regeneration.

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