ISSN (Print): 1389-2010
ISSN (Online): 1873-4316
Volume 19, 15 Issues, 2018
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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316
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Davide Prosperi Department of Biotechnology and BioscienceUniversity of Milan Bicocca Milano Italy
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Special Issue Submission
"Current Pharmaceutical Biotechnology presents the latest developments in the area of biotechnology. This is strongly recommended."
PREECLAMPSIA - AETIOPATHOGENESIS AND CLINICAL MANAGEMENT
Guest Editor(s): Marzena Laskowska
Tentative Publication Date: March, 2018
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DIAGNOSTIC AND PROGNOSTIC INSIGHTS OF BIOMARKERS IN CARDIOVASCULAR DISEASES
Guest Editor(s): Michael Behnes, Ibrahim Akin
It was a great experience for me working with Bentham Science Publishers because of the following reasons:
-High quality services
-Great and kind cooperation and collaboration
Dr. Helmy Selman(The CIVF Center Doha Center Clinic Hospital Doha, Qatar)
Has contributed: Ovarian Stimulation Protocol in IVF: An Up-to-Date Review of the Literature
7 Abstract Ahead of Print are available electronically
17 Articles Ahead of Print are available electronically
The mechanism of RNA interference (RNAi) mediated by small non-coding RNAs (ncRNAs) was
discovered only two decades ago, and research into this field has already achieved therapeutical results
by the development of a small interfering RNA (siRNA)-based drug for the treatment of the Hereditary
Transthyretin Amyloidosis, an autosomal dominant disease . Moreover, microRNAs (miRNAs)
known to trigger the RNAi pathway in human cells have also shown to be useful biomarkers for disease
diagnosis and therapy response [2-4]. Nowadays, ncRNAs are recognized to be important
transcriptional modulators not only capable of suppressing but also of promoting gene expression. This
mechanism, referred to as RNA-mediated gene activation (RNAa), is triggered by small activating
RNA (saRNA) molecules that bind to complementary gene sequences and activate transcription [5-9].
Recent research into RNAa has started to unravel the underlying basis linked to saRNA-based activation
phenomena and enabled the design of saRNAs with ability to regulate the expression of target genes in different cells types
[10-13], even being in the process of developing a RNAa therapy against hepatocellular carcinoma [14,15]. Similarly to siRNAs,
short activating RNAs might be used as therapeutic agents for treatment of different diseases, associated in this last case
with the occurrence of loss of function mutations and/or haploinsufficiencies [8,16]. In the near future, it is expected that versatile
delivery systems consisting of siRNA/saRNA-based drugs enable the setup of personalized therapeutic treatments and targeted
molecular therapies, thereby opening exciting new possibilities in clinical medicine and pharmaceutical biotechnology.
In this thematic issue, Drs. Yoon and Rossi  provided a comprehensive overview about the RNAa mechanism, methodologies/
insights for the design and delivery of saRNAs, intracellular functioning and chemical modifications to increase the
oligonucleotide's resistance to nuclease degradation. This work is an analytical overview that focuses on the potential that
RNAa have for the development of therapeutic strategies. Moreover, canonical and non-canonical mechanisms involving
saRNA-mediated gene activation phenomena are also illustrated here.
In the next article, Setten et al.  described the progress of MTL-CEBPA (MiNA Therapeutics, UK), the first saRNAtargeting
drug currently tested in clinical trials (Phase I). Remarkably, this oligonucleotide can be used to induce targeted expression
of the CCAAT/enhancer-binding protein alpha (CEBPα) gene, a known tumor suppressor capable of modulating transcriptional
activity in hepatic cells . In this work, the authors considered the reasons for which MTL-CEBPA represents a
promising saRNA drug against hepatocellular carcinoma, thereby opening the door to the development of new therapeutic
agents in the treatment of patients with cancer and other diseases.
Finally, Drs. Li and Hu  reviewed the state of the research in the RNAa field and underlie the potential of saRNAs to act
as gene modulators, with special emphasis on their use in the treatment of kidney diseases. In this article, the authors associated
short ncRNA-mediated gene regulation pathways (i.e., RNAi and RNAa), and discussed how research into RNAi might be useful
for understanding the molecular mechanisms underlying the endogenous RNAa phenomena.
We here introduce the second part of a thematic issue devoted to the analytical advances in clinical and forensic toxicology,
with a particular focus on the determination of new psychoactive substances and eventual metabolites in conventional and nonconventional
biological matrices .
This second part opens with a review which explores the close connections between clinical and forensic toxicology in
overlapping areas of interest, such as prenatal exposure to drugs or fetal alcohol syndrome, doping control, sudden cardiac
death, determination of brain death, sudden infant death syndrome, Munchausen syndrome by proxy, drug-facilitated crimes
and intoxications by new psychoactive substances. Some of these topics are initially treated in hospital emergency departments,
involving clinical laboratories and sometimes lately derived to forensic laboratories. Conversely, cases with initial medicallegal
implications and fatalities are directly handled by forensic toxicology, but may trigger further studies in the clinical setting.
Thus, increasing relationships are improving the growth, reliability and robustness of both kind of laboratories, respecting
in both cases most recent updated and standard practices for the development and validation of the analytical methods [2-4].
The first example of the bridges between clinical and forensic toxicology laboratories is given by the case report described
by Jarque et al. concerning a case report of prenatal methamphetamine exposure with toxicological analytical confirmation in
maternal and biological matrices. The toxicological findings prompted the removal of guardianship to the parents and authorized
a temporary foster care. In addition, authors reviewed the updated literature regarding this new outbreak of methamphetamine
abuse with several consequences in young male and male adults .
Not only a case report was presented concerning prenatal exposure to a psychotropic drug, but also an epidemiological
study on gestational consumption and consequent prenatal exposure to drugs of abuse and psychoactive prescription drugs in
513 mother-newborn dyads from Sant Joan de Déu Barcelona Hospital analysing maternal hair and neonatal meconium by
validated chromatographic mass spectrometric methodologies.
An amount of 1.2% gestational drugs of abuse consumption was objectively assessed in maternal hair and 0.4% prenatal
exposure measured in meconium while gestational consumption of psychoactive prescription drugs was 1.7% as measured maternal
hair and prenatal exposure 1.2% in meconium .
Another interesting issue in clinical and forensic toxicology is that of ethyl glucuronide in hair (hEtG) used as a biomarker
in the diagnosis of chronic excessive alcohol consumption. Since some cosmetic treatments may influence the hEtG concentration
leading to false positive results, the effect of alcohol-based perfumes was studied in four different subjects. The liquid
chromatographic mass spectrometric analysis showed in all the cases that prolonged exposition of hair to alcohol-based perfumes
may increase hEtG levels, resulting in false positive results .
Analytical advances were also reported in a remarkable study concerning a striking problem in doping control: the detection
of autologous blood transfusion. The article of Donati et al. reported the results of an investigation aimed to pre-select potential
biomarkers of blood aging and storage that can be measured to identify the presence in the sample of re-infused blood. The parameters
more strongly affected by the ex vivo storage of whole blood resulted to be erythrocytes size and density, annexin V
and microparticles, appearing as a very encouraging suggestion towards the development of a direct method for detecting
autologous blood transfusion in sport doping .
With respect to the determination of new psychoactive substances and eventual metabolites in conventional and nonconventional
biological matrices, an essential contribution has been that of Guillou et al. from the Joint Research Centre of
European Commission in charge of providing its scientific support to the EU Customs laboratories and more in general to the
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) to facilitate the rapid identification and characterisation
of new psychoactive substances in suspected seized samples.
In the presented report the research group described and discussed the implementation of the workflow mechanism, regarding
the harmonisation of procedures to facilitate the monitoring, communication and management of analytical data obtained by
extensive analysis of unknown seized material with some recent real examples. The rapid dissemination of the obtained information
is at the moment an essential tool for control authorities to facilitate the protection against the health risks posed by potential
harmful psychotropic substances .
On the same line of the previous report has been that of the analytical approaches reviewed by Gerace et al. to disclose the
presence of new synthetic opioids in fatal intoxications . Due to the high potency and the low doses required to produce
desired effects, the risk of overdose for these compounds including severe health implications, is quite high. For this reason, the
detection of these compounds in biological samples is crucial in order to get a better understanding of their concentration and
distribution in body fluids.
A specific example of analytical approach to detect a new synthetic opioid as a cause of an intoxication is that of Vogliardi
et al. using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in a case involving U-47700, a synthetic hair and a white powder found at consumer home were analysed by LC-HRMS, which allowed to reveal the presence of
U-47700 and its phase I and phase II metabolites in blood, urine and pubic hair and also cocaine, benzoylecgonine, norcocaine,
mephedrone, ketamine, norketamine, 3,4-methylenedioxymethamphetamine, tetrahydrocannabinol and cannabinol only in pubic
hair . Conclusion. The toxicological findings confirmed the use of U-47700 in the intoxicated patient and also revealed a
history of a poly-drug use. The use of LC-HRMS allowed the easy identification of the NPS and its metabolites in fluids and
The thematic issue closes with a noteworthy investigation on the metabolites of synthetic cannabinoids most recently used
and encountered in clinical/forensic caseworks . This is the last of a series of studies leadered by Prof Auwarter [13-15],
which provided useful information on what to look for in biological fluids of suspected intoxications by risky synthetic cannabinoids
and analytical methods to better recognize the causing substances.
We wish to thank all the authors who have contributed with valuable manuscripts to this Thematic Issue, the Reviewers who
carried out an excellent job in guarantying the highest standard of quality for each manuscript, the Editorial Manager (Ms. Sumaiya
Azhar) of the Journal for the continuous support and expertise and finally a special thanks to Prof. Davide Prosperi, Editor
in Chief of Current Pharmaceutical Biotechnology, who allowed us to guest edit this thematic issue.
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