ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
Volume 25, 42 Issues, 2018
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ISSN (Print): 0929-8673
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Cancer, an abnormal division of cells, is one of leading causes of death worldwide. A large number of
anti-cancer drugs, which have been approved commercially, are derived from plants. To meet the ever
increasing demand for anti-cancer compounds, plants have been harvested ruthlessly from their natural
habitat. Due to this, many plants have become extinct or are at the risk of becoming endangered.
Production of anti-cancer drugs through chemical synthesis is not economically viable due to highly
complex structures of compounds involved in biosynthesis pathways and high cost.
Biotechnology by employing plant tissue and cell culture offers a valuable tool to produce compounds of
interest for treating the cancer diseases. It is also possible to advantageously alter the biosynthesis
pathway of plants to obtain the desired products in required amount as well as within shortest possible
time. This method has successfully been employed for the large scale production of anti-cancer
compounds e.g. vincristine, vinblastine, taxol and podophyllotoxin.
We invite investigators to contribute original research as well as review articles that encourage the
ongoing efforts on enhanced production of anti-cancer compounds from different plant species using
various biotechnological means. A particular interest will be given to papers exploring or discussing the
different strategies to produce anti-cancer compounds from plants in an environment friendly way.
Circulating progenitors cells (CPCs), including Endothelial progenitor cells (EPCs), are a heterogeneous population
of cells in different states of maturation, originated from bone marrow (BM). Since their first identification in
1997 , great efforts are being made to explore the regenerative/reparative potential of EPCs, including their abilities
of self-renewal, of starting reparative mechanisms, and of neoangiogenesis. The role of CPCs in vivo is still
debated; however, the evidence of the involvement of CPCs in the pathophysiology of disease and their complications,
as well as in aging and other physiological conditions, are growing [2-6]. There are many reports on associations
between cell number, their activity and oxidoreductive status, and disease; growing evidence are being provided
on the effects of different pharmacological treatments on CPCs, and also preliminary observations of the potential
role of CPCs as therapy [7-11]. The mechanisms underlying cell mobilization into peripheral blood, circulation,
and activities, and their relationships with medical therapy are far to be completely clarified .
The challenge of this special issue will be to bring together the leading experts in the field to add new insight
into pathophysiological, drug-related and pharmacological aspects of CPCs, also to address the issue of why different
subjects with similar risk profile could have a different outcome. This Thematic issue aims to provide a comprehensive
literature review of the current knowledge, by different points of view. It is accepted that excessive inflammatory
burden or imbalanced immune responses may underlie number or function alterations of EPC . Rodriguez-
Carrìo and coll. summarize the current knowledge regarding the cutting-edge area of the modulation of EPC
levels and function by inflammatory cytokines in systemic diseases, suggesting these mediators as potential biomarkers
for risk stratification in non-CV disease [14, 15]. Rigato and Fadini describe the prognostic role of
CPCs/EPCs measurement on the development of cardiovascular disease and microangiopathy confirming that low
CPCs/EPCs levels predict the onset or worsening of microalbuminuria and retinopathy in diabetic patients .
Autologous cell therapy represents a novel treatment option for vascular regeneration in different disease conditions.
Bianconi, Pirro et al. report on therapeutic potential of different proangiogenic cells (PCs), including endothelial
progenitor cells (EPCs), in the treatment of peripheral artery disease; however, despite a number of potential
clinical applications of PCs are emerging, there is evidence that CV risk factors and chronic inflammation may induce
PC dysfunction, rising possible limitations for the efficacy of autologous PC therapy . In their article,
Ruggeri and coworkers address another aspect: elevated CECs and EPCs levels have been reported in the peripheral
blood of patients with different types of cancers and some other diseases, suggesting that these cells may be involved
in disease progression and the neoplastic angiogenesis process. Moreover, abnormal CECs and EPCs are
probably involved in endothelial damage that is a marker of several complications following allogeneic hematopoietic
stem cell transplantation . Last, another current challenge about EPCs as therapy regards the chronic
kidney disease (CKD). Coppolino and coll. describe the potential role of EPC therapy in repairing injured renal tissue;
strategies using EPCs to induce a reparative process with functional restoring of a diseased kidney or to delay
CKD by direct stem cells infusion or stimulating endogenous release of EPCs are also described .
Nanomedicine is a growing field of medical research focused on the development of therapeutics and diagnostics
tools in the nanoscale range (from 1 nm to 100 nm). Early diagnosis and effective cancer therapy are required to
treat cancer, which causes approximately 14.1 million new cases and 8.2 million deaths in a year worldwide.
“Nanomedicine uses nano-sized tools for the diagnosis, prevention and treatment of disease and to gain increased
understanding of the complex underlying pathophysiology of disease. The ultimate goal is improved quality of life”
as defined by the European Science Foundation.
Nowadays, this new branch of science is a point of interest for many investigators, due to the important scientific
and technological advances over the last few decades, in particular for cancer treatment. Cancer nanomedicine has
been applied in different fields, such as drug delivery, nanoformulation and nanoanalytical contrast reagents. In the
last two decades, nanotechnology has been rapidly developed allowing the incorporation of multiple therapeutics,
sensing and targeting agents into nanoparticles in order to set up new nanodevices capable of detecting, preventing
and treating complex diseases, such as cancer.
The aim of this special issue is to highlight the state-of-art of diagnostic and therapeutic tools that nanomedicine
is offering to fight cancer.
In the first review, Mascheroni and Schrefler  take into consideration computational models that help in understanding
biological mechanisms to provide quantitative analyses. To date, the use of mathematical modeling in
cancer is a long-standing practice, covering several aspects such as tumor biology, cancer progression and tumor
treatments. The authors report computational models based on in silico approaches, which address several aspects
of tumor treatment through the use of nanoparticles. The authors also highlight four main topics related to nanoparticle
formulations, namely the delivery to the tumor tissue, their uptake by tumor cells, drug release from the nanocarriers
and their therapeutic use. In silico approaches constitute a valuable tool to aid clinical studies, guiding the
rational design of new nanoparticle formulations and identifying the optimal strategies for existing treatments.
Molinaro et al.  examine the role of inflammation in different steps of tumor development and the strategies
based on the use of both conventional and biomimetic nanoparticles, which exploit the inflammatory pathways to
selectively target the tumor-associated microenvironment for therapeutic and diagnostic purposes.
In the review of Palazzolo et al.  the authors describe the main drug nanoformulations based on different
types of organic nanoparticles (e.g. polymeric nanoparticles, liposomes, micelles and exosomes), including the advantages
presented by the encapsulated drugs compared to their free form and how nanodrugs have improved the
Bayda et al.  illustrate the development of nanotechnology for diagnostic and therapeutic purposes of different
types of inorganic nanoparticles, which are currently undergoing clinical development, and of those already approved
by the FDA, which are being used in the market. In addition, the authors investigate the preclinical work and
clinical trials to highlight the path of these NPs from the lab to the clinic.
The review by Bedin et al.  aims at surveying the nanotechnological devices and approaches applied to the
detection of circulating cancer biomarkers and to show how the integration of biotechnology, nanotechnology and
microfluidic can produce quantitative, sensitive and high-throughput assays useful for new point-of-care testing
(POCT) development. Specifically, the authors give an overview of nanomaterial-based approaches for the detection
of nucleic acids and proteins for the diagnosis, prognosis or monitoring of cancer. Furthermore, the authors envision
that the current molecular diagnostics frontiers will be pushed forward by nanobiosensors evolution in the
next decade, thus allowing the introduction of new POCT in the personalized medicine.
Several nanoscale carriers have been developed for diagnostic purposes or were studied by imaging techniques
to design a prospective drug delivery process. Molecular imaging modalities include magnetic resonance imaging (MRI) and spectroscopy methods (fMRI), optical imaging techniques, ultrasonography and the nuclear medicinal
modalities such as single photon emission computed tomography (SPECT) and positron emission tomography
(PET). The review by Polyak and Ross  takes a short historical overview to radiocolloids, the great ancestors of
(radiolabeled) nanoparticles, and then describes the general features of current types of PET and SPECT imaging
associated with nanoparticle-based products and key radiolabeling methods. Finally, insights on potential prospective
challenges related to radiotheranostic approaches and imaging guided therapies are described.
Finally, Meneghello et al.  define how biosensors of different technological nature are gaining an increasing
share of attention for therapeutic drug monitoring as a valid, effective alternative to conventional laboratory tests,
since they can provide a revolutionary technology and tools with superior performances. Although there are still
challenges that have to be addressed before such devices will enter the clinical practice, several analytical platforms
have emerged in recent years, which show promising results. Primarily, the techniques employing nanobiosensors
are mainly based on electrochemical, optical, and mass detection systems. In the very next future, the portability,
rapid analyses, user friendly and low fabrication costs will make biosensors advantageous in view of a point of care
After the development of technology, pharmaceutical analysis in medicinal chemistry has become important for
the drug development, fabrication stage, formulation, stability and quality.. The development of sensitive, selective
and fully validated, new analyzing methods for pharmaceutical dosage forms is important and continuous. From this
point of view, I invite you to meet “Current Medicinal Chemistry” current issue under the thematic issue called as
“Advances in Medicinal Chemistry from Analytical Perspectives”.
The aim of the proposed special issue is to focus on the novel developments in medicinal chemistry from analytical
point of view including novel developments on drug analysis, medicinal chemistry, drug targets and disease
mechanism, dissolution test profiles, all analytical techniques for medicinal chemistry such as solid phase extraction,
LC analysis, spectroscopic, chemometric, electrochemical techniques etc. This special issue is contributed to
the field since the recent developments in medicinal chemistry researches are important and continuous. In this
thematic issue you may find new innovations in medicinal chemistry, recent researches on drug targets and disease
mechanism, dissolution test profiles, new analytical methods for medicinal products, novel developments on drug
assay, assay methods and validation processes in drug analysis.
In this thematic issue, there exist 13 review papers by several important scientists who contributed their ideas. In
the latest years, a large number of adsorbent carriers of natural and synthetic origin have increasingly attracted attention
due to their biocompatibility, acceptable ecological and toxicological characteristics, high capability for
simple modification of physical chemical characteristics, high stability and a relatively low price.
Subsequently, in this issue, the first review, by Razic, addresses the “Analytical approaches to the characterization
of solid drugs delivery systems with porous adsorbent carriers”. Korecká et al., shared their ideas about “Immunosensors
in Early Cancer Diagnostics: From Individual to Multiple Biomarker Assays”. In this review, recent
developments in the area of electrochemical immunosensors applicable for the detection of cancer biomarkers that
occur in a wide concentration range including extremely low levels, which are typical for the early stage of the disease,
are discussed. Furthermore, “Tyrosinase electrochemical biosensors monitoring medicinally significant substances”
topic is well discussed by the authors Milan Sýs and Karel Vytřas. In this review overview of applications
of electrochemical tyrosinase biosensors in the analysis of medicinally significant substances, otherwise also known as
biomarkers are shared. In the review entitled “In-vitro Drug Dissolution Studies in Medicinal Compounds”, the topic
is well discussed by Bozal-Palabiyik, et al. This review paper aims to analyze in-vitro drug dissolution testing in
solid dosage forms since 2010 in order to present a comprehensive outlook of recent trends. Another interesting
study entitled as “Advanced methods for analysis of testosterone suggested by Livia Alexandra Gugoasa and Raluca-
Ioana Stefan-van Staden. This review is dedicated to surveying recent determination methods of testosterone from
different biological samples such as: serum, saliva, plasma, urine or fingernail samples. Besides, Jean-Michel
Kauffmann et al., contributed to this thematic issue with a fascinating review paper entitled “Electrochemical Detectors
in Liquid Chromatography: Recent Trends in Pharmaceutical and Biomedical Analysis”. The authors review the
selected data in the literature devoted to pharmacologically active compounds in their dosage forms, herbal drugs in
natural products, drug residues in feed and/or in biological samples. Ana-Maria Chiorcea-Paquim, Teodor Adrian Enache,
and Ana Maria Oliveira-Brett, contributed a review paper entitled “Electrochemistry of Alzheimer disease amyloid
beta peptides”. The recent advances on the Aβ peptides electrochemical characterization are reported in this review.
In another contribution, “The role of oxidative stress modulators in breast cancer” is discussed by Gurer-Orhan
et al. The authors focuses more on melatonin which we have been working on during the last decade. Since a large
spectrum of electrochemical MIP-sensors has been described in the literature for the whole arsenal of drugs, e.g. the
most frequently used analgesics, antibiotics and anticancer drugs, “Yarman et al., stated the recent studies on “Electrochemical
MIP-Sensors for Drugs”. Meanwhile the studies of the interactions of DNA with small molecular drugs,
especially anti-tumor agents, antibiotics and drugs of abuse are currently being performed to explore their mechanism
of action and develop new drugs with lower side effects and high curative properties, Campuzano et al., contributed their interesting review paper “Electrochemical Nucleic Acid-Based Biosensing of Drugs of Abuse and Pharmaceuticals”.
In the review by Hosu et al. “Electrochemical Immunosensors for Disease Detection and Diagnosis” topic
was discussed. The authors report the research progresses of electrochemical immunosensors applied in clinical
analysis that have been published in the last years. Smarzewska et al., also contributed the review paper entitled “Recent
Applications of Silver Amalgam Electrodes for Analysis of Pharmaceuticals and Vitamins”. The features and applications
of silver amalgam electrodes in electroanalysis of pharmaceuticals and vitamins are summarized in this review.
The state-of-art in the preparation and construction of solid silver amalgam electrodes for prolonged and userfriendly
use is presented. And finally, Gumustas et al., shared a short summary of the basic principles of chiral separations
on an analytical and preparative scale, with the review paper entitled “Analytical and preparative scale separation
of enantiomers of chiral drugs by chromatography and related methods”. In addition, some selected applications
for analytical techniques, such as gas chromatography, supercritical fluid chromatography, high performance
liquid chromatography, capillary electrophoresis and capillary electrochromatography for the separation of enantiomers
of chiral pharmaceuticals published in last two years are also discussed.
We tried to combine all different kinds of analyzing methods to maintenance the richness of analytical chemistry.
Therefore, this thematic issue entitled “Advances in Medicinal Chemistry from Analytical Perspectives” will be
very useful for the readers who want to have broad knowledge.
I believe that you, as the valuable readers of Current Medicinal Chemistry journal, will find out new information,
topic of interest and new ideas in this thematic issue and I hope that this thematic issue will encourage researchers to
achieve the analysis of pharmaceutical active compounds using different kinds of methods.
I would like to thank to all of the authors for their excellent contributions, and Prof. Dr. Atta-ur-Rahman , the
Editor-in-Chief of “Current Medicinal Chemistry”, his kind invitation to act as a guest editor for this thematic issue.
Inflammatory response is originated by tissue injury and triggers a cascade of biochemical reactions that prime
the nervous system for pain perception. Protracted inflammation supports adaptive changes that can cause altered
pain signal processes. Indeed, different chronic (i.e. neuropathic) or inflammatory injuries to nervous system trigger
structural and functional changes in the peripheral or central sensory circuits, resulting in behavioral dysfunctions,
such as hyperalgesia and allodynia, and comorbidities. Current treatments for chronic pain are quite unsatisfying.
Hence, there is a great, unmet need for research aimed at discovering novel biological targets together with the development
of new pharmacological approaches for optimizing the side-effects of the classical drugs.
In this mini special issue, different signaling pathways in the peripheral and central nervous systems implicated
in inflammation and chronic pain and possible therapeutic approaches have been described.
- The review by Magni et al.  focuses on the pathophysiology and therapeutic potential of purinergic signaling
in pain, by reporting the available literature pre-clinical data together with the results of clinical trials. The
authors accurately illustrate the complex organization of purinergic system by providing the vast variety of
different (neuronal and non-neuronal) targets for resolution of chronic pain and inflammation. They also highlight
the role of purines in non-conventional therapeutic approaches.
- Posa and collaborators  show the analgesic properties of the neurohormone melatonin in several preclinical
studies and patients. They systematically describe the melatonin receptor functions in the neurobiology of
pain. Given the weakness of pharmacokinetic profile of melatonin per sè, they suggest the importance of developing
new pharmaceutical formulations or synthetic drugs acting on melatonin receptors, giving particular
emphasis to the effects mediated by MT2 receptors. Indeed, they discuss the analgesic properties of MT2 receptor
partial agonists in different chronic and acute/inflammatory pain conditions.
Negri et al.  summarize the evidence for the involvement of a new class of chemokine, the prokineticins
and their receptors, in chronic pain. They appropriately describe distribution of ligands and their receptors in
the periphery and at central nervous system level, by giving detailed information on their role in nociceptive,
as well as, chronic pain modulation. Indeed, they indicate that a number of preclinical studies proved the effects
of endogenous ligands or novel non-peptide drugs in controlling inflammation and inflammatory/
neuropathic pain. They discuss the possible molecular mechanisms responsible for prokineticins effects,
by highlighting the neuron-glia and neuron-immune cells interaction in prokineticins signaling.
Bedini et al.  remark advantages and drawbacks in the pharmacological manipulation of opioid system, by
highlighting the poor effectiveness of opiates in neuropathic pain condition. In this context, they describe innovative
opioid peptides (analogues of endomorphin 1 and dermorphin), showing similar analgesic properties,
but reduced side effects, as compared to classic opiates (i.e. morphine), as possible lead compounds for the
development of new drugs.
Roohbakhsh et al.  describe the orexinergic system as a potential candidate for finding alternative analgesics
with good efficacy and low side effects. Indeed, they clearly describe the cellular and molecular mechanisms
responsible for orexins effects in pain control at both spinal and supraspinal levels. Moreover, they give
information about recent preclinical findings on the manipulation of orexin signaling in pain modulation.
Russo and collaborators  discuss the possible involvement of gut-brain axis in the regulation of inflammation
and pain, that nowadays represents a hot topic research area. They report recent studies showing that the
deregulation of intestinal microbioma, commonly associated with gut inflammatory disorders, is responsible
for the development of several CNS pathologies. In this contest, they highlight the role of endogenous lipids,
as NAEs (AEA, PEA and OEA) and the most well studied short fatty acid (butyrate) in the inflammation
process, pain perception and in the CNS dysfunctions, by mainly focusing on endocannabinoids system involvement.
Since its introduction in the current clinical practice, Positron Emission Tomography (PET) provided a sensitive
tool for the evaluation of several biochemical processes and for the imaging of pathological substances in-vivo.
Several radiolabelled compounds for PET use were developed for the evaluation of central nervous system in the
last decade. These compounds allow the evaluation of tumour metabolism, the pathological accumulation of several
substances responsible for various neurodegenerative diseases and inflammation. In nuclear medicine, the creation
of a radiotracer that is able to satisfy these purposes is challenging. In particular, a radiotracer for clinical use is
characterized by a rapid pharmacodynamics with a significant affinity for the target thus resulting in a good signal
to noise ratio. As for radiolabelled compounds designed for the evaluation of metabolic processes, a good target to
background is desirable especially in brain tumours. The radiolabelled compound must ensure the detection of relapse
by detecting a pathological metabolic process that is different from those of the surrounding normal brain tissue.
Lastly, all these compounds should cross the blood brain barrier rapidly and, finally, levels of radiation exposure
for patients should be limited.
In this issue, the authors will address the pharmacological aspects and the in vivo applications of the radiotracers
used for PET imaging of brain in various diseases, thus providing an in depth review of the properties and applications
of these novel radiolabelled compounds.
We are pleased to introduce the present Special Thematic Issue “Brain Imaging with Positron Emission Tomography:
novel radiopharmaceuticals” that reviews different aspects concerning the usefulness of Positron Emission
Tomography in the field of neurological sciences and cutting-edge frontiers of neuroscience. The aim of the present
volume is to give an up-to-dated state of the art of those clinical and research boundaries within which this kind of
methodology achieved interesting advances.
In the field of clinical neuro-oncology, On hand interesting works by Treglia et al. highlighted the implementation
of 18F-FET PET in differentiating brain tumours from non-neoplastic lesions as well as low-grade from highgrade
gliomas, on the other hand the revised work of Quartuccio and Asselin evaluated the availability of PET radiotracers
availability in measuring the high-grade gliomas related adverse hypoxia. These themes appear of relevance,
considering the fundamental consequences related to treatment planning in terms of clinical efficacy, patients’
quality of life and targeting treatments.
However, the present volume - overcoming these aspects also by an in depth study of PET imaging diagnostic
procedures showing the involvement of Central Nervous System in systemic autoimmune diseases (Ursini et al.),
focused on recent important advantages related to PET procedures in neurodegenerative disorders. In particular,
Bauckneht et al. and Cistaro et al. respectively deepened the feasibility of PET procedures in evaluating Lewy bodies
and Amyloid-related neurodegenerative disorders, thus representing new frontiers in diagnosis, treatment and
prognosis of such health and social burden.
In conclusion, this Special Issue is really trustworthy to be read considering that PET imaging may be actually
considered as the present and the future in clinical research.
Cancer has become one of the fatal human diseases around the world. Every year there are millions of deaths because
of cancer in the world. The golden rule for cancer is early detection/diagnosis and early treatment. If cancer
can be detected or diagnosed early, particularly before its metastasis, it can prolong the lifetime and improve the
quality of life. Early detection and diagnosis of cancer is still a huge challenge. The various types of functional materials,
especially, a lot of functional nanomaterials can provide some opportunities for early detection and diagnosis
of cancer. Based on the functional materials, it can enhance the contrast properties between the tumor area and the
normal tissue, for example, contrast agents in magnetic resonance imaging (MRI) and fluorescent imaging, etc.
Moreover, the diverse contrast agents are with some additional therapeutic functions, which extend the function of
the contrast agents and offer the visualization capability during the therapy/treatment of cancer. In this thematic issue,
we will provide new progress in some following interesting fields for cancer imaging, therapy and theranostics
based on different types of functional materials:
The first work was reported by Dr. Gang Wei and Prof. Zhiqiang Su and their collaborators. They reviewed “Recent
advance in the cancer bioimaging with graphene quantum dots”. They present the synthesis and chemical
modification of GQDs firstly, and then introduce their unique physical, chemical, and biological properties like the
absorption, PL, and cytotoxicity of GQDs. Finally and most importantly, the recent applications of GQDs in cancer
bioimaging are demonstrated in detail, in which they focused on the biofunctionalization of GQDs for specific cancer
cell imaging and real-time molecular imaging in live cells. This work would provide valuable information on the
synthesis and modification of GQDs with adjustable properties for various biomedical applications in the future.
The second work was presented by Prof. Mingqian Tan and his co-workers. The title of his paper is “Multicolorful
carbon dots for tumor theranostics”. This review introduces a brief history and basic photoluminescence properties
of carbon dots, and then discusses synthesis strategies and applications of carbon dots in biological imaging,
targeted drug delivery, photodynamic therapy, photothermal therapy as well as gene delivery for cancer theranostics.
Future directions of carbon dots in cancer theranostics are also highlighted.
The third work came from Prof. Renjun Pei and his group. In their review work entitled “Biocompatible Gdbased
Polymeric Magnetic Resonance Imaging Agents for Tumor-Targeted Imaging”, Prof. Pei and co-workers focused
on the recent progress of biocompatible Gd-based polymeric MRI agents for tumor-targeted imaging, including
structures, properties and applications. Meanwhile, his review also highlights the emerging MRI mCAs with
smart response and multi-function: tumor microenvironment-stimulated MRI, multi-mode imaging and MRI-based
The fourth work reported by Prof. Bingbo Zhang and his group is entitled
The pharmacological therapy of children diseases is changing very quickly in the last decades. In this
respect, chronic autoimmune and inflammatory diseases are becoming a major issue for the pediatricians.
In spite of the availability of new biological drugs, which has allowed to assist to a great improvement in
the prognosis and quality of life of many patients, new therapeutic tools are urgently needed. This special
issue will discuss innovative approaches for rational drug design and therapy personalization in the
pediatric population, potentially leading to precision medicine improving efficacy and reducing adverse
effects of therapy, that are particularly significant in chronic diseases. The repositioning of old drugs to
treat rare pediatric immune diseases will be discussed, such as lapaquistat for Mevalonate Kinase Disease
and antimalarials in interferonopathies. Also severe oncological pediatric diseases could benefit from
precision drugs such as kinase inhibitors targeting specific genetic alterations; this approach will be
considered. Innovative disease models are needed to lead to improved drug design and innovative
therapies, and the promising application of pluripotent induced stem cells will be presented. Finally,
pharmacokinetics and pharmacogenomics based on innovative molecular markers such as
transcriptomics, and their application to therapy personalization and drug discovery for pediatric
inflammatory bowel disease, will be also discussed.
The potassium channels family represents the most widely distributed among ion channels families.
Thanks to this feature and to their ability of inducing hyperpolarization, potassium channels are involved
in many physiologic processes such as tune of musculature, release of neurotransmitters, regulation of
diuresis or glycemia and so on, and these properties make potassium channels suitable targets for many
pharmacological approaches to different pathologies in several districts. The purpose of this issue is to
offer a broad overview on the most important pharmacological tools, novel and well-known molecules,
having potassium channels as therapeutic target in order to highlight promising drugs with exciting
perspectives for the treatment of cardiovascular, neurological and metabolic diseases.
Keywords: KATP potassium channels, BKCa potassium channels, ROMK potassium channels, Kv
potassium channels, Mito-K+ potassium channels.
Pharmacological and chemical aspects of drugs or new molecules targeting: ATP-sensitive
(KATP) potassium channels.
Large conductance Ca2+-activated (BKCa) potassium channels.
Renal Outer Medullary (ROMK) potassium channels.
Voltage-gated (Kv) potassium channels and mitochondrial potassium (Mito-K+) channels.
Pancreatic cancer (PC) is a highly aggressive cancer usually diagnosed at an advanced stage, and has the worst
prognosis of any cancer malignancy, with a 5-year survival rate of <8%. Lack of early detection and effective interventions
are major factors contributing to the poor prognosis and dismal survival rates of pancreatic cancer patients.
Moreover, recent incidence and mortality rates suggest an increasing trend of pancreatic cancer patients.
Recent developments demonstrate that pre-invasive precursors, such as PanINs, IPMNs, and cystadenomas, progress
slowly over many years to develop into invasive pancreatic cancers. Thus, there is a time frame of several
years for effective chemoprevention and intervention strategies. Despite many advances in the molecular genetics of
human pancreatic cancers, targeted therapies have not yet translated to improved overall survival. Hence, developing
chemoprevention strategies that delay/inhibit/prevent the progression of each subtype of pre-invasive lesions to
pancreatic cancer is of utmost importance. Several genetically engineered mouse models (GEMs) of pancreatic cancer
that recapitulate human disease progression have recently been developed. The KrasG12D and KrasG12V dependent
GEM models which mimic the therapeutic response of human pancreatic cancer offer novel treatment development
opportunities. The biggest challenges are to elucidate the regulatory mechanisms controlling the progression of pancreatic
precursor lesions to pancreatic cancer, and to develop strategies that provide effective chemoprevention.
Equally challenging is identifying high-risk cohorts with specific pancreatic precursor lesions using early detection
In this special issue, different aspects of this problem are presented focusing on current challenges and opportunities
aimed to address chemoprevention aspects for pancreatic cancer. Possible pancreatic cancer chemoprevention
targets, mouse models and early detection, immuno-prevention of pancreatic cancer, drug candidates for pancreatic
cancer chemoprevention, regulatory mechanisms controlling pancreatic cancer progression, combination chemoprevention
strategies and different approaches are also considered and discussed.
The first review by Mohammed et al addresses the current challenges and potential opportunities for chemoprevention
of pancreatic cancer. In this review, they focused on the current situation of PC, the potential challenges, the
progress in existing strategies and available opportunities, as well as suggested key areas for research within the
increasingly important area of pancreatic cancer chemoprevention. They suggested that novel technologies such as
next generation sequencing should be employed to identify high-risk individuals with early genetic changes in the
initial lesions or even explored in blood samples to detect the presence of circulating tumor derived or related
mRNA, miRNA, DNA, tumor educated platelet-mRNA as biomarkers of early detection. GEM serve as excellent
models to study the early stages of PC and for early detection by molecular imaging technologies. GEM models
should be extensively utilized for developing existing chemoprevention agents or screening and optimizing new
agents and identifying ideal chemoprevention targets. High-risk individuals presenting IPMN/PanINs and those
with hereditary PC history should be considered for chemopreventive clinical trials. Combination chemoprevention,
multi-targeted agents and multi-agent low dose chemoprevention strategies might be considered to reduce toxicity
and enhance efficacy.
The contribution by Dhar et al. takes into consideration the mechanisms and drug targets for pancreatic cancer
chemoprevention. They discussed the available drugs and their limitations, and move on to discuss the wide realm
of chemopreventive efficacy that natural agents offer. While the intake of fruits and vegetables in routine diets has
been linked to reduced risk of developing pancreatic cancer, a wide variety of natural agents is being evaluated as
adjuvant therapies in combination with frontline chemotherapeutics in pancreatic cancer clinical trials. Completed
and ongoing human studies with these natural agents have shown surprisingly successful rates for regulating pancreatic
carcinogenesis. Furthermore, the underlying mechanisms of action and available information from extensive
literature analysis to highlighting the novelty of these agents for their antitumor effects against pancreatic cancer,
In the review by Hildegard, the regulatory role of G protein-coupled receptors in pancreatic cancer development
and progression are described. Smoking, psychological stress, diabetes, pancreatitis and alcohol abuse are known
risk factors for pancreatic cancer that cause hyperactive cyclic adenosine monophosphate (cAMP) signaling via
cancer stimulating Gαs-coupled β-adrenergic and prostaglandin (PG) E2 receptors and/or by suppressing signaling
via inhibitory Gαi-coupled GABAB-receptors. The activation of Gαi-coupled GABAB-receptor signaling by treatment
with GABA, inhibition of β-adrenergic signaling by a beta-blocker and/or suppression of Gαs-coupled PGE2
receptor signaling by a cyclooxygenase (COX) inhibitor prevented the development and progression of PC in hamsters
induced by carcinogenic nitrosamines and in transgenic mice. The re-purposing of cardiovascular therapeutics
(beta-blockers, COX-2 inhibitors, Ca2+-channel blockers) that inhibit β-adrenergic and PGE2 signaling for PC intervention
is problematic due to undesirable side effects under chronic treatment protocols. To avoid such side effects
while effectively reducing excessive cAMP signaling, nutritional GABA supplementation or positive allosteric
modulators (PAMs) of Gαi-coupled receptors (GABAB-Rs) currently in clinical trials for the treatment of addiction
should be explored for pancreatic cancer intervention.
Rao et al. review discusses the novel approaches of immunoprevention for PC. Vaccine-based treatments for
several cancers are currently under intense investigation. Current vaccine testing for PC is usually performed in advanced
stages of cancer, during which the patient's impaired immune responses improved to suppress the growing
tumor. However, so far such strategies have had limited success and have not become mainstream therapies. Thus,
early diagnosis is imperative for immunoprevention using vaccines. Developing vaccines towards non-self-antigens
has been successful, whereas vaccines against self-antigens, without any adverse effects on normal cells, have been
challenging. The development of new technologies to identify mutated antigens, post-translational alterations in
proteins, and tumor-specific antigens is currently underway, with a view toward vaccine development. Combining
vaccines with immune stimulators or non-toxic anticancer agents are promising for cancer prevention. Successful
vaccination strategies for PC at different stages of tumor development and future challenges for immunoprevention
are discussed in this review.
Along this line, the paper by Subramaniam and co-authors reviewed approaches to target cancer stem cells for
chemoprevention of pancreatic cancer. Emerging evidence supports the presence of a unique population of cells
called cancer stem cells (CSCs) as potential cancer inducing cells and efforts are underway to develop therapeutic
strategies targeting these cells. Studies have been shown that CSCs are highly resistant to standard therapy and responsible
for drug resistance, cancer recurrence and metastasis. To overcome this problem, novel preventive agents
that target these CSCs are needed. Natural compounds or phytochemicals have the ability to target these CSCs and
their signaling pathways. Therefore, they summarized current understanding of pancreatic CSCs and their signaling
pathways, and the phytochemicals that target these cells including curcumin, resveratrol, tea polyphenol EGCG
(epigallocatechin-3-gallate), crocetinic acid, sulforaphane, genistein, indole-3-carbinol, vitamin E δ-tocotrienol,
Plumbagin, quercetin, triptolide, Licofelene and Quinomycin. These natural/synthetic compounds or phytochemicals,
which inhibit cancer stem cells, may prove to be promising agents for the prevention and treatment of pancreatic
Together with the data summarized by Yu et al., the paper provides a systematic literature review and metaanalysis
on the effect of metformin and statin use on survival in PC patients. Current epidemiological studies report
conflicting results for the effect of statin or metformin on overall PC survival. They systematically searched for
studies about the association between statin or metformin use and overall pancreatic cancer survival in electronic
databases. A meta-analysis based on hazard ratios (HRs) and 95% confidence intervals (CIs) was performed using
random effect models. Heterogeneity between the studies was examined using I2 statistics, and sensitivity analyses
were conducted to assess the robustness of the findings. Of 116 statin-related articles identified, 6 retrospective cohort
studies representing 12,057 patients were included. There was significant heterogeneity between the studies.
Statin use was associated with improved survival among pancreatic cancer patients. Of 311 metformin-related articles,
8 retrospective cohort studies and 2 randomized clinical trials, representing 3,042 patients were identified.
Metformin use was associated with better overall survival among pancreatic cancer patients (meta-HR = 0.79; 95%
CI: 0.70, 0.92, P < 0.001), and significant heterogeneity was observed between the studies. These findings suggest
that the improved survival time of pancreatic cancer patients is associated with statin or metformin use. Due to the
multiple sources of heterogeneity of the original studies, these findings should be considered cautiously, and confirmed
with larger prospective individual-level studies.
The last review by Torres and co-authors focused on the complexity of omega-3 fatty acids modulation of signaling
pathways related to PC. Recently, the role of nutrition in health and disease has attracted much attention.
Several dietary ingredients are involved in metabolic, physiological, and cellular signaling affecting tumor growth
and progression. Although lipids, and more specifically polyunsaturated fatty acids, have been traditionally studied
due to their health effects in cardiovascular disease, it is now clear that they can affect an extensive array of cellular
processes that influence a wide range of diseases such as type II diabetes, inflammatory disorders and cancer. These
biological activities may be grouped as regulation of membrane structure and function, intracellular signaling pathways,
transcription factor activity, gene expression, and production of bioactive lipid mediators. In this review, specifically,
the current state of knowledge about the potential mechanism(s) of action and signaling pathways modulated
by polyunsaturated fatty acids in pancreatic cancer are discussed.
Cardio-metabolic complications are multifactorial diseases with different facets, many of which are poorly understood,
although genetics, epigenetics, humoral, habitual and environmental factors may be involved. Moreover,
with the dramatic escalation of obesity, diabetes and hypertension in all segments of the population including adults,
adolescence and children, the incidence of cardio-metabolic disease and related complications will further increase.
Therefore, this special issue puts together a collection of review articles by leading experts in the area to give a
critical appraisal of the current state of knowledge and recent accomplishments as well as challenges and future directions.
The role of pigment epithelium-derived factor (PEDF) in cardiometabolic disease is a among the emerging
themes of scientific interest, with the role of pigment epithelium-derived factor (PEDF) in cardiometabolic disease.
PEDF is a glycoprotein that has been shown to possess anti-thrombotic and anti-fibrotic properties besides its effects
against oxidative stress and inflammatory. Accordingly, in an article featuring in this special issue, Yamagishi
& Matsui underscored the role of PEDF in cardiometabolic diseases and related complications, with particular focus
on diseases such as diabetic retinopathy, renal dysfunction, hepatic insufficiency and disorders affecting the male
and female reproductive systems. The authors discussed the potential clinical relevance of modulating PEDF for the
prevention and management of these cardiometabolic disorders. In another related article, Shinlapawittayatorn et al.
gave profound insights on the effects of obese insulin-resistance, a common risk factor for ischemic heart disease on
ischemia-reperfusion injury of the heart. Amongst the pertinent points raised by the authors is whether improving
insulin sensitivity by pharmacological interventions could ameliorate reperfusion induced myocardial injury. Dysfunctional
myocardium is a common complication of diabetes. To expatiate on this problem further, Tarquini et al.
wrote an article about diabetic cardiomyopathy, a pathophysiological condition in which the myocardial interstitium
undergoes alterations resulting in abnormal contractile function. The authors reported that in the early stages of the
disease, diastolic dysfunction is the only abnormality, but systolic dysfunction supervenes at later stages with impaired
left ventricular ejection fraction. Furthermore, the authors underscored a putative correlation between diabetes
and cardiomyopathy, especially in diabetic patients with co-morbid with microvascular complications, and suggested
that this correlation parallels the duration and severity of hyperglycemia.
Besides the heart, the kidney is an important organ for the regulation of extracellular volume and thus blood
pressure. Renal dysfunction is associated with hypertension, proteinuria and kidney failure. Accordingly, novel insights
on structures of the kidney, such as the glomerular filtration barrier, are important. In a related article that
appears in this special issue, Ndisang wrote about the putative cross-talk amongst the major components of the
glomerular filtration barrier including podocytes, endothelial cells and the basement membrane, and how the dynamic
interplay and interaction between these constituents may be fundamental for effective filtration. Furthermore,
the author highlighted some of the challenging issues about the interaction between: (i) glomerular endothelial cells
and podocytes; (ii) glomerular endothelial cells and glomerular basement membrane; (iii) podocytes and glomerular
basement membrane; (iv) the simultaneous interaction among the three components, and suggested that the elucidation
of these multifaceted interactions will pave the way for greater understanding of the pathophysiology of kidney
dysfunction and the formulation of novel therapies for kidney disease. In another related article, Krämer and Weidemann
gave their insights on Fabry disease, pathophysiological condition associated with X-linked lysosomal storage
caused by deficient activity of α-galactosidase A and intracellular accumulation of globotriaosylceramide in
different physiological entities such as the vascular endothelium, nervous system, eyes, skin, heart and kidneys.
A wide variety of drugs are used for the treatment and management of cardiometabolic diseases. For example,
proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors are used to lower low-density lipoprotein cholesterol in
patients with dyslipidemia, hypercholesterolemia or atherosclerosis. In an article, in this special issue, Schremla and Gouni-Berthold gave an in-depth insight on the use of monoclonal antibodies against PCSK9 to attenuate hypercholesterolemia,
and reported that antibody-derived PCSK9 drugs such as alirocumab (Praluent®) and evolocumab
(Repatha®) can reduce low-density lipoprotein cholesterol by 70%. Generally, drugs are routinely reviewed for their
efficacy and safetyly. In this light, Eleftheriadou and co-workers insights on the cardiovascular safety of older and
newer anti-diabetic medications. The authors reported that metformin, a first line drug for the treatment of type 2
diabetes, is also endowed with cardio- protective effects and should be considered the primary choice, while second
line agents such as empagliflozin, liraglutide and semaglutide are reasonable options for patients with cardiovascular
disease, whereas the class of sulfonylureas with the exception of gliclazide should be administered to diabetic
patients co-morbid with other cardiometabolic diseases. In addition, the authors reported that Saxagliptin, alogliptin,
sitagliptin and lixisenatide have been evaluated in cardiovascular safety trials and were shown to have neutral effects
on cardiovascular outcomes, whereas pioglitazone has some cardiovascular benefits. However, Saxagliptin
and alogliptin should be avoided in patients with heart failure. Consistently, in another article featuring in this special
issue, Schmitz and Gouni- Berthold gave clinical evidence on the efficacy and safety of volanesorsen for the
treatment of hypertriglyceridemia.
Besides, drugs and other pharmaceutical formulations, dietary fibres and polyphenols are cyto-protective. Accordingly,
the protective effects of dietary fibres and the antioxidant and anti- inflammatory properties of polyphenols
such as curcumin, quercetin, genistein, caffeic acid phenethyl ester were examined by Pittala and co-workers.
They discussed the effects of various naturally occurring polyphenols in the management of metabolic dysfunctions
Collectively, the contributions of the authors of this special issue have underscored to the complexity of cardiometabolic
diseases, highlighting the different facets, the accomplishments to date, the challenges that obscure the
horizon and the prospects for the future, to which we can all look toward with some degree of optimism.
Nanotechnology is growing in prevalence in consumer products and medicine. Most nanomedicine are carriers that are capable of homing in, taken up easily by the target cells and eventually delivering their drug payload to the target sites and some have smart designs that release the payload according to designed stimuli. However, while there are many advantages offered through bionanotechnology, there are potential unintended consequences especially on the non-targeted cells remain a problem of toxicity of these very small particles. This special issue describes a series of the latest most exciting research in the fields of nano medicine covering cancer and anti-microbial applications and balanced with some nanotoxiological studies covering nano biology and more realistic nano materials testing platforms.
Growing evidence supports a primary role of inflammatory reactions, both acute and chronic, in the development and progression of the main human diseases. The redoxmediated pathophysiological mechanisms are crucial in the evolution of various diseases, in which inflammation is involved. In this theme issue we would like to consider the role of inflammation and redox balance in the genesis and worsening of diseases, such as atherosclerosis, metabolic syndrome, and ischemia/reperfusion injury. Reviews by scientists, with basic and clinical background, will contribute to give a comprehensive picture of the inflammation- and redox-mediated pathogenesis of the diseases and an up-to-date scenario of therapeutic approaches.
This mini theme issue will consider some classes of bioactive natural products and their role in the medicinal chemistry. Many studies have pointed out new bioactivities for well-known natural products, showing that not only” new chemical entities” obtained by natural sources but also known and “old” natural products can be a valuable source of new therapeutic agents. In the issue triterpene, sesquiterpene, coumarins, stilbenoids, and also phenolics from Cannabis will be considered focusing on both natural and
synthetic (or semisynthetic) compounds, their bioactivity and their potential importance in the field of medicinal chemistry.
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