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Volume 21, 16 Issues, 2020
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Special Issue Submission
"In view of the growing volume of literature, the role of high quality review journals has become increasingly important. Current Drug Targets is an important journal in the field of medicinal chemistry and drug design, which is strongly recommended to the scientific community."
Mitochondrial dysfunction and traffic jams in neurodegenerative disorders
Guest Editor(s): Bijo Mathew, Ghulam Md. Ashraf, Md. Sahab Uddin
Submit Abstract via Email
Apixaban from Bench to Bedside
Current Drug Targets, Volume 19, Number 06
Guest Editor(s): Marco Matteo Ciccone
It was a nice experience to publish our article in current drug target. I felt that the journal is quick and has maintained very high standard by independently reviewing article from more than five reviewers. The communication between the author and the Journals editorial is also speedy. I hope the journal will continue to maintain and sustain its reputation.
Pushpender K. Sharma (Department of Biotechnology, Sri Guru Granth Sahib World University, Fatehgarh Sahib, Pb, India.)
47 Articles Ahead of Print are available electronically
In 1994, The American Journal of Pathology published a key article reporting that hypoxic retina produces vascular endothelial
growth factor (VEGF), sug- gesting a role for VEGF in ocular neovascularization .
Subsequently, several studies have demonstrated that VEGF is not only necessary but also sufficient to induce new vessels
growth in the eye .
Based on these robust scientific data, Napoleone Ferrara at Genentech (South San Francisco, CA) developed the first humanized
anti-VEGF antibody designed to block all VEGF isoforms (bevacizumab). This antibody was approved by the Food
and Drug Administration (FDA) in 2004 for the treatment of colon cancer in combination with chemotherapy. In the same year,
FDA also approved an RNA aptamer that binds and neutralizes VEGF165 (Pegaptanib - Macugen) for the treatment of neovascular
age-related macular degeneration (nAMD). Afterwards ranibizumab (Lucentis) in 2006 and aflibercept (Eyelea) in 2011
were approved for the same disease. Moreover, bevacizumab, although licensed only for treating different types of cancers, has
been used off-label in ophthalmology worldwild.
With time, the use of these drugs was extended to many ocular conditions, including pathologic myopia, diabetic retinopathy,
retinal vein occlusions, neovascular glaucoma, retinopathy of prematurity, idiopathic choroidal and corneal neovascularization.
Anti-VEGF therapy has improved visual outcomes in many eye diseases and has changed the standard of care in ophthalmology
in the last 15 years.
The aim of this thematic issue is to retrace the story of anti-VEGF therapy for ocular diseases, showing the results obtained
both in clinical trials and real life:
• Battaglia Parodi M. et al. discuss the use of anti-VEGF molecules to treat two important complications of retinal dystrophies:
choroidal neovascularization and macular edema ;
• Vilela M.A.P reviews the results of anti-VEGF therapy in retinal vein occlusions ;
• Giannaccare G. et al. highlight the efficacy and safety of the adoption of anti-VEGF agents into the daily clinical practice
for the management of corneal neovascularization ;
• Sorrentino F.S. et al. review recent advances by artificial intelligence for individualized anti-VEGF therapy in several eye
• The last paper (Campa C.) 5 new anti-VEGF drugs in an advanced stage of clinical development (conbercept, brolucizumab,
port delivery system with ranibizumab, abicipar pegol and faricimab) are presented .
Finally, we are grateful to the Editor in Chief Prof. Francis J. Castellino and editorial manager K.M. Qamar of Current Drug
Targets (Bentham Science Publishers) for their valualbe support to publish this thematic issue.
Epigenetics is defined as heritable changes in gene expression that do not result from an alteration in the DNA sequence
itself . DNA/RNA modification, histone variants and modifications, and nucleosome positioning work together to determine
the epigenetic landscape of a cell. Until now, there is a growing awareness that epigenetic dysregulation plays a significant role
in many types of diseases, and that is fueling an increasing number of studies into drugs that target epigenetic regulators, and
several epigenetic targeted drugs have entered into clinic trials, including DNA methyltransferase inhibitor, bromo domain
reader inhibitor, histone acetylase or deacetylase inhibitor, histone methyltransferase or demethylase inhibitor, deubiquitinase
inhibitor or neddylation inhibitor.
Among these modifiers, several of them have been approved for clinical use. For examples, DNMT inhibitors 5-azacytidine
(5azaC) and 5-aza-2’-deoxycytidine (5azadC) have been approved for clinical use in haematological malignancies as myelodysplastic
syndrome (MDS), acute myeloid leukaemia (AML) and chronic myelomonocytic leukaemia (CMML) , vorinostat
(Zolinza, SAHA) earned FDA approval for the treatment of cutaneous T-cell lymphoma (CTCL) as histone deacetylase
(HDAC)1, 2, 3 and 6 inhibitor, panobinostat (Farydak) is the first HDAC inhibitor to gain approval for a nonlymphoma cancer,
a unique natural product Romidepsin isolated from the bacterium Chromobacterium violaceum gained approval to treat both
CTCL and peripheral T-cell lymphomas (PTCL) , tazemetostat (Tazverik, EPZ-6438, E7438) is the first epigenetic therapy
to gain FDA approval in a solid tumor by targeting the S-adenosylmethionine (SAM, AdoMet) binding pocket of H3K27 methyltransferase
Enhancer of zeste homolog 2 (EZH2) for epithelioid sarcoma treatment , et al. All these FDA approved drugs
indicate that epigenetic modifications are promising therapeutic targets for solid tumors and hematological malignancies.
Due to the fast-growing number of epigenetics and epigenetic targeted drugs, it is becoming a hot area in drug discovery for
cancer therapy. This thematic issue aims to review about epigenetic modification related drug target, drug discovery, assay development,
biological function, molecular modeling, target structure analysis, showing the progress of epigenetic modifications
as therapeutic targets.
Finally, we are grateful to the Editor in Chief Prof. Francis J. Castellino and editorial manager K.M. Qamar of Current Drug
Targets (Bentham Science Publishers) for their valualbe support to publish this thematic issue.
Research on gynecological cancers particularly breast and tubo-ovarian cancers is evolving. Every year, randomized and
controlled trials in the area of women’s cancer provide considerable improvements in survival outcomes. Moreover, previously
known aggressive gynecological malignancies with poor outcomes are now reconsidered for novel treatments. However, drug
resistance is a serious challenge for this significant progress. Notably, predictive and prognostic biomarkers are increasingly
used to offer therapeutic decision-making in gynecological cancers especially with the remarkable advances in targeted therapies
in the last decade such as antiangiogenics, poly-ADP-ribose polymerase (PARP) inhibitors and immune-checkpoint blockers
[1-4]. With the emergence of precision medicine, the role of cancer biomarkers is promising as they enable the selection of
the best treatment options for the right patients. FDA-approved predictive biomarkers such as BRCA mutational status and programmed
death-ligand 1 (PD-L1) assays are enthusiastic examples of successful development of companion diagnostics. In this
special issue and as a part of the scientific activities of our recently launched Cancer Biomarkers Working Group, many basic
and clinical scientists from different countries were invited to participate in the review writing and share their experiences with
this hot topic. Various areas in cancer biomarkers were covered, including proteomic biomarkers, liquid biopsy, genomic signatures,
and other emerging biomarkers for several gynecological malignancies including breast cancer, ovarian cancer, endometrial
cancer, and other types. Biomarkers that have potential impact on predicting prognosis, survival, and therapy response are
discussed based on recently published findings from clinical trials and real-world studies. We strongly believe that our thematic
issue will provide clinically actionable information for evidence-based practice in modern cancer management and potential
perspectives for further research in gynecologic oncology.
In the present thematic issue of Current Drug Targets, we were fortunate to team up reputed scientists from clinical, translational,
and basic cancer research on gynecologic neoplasms to highlight important advances in this field of oncology:
1. Le Page et al. reviewed recent progress in biomarkers for serous ovarian cancer, particularly those who lead to new therapeutic
strategies encompassing PARP inhibitors, immunotherapy and antiangiogenic drugs and provided potential perspectives
for implementing personalized care in the future .
2. Lengyel et al. summarized the role of and clinical impact of PI3K-AKT-mTOR signaling in ovarian and endometrial cancers
and therefore, providing a rationale for further drug development in human clinical trials .
3. Tazzite et al. reviewed the genomic predictors of outcomes in triple-negative breast cancer with a special focus on platinumbased
chemotherapy which is the cornerstone in the management of this aggressive woman cancer .
4. Souid et al. reviewed predictive biomarkers for a promising marine-derived anticancer drug (trabectedin) that showed clinical
activity in various gynecological cancers with poor outcomes . The authors focused their discussion on the mechanisms
of action of trabectedin on multiple cancer hallmarks as well as the potential clinical outcomes from clinical trials and
the genomic predictors of therapy response.
5. Gouri et al. discussed the prediction of late recurrence and distant metastasis in early-stage breast cancer based on current
and emerging molecular signatures encompassing serum biomarkers and multigene profiling scores .
6. The last paper (El Bairi et al.) from our team aimed to discuss the potential of the human epididymis protein 4 (HE4) as a
promising prognostic biomarker for detecting recurrent epithelial ovarian cancer. This topic is highly important since the detection
of early recurrence considerably impacts the survival outcomes of this aggressive woman’s cancer .
Finally, we would like to express our sincere appreciation to the Editor in Chief Prof. Francis J. Castellino, editorial manager
K.M. Qamar, authors, reviewers, copy-editors and the entire editorial team of Current Drug Targets (Bentham Science Publishers)
for their professionalism and providing support to publish this thematic issue on this emerging topic in modern oncology.
The integrity of skeleton homeostasis is preserved by a balance maintaining between the activity of osteogenesis and osteoclastogenesis.
Document factors and stimuli have been determined involved in these two processes over the past century, however,
further understanding for exploring the physiological and pathological cellular processes are imperative requirement.
Here, in the current special theme issue, we have organize experts in the relevant fields to contribute novel understanding of
osteoclastogenesis, potential detective and therapeutic targets for skeleton diseases.
Five reviews included from the experts in the medical research and clinical therapeutic practice provided the novel understanding
for osteoclastogenesis relevant disease development and detection, osteoclastic cellular functional regulating,
intercellular signaling cascades and potential therapeutic natural compounds studies. Wang et al.  comprehensively reviewed
various diagnostic targets for its role diagnosis rate of spinal tuberculosis. In this review, authors specifically presented
the current novel progression of laboratory, imaging and gene detection in the diagnostic process of spinal tuberculosis
last several years.
Integrins in bone homeostasis, especially in osteoclastogenesis, have been taken as the novel and promising therapeutic drug
target for bone loss diseases, such as: osteolysis. However, its cellular mechanism is still elusive. Kong et al.  collected and
reviewed several novel studies on integrin and its sub-molecules ICAM-1 on bone homeostasis. Specifically, authors have focused
on the ICAM-1 which might play dual effects on osteoclastognesis by directly affecting the adhesion of mature osteoclast
and indirectly participates in the RANKL/RANK induced osteoclastic precursors differentiation. Although these results are still
conducted by a series of studies for further demonstration, exploring the role of ICAM-1 in osteoclastogenesis will definitely
provide promising therapeutic targets for treating bone loss diseases.
Besides that, inflammation is the most common pathology in many orthopedic diseases, such as: rheumatoid arthritis (RA),
osteoarthritis (OA) and inflammatory osteolysis. The leading factor of inflammation was considered as the differentiation of
monocyte and the polarization of macrophage. However, various cytokines and different cell models could regulate this progress
in some aspect. Liu et al. , therefore reviewed several cytokines and cell models, which lead to inflammatory orthopedic
diseases via regulating monocytes and macrophages. This review extensively explored the potential therapeutic and drug
targets for inflammatory induced bone diseases.
Liu et al.  reviewed the current novel research progress of RANKL and its downstream signaling pathways in bone cells,
and as an important drug target for its role in bone loss diseases. In this review, the authors also briefly introduced the current
application of several natural compounds for treating RANKL-mediated osteoclastic activation by modulating the RANKL signaling
pathway and their effects on the treatment and prevention of osteoporosis, OA and RA.
Finally, Wang et al.  extensively reviewed the naturally occurring compounds with less or no side effects, for their role in
the present clinical and fundamental study in osteoclastogenesis.
We hope this thematic issue will be beneficial for the vast readers and could serve as a good source of literature for scholars
in relevant study fields.
In continuation with computational advances in chronic diseases diagnostics and therapy – I , this part II consists of articles
which contribute to develop new ideas, algorithm design and rational drug discovery techniques to antiviral drug targets of
single-stranded ribonucleic acid (RNA) viruses, homeostasis in the cardiovascular system, ion channels as therapeutic targets
for type 1 diabetes mellitus and amyloid beta (Aβ) in Alzheimer's disease (AD).
Dinesh et al.  demonstrated that antiviral drug targets of single-stranded ribonucleic acid (RNA) viruses cause chronic
human diseases. RNA containing viruses associated with chronic diseases in humans are major threats to public health causing
high mortality globally. Extremely high mutation rates of RNA viruses make them deadliest and thus difficult to design an effective
drug. Chronic infections caused by human immunodeficiency virus (HIV-1) and hepatitis virus (HBV and HCV) lead to
acquired immunodeficiency syndrome (AIDS) and hepatocellular carcinoma, respectively, they are the primary cause of human
deaths. Effective preventive measures to limit chronic and re-emerging viral infections are absolutely necessary; and remains a
challenging issue. Antivirals usually inhibit different stages of the virus life-cycle, instead of killing them as in the case of the
bacterial antibiotics. Most often antiviral drugs are targeted against specific viral and host protein, whereas a few broadspectrum
drugs are available for targeting multiple viruses. In the recent past, an exponential increase in the number of available
three-dimensional protein structures and advancements in the in silico approaches, have paved the way to design and develop
several novel, highly specific small molecule inhibitors against protein drug targets. The present review briefly discussed
about selected single-stranded (ss) RNA genome containing human pathogenic viruses, causing chronic infections and are of
special importance for e.g. HIV-1, HCV, Flaviviruses, Ebola etc., their selected viral target proteins and an update about the
available small-molecule inhibitors or antivirals acting against them have also been discussed.
Singh and Karnik  clearly summarized homeostasis in the cardiovascular system maintained by physiological functions
of the renin angiotensin aldosterone system (RAAS). In pathophysiological conditions, over activation of RAAS leads to an
increase in the concentration of angiotensin II (AngII) and over activation of angiotensin type 1 receptor (AT1R) resulting in
vasoconstriction, sodium retention and change in myocyte growth. In the heart, it causes cardiac remodeling which results in
left ventricular hypertrophy, dilation and dysfunction which eventually leads to heart failure (HF). Inhibition of RAAS using
angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) has shown to significantly reduce
morbidity and mortality due to HF. ACEi have been shown to have higher drug withdrawal rates due to discomfort when compared
to ARBs; therefore, ARBs are the preferred choice of physicians for the treatment of HF in combination with other antihypertensive
agents. Out of eight FDA approved ARBs, irbesartan and telmisartan are shown to have PPARϒ agonistic properties
resulting in improved insulin intolerance. Olmesartan treatment also improves insulin sensitivity and produces antiatherogenic
and anti-inflammatory effects in patients with diabetic nephropathy. All the ARBs demonstrate beneficial effects
similar to ACEi in the treatment of HF except the lower doses of losartan which leads to increase mortality in HF patients. Valsartan
in combination with sacubitril therapy has shown to be a promising therapy for HF. Eprosartan has an effect on the sympathetic
nervous system when compared to other ARBs and it is also able to reduce catecholamine release in animal models.
Therefore, eprosartan therapy may have an additional beneficial effect in the treatment of heart failure. However, eprosartan has
the shortest bioavailability (< 6 hours) when compared to other ARBs. Large numbers of studies that show beneficial effects on
animals have been reported but there are limited studies on humans. Hence, more human studies are warranted. Recently, crystal
structures of AT1R in inactive and active state structure have been solved. Using these crystal structures and cheminformatics
tools, exploring structures similar to eprosartan with an increase in bioavailability and affinity may enhance the treatment of
The review of Selvaraj et al.  demonstrated ion channels as therapeutic targets for type 1 diabetes mellitus. Ion channels
are integral proteins expressed in almost all living cells involved in muscle contraction and nutrient transport. It plays a critical
role in the normal function of the excitable tissues of the nervous system and regulates the action potential and contraction
events. Dysfunction of genes, which encodes ion channel proteins that disrupt the channel function, leads to a number of diseases,
which include type 1 diabetes mellitus (T1DM). Therefore, to understand the complex mechanism of ion channel receptors
it is necessary to facilitate the diagnosis and management of treatment. In this review, we summarizes the mechanism of
important ion channels involved in T1DM and the role in the regulation of insulin secretion along with the limitations for ion
channels as therapeutic targets. Furthermore, we discussed the recent investigations of mechanism regulating the ion channels
in beta cells, which suggest that ions channels are active participants in the regulation of insulin secretion.
Vijayan and C  discussed and summarized recent therapeutic strategies of amyloid beta (Aβ) in Alzheimer's disease
(AD). AD is one of the most common forms of dementia and has been a global concern for several years. Due to the multifactorial
nature of the disease, AD has become irreversible, fatal and imposes a tremendous socio-economic burden. Even though
experimental medicines suggested moderate benefits, AD still lacks an effective treatment strategy for the management of
symptoms or cure. Among various hypotheses which describe the development and progression of AD, the amyloid hypothesis
has been a long-term adherent to the AD due to the involvement of various forms of Aβ peptides in the impairment of neuronal
and cognitive functions. Hence, the majority of the drug discovery approaches in the past have focused on preventing the accumulation of Aβ peptides. Currently, there are several agents in the phase III clinical trials that target Aβ or the various macromolecules
triggering Aβ deposition. Here, the author discussed some of the state-of-the- art knowledge on the functional aspects
of the key players involved in the amyloid hypothesis. Furthermore, authors conferred about anti-amyloid agents present
in phase III clinical trials.
We hope multidisciplinary topics discussed with the theme issue will promote further discussions between the researchers
of computational advances in chronic diseases diagnostics and therapy.
As the guest editors, we would like to thank all the authors and co-authors for their excellent contributions. In addition, we
would like to thank a group of scientific experts in computation and chronic diseases diagnostics and therapy who offered their
strong comments and suggestions to improve the quality of this special issue. Finally, we would like to express our sincere appreciation
to the Editor in Chief Prof. Francis J. Castellino, editorial manager K.M. Qamar, copy-editors and all the editorial
staff in Current Drug Targets, Bentham Science Publishers for the excellent opportunity, and experience while working with
this thematic issue.
Recently, omics data explosion is transforming diagnostics research and healthcare industry, offering both opportunities and
challenges. Huge data of chronic disease diagnosis distributes equal IT challenges as in other fields, including data storage,
transfer, access control, and management. Another challenge is the computational modeling of complex biological systems.
High-throughput RNA-sequencing based transcriptomics, mass spectrometry based proteomics and nuclear magnetic resonance
spectroscopy-mass spectra based metabolomics are the most common popular statistical approaches that can be used for biomarker
detection of deadly diseases namely cancer, cardiovascular disease, and other chronic diseases, and to find out the composition
of material that the cells obtain from their micro-environment. Many recent studies have successfully applied network
models for describing and simplifying such complex systems. The proposed articles contribute to develop new ideas, algorithm
design and rational drug discovery techniques to chronic diseases (cancer and cardiovascular disease, etc.) diagnostics and therapy.
The first article demonstrated the importance of bioinformatics in anti-cancer drug discovery. High-throughput transcriptome
data were widely used in biomarker identification and drug prediction by integrating with drug-response data. In addition,
biological network theory and methodology were also successfully applied to the anti-cancer drug discovery, such as studies
based on protein-protein interaction network, drug-target network and disease-gene network. Moreover, the authors discussed
different bioinformatics approaches for predicting anti-cancer drugs and drug combinations based on the multi-omic data includes
transcriptomics, toxicogenomics, function genomics and biological network. Further, the authors overviewed the available
databases and current computational methods assisting in the development of novel cancer therapy strategies .
Loganathan et al.  summarized and discussed the computational and pharmacogenomics insights into hypertension treatment
towards rational drug design and optimization strategies. Among hypertension-related signaling mechanisms, the reninangiotensin-
aldosterone system is the leading genetic target for hypertension treatment. Identifying a single drug that acts on
multiple targets is an emerging strategy for hypertension treatment and could be achieved by discovering potential targets with
less mutation and highly conserved regions. Expanding pharmacogenomics research to include patients with hypertension receiving
multiple antihypertensive drugs could assist in identifying the genetic markers of hypertension. However, available
evidence on pharmacogenomics role in hypertension is limited and primarily focused on candidate genes. Genetic association
studies have identified single nucleotide polymorphisms affecting drug responses. To understand how genetic traits alter drug
responses, computational screening of mutagenesis can be utilized to observe drug response variations at the protein level,
which can help identify new inhibitors and drug targets to manage hypertension. Rational drug design facilitates the discovery
and design of potent inhibitors. However, further research and clinical validation are required before novel inhibitors can be
clinically used as antihypertensive therapies.
Fu et al.  systematically reviewed in light of this, the label-free quantification proteomics (LFQ) and diabetic marker selection
methods have been applied to elucidate the underlying mechanisms associated with insulin resistance, explore novel
protein biomarkers, and discover innovative therapeutic protein targets. Firstly, different popular quantification measurements
and proteomic quantification tools have been applied to the diabetes studies which are comprehensively discussed. Secondly, a
number of popular manipulation methods including transformation, pretreatment (centering, scaling, and normalization), missing
value imputation methods and a variety of popular feature selection techniques applied to diabetes proteomic data are overviewed
with objective evaluation on their advantages and disadvantage. Finally, the guidelines for the efficient use of the computation-
based LFQ technology and feature selection methods in diabetes proteomics are proposed. Finally, the authors have
provided guidelines for the researchers who are engaged in proteomics biomarker discovery and by properly applying these
proteomic computational advances, more reliable therapeutic targets can be found in the field of diabetes mellitus.
Calcium (Ca2+) ion is a major intracellular signaling messenger, controlling a diverse array of cellular functions like gene
expression, secretion, cell growth, proliferation, and apoptosis. This review aims to provide the key structural and mechanical
insights of stromal interaction molecule (STIM), ORAI1 and other molecular modulators involved in Ca2+ release-activated
Ca2+ (CRAC) channel regulation. Understanding the structure and function of the protein is the foremost step towards improving
the effective target specificity by limiting their potential side effects. The major mechanism controlling the Ca2+ homeostasis
is store-operated CRAC channels. Following Ca2+ depletion in the Endoplasmic reticulum (ER) store, STIM1 interacts with
ORAI1 and leads to the opening of the CRAC channel gate and consequently allows the influx of Ca2+ ions. A plethora of
studies reported that aberrant CRAC channel activity due to loss-or-gain-of-function mutations in ORAI1 and STIM1 disturbs
this Ca2+ homeostasis and causes several autoimmune disorders. Hence, it is clearly defined that the therapeutic target of
CRAC channels provides the space for a new approach to treat autoimmune disorders. Herein, the authors mainly focused on
the structural underpinnings of the CRAC channel gating mechanism along with its biophysical properties that would provide a
solid foundation to aid the development of novel targeted drugs for an autoimmune disorder. Finally, the immune deficiencies
caused due to mutations in CRAC channel and currently used pharmacological blockers with their limitations are briefly summarized
The last article discussed about the computational strategy revealing the structural determinant of ligand selectivity towards
highly similar protein targets . Poor selectivity of drug candidates may lead to toxicity and side effects accounting for as high
as 60% failure rate, thus selectivity is consistently significant and challenging for drug discovery. To find highly specific small
molecules towards very similar protein targets, multiple strategies are always employed, including (1) To make use of the diverse
shape of binding pocket to avoid steric bump; (2) To increase binding affinities for favorite residues; (3) To achieve selectivity
through allosteric regulation of target; (4) To stabilize the inactive conformation of protein target and (5) To occupy
dual binding pockets of single target. Here, the authors summarized computational strategies along with examples of their successful
applications in designing selective ligands, with the aim to provide insights into ever-diversifying drug development
practice and inspire medicinal chemists to utilize computational strategies to avoid potential side effects due to low selectivity
We hope that multidisciplinary topics discussed with the theme issue will promote further discussion between the researchers
of computational advances in diagnostics and therapy of chronic diseases.
As the guest editors, we would like to thank all the authors and co-authors for their excellent contributions. In addition, we
would like to thank a group of scientific experts in computation and chronic diseases’ diagnostics and therapy, who offered
their strong comments and suggestions to improve the quality of this special issue. Finally, we would like to express our sincere
appreciation to the Editor in Chief Prof. Francis J. Castellino, editorial manager K.M. Qamar, copy-editors and the entire editorial
staff of the Current Drug Targets, Bentham Science Publishers for the excellent opportunity, and the wonderful experience
we had while working with this thematic issue.
The incidence and prevalence of Inflammatory bowel diseases (IBD), represented by Crohn's disease (CD) and ulcerative
colitis (UC) are globally increasing over the past few decades .
Surgery is still needed in a significant number of IBD patients and represents an important therapeutic tool in the management
of both diseases [2, 3]. Surgical rates are decreasing over time following the overspread use of biological agents, such as
anti-TNFs, anti-IL-23 or anti-integrins . However, proper care and a timely indication for these new agents vary across the
world . In parallel, the evolving role of surgery in IBD management is noteworthy . In 2019, management of IBD and its
disease complications often require a combined medical and surgical approach.
As a consequence, surgical participation interacting with gastroenterologists in the care of IBD patients is essential in the
multidisciplinary management of CD and UC. The correct timing of surgical indication in IBD is essential to maximize the
benefits for the patients. As an example, it is not uncommon to see patients with fibrotic disease, which can be managed surgically,
being treated with medical therapy. This can be observed in centers where there is no interaction between colorectal surgeons
and IBD gastroenterologists, where patients sit in an uncomfortable position between both specialties with no proper
communication between the specialists. Clearly, the efficacy of medication will be lower in these situations, leading to a delay
in surgical indication, with malnourished patients, resulting in higher postoperative complication rates.
In this issue of Current Drug Targets, entitled “Medical-surgical approach in inflammatory bowel disease: doing it together!",
several specific situations where the joint care of IBD patients including surgeons and gastroenterologists is optimized
are discussed in detail. Perioperative therapy with different drugs, as steroids, immunomodulators and biologics, is explored in
different scenarios. The evidence clearly demonstrates that preoperative steroids do worsen postoperative outcomes in both CD
and UC. Immunomodulators, such as azathioprine, can be safely used in the perioperative period, with no impact on postoperative
infections. Evidence with different classes of biologics also demonstrates the controversy regarding these agents, where
conflicting evidence exploring the impact of anti-TNFs, anti-integrins and anti-interleukins in postoperative complications
demonstrates the need for a tailored approach in a case-by-case basis. When to initiate or re-initiate biologics after surgery in
CD? This is also another example of the need for a close relationship between medical and surgical care specialists.
Other situations in IBD also benefit from multidisciplinary team (MDT) frequent discussions. A perfect example of that is
the management of perianal CD, usually a challenging scenario for patients and health care specialists. Several sequential steps
are needed aiming better outcomes to these patients. A proper diagnosis, with adequate imaging tests, followed by early referral
for surgical preparation with curettage of fistula tracks, placement of setons and eradication of perianal sepsis before initiation
of biological therapy, exemplify different specialties that are involved in the management of this important phenotype of CD.
Radiologists, gastroenterologists and surgeons sitting together, having joint clinics, and discussing each case on a multidisciplinary
basis, can lead to optimized outcomes by improving patients' quality of life, which is one of the important treatment goals
in this scenario.
In UC, the need for joint efforts between gastroenterologists and surgeons can also improve the outcomes for patients. Usually,
patients are exhausted with multiple medications, with an impaired nutritional status when they finally have referrals for
colectomy. This often impacts a change in the surgical strategy, where staging operations and delaying pouch construction can
represent a safer alternative, with decreased major postoperative complications. Involvement of surgeons early in admissions
for severe colitis, aiming early recognition of complications, such as toxic megacolon and blocked perforations can also contribute
for proper timing of surgery. It is known that a delay in colectomy in this specific scenario increases significant morbidity
and mortality, and this can be avoided by a proximal relation between specialists in the MDTs. Therefore, discussion regarding
the proper timing of surgery and the specific medications used perioperatively can lead to individualized decisions and need
to be discussed between different specialties also in UC. (Table 1) summarizes some of the main indications and specific advantages
of joint MDT care in IBD.
The 21st century has seen a massive spring up in the applications of nanotechnology. Incorporation of functionalized and
modified nanostructures in various biomedical applications has generated significant research interest. The applications of
nanotechnology in medicine and biomedical engineering are vast and span areas such as implant and tissue engineering,
diagnosis and therapy. There is a need of designing nanotools, which can respond to the needs of health problems and develop
more efficient biomedical approaches.
The present special issue includes four articles with the goal of reviewing the recent developments in nanobiotechnology
with special emphasis on novel tissue engineered scaffolds and the development of nanonetworks as new communication tools
for medical approaches. Nanomaterials are also at the leading edge of the rapidly developing field of nanotechnology. In particular,
Marzo J.L. et al. started the thematic issue with a very innovative perspective. Marzo J.L. et al. reviewed the IT systems
and networks’ role in medical applications and how nanostructures can contribute medical services. As a perspective of IT on
medical field, Laromaine, A. and Roig A. reviewed biomedical application by challenging materials, which can help in tissue
treatment. In fact, the paper is focused on new developments in organic material such as cellulose to repair epithelial tissues. In
their article, Dean D. et al. focused on tissue regeneration as well. However, their focus as not only on materials which are synthetic
and not organic, but on new technologies such as 3D printing methods. A combination of materials and technologies has
been summarized to rebuilt biomedical implants. Finally, Puig M et al. reviewed the potential of different biocompatible materials
such as PCL and PLA to manufacture scaffolds for cell culture. Cell culture in 3D mimics better the human body cells,
thus it helps in the cells enrichment, and thus, the cancer cells characterization with the idea of targeting new treatments.
Overall, the aim of this issue is to offering new data to investigators to help them realize about the most recent
developments in the field of applied nanomaterials in biomedicine from different perspectives. In addition, the safety aspects in
the applications of nanotechnology to biomedical practical applications have also been examined.
We greatly acknowledge the Editor-in-Chief, Francis J. Costellino and Bentham Science Publisher for their continuous
encouragement and professional support throughout the preparation of this special issue. Finally, we would like to thank all the
authors and all the referees for their availability and their thorough evaluations of the articles published in this issue.
With the development of high-throughput sequencing techniques, more and more sequencing data is available,
including genomics reads, transcriptomes data, and proteomics sequences, which provide us an opportunity for
disease treatment and prevention that takes into account individual variability in environment, lifestyle and genes
for each person. Thus, it is critical to develop various methods in the identification of drug targets. Application of
computational methods in drugs targets discovery is more and more popular because these techniques can extract
the essential characteristics of research object and improve accuracies of models, which is needed by all biological
scholars. This special issue will focus on various aspects of the development and application of machine learning
techniques in drug targets recognition analysis.
The complete perspectives of bio-psycho-social standing of pharmacological agents are the key-features in the observation
how a drug act. This thoughtful approach is indeed imperative when managing patient's anticipation and expectation, especially
during the disease process and recuperation process. In clinical practice, the core knowledge on the art of prescribing drugs and
understanding their current drug targets in vivo and vitro can be very helpful. Hence, it may help the physician to choose the
right pharmacological agents in the therapeutic alliance.
Research has robustly documented the role of the bio-psycho-social contributing factor, and how they may influence an
individual’s experience of receptor targets for the prescribed drugs. The purpose of bio-psycho-social contribution, i.e. relationships
between drug-drug interactions are worth to be understood when prescribing antidepressants among patients with erectile
dysfunction, as the former is associated with a significant sexual dysfunction. Sexual dysfunction is also seen among women
and the role agent to promote sexual desire is considered pivotal in the intimacy-relationship domain. The cognition and emotional
states are essential in managing patients with morbid jealousy, the ‘green-eyed monster’. Cognitive-emotion domain is
also important in addressing problems of a substance-use disorder. Kratom, one of the prevalent substance-use disorders in
South-East Asian countries are an example of the problematic dilemma in an attempt to balance between the side-effects and
the benefit as a pain-killers. Another substance-use problem of nicotine dependence will be discussed in this segment of thematic
issue, especially in relation to patients with mental-health issues. We also discussed the role of bupropion in helping patients
with an Adult Attention Deficit Hyperactive Disorder, besides prescribing a psychostimulant to reward the pleasure centre
of the brain. Changes in the body, as the result of menopause also will be outlined on the role of Phytoestrogens, the Thermoregulatory
The holistic standpoint of biopsychosocial importance of mediation is crucial in terms of the perception regarding how the
psychopharmacological agent acts. This understanding is indeed important when dealing with patient's expectation and hope,
specifically during their illness and recovery process. In clinical setting, the fundamental knowledge of know-how art of prescribing
medication and dietary advice can be of great help in the real-world practice of medicine. Subsequently, this manoeuvre
may influence the choice of the pharmacological agents, dietary choice of intake and managing the adverse-effect of the
existing drug intervention routine. The relationship of the mind-body is well described in the literature especially in the context
of pharmacological therapy. The relationship is important in order to be understood for the management of patients in the clinical
Research studies have been conducted to ascertain the role of the psychosocial contributing factors, and how they may influence
an individual’s experience of drug targets. In this thematic issue, the articles focussed on the role of drug targets, which
was augmented by the emotional-cognitive and behavioral mediation in enhancing the effects of biological therapy. Emotionalcognitive
determinants may influence the processing of neurochemical actions, e.g. the dopamine-oxytocin-nitric oxide neural
pathway in patients who were given treatment in order to improve their sexual intimacy with his or her partner. These determinants
are also relevant while elaborating the role of psychopharmacological agents in alleviating the patient’s somatic symptoms.
Behavioural modification advice may help patients regain their self-confidence in their journey to recovery, despite petite
guidance given by the clinician.
The purpose of biopsychopsychological input, i.e. intimacy-relationship, cognition and emotional states is important in
helping the patient’s self-esteem with successful treatment of the PDE-5 inhibitors. Selecting the right psychopharmacological
agents to reduce the sexual-adverse effect of drugs is essential in patients with both depression and schizophrenia. The roles of
new novel antidepressants are portrayed in their multi-modality function to treat depression. Antidepressant’s effect on managing
physical symptoms is important. The stress model diathesis of alcohol in mental health was underlined with the perspective
of neuronal basis of cognition memory.
In the present thematic issue, the association of serotonin selective reuptake inhibitors and female sexual dysfunction was
discussed with special emphasis on its treatment. Interesting articles on the antinociceptive effect of Mitragyna speciosa, the
phosphodiasterase 5-inhibitors (PDE-5i) for erectile dysfunction, the recent approaches on treatment of alcohol addiction, the
neurobiology of hypersexuality and its treatment, role of atypical antipsychotics in sexuality, treatment of anxiety disorders
with Vortioxetine and the role of dietary compounds in the treatment of anxiety disorders were highlighted. Last but not the
least, the present issue also focused on the use of antidepressants for physical and psychological symptoms in cancer and discussed
the dietary issue in the biopsychopsychological context of treatment, which included tocopherol and tocotrienol.
Abdominal aortic aneurysm (AAA) is a common inflammatory cardiovascular disease among the elderly . Since the
1990s, several animal models have been developed and basic researches have been conducted to understand the pathological
conditions . Many molecules and drugs that inhibit the activity of MMPs and suppress the formation of aortic aneurysms
were found in these animal models . In particular, those which inhibit c-Jun N-terminal kinase and suppress the activity of
MMPs, regressed aortic aneurysms in animal models, and were considered as promising therapeutic drugs . However, the
pathogenesis of AAA still remains unknown. Therefore, “no” drug treatments of AAA have been approved in clinical practice,
so that surgery is currently the only treatment of AAA .
The established animal models of AAA have been employed to advance the understanding of the mechanisms in order to
identify potential treatment targets . And the models are constructed by inducing inflammatory responses by using substances
such as Angiotensin II, CaCl2 and elastase, because inflammation of the medial region and vulnerable vessel walls are
recognized as the main cause of AAA development . However, the upstream factor of inflammation associated with the development
of AAA remains unknown. More importantly, there is debate that there are discrepancies in the pathological findings
between humans and established animal models used in AAA research. Similarities in the pathogenesis between human
AAA and animal AAA models are essential for the development of pharmacological treatments.
In order to have a better opinion of experimental study using animal model and to introduce novel methodology and tool for
AAA samples, we would like to have specials relating to present and future of pharmacological therapy for AAA. At present,
there are few clinical trials associated with AAA. However, several pharmaceutical companies are interested in testing therapies
for AAA. There are as yet not few researchers studying AAA. I believe that lots of readers take a considerable interest in AAA
research through the special feature.
Cardiometabolic syndrome refers to a group of cardiometabolic risk factors that greatly increase the risk for cardiovascular
diseases and other health problems. As per the consensus of the National Heart, Lung and Blood Institute (NHLBI) and American
Heart Association (AHA), cardiometabolic syndrome is a constellation of 3 or more of the following risk factors: abdominal
obesity, high triglycerides, dyslipidemia (low- and high-density lipoprotein cholesterol), hypertension, and elevated fasting
blood glucose . At this time, the therapeutic strategies are mainly aimed at the management of individual risk factors including
dyslipidemia, hypertension and diabetes . With the ever-rising prevalence of cardiovascular anomalies including cardiac
hypertrophy, hypertension, arrhythmias, and heart failure in cardiometabolic diseases , it is pertinent to identify and develop
novel diagnostic and therapeutic techniques to better manage the cardiovascular risk in cardiometabolic diseases. For example,
the recent application of the new class of anti-diabetic drugs sodium glucose co-transporter 2 (SGLT2) inhibitors has greatly
improved the cardiovascular benefits for drugs targeting cardiometabolic syndrome . Here we will present this special issue
of “Current Drug Target” on “Drug discovery and development in the management cardiometabolic diseases” to discuss a
number of new therapeutic options in the field. Our enthusiasm for this topic came from the profound opportunities for novel
therapeutic concepts in cardiometabolic diseases. It is essential to broaden our understanding for the precise mechanisms behind
these therapeutic modalities in the management of cardiometabolic diseases.
In the first review article of this series, Li and colleagues discussed the pivotal role of ubiquitin (Ub) and ubiquitin-like proteins
(UBLs)-associated post-translational modification in the regulation of protein function in cardiac cells. Conjugation of Ub
or UBLs to target proteins may modulate both physical and physiological properties of protein substrates, thus governing a
number of disease processes including cardiac diseases . In the second article, Zhu and Zhang reviewed how the interplay
between apoptosis and autophagy controls cell death or proliferation in vascular smooth muscle cells, neointimal hyperplasia
and restenosis pathogenesis . In the third article of this series, the authors also shed light on the conservative autophagy
process to provide some valuable insights into the potential mechanism of autophagy in the onset and development of rheumatic
autoimmune diseases . In the fourth article, the authors discussed the forefront of pancreatic cancer treatment, and the
potential role of pargeting autophagy in therapeutics against pancreatic cancer . Autophagy has recently drawn some attention
as a novel drug target in the management of cardiovascular and metabolic diseases , although the potential of autophagy
in drug development may be a daunting process for cardiometabolic and other human disorders. In the fifth review, Janardhanan
reported that endocrine disrupting chemicals impair physiological homeostasis, leading to developmental and reproductive
abnormalities. Ample evidence has validated the significance of exposure to endocrine disrupting chemicals in cardiometabolic
disorders . In the next article, Chen and associates discussed the promises of ApoE4 as a potential target for the
management of coronary heart disease and Alzheimer's disease. Carriers of the ApoE4 allele seem to display hypercholesterolemia,
which would accelerate the progression of coronary atherosclerosis and Alzheimer’s disease. They have discussed
the interconnection between coronary heart disease and the devastating neurodegenerative diseases . In the seventh article,
Ceylan and colleagues discussed the SGLT2 inhibitors as the new class of antidiabetic agents, and possible advantages of the
new SGLT2 inhibitors over the traditional hypoglycemic agents in the control of body weight, blood pressure and hyperuricemia
. In the eighth article, the authors revisited the recent clinical trials on SGLT2 inhibitors including empagliflozin and
canagliflozin and highlighted the cardiovascular benefits of these SGLT2 inhibitors in type 2 diabetic patients. They dissected
the regulatory roles of SGLT2 inhibitors in energy metabolism and cardiovascular function, and factors that may compromise
the therapeutic benefit . In the ninth article, Obradovic and colleagues discussed the potential role of proprotein convertase
subtilisin/kexin type 9 (PCSK9) in the treatment of hypercholesterolemia. They also highlighted the potential opportunities and
challenges in targeting PCSK9 in the clinical settings . In the next article, Kobayashi and colleagues discussed the role of
iron as a risk factor for coronary artery disease, in particularly whether iron is toxic or not in patients with coronary heart diseases
. In the last article of this series, Feng and colleagues from Fuwai Hospital reviewed the recent concept and knowledge
of non-cardiomyocytes in the regulation of cardiomyocyte proliferation and differentiation during postnatal cardiac regeneration,
in an effort to identify potential targets for the treatment of heart failure .
Although our special issue has updated some of the recent hot topics in the understanding of cardiometabolic diseases, it
leaves behind much more unanswered questions that remain to be explored with intense research effort in future. First, cardiometabolic
syndrome is not a disease entity, thus making it rather challenging to formulate a unified therapeutic regimen for a
given individual with cardiometabolic diseases. Second, experimental animal or cell culture models for cardiometabolic diseases
may not be able to recapitulate the true pathological changes under clinical settings. Therefore, the translation of knowledge
from bench-side to the bed-side practice remains a long journey. Third, given the complexity and multiple independent
risk factors in the etiology of cardiometabolic diseases, it is almost impossible to rule a particular intervention to be superior
than others, letting alone the option of life style modification as a key element in the management of cardiometabolic syndrome
(not included in our special issue considering the central theme). We would hope that this special series will help the scientific
society to identify novel therapeutic targets or concepts in the management of cardiometabolic diseases.
The holistic perspective of bio-psychosocial dimension of intervention is important to understand how the psychopharmacological
agent works. In this thematic issue, we highlight the role of psychological and behavioural intervention to augment the
effects of current drug targets. The articles highlight the role of psychological perspective in understanding emotional responses,
cognitive-memory and vitality of the biological therapy.
The role of psychological input, i.e. psychosexual and intimacy is vital to help the patient regain full recovery with the PDE-
5 inhibitors treatment. Cognitive and counselling will enhance the treatment for women with vaginismus. Vitamin D and hormonal
preparation improves the individual's vitality. Regarding cancer patients, methylphenidate have a role for better recovery
in the treatment outcome. In addiction and Alzheimer disease, the common pathway for the human memory is better understood.
Knowledge of the pharmacokinetic of drug will surely improve the treatment strategy for psychotropic agents in psychosis.
Inflammatory Bowel Disease (IBD) is a frequent, chronic, incurable and disabling condition . Personalized medicine is a
unique opportunity to face these health challenges in the new millennium. The use of personalized medicine will allow the physician
to select the best treatment protocol and will avoid passing the expense and risks of unnecessary medical treatments that
are not properly metabolized nor are the cause of disease complications. The identification of predictors (biomarkers) of efficacy
and safety of biologics as well as predictors of disease progression is a prerequisite to the development of strategies tailored
to each individual. It is worth noting the quasi-absence of biomarkers of responsiveness to therapies despite the relatively
limited success of biologicals available to treat IBD. Identifying predictors of disease progression and of safety/efficacy of biologics
is the next step toward personalized medicine before determining the right dose for a patient, helping to avoid hazards.
In this issue of Current Drug Targets dedicated to personalized medicine in IBD, we review many aspects of the future of
IBD management and discuss whether we can predict disease course with clinical factors  and improve the safety profile of
drugs  using a personalized approach. Non-invasive monitoring of IBD patients and the clinical utility of therapeutic drug
monitoring of biologics and serological markers in clinical practice remain a matter of debate in 2016 [4-7]. The final aim of
personalized medicine is to improve quality of care of IBD patients. This will lead to evolving treatment algorithms in the preand
post-operative setting for these patients [8-11]. Embarking the patient into the management plan is the key to success. In
this regard, personalized psychological treatment of IBD patients should be systematically considered in routine practice.
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