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Pharmaceuticals, Volume 9, Issue 4 (December 2016)

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Research

Jump to: Review, Other

Open AccessArticle pMPES: A Modular Peptide Expression System for the Delivery of Antimicrobial Peptides to the Site of Gastrointestinal Infections Using Probiotics
Pharmaceuticals 2016, 9(4), 60; doi:10.3390/ph9040060
Received: 6 July 2016 / Accepted: 14 September 2016 / Published: 5 October 2016
Cited by 1 | PDF Full-text (2243 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Antimicrobial peptides are a promising alternative to traditional antibiotics, but their utility is limited by high production costs and poor bioavailability profiles. Bacterial production and delivery of antimicrobial peptides (AMPs) directly at the site of infection may offer a path for effective therapeutic
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Antimicrobial peptides are a promising alternative to traditional antibiotics, but their utility is limited by high production costs and poor bioavailability profiles. Bacterial production and delivery of antimicrobial peptides (AMPs) directly at the site of infection may offer a path for effective therapeutic application. In this study, we have developed a vector that can be used for the production and secretion of seven antimicrobial peptides from both Escherichia coli MC1061 F’ and probiotic E.coli Nissle 1917. The vector pMPES (Modular Peptide Expression System) employs the Microcin V (MccV) secretion system and a powerful synthetic promoter to drive AMP production. Herein, we demonstrate the capacity of pMPES to produce inhibitory levels of MccV, Microcin L (MccL), Microcin N (McnN), Enterocin A (EntA), Enterocin P (EntP), Hiracin JM79 (HirJM79) and Enterocin B (EntB). To our knowledge, this is the first demonstration of such a broadly-applicable secretion system for AMP production. This type of modular expression system could expedite the development of sorely needed antimicrobial technologies Full article
(This article belongs to the Special Issue Antimicrobial Peptides: Expanded Activity Spectrum and Applications)
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Open AccessFeature PaperArticle Green Extraction from Pomegranate Marcs for the Production of Functional Foods and Cosmetics
Pharmaceuticals 2016, 9(4), 63; doi:10.3390/ph9040063
Received: 3 August 2016 / Revised: 12 October 2016 / Accepted: 13 October 2016 / Published: 18 October 2016
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Abstract
The aim of this study was to investigate the potential of retrieving polyphenolic antioxidants directly from wet pomegranate marcs: the fresh by-products obtained after pomegranate juice processing. These by-products mainly consist of internal membranes (endocarp) and aril residues. Even if they are still
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The aim of this study was to investigate the potential of retrieving polyphenolic antioxidants directly from wet pomegranate marcs: the fresh by-products obtained after pomegranate juice processing. These by-products mainly consist of internal membranes (endocarp) and aril residues. Even if they are still edible, they are usually discharged during juice production and, thus, they represent a great challenge in an eco-sustainable industrial context. Green technologies, such as ultrasound assisted extraction (UAE) and microwave assisted extraction (MAE), have been employed to convert these organic residues into recycled products with high added value. UAE and MAE were used both in parallel and in series in order to make a comparison and to ensure exhaustive extractions, respectively. Water, as an environmentally friendly extraction solvent, has been employed. The results were compared with those ones coming from a conventional extraction. The most promising extract, in terms of total polyphenol yield and radical scavenging activity, has been tested both as a potential natural additive and as a functional ingredient after its incorporation in a real food model and in a real cosmetic matrix, respectively. This study represents a proposal to the agro-alimentary sector given the general need of environmental “responsible care”. Full article
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Open AccessArticle Assessment of the Activity of Tigecycline against Gram-Positive and Gram-Negative Organisms Collected from Italy between 2012 and 2014, as Part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.)
Pharmaceuticals 2016, 9(4), 74; doi:10.3390/ph9040074
Received: 25 August 2016 / Revised: 15 November 2016 / Accepted: 22 November 2016 / Published: 26 November 2016
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Abstract
As part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T) we report the in vitro activity of tigecycline and its comparators against Gram-negative and Gram-positive organisms collected from Italian centers between 2012 and 2014. Minimum inhibitory concentrations were determined according to the broth
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As part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T) we report the in vitro activity of tigecycline and its comparators against Gram-negative and Gram-positive organisms collected from Italian centers between 2012 and 2014. Minimum inhibitory concentrations were determined according to the broth microdilution methodology of the Clinical and Laboratory Standards Institute, and antimicrobial resistance was determined using the European Committee on Antimicrobial Susceptibility Testing interpretive criteria. Among the Enterobacteriaceae, 31% of Escherichia coli isolates, 22% of Klebsiella pneumoniae, and 1% of Klebsiella oxytoca were extended-spectrum β-lactamase producers (ESBLs). Resistance rates among ESBL-K. pneumoniae and ESBL-E. coli to meropenem were 24% and <1%, respectively. Thirty-seven percent of K. pneumoniae were multidrug resistant (MDR) strains. Resistance rates among isolates of Acinetobacter baumannii to amikacin, levofloxacin and meropenem were between 84% and 94%. Eighty percent of A. baumannii isolates were MDR strains. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 38% of S. aureus isolates. No isolates of MRSA were resistant to linezolid, tigecycline or vancomycin. Antimicrobial resistance remains a problem in Italy with increasing numbers of MDR organisms. Despite high levels, MRSA rates appear to be stabilising. Tigecycline retains its in vitro activity against the majority of organisms, including those with multidrug resistance. Full article
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Open AccessArticle The Development of a Parenteral Pharmaceutical Formulation of a New Class of Compounds of Nitrosourea
Pharmaceuticals 2016, 9(4), 68; doi:10.3390/ph9040068
Received: 13 May 2016 / Revised: 24 October 2016 / Accepted: 25 October 2016 / Published: 1 November 2016
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Abstract
Despite the rapid development of medical technologies, chemotherapy treatment still occupies an important place in clinical oncology. In this regard, the current research in this area focuses on the synthesis of new highly effective antitumor substances that have minimal side effects and the
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Despite the rapid development of medical technologies, chemotherapy treatment still occupies an important place in clinical oncology. In this regard, the current research in this area focuses on the synthesis of new highly effective antitumor substances that have minimal side effects and the development of stable pharmaceutical formulations (PF) on their basis. In order to solve this problem, the I. Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences actively sought for original substances, namely, nitrosourea (NU) derivatives, one of the most promising classes of anticancer drugs. As a result of this research, a novel NU derivative was synthesized, namely ormustine, which showed high antitumor activity in preliminary preclinical trials. It is now crucial to develop an ormustine pharmaceutical formulation. Conducted technological studies showed that the most suitable solvent for the drug substance is 0.1 M hydrochloric acid, which ensures its rapid dissolution by ultrasonic treatment. A significant reduction in the concentration of the active ingredient during the storage of the solution required the development of a technique of its lyophilization and the selection of a shaper such as a Kollidon 17 PF. Upon completion of the development of a pharmaceutical formulation of ormustine, its stability after lyophilization was demonstrated, and a sufficient amount of the drug has been acquired for preclinical research. Full article
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Review

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Open AccessReview The New Role for an Old Kinase: Protein Kinase CK2 Regulates Metal Ion Transport
Pharmaceuticals 2016, 9(4), 80; doi:10.3390/ph9040080
Received: 18 November 2016 / Revised: 13 December 2016 / Accepted: 16 December 2016 / Published: 21 December 2016
Cited by 1 | PDF Full-text (606 KB) | HTML Full-text | XML Full-text
Abstract
The pleiotropic serine/threonine protein kinase CK2 was the first kinase discovered. It is renowned for its role in cell proliferation and anti-apoptosis. The complexity of this kinase is well reflected by the findings of past decades in terms of its heterotetrameric structure, subcellular
[...] Read more.
The pleiotropic serine/threonine protein kinase CK2 was the first kinase discovered. It is renowned for its role in cell proliferation and anti-apoptosis. The complexity of this kinase is well reflected by the findings of past decades in terms of its heterotetrameric structure, subcellular location, constitutive activity and the extensive catalogue of substrates. With the advent of non-biased high-throughput functional genomics such as genome-wide deletion mutant screening, novel aspects of CK2 functionality have been revealed. Our recent discoveries using the model organism Saccharomyces cerevisiae and mammalian cells demonstrate that CK2 regulates metal toxicity. Extensive literature search reveals that there are few but elegant works on the role of CK2 in regulating the sodium and zinc channels. As both CK2 and metal ions are key players in cell biology and oncogenesis, understanding the details of CK2’s regulation of metal ion homeostasis has a direct bearing on cancer research. In this review, we aim to garner the recent data and gain insights into the role of CK2 in metal ion transport. Full article
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Open AccessReview Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise?
Pharmaceuticals 2016, 9(4), 70; doi:10.3390/ph9040070
Received: 14 July 2016 / Revised: 23 September 2016 / Accepted: 28 September 2016 / Published: 5 November 2016
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Abstract
Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli.
[...] Read more.
Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of “chemosensor”, detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and cystic fibrosis. TRPA1 can remain activated chronically due to elevated levels and continued presence of such endogenous ligands and pro-inflammatory mediators. Several selective TRPA1 antagonists have been tested in animal models of respiratory disease and their performance is very promising. Although there is no TRPA1 antagonist in advanced clinical trials or approved on market yet to treat respiratory diseases, however, limited but promising evidences available so far indicate likelihood that targeting TRPA1 may present a new therapy in treatment of respiratory diseases in near future. This review will focus on in vitro, animal and human evidences that strengthen the proposed role of TRPA1 in modulation of specific airway sensory responses and also on preclinical and clinical progress of selected TRPA1 antagonists. Full article
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Open AccessFeature PaperReview Curcumin as a Modulator of P-Glycoprotein in Cancer: Challenges and Perspectives
Pharmaceuticals 2016, 9(4), 71; doi:10.3390/ph9040071
Received: 18 August 2016 / Revised: 2 November 2016 / Accepted: 2 November 2016 / Published: 10 November 2016
Cited by 1 | PDF Full-text (561 KB) | HTML Full-text | XML Full-text
Abstract
Multidrug resistance (MDR) presents a serious challenge to the efficiency of cancer treatment, and may be associated with the overexpression of drug efflux pumps. P-glycoprotein (P-gp) is a drug efflux pump often found overexpressed in cases of acquired MDR. Nevertheless, there are no
[...] Read more.
Multidrug resistance (MDR) presents a serious challenge to the efficiency of cancer treatment, and may be associated with the overexpression of drug efflux pumps. P-glycoprotein (P-gp) is a drug efflux pump often found overexpressed in cases of acquired MDR. Nevertheless, there are no P-gp inhibitors being used in the current clinical practice, due to toxicity problems, drug interactions, or pharmacokinetic issues. Therefore, it is important to identify novel inhibitors of P-gp activity or expression. Curcumin is a secondary metabolite isolated from the turmeric of Curcuma longa L. which has been associated with several biological activities, particularly P-gp modulatory activity (by inhibiting both P-gp function and expression). However, curcumin shows extensive metabolism and instability, which has justified the recent and intensive search for analogs of curcumin that maintain the P-gp modulatory activity but have enhanced stability. This review summarizes and compares the effects of curcumin and several curcumin analogs on P-glycoprotein function and expression, emphasizing the potential of these molecules for the possible development of safe and effective inhibitors of P-gp to overcome MDR in human cancer. Full article
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Open AccessReview Lactoferrin from Milk: Nutraceutical and Pharmacological Properties
Pharmaceuticals 2016, 9(4), 61; doi:10.3390/ph9040061
Received: 29 July 2016 / Revised: 15 September 2016 / Accepted: 21 September 2016 / Published: 27 September 2016
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Abstract
Lactoferrin is an iron-binding protein present in large quantities in colostrum and in breast milk, in external secretions and in polymorphonuclear leukocytes. Lactoferrin’s main function is non-immune protection. Among several protective activities shown by lactoferrin, those displayed by orally administered lactoferrin are: (i)
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Lactoferrin is an iron-binding protein present in large quantities in colostrum and in breast milk, in external secretions and in polymorphonuclear leukocytes. Lactoferrin’s main function is non-immune protection. Among several protective activities shown by lactoferrin, those displayed by orally administered lactoferrin are: (i) antimicrobial activity, which has been presumed due to iron deprivation, but more recently attributed also to a specific interaction with the bacterial cell wall and extended to viruses and parasites; (ii) immunomodulatory activity, with a direct effect on the development of the immune system in the newborn, together with a specific antinflammatory effects; (iii) a more recently discovered anticancer activity. It is worth noting that most of the protective activities of lactoferrin have been found, sometimes to a greater extent, also in peptides derived from limited proteolysis of lactoferrin that could be generated after lactoferrin ingestion. Lactoferrin could therefore be considered an ideal nutraceutic product because of its relatively cheap production from bovine milk and of its widely recognized tolerance after ingestion, along with its well demonstrated protective activities. The most important protective activities shown by orally administered bovine lactoferrin are reviewed in this article. Full article
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Open AccessReview Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies
Pharmaceuticals 2016, 9(4), 72; doi:10.3390/ph9040072
Received: 24 August 2016 / Revised: 7 November 2016 / Accepted: 9 November 2016 / Published: 14 November 2016
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Abstract
Specialized receptors belonging to the transient receptor potential (TRP) family of ligand-gated ion channels constitute the critical detectors and transducers of pain-causing stimuli. Nociceptive TRP channels are predominantly expressed by distinct subsets of sensory neurons of the peripheral nervous system. Several of these
[...] Read more.
Specialized receptors belonging to the transient receptor potential (TRP) family of ligand-gated ion channels constitute the critical detectors and transducers of pain-causing stimuli. Nociceptive TRP channels are predominantly expressed by distinct subsets of sensory neurons of the peripheral nervous system. Several of these TRP channels are also expressed in neurons of the central nervous system, and in non-neuronal cells that communicate with sensory nerves. Nociceptive TRPs are activated by specific physico-chemical stimuli to provide the excitatory trigger in neurons. In addition, decades of research has identified a large number of immune and neuromodulators as mediators of nociceptive TRP channel activation during injury, inflammatory and other pathological conditions. These findings have led to aggressive targeting of TRP channels for the development of new-generation analgesics. This review summarizes the complex activation and/or modulation of nociceptive TRP channels under pathophysiological conditions, and how these changes underlie acute and chronic pain conditions. Furthermore, development of small-molecule antagonists for several TRP channels as analgesics, and the positive and negative outcomes of these drugs in clinical trials are discussed. Understanding the diverse functional and modulatory properties of nociceptive TRP channels is critical to function-based drug targeting for the development of evidence-based and efficacious new generation analgesics. Full article
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Open AccessReview Nanosized Drug Delivery Systems in Gastrointestinal Targeting: Interactions with Microbiota
Pharmaceuticals 2016, 9(4), 62; doi:10.3390/ph9040062
Received: 24 August 2016 / Revised: 23 September 2016 / Accepted: 26 September 2016 / Published: 29 September 2016
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Abstract
The new age of nanotechnology has signaled a stream of entrepreneurial possibilities in various areas, form industry to medicine. Drug delivery has benefited the most by introducing nanostructured systems in the transport and controlled release of therapeutic molecules at targeted sites associated with
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The new age of nanotechnology has signaled a stream of entrepreneurial possibilities in various areas, form industry to medicine. Drug delivery has benefited the most by introducing nanostructured systems in the transport and controlled release of therapeutic molecules at targeted sites associated with a particular disease. As many nanosized particles reach the gastrointestinal tract by various means, their interactions with the molecular components of this highly active niche are intensively investigated. The well-characterized antimicrobial activities of numerous nanoparticles are currently being considered as a reliable and efficient alternative to the eminent world crisis in antimicrobial drug discovery. The interactions of nanosystems present in the gastrointestinal route with host microbiota is unavoidable; hence, a major research initiative is needed to explore the mechanisms and effects of these nanomaterials on microbiota and the impact that microbiota may have in the outcome of therapies entailing drug delivery nanosystems through the gastrointestinal route. These coordinated studies will provide novel techniques to replace or act synergistically with current technologies and help develop new treatments for major diseases via the discovery of unique antimicrobial molecules. Full article
(This article belongs to the Special Issue Nanobiotechnology in Medicinal Chemistry)
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Open AccessReview Aptamers: A New Technological Platform in Cancer Immunotherapy
Pharmaceuticals 2016, 9(4), 64; doi:10.3390/ph9040064
Received: 29 August 2016 / Revised: 29 September 2016 / Accepted: 19 October 2016 / Published: 24 October 2016
Cited by 2 | PDF Full-text (757 KB) | HTML Full-text | XML Full-text
Abstract
The renaissance of cancer immunotherapy is, nowadays, a reality. In the near future, it will be very likely among the first-line treatments for cancer patients. There are several different approaches to modulate the immune system to fight against tumor maladies but, so far,
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The renaissance of cancer immunotherapy is, nowadays, a reality. In the near future, it will be very likely among the first-line treatments for cancer patients. There are several different approaches to modulate the immune system to fight against tumor maladies but, so far, monoclonal antibodies may currently be the most successful immuno-tools used to that end. The number of ongoing clinical trials with monoclonal antibodies has been increasing exponentially over the last few years upon the Food and Drug Administration (FDA) approval of the first immune-checkpoint blockade antibodies. In spite of the proved antitumor effect of these reagents, the unleashing of the immune system to fight cancer cells has a cost, namely auto-inflammatory toxicity. Additionally, only a small fraction of all patients treated with immune-checkpoint antibodies have a clinical benefit. Taking into account all this, it is urgent new therapeutic reagents are developed with a contained toxicity that could facilitate the combination of different immune-modulating pathways to broaden the antitumor effect in most cancer patients. Based on preclinical data, oligonucleotide aptamers could fulfill this need. Aptamers have not only been successfully used as antagonists of immune-checkpoint receptors, but also as agonists of immunostimulatory receptors in cancer immunotherapy. The simplicity of aptamers to be engineered for the specific delivery of different types of cargos to tumor cells and immune cells so as to harvest an efficient antitumor immune response gives aptamers a significant advantage over antibodies. In this review all of the recent applications of aptamers in cancer immunotherapy will be described. Full article
(This article belongs to the Special Issue Aptamers: Biomedical Interest and Applications)
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Open AccessReview Herbal Products in Italy: The Thin Line between Phytotherapy, Nutrition and Parapharmaceuticals; A Normative Overview of the Fastest Growing Market in Europe
Pharmaceuticals 2016, 9(4), 65; doi:10.3390/ph9040065
Received: 7 September 2016 / Revised: 24 October 2016 / Accepted: 26 October 2016 / Published: 29 October 2016
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Abstract
The Italian herbal products market is the most prosperous in Europe. The proof is represented by the use of these products in several marketing categories, ranging from medicine to nutrition and cosmetics. Market and legislation in Italy are at the same time cause
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The Italian herbal products market is the most prosperous in Europe. The proof is represented by the use of these products in several marketing categories, ranging from medicine to nutrition and cosmetics. Market and legislation in Italy are at the same time cause and consequence of this peculiar situation. In fact, the legislation on botanical food supplements in Italy is very permissive and at the same time the market shows an overall satisfaction of users and strong feedback in terms of consumption, which brings a widening use of medicinal plants, formerly the prerogative of pharmaceuticals, to other fields such as nutrition. This review summarizes the market and normative panorama of herbal products in Italy, highlighting the blurred boundaries of health indications, marketing authorizations and quality controls between herbal medicines and non pharmaceutical products, such as food supplements, cosmetics and other herbal-based “parapharmaceuticals”. Full article
Open AccessReview Methods of Synthesis, Properties and Biomedical Applications of CuO Nanoparticles
Pharmaceuticals 2016, 9(4), 75; doi:10.3390/ph9040075
Received: 17 August 2016 / Revised: 21 November 2016 / Accepted: 22 November 2016 / Published: 30 November 2016
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Abstract
This study aims to provide an updated survey of the main synthesis methods of copper oxide (CuO) nanoparticles in order to obtain tailored nanosystems for various biomedical applications. The synthesis approach significantly impacts the properties of such nanoparticles and these properties in turn
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This study aims to provide an updated survey of the main synthesis methods of copper oxide (CuO) nanoparticles in order to obtain tailored nanosystems for various biomedical applications. The synthesis approach significantly impacts the properties of such nanoparticles and these properties in turn have a significant impact on their biomedical applications. Although not widely investigated as an efficient drug delivery system, CuO nanoparticles have great biological properties including effective antimicrobial action against a wide range of pathogens and also drug resistant bacteria. These properties have led to the development of various approaches with direct applications to the biomedical field, such as tailored surfaces with antimicrobial effect, wound dressings and modified textiles. It is also believed that these nanosystems could represent efficient alternatives in the development of smart systems utilized both for the detection of pathogens and for the treatment of infections. Full article
(This article belongs to the Special Issue Nanobiotechnology in Medicinal Chemistry)
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Open AccessReview Use of Capsaicin to Treat Pain: Mechanistic and Therapeutic Considerations
Pharmaceuticals 2016, 9(4), 66; doi:10.3390/ph9040066
Received: 7 September 2016 / Revised: 25 October 2016 / Accepted: 27 October 2016 / Published: 1 November 2016
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Abstract
Capsaicin is the pungent ingredient of chili peppers and is approved as a topical treatment of neuropathic pain. The analgesia lasts for several months after a single treatment. Capsaicin selectively activates TRPV1, a Ca2+-permeable cationic ion channel that is enriched in
[...] Read more.
Capsaicin is the pungent ingredient of chili peppers and is approved as a topical treatment of neuropathic pain. The analgesia lasts for several months after a single treatment. Capsaicin selectively activates TRPV1, a Ca2+-permeable cationic ion channel that is enriched in the terminals of certain nociceptors. Activation is followed by a prolonged decreased response to noxious stimuli. Interest also exists in the use of injectable capsaicin as a treatment for focal pain conditions, such as arthritis and other musculoskeletal conditions. Recently injection of capsaicin showed therapeutic efficacy in patients with Morton’s neuroma, a painful foot condition associated with compression of one of the digital nerves. The relief of pain was associated with no change in tactile sensibility. Though injection evokes short term pain, the brief systemic exposure and potential to establish long term analgesia without other sensory changes creates an attractive clinical profile. Short-term and long-term effects arise from both functional and structural changes in nociceptive terminals. In this review, we discuss how local administration of capsaicin may induce ablation of nociceptive terminals and the clinical implications. Full article
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Open AccessReview Applications of High-Throughput Sequencing for In Vitro Selection and Characterization of Aptamers
Pharmaceuticals 2016, 9(4), 76; doi:10.3390/ph9040076
Received: 15 November 2016 / Revised: 6 December 2016 / Accepted: 7 December 2016 / Published: 10 December 2016
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Abstract
Aptamers are identified through an iterative process of evolutionary selection starting from a random pool containing billions of sequences. Simultaneously to the amplification of high-affinity candidates, the diversity in the pool is exponentially reduced after several rounds of in vitro selection. Until now,
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Aptamers are identified through an iterative process of evolutionary selection starting from a random pool containing billions of sequences. Simultaneously to the amplification of high-affinity candidates, the diversity in the pool is exponentially reduced after several rounds of in vitro selection. Until now, cloning and Sanger sequencing of about 100 sequences was usually used to identify the enriched candidates. However, High-Throughput Sequencing (HTS) is now extensively used to replace such low throughput sequencing approaches. Providing a deeper analysis of the library, HTS is expected to accelerate the identification of aptamers as well as to identify aptamers with higher affinity. It is also expected that it can provide important information on the binding site of the aptamers. Nevertheless, HTS requires handling a large amount of data that is only possible through the development of new in silico methods. Here, this review presents these different strategies that have been recently developed to improve the identification and characterization of aptamers using HTS. Full article
(This article belongs to the Special Issue Aptamers: Biomedical Interest and Applications)
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Open AccessReview TRP Channels in Skin Biology and Pathophysiology
Pharmaceuticals 2016, 9(4), 77; doi:10.3390/ph9040077
Received: 25 October 2016 / Revised: 8 December 2016 / Accepted: 9 December 2016 / Published: 14 December 2016
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Abstract
Ion channels of the Transient Receptor Potential (TRP) family mediate the influx of monovalent and/or divalent cations into cells in response to a host of chemical or physical stimuli. In the skin, TRP channels are expressed in many cell types, including keratinocytes, sensory
[...] Read more.
Ion channels of the Transient Receptor Potential (TRP) family mediate the influx of monovalent and/or divalent cations into cells in response to a host of chemical or physical stimuli. In the skin, TRP channels are expressed in many cell types, including keratinocytes, sensory neurons, melanocytes, and immune/inflammatory cells. Within these diverse cell types, TRP channels participate in physiological processes ranging from sensation to skin homeostasis. In addition, there is a growing body of evidence implicating abnormal TRP channel function, as a product of excessive or deficient channel activity, in pathological skin conditions such as chronic pain and itch, dermatitis, vitiligo, alopecia, wound healing, skin carcinogenesis, and skin barrier compromise. These diverse functions, coupled with the fact that many TRP channels possess pharmacologically accessible sites, make this family of proteins appealing therapeutic targets for skin disorders. Full article
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Open AccessReview pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents
Pharmaceuticals 2016, 9(4), 67; doi:10.3390/ph9040067
Received: 5 July 2016 / Revised: 25 October 2016 / Accepted: 26 October 2016 / Published: 1 November 2016
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Abstract
Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that
[...] Read more.
Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations and hydrogel delivery systems. Nonetheless, many pH dependent AMPs and antimicrobial proteins have yet to be fully characterized and these molecules, as a whole, represent an untapped source of novel biologically active agents that could aid fulfillment of the urgent need for alternatives to conventional antibiotics, helping to avert a return to the pre-antibiotic era. Full article
(This article belongs to the Special Issue Antimicrobial Peptides: Expanded Activity Spectrum and Applications)
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Open AccessReview Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses
Pharmaceuticals 2016, 9(4), 78; doi:10.3390/ph9040078
Received: 13 October 2016 / Revised: 12 December 2016 / Accepted: 13 December 2016 / Published: 16 December 2016
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Abstract
Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and
[...] Read more.
Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins. From a diagnostics point of view, aptamers are being designed as a bio-recognition element in diagnostic systems to detect viral proteins either in the blood (serum or plasma) or into infected cells. Another potential use of aptamers is for therapeutics of viral infections, interfering in the interaction between the virus and the host using aptamers targeting host-cell matrix receptors, or attacking the virus intracellularly, targeting proteins implicated in the viral replication cycle. In this paper, we review how aptamers working against viral proteins are discovered, with a focus on recent advances that improve the aptamers’ properties as a real tool for viral infection detection and treatment. Full article
(This article belongs to the Special Issue Aptamers: Biomedical Interest and Applications)
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Open AccessFeature PaperReview Aptamer-Mediated Targeted Delivery of Therapeutics: An Update
Pharmaceuticals 2016, 9(4), 69; doi:10.3390/ph9040069
Received: 5 October 2016 / Revised: 27 October 2016 / Accepted: 28 October 2016 / Published: 3 November 2016
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Abstract
The selective delivery of drugs in a cell- or tissue-specific manner represents the main challenge for medical research; in order to reduce the occurrence of unwanted off-target effects. In this regard, nucleic acid aptamers have emerged as an attractive class of carrier molecules
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The selective delivery of drugs in a cell- or tissue-specific manner represents the main challenge for medical research; in order to reduce the occurrence of unwanted off-target effects. In this regard, nucleic acid aptamers have emerged as an attractive class of carrier molecules due to their ability to bind with high affinity to specific ligands; their high chemical flexibility; as well as tissue penetration capability. To date, different aptamer-drug systems and aptamer–nanoparticles systems, in which nanoparticles function together with aptamers for the targeted delivery, have been successfully developed for a wide range of therapeutics, including toxins; peptides; chemotherapeutics and oligonucleotides. Therefore, aptamer-mediated drug delivery represents a powerful tool for the safe and effective treatment of different human pathologies, including cancer; neurological diseases; immunological diseases and so on. In this review, we will summarize recent progress in the field of aptamer-mediated drug delivery and we will discuss the advantages, the achieved objectives and the challenges to be still addressed in the near future, in order to improve the effectiveness of therapies. Full article
(This article belongs to the Special Issue Aptamers: Biomedical Interest and Applications)
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Open AccessMeeting Report 30ièmes Journées Franco-Belges de Pharmacochimie
Pharmaceuticals 2016, 9(4), 73; doi:10.3390/ph9040073
Received: 8 November 2016 / Accepted: 10 November 2016 / Published: 18 November 2016
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Abstract
The “Journées Franco-Belges de Pharmacochimie” is a recognized annual meeting in organic and medicinal chemistry known for the quality of scientific exchange and conviviality. Young researchers were encouraged to present their work and share ideas with senior scientists. Abstracts of plenary lectures, oral
[...] Read more.
The “Journées Franco-Belges de Pharmacochimie” is a recognized annual meeting in organic and medicinal chemistry known for the quality of scientific exchange and conviviality. Young researchers were encouraged to present their work and share ideas with senior scientists. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report. Full article
(This article belongs to the collection Choices of the Journal)

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