EDITOR’S CHOICE – Differential Regulation of CYP3A4 and CYP3A5 and its Implication in Drug Discovery – INFECTIOUS DISORDERS – Current Drug Metabolism

Journal: Current Drug Metabolism

Author(s): Ogheneochukome Lolodi, Yue-Ming Wang, William C. Wright, Taosheng Chen*

Graphical Abstract:

 

Abstract:

Background: Cancer cells use several mechanisms to resist the cytotoxic effects of drugs, resulting in tumor progression and invasion. One such mechanism capitalizes on the body’s natural defense against xenobiotics by increasing the rate of xenobiotic efflux and metabolic inactivation. Xenobiotic metabolism typically involves conversion of parent molecules to more soluble and easily excreted derivatives in reactions catalyzed by Phase I and Phase II drug metabolizing enzymes.

Methods: We performed a structured search of peer-reviewed literature on P450 (CYP) 3A, with a focus on CYP3A4 and CYP3A5.

Results: Recent reports indicate that components of the xenobiotic response system are upregulated in some diseases, including many cancers. Such components include the pregnane X receptor (PXR), CYP3A4 and CYP3A5 enzymes. The CYP3A enzymes are a subset of the numerous enzymes that are transcriptionally activated following the interaction of PXR and many ligands.

Conclusion: Intense research is ongoing to understand the functional ramifications of aberrant expression of these components in diseased states with the goal of designing novel drugs that can selectively target them.

Read more here: http://www.eurekaselect.com/152811

 

EDITOR’S CHOICE – Targeted Drug Delivery Systems and Their Therapeutic Applications in Cancer and Immune Pathological Conditions – Infectious Disorders – Drug Targets

Journal: Infectious Disorders – Drug Targets

Author(s): Jamshed Iqbal*, Fareeha Anwar, Saifullah Afridi*

Graphical Abstract:

 

Abstract:

Background: More than a century ago, Paul Ehrlich proposed the idea of a drug working as a “magic bullet” that selectively eliminates diseased cells without harming the surrounding normal cells. Since then, much progress has been made in this field to broaden the scope for targeted delivery of drugs. A major problem remain the toxic effects of targeted drugs on healthy cells. In order to reduce the adverse effects of chemotherapy on healthy tissues, we survey the use of recent drug delivery systems for targeted therapy.

Objective: The selective delivery of the drugs to specific diseased cells or tissues still is a daunting task. Ideally, for target drug delivery systems, the system should be made up of carriers and drugs, where carriers precisely target the desired drug. This issue covers the recent advancements in modern techniques for such purposes.

Result and Conclusion: It encompasses advances, benefits and limitations in state of art work of targeted drug delivery through hydrogels, microfluidics, nanoparticles, carbon nanotubes, polymeric micelles, liposomes, lipoprotein based drug carriers and dendrites.

 

EDITOR’S CHOICE – Ongoing Electroencephalographic Activity Associated with Cortical Arousal in Transgenic PDAPP Mice (hAPP V717F) – Current Alzheimer Research

Journal: Current Alzheimer Research

Author(s): Claudio Del Percio, Wilhelmus Drinkenburg, Susanna Lopez, Cristina Limatola, Jesper F. Bastlund,Ditte Z. Christensen, Jan T. Pedersen, Gianluigi Forloni, Angelisa Frasca, Francesco M. Noe, Marina Bentivoglio, Paolo F. Fabene, Giuseppe Bertini, Valeria Colavito, Sophie Dix, Raffaele Ferri, Regis Bordet, Jill C. Richardson, Claudio Babiloni

Abstract:

Background: It has been shown that theta (6-10 Hz) and delta (1-6 Hz) ongoing electroencephalographic (EEG) rhythms revealed variations in the cortical arousal in C57 Wild Type (WT) mice during cage exploration (active condition) compared to awake quiet behavior (passive condition; IMI PharmaCog project, http://www.pharmacog.eu).

Objective: The objective was to test if these EEG rhythms might be abnormal in old PDAPP mice modeling Alzheimer’s disease (AD) with a hAPP Indiana V717F mutation (They show abnormal neural transmission, cognitive deficits, and brain accumulation of Aβ1-42).

Methods: Ongoing EEG rhythms were recorded by a frontoparietal bipolar channel in 15 PDAPP and 23 WT C57 male mice (mean age of 22.8 months ±0.4 and 0.3 standard error, respectively). EEG absolute power (density) was calculated. Frequency and amplitude of individual delta and theta frequency (IDF and ITF) peaks were considered during passive and active states in the wakefulness.

Results: Compared with the WT group, the PDAPP group showed higher frequency of the IDF during the passive condition and lower frequency of the ITF during the active state. Furthermore, the WT but not PDAPP group showed significant changes in the frontoparietal EEG power (IDF, ITF) during active over passive state.

Conclusion: PDAPP mice were characterized by less changes in the brain arousal during an active state as revealed by frontoparietal EEG rhythms. Future studies will have to cross-validate the present results on large animal groups, clarify the neurophysiological underpinning of the effect, and test if the disease modifying drugs against AD amyloidosis normalize those candiate EEG biomarkers in PDAPP mice

Read more here: http://www.eurekaselect.com/153722

 

EDITOR’S CHOICE – Diagnosis and Treatment of Drug-Resistant Tuberculosis – Current Respiratory Medicine Reviews

Journal: Current Respiratory Medicine Reviews

Author(s): Rafael Laniado-Laborin

Graphical Abstract:

 

Abstract:

Background: For decades there were no significant advances in the development of diagnostic procedures for drug resistant TB (DR-TB), or the availability of new, effective drugs specifically developed for DR-TB. Now, we have witnessed during the last decade, the arrival of several new diagnostic techniques and new drugs, already available for clinical use. This review aims to critically analyze evidence-based recommendations on the most recent developments in the diagnosis and treatment of multidrug-resistant tuberculosis (MDR.TB).

Methods: PubMed search for papers describing innovative diagnostic techniques and newer drugs and treatment regimens for MDR-TB. All World Health Organization (WHO) evidence-based guidelines on the subject of diagnostic techniques and new drugs and treatment regimens were also reviewed.

Results: 21 papers, 10 WHO guidelines and one Global Tuberculosis Report (2016) were included in the review. Nineteen were original papers on diagnostic techniques or newer drugs and 2 were editorials on the global burden of MDR-TB. One WHO global report dealt with the burden of MDRTB, 6 guidelines had evidence-based recommendations on newer diagnostic techniques for MDR-TB and 4 had evidence based recommendations on new drugs and treatment regimens for MDR-TB.

Conclusion: The findings of this review confirm that genotypic diagnostic methods have revolutionized the diagnosis of MDR-TB, from a process that used to take months to one that now takes just a few hours. Also, for the first time in more than 50 years, two new antituberculosis drugs, delamanid and bedaquiline, are now added to the armamentarium, a greatly needed alternative for the treatment of MDR-TB.

To access the article, please visit: http://www.eurekaselect.com/155876

 

 

EDITOR’S CHOICE – Mass Spectrometric Identification of Collagen Alpha-1 (III) Chain and Chondroitin Sulfate Proteoglycan-4 Nitration in Patients with Acute Pulmonary Embolism – Current Proteomics

Journal: Current Proteomics

Author(s): Oktay H. Ozturk, Cenker Eken, Zeynep Avcil, Filiz Ozcan, Mutay Aslan*

Graphical Abstract:

 

Abstract:

Background: Pulmonary embolism (PE) is a cardiovascular emergency that affects many patients. Acute PE-induced oxidative stress can lead to the accumulation of nitroproteins that may play a role in disease progression. The impact of nitration of a single tyrosine residue often has broad implications on the activity of biologically critical proteins, related to pathological conditions.

Methods: We used a proteomic approach to analyze nitrated plasma proteins in patients diagnosed with acute PE. Nitrotyrosine (NO2Tyr)-containing proteins were immunoprecipitated with a NO2Tyr affinity sorbent. Precipitated proteins were separated by SDS-PAGE and visualized by either Coomassie Blue staining or western blotting with mouse monoclonal anti-NO2Tyr antibody. Immunoreactive bands observed in disease patients were in-gel digested and analyzed by MALDI-TOF mass spectrometry (MS).

Results: Mass fingerprint data sets obtained from the 138 kDa peptide fragment ions matched human collagen alpha-1 (III) chain (CO3A1) with Mascot algorithm analysis giving a score of 65 (p< 0.05). Mass fingerprint data sets obtained from the 250 kDa peptide fragment ions matched human chondroitin sulfate proteoglycan 4 (CSPG4) with Mascot algorithm analysis giving a score of 57 (p< 0.05). Nitration-induced alterations of CSPG4 activity can thus possibly lead to decreased fibrin degradation and enhanced complement system activity.

Conclusion: In vivo characteristics of these nitroproteins could be significant with regards to biomarker studies and understanding of disease mechanism in patients with PE. Future studies are aimed to understand the relevance of NO2Tyr modifications in CO3A1 and CSPG4 relating to changes in protein structure and function.

To access the article, please visit: http://www.eurekaselect.com/153574

 

EDITOR’S CHOICE – A Water-soluble Cobalt(II) Compound Co(TCNQ)2, An Electrocatalyst for Hydrogen Evolution from Acetic Acid and Water – Current Catalysis

Journal: Current Catalysis

Author(s):  Ling-Zhi Tang, Shu-Zhong Zhan

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Abstract:

Background: The generation of hydrogen by electrochemical reduction of water, represents an attractive approach for storing the electrical energy transiently produced by renewable energy sources, and catalysts based on transition metal compounds are used to increase the reaction rate. Despite much progress in water reduction catalysis, structural complexity, insolubility in aqueous media and low pH conditions severely limit their practical utility. To meet this goal, we design an electrocatalyst based on Co(TCNQ)2 (TCNQ: 7,7,8,8-tetracyanoquinodimethane). This compound is water soluble and can catalyze proton or water reduction.

Methods: The reaction of LiTCNQ with CoCl2.6H2O yields a cobalt-TCNQ compound, Co(TCNQ)2 1. This compound has been characterized by spectroscopic, physics-chemical and electro-chemical methods.

Results: Electrochemical studies show that the electrocatalytic system formed by compound 1 achieves a turnover frequency (TOF) of 767 moles h-1 H2 from a neutral buffer solution (pH 7.0) at an overpotential (OP) of 0.638 V.

Conlusions: The result suggests that the addition of TCNQ is the key feature for highly catalytic activity of 1. This can be attributed to the introduction of TCNQ- ion to cobalt center, stabilizing the low oxidation state of cobalt.

Read more here: http://www.eurekaselect.com/147749

 

EDITOR’S CHOICE – C60-fullerenes as Drug Delivery Carriers for Anticancer Agents – Pharmaceutical Nanotechnology

Journal: Pharmaceutical Nanotechnology

Author(s): Manish Kumar, Kaisar Raza

Graphical Abstract:

 

Abstract:

Background: C60-fullerenes (CFs) constitute a carbon-allotropic family with cage-like fused-ring structure, comprising of 20 hexagons and 12 pentagons. Since discovery in 1985, CFs attracted the scientists from various strata for unique properties like tensile strength, nanometeric size, symmetric nature, thermal and photo conductivity, chemical tailoring opportunities and drug loading capabilities. Surprisingly, CFs are also established to possess antiviral, neuroprotective, antiinflammatory, MRI contrast and antioxidant properties. Though extensively explored for chemical modifications and therapeutic benefits, CFs and derivatives also offer immense promises in drug delivery, especially to the cancerous cells.

Objective: The present review is an attempt to highlight the promises of CFs in drug delivery, esp. of anticancer agents. The review also analyzes the safety concerns of CF-based drug delivery and attempts to discuss the promises and challenges in the light of preclinical and clinical data.

Methods: The raw material (research/review articles) for the manuscript was collected from Pubmed, Google scholar and Scopus and the keywords used were fullerenes, nanotechnology, nanomedicine, functionalization, safety, drug delivery and biomedical applications.

Conclusion: The drug release rate controlling behavior, higher drug loading, immuno-neutrality, substantial biocompatibility, capability to bypass mononuclear phagocytic system, long circulating nature and tissue extraction by virtue of enhanced permeability and retention effect are the major promises of these nanocarriers. On the other hand, the concerns like elimination from the biological system, anticipated tissue toxicity, stability of the final product, sterility issues and commercial viability pose challenges in proper utilization of CFs as ideal drug delivery carriers. However, a few commercial products based on CFs with human safety evidences provide a ray of hope.

Read more here: http://www.eurekaselect.com/150572/article

 

EDITOR’S CHOICE – PHOTOCHEMICAL REACTIONS – CURRENT ORGANIC SYNTHESIS

Journal: Current Organic Synthesis

Author(s): Navjeet Kaur

Graphical Abstract:

 

Abstract:

Background: Chemists have been interested in light as an energy source to induce chemical reactions since the beginning of scientific chemistry. The organic photochemical reactions do not require toxic or polluting reagents so these reactions presented perspectives in the context of green chemistry and sustainable processes.

Objective: The largest classical divisions of organic chemistry are constituted by heterocycles. The role of heterocyclic compounds in a number of areas cannot be ignored. That’s why the chemists are continuously trying to design and synthesize heterocycles. This review summarizes the chemistry of photochemical reactions with emphasis on their synthetic applications. In this review, the most important photochemical transformations that have been employed in six-membered N-heterocycles synthesis are presented.

Conclusion: This review discussed the research activities in organic photochemistry that are applicable in organic synthesis. This review outlined the synthesis of heterocyclic compounds. Traditional approaches require highly specialized or expensive equipment, are highly inconvenient, or would be of limited use to the synthetic organic chemist. Therefore, these have been omitted by them. Photochemistry can be used to prepare a number of heterocycles selectively, efficiently and in high yield.

Read more here: http://www.eurekaselect.com/149678/article

 

EDITOR’S CHOICE – Aspergillus Biotechnology – Current Biotechnology

Journal: Current Biotechnology

Author(s): Luis Henrique Souza Guimaraes, Patricia Nirlane da Costa Souza

Graphical Abstract:

 

Abstract:

Background: Microorganisms such as filamentous fungi are important sources of enzymes and secondary metabolites with wide application in biotechnological processes conducted in different industrial areas. Aspergillus, one of the most important genera of filamentous fungi for this purpose, has been used as a model to understand different biological processes. Despite the existence of some pathogenic Aspergillus strains, many others have been explored from a biotechnological perspective. Characteristics such as the presence of a secretory pathway, the possibility of genetic manipulation, and high productivity using different fermentative processes are advantageous and favorable for the use of Aspergillus spp. for different purposes. Production of both hydrolases and secondary metabolites has been reported for different Aspergillus species.

Objective: This review describes the production, importance, and application of the main hydrolases (amylases, cellulases, fructofuranosidases, xylanases, proteases, tannases, and phytases) produced by Aspergillus spp. considering their importance in the global enzyme market. The production of secondary metabolites such as bioactive peptides and pigments is also presented.

Conclusion: Different Aspergillus strains have demonstrated biotechnological potential for the production of hydrolases and secondary metabolites for application in food and feed, beverage, pharmaceutical, pulp, and bioremediation industries among others. In the future new species should be described and their biotechnological potential evaluated.

To access the article, please visit: http://www.eurekaselect.com/143026/article

 

EDITOR’S CHOICE – Neonatal Abstinence Syndrome Management – Reviews on Recent Clinical Trials

Journal: Reviews on Recent Clinical Trials

Author(s): Matthew Grossman*, Carl Seashore, Alison Volpe Holmes.

Abstract:

Background: The evaluation and management of infants with neonatal abstinence syndrome (NAS), the constellation of opioid withdrawal specific to newborns, have received renewed attention over the past decade during a new epidemic of opioid use, misuse, abuse, and dependence. Infants with NAS often endure long and costly hospital stays.

Objective: We aim to review recent literature on the management and outcomes of infants with, and at risk for, opioid withdrawal.

Methods: We reviewed articles indexed in PubMed over the past 5 years that examined interventions and/or outcomes related to the management of infants with NAS. Thirty-seven studies were included in our review comprising 8 categories: 1) identification of infants at risk for NAS, 2) prenatal factors, 3) evaluation of signs and symptoms, 4) non-pharmacologic care, including rooming-in and breastfeeding, 5) standardization of traditional protocols, 6) pharmacologic management, 7) alternative treatment approaches, and 8) long-term outcomes.

Results: Non-pharmacologic interventions, standardization of traditional protocols, and alternative treatment approaches were all associated with improved outcomes. Lengths of stay were generally lowest in the studies of non-pharmacologic interventions. Patients exposed to buprenorphine in utero tended to have better short-term outcomes than those exposed to methadone. Longer-term outcomes for infants with NAS appear to be worse than those of control groups.

Conclusion: The current epidemic necessitates both continued research, and the application of new evidence-based practices in the assessment and treatment of newborns exposed to opioids in utero. Projects focused on non-pharmacologic interventions appear to hold the most promise.

To access the article, please visit: http://www.eurekaselect.com/154969