Editors Choice Article | Small Animal Models for Human Immunodeficiency Virus (HIV), Hepatitis B, and Tuberculosis: Proceedings of an NIAID Workshop

Journal Name: Current HIV Research

Author(s): Ramesh Akkina, Daniel L. Barber, Moses T. Bility, Karl-Dimiter Bissig, Benjamin J. Burwitz, Katrin Eichelberg, Janice J. Endsley, J. Victor Garcia, Richard Hafner, Petros C. Karakousis, Brent E. Korba, Rajen Koshy, Chris Lambros, Stephan Menne, Eric L. Nuermberger, Alexander Ploss, Brendan K. Podell, Larisa Y. Poluektova, Brigitte E. Sanders-Beer*, Selvakumar Subbian, Angela Wahl.

 

 

 

Graphical Abstract:

 

 

Abstract:

The main advantage of animal models of infectious diseases over in vitro studies is the gain in the understanding of the complex dynamics between the immune system and the pathogen. While small animal models have practical advantages over large animal models, it is crucial to be aware of their limitations. Although the small animal model at least needs to be susceptible to the pathogen under study to obtain meaningful data, key elements of pathogenesis should also be reflected when compared to humans. Welldesigned small animal models for HIV, hepatitis viruses and tuberculosis require, additionally, a thorough understanding of the similarities and differences in the immune responses between humans and small animals and should incorporate that knowledge into the goals of the study. To discuss these considerations, the NIAID hosted a workshop on ‘Small Animal Models for HIV, Hepatitis B, and Tuberculosis’ on May 30, 2019. Highlights of the workshop are outlined below.

 

To read out more, please visit: http://www.eurekaselect.com/177698/article

Editors Choice Article | Crossing the Blood-Brain Barrier: A Review on Drug Delivery Strategies for Treatment of the Central Nervous System Diseases

Journal Name: Current Drug Delivery

Author(s): Nur Izzati Mansor, Norshariza Nordin*, Farahidah Mohamed, King Hwa Ling, Rozita Rosli, Zurina Hassan.

 

 

 

Graphical Abstract:

 

Abstract:

Many drugs have been designed to treat diseases of the central nervous system (CNS), especially neurodegenerative diseases. However, the presence of tight junctions at the blood-brain barrier has often compromised the efficiency of drug delivery to target sites in the brain. The principles of drug delivery systems across the blood-brain barrier are dependent on substrate-specific (i.e. protein transport and transcytosis) and non-specific (i.e. transcellular and paracellular) transport pathways, which are crucial factors in attempts to design efficient drug delivery strategies. This review describes how the blood-brain barrier presents the main challenge in delivering drugs to treat brain diseases and discusses the advantages and disadvantages of ongoing neurotherapeutic delivery strategies in overcoming this limitation. In addition, we discuss the application of colloidal carrier systems, particularly nanoparticles, as potential tools for therapy for the CNS diseases. To read out more, please visit: http://www.eurekaselect.com/174513/article

Editors Choice Article | Genus Moquiniastrum (Asteraceae): Overview of Chemical and Bioactivity Studies

 

Journal Name: Current Bioactive Compounds

Author(s): Victoria de Moraes Goncalves, Angelita Da Silveira Moreira*, Patricia Diaz de Oliveira.

 

Abstract:

The genus Moquiniastrum belongs to the Asteraceae family and is widely and exclusively dispersed throughout South America. Its species adapt easily to different cultivation conditions, and present a varied chemical composition with a great performance in pharmacological and pharmacognosy studies, mainly for sesquiterpene lactones. Moquiniastrum polymorphum is a species distinguished in the genus, presenting socioeconomic potential in several sectors, besides great application in folk medicine to treat respiratory diseases. The bioactive properties highlighted in the research are antioxidant, allelopathic, anti-inflammatory, insecticidal, antiviral and antimicrobial activity, and toxicity against different cancer lines, among others. To date, from 21 species belonging to the genus Moquiniastrum 11 species have been studied for their chemical composition, and only five species have been studied for their biological or toxicological activity. Different parts of the plants have been analysed, such as flowers, leaves and bark of the trunk and roots, and extracts obtained by different extraction methods and solvents. The genus has in its chemical composition classes of molecules such as sesquiterpene lactones, sesquiterpenes, diterpenes, triterpenes, flavonoids, coumarins, caffeic acid derivatives, acetylene and non-protein amino acids. Isolation studies of the chemical constituents of the species are promising considering that they are safe to use since they do not cause changes in DNA and can be used even during the gestational period. To read out more, please visit: http://www.eurekaselect.com/162417/article

Editors Choice Article | Bioactive Medications for the Delivery of Platelet Derivatives to Skin Wounds

Journal Name: Current Drug Delivery

Author(s): Maria Cristina Bonferoni*, Silvia Rossi, Giuseppina Sandri, Carla Caramella, Claudia Del Fante, Cesare Perotti, Dalila Miele, Barbara Vigani, Franca Ferrari.

 

 

Chronic wounds are the result of alterations in the complex series of events of physiological wound healing. In particular, the prolonged inflammation results in increased protease activity, in the degradation of extracellular matrix (ECM) and of growth factors (GFs). The relevance of platelet GFs in maintaining and restoring the complex equilibrium of different moments in wound healing is well recognized. Moreover, the observed decrease of their levels in chronic wounds suggested a possible therapeutic role of the external application to the wounds. It has been also pointed out that tissue regeneration can be more efficiently obtained by the synergic use of different GFs. Platelet derivatives such as platelet- rich plasma (PRP) and platelet lysate (PL) are able to release GFs in a balanced pool. Their therapeutic use in regenerative medicine and wound healing has been therefore more and more frequently proposed in clinical trials and in the literature. The development of a suitable formulation able to control the GFs release rate, to protect the GFs, and to assure their prolonged contact with the wound site, is of paramount importance for the therapeutic success. The present review considers some formulation approaches for PRP and PL application to wounds. Read out full article at: http://www.eurekaselect.com/170878/article

 

 

Editors Choice Article | Detecting Non-cognitive Features of Prodromal Neurodegenerative Diseases

 

Journal Name: Current Aging Science

Author(s): Alon Seifan, Christine A. Ganzer*, Krista Ryon, Michael Lin, Rahman Mahmudur, Henriquez Adolfo, Cindy Shih, Alan R. Jacobs, Molly Greenwald, Richard S. Isaacson.

 

Background: Prodromal Neurodegenerative Disease (ND) due to tauopathies such as Alzheimer’s Disease (AD) and Synucleinopathies (SN) such as Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB) present subtly. Although ND are considered cognitive disorders, in fact ND present with behavioral and even medical symptomatology years to decades prior to the onset of cognitive changes. Recognizing prodromal ND syndromes is a public health priority because ND is common, disabling and expensive. Diagnosing prodromal ND in real world clinical settings is challenging because ND of the same pathology can present with different symptoms in different people. Individual variability in nature and variability in nurture across the life course influence how ND pathology manifests clinically. The objective of this study was to describe how non-cognitive symptoms from behavioral, medical, neurological and psychiatric domains cluster in prodromal and early stages of ND.

Methods: This was an observational study of patients receiving routine clinical care for memory disorders. All patients receiving a standardized evaluation including complete neurological history and examination and standardized brief neuropsychological testing. A Principal Component Analysis (PCA) considering emotion, motor, sensory and sleep factors was performed on the entire sample of patients in order to identify co-occurring symptom clusters. All patients received a consensus diagnosis adjudicated by at least two dementia experts. Patients were grouped into Cognitively Normal, Detectable Cognitive Impairment, and Mild Cognitive Impairment categories due to AD and/or PD/LBD or NOS pathology. Symptom cluster scores were compared between clinical diagnostic groups. Read out full article at: http://www.eurekaselect.com/169580/article

Editor’s Choice Article | Functional Cross-Talk between Adenosine and Metabotropic Glutamate Receptors

 

Journal Name: Current Neuropharmacology

Author(s): David Agustín León-Navarro, José Luis Albasanz, Mairena Martín*.

 

G-protein coupled receptors are transmembrane proteins widely expressed in cells and their transduction pathways are mediated by controlling second messenger levels through different G-protein interactions. Many of these receptors have been described as involved in the physiopathology of neurodegenerative diseases and even considered as potential targets for the design of novel therapeutic strategies. Endogenous and synthetic allosteric and orthosteric selective ligands are able to modulate GPCRs at both gene and protein expression levels and can also modify their physiological function. GPCRs that coexist in the same cells can homo- and heteromerize, therefore, modulating their function. Adenosine receptors are GPCRs which stimulate or inhibit adenylyl cyclase activity through Gi/Gs protein and are involved in the control of neurotransmitter release as glutamate. In turn, metabotropic glutamate receptors are also GPCRs which inhibit adenylyl cyclase or stimulate phospholipase C activities through Gi or Gq proteins, respectively. In recent years, evidence of crosstalk mechanisms between different GPCRs have been described. The aim of the present review was to summarize the described mechanisms of interaction and crosstalking between adenosine and metabotropic glutamate receptors, mainly of group I, in both in vitro and in vivo systems, and their possible use for the design of novel ligands for the treatment of neurodegenerative diseases. Read out full article at: http://www.eurekaselect.com/161279/article

Editor’s Choice Article | Unequal Absorption of Radiolabeled and Nonradiolabeled Drug from the Oral Dose Leads to Incorrect Estimates of Drug Absorption and Circulating Metabolites in a Mass Balance Study

Journal Name: Drug Metabolism Letters

Author(s): Ryan H. Takahashi*, Jae H. Chang, Jodie Pang, Xiaorong Liang, Shuguang Ma.

 

 

Mass balance studies conducted using radiolabeled material (14C or 3H) definitively characterize the Absorption, Metabolism, and Excretion (AME) of a drug. A critical aspect of these studies is that the radiotracer maintains its proportion to total drug from its administration to its complete elimination from the body. In the study of GDC-0276 in beagle dogs, we observed that the 14C radiotracer proportion (specific activity) varied through the study.

High resolution-accurate mass spectrometric measurements of 12C and 14C isotopes of GDC- 0276 and its metabolites in plasma and excreta samples were used to determine the apparent specific activities, which were higher than the specific activity of the dosing formulation. Drug concentrations were adjusted to the observed specific activities to correct the readouts for GDC-0276 AME and PK. Read out full article at:  http://www.eurekaselect.com/167902/article

 

Editor’s Choice Article | Stimulus Sensitive Smart Nanoplatforms: An Emerging Paradigm for the Treatment of Skin Diseases

Author(s): Divya, Gurpreet Kaur*.

Journal Name: Current Drug Delivery

 

Over the past century, the prevalence of skin diseases has substantially increased. These diseases present a significant physical, emotional and socio-economic burden to the society. Such conditions are also associated with a multitude of psychological traumas to the suffering patients.

The effective treatment strategy implicates targeting of drugs to the skin. The field of drug targeting has been revolutionized with the advent of nanotechnology. The emergence of stimulus-responsive nanoplatforms has provided remarkable control over fundamental polymer properties for external triggers. This enhanced control has empowered pioneering approaches in the treatment of chronic inflammatory skin diseases. Read out more at: http://www.eurekaselect.com/169276/article

Editor’s Choice Article | A Novel Amino Acid Sequence-based Computational Approach to Predicting Cell-penetrating Peptides

Author(s): Jihui Tang*, Jie Ning , Xiaoyan Liu , Baoming Wu , Rongfeng Hu *.

Journal Name: Current Computer-Aided Drug Design

 

Introduction: Machine Learning is a useful tool for the prediction of cell-penetration compounds as drug candidates.

Materials and Methods: In this study, we developed a novel method for predicting Cell-Penetrating Peptides (CPPs) membrane penetrating capability. For this, we used orthogonal encoding to encode amino acid and each amino acid position as one variable. Then a software of IBM spss modeler and a dataset including 533 CPPs, were used for model screening.

Results: The results indicated that the machine learning model of Support Vector Machine (SVM) was suitable for predicting membrane penetrating capability. For improvement, the three CPPs with the most longer lengths were used to predict CPPs. The penetration capability can be predicted with an accuracy of close to 95%.

Conclusion: All the results indicated that by using amino acid position as a variable can be a perspective method for predicting CPPs membrane penetrating capability.

 

To find out more, please visit: http://www.eurekaselect.com/165627/article

Editor’s Choice Article | Probiotics and Prebiotics as Functional Foods: State of the Art

 

Author(s): Amin Mousavi Khaneghah*, Yadolah Fakhri.

Journal Name: Current Nutrition & Food Science

 

Foods, besides their nutritional value, are used to be as a tool in maintaining of physical and mental well-being and prevent disease. Based on the definition of Functional foods as foods, which may offer health benefits beyond basic nutrition, functional foods, are categorized as foods, not medicine. Among the last decades, the growing market for functional foods, representing both opportunities and challenges to food producers as well academic sections to cover such demand and furthermore conquer the acceptance of consumer. In this article, an overview regarding the probiotics as well as prebiotics as outstanding components of functional foods, compatibility and their use in food products have been reviewed.

Read out full article here: http://www.eurekaselect.com/161293/article