Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases

Over the last 10 years, the evaluation of the neutrophil-to-lymphocyte ratio (NLR) as an emerging marker of diseases has become a compelling field of bio-medical research. Although a precise and unique cut-off value has not been yet found, its role as a flag of immune system homeostasis is well established. NLR has a well-known prognostic value and independently correlates with mortality in the general population and in several specific subsets of disease (sepsis, pneumonia, COVID-19, cancer, etc.). Moreover, NLR was recently considered as part of the decision-making processes concerning the admission/recovery of patients with COVID-19 pneumonia. This review aims to provide an overview of the main use of this biomarker, focusing on the pathophysiology and the molecular basis underlying its central role as a reliable mirror of inflammatory status and adaptive immunity.     

A Comparison of Network-Based Methods for Drug Repurposing along with an Application to Human Complex Diseases

Drug repurposing strategy, proposing a therapeutic switching of already approved drugs with known medical indications to new therapeutic purposes, has been considered as an efficient approach to unveil novel drug candidates with new pharmacological activities, significantly reducing the cost and shortening the time of de novo drug discovery. Meaningful computational approaches for drug repurposing exploit the principles of the emerging field of Network Medicine, according to which human diseases can be interpreted as local perturbations of the human interactome network, where the molecular determinants of each disease (disease genes) are not randomly scattered, but co-localized in highly interconnected subnetworks (disease modules), whose perturbation is linked to the pathophenotype manifestation. By interpreting drug effects as local perturbations of the interactome, for a drug to be on-target effective against a specific disease or to cause off-target adverse effects, its targets should be in the nearby of disease-associated genes. Here, we used the network-based proximity measure to compute the distance between the drug module and the disease module in the human interactome by exploiting five different metrics (minimum, maximum, mean, median, mode), with the aim to compare different frameworks for highlighting putative repurposable drugs to treat complex human diseases, including malignant breast and prostate neoplasms, schizophrenia, and liver cirrhosis. Whilst the standard metric (that is the minimum) for the network-based proximity remained a valid tool for efficiently screening off-label drugs, we observed that the other implemented metrics specifically predicted further interesting drug candidates worthy of investigation for yielding a potentially significant clinical benefit.     

Evaluation of Cell Migration and Cytokines Expression Changes under the Radiofrequency Electromagnetic Field on Wound Healing In Vitro Model

Wound healing (WH) proceeds through four distinct phases: hemostasis, inflammation, proliferation, and remodeling. Impaired WH may be the consequence of the alteration of one of these phases and represents a significant health and economic burden to millions of individuals. Thus, new therapeutic strategies are the topics of intense research worldwide. Although radiofrequency electromagnetic field (RF-EMF) has many medical applications in rehabilitation, pain associated with musculoskeletal disorders, and degenerative joint disorders, its impact on WH is not fully understood. The process of WH begins just after injury and continues during the inflammatory and proliferative phases. A thorough understanding of the mechanisms by which RF-EMF can improve WH is required before it can be used as a non-invasive, inexpensive, and easily self-applicable therapeutic strategy. Thus, the aim of this study is to explore the therapeutic potential of different exposure setups of RF-EMF to drive faster healing, evaluating the keratinocytes migration, cytokines, and matrix metalloproteinases (MMPs) expression. The results showed that RF-EMF treatment promotes keratinocytes’ migration and regulates the expression of genes involved in healing, such as MMPs, tissue inhibitors of metalloproteinases, and pro/anti-inflammatory cytokines, to improve WH.     

A general battery model for PV system simulation

A battery model is proposed as a tool to simulate and optimize photovoltaic (PV) / storage systems. the normalized form of the equations with respect to the battery capacity allows us to generalize its use for any type and size of lead-acid batteries. The validity of this model to represent the battery voltage evolution during charge, overcharge and discharge processes and to predict the performance of solar systems under different operational conditions is analysed. Moreover, the battery efficiency losses are presented as a function of the upper regulation thresholds of the charge controllers and the size of the array and storage systems in a domestic application in the climate of Madrid.     

An energy consumption scenario for sizing rural electrification PV systems

This paper submits a systematic analysis of user consumption patterns of several photovoltaic (PV)-powered rural dwellings in a Mediterranean area of Spain. the measurements have been carried out within the framework of two projects and assessed in contrast with other experiences. This analysis allows a consumption scenario developed previsouly to be tested by means of the classification of families according to the number and age of their members into three types—extended, mean and reduced—with the aim of establishing a few standard cases of optimization for sizing purposes. Because the use of AC current is indispensable, at least for domestic appliances, the scenario hereby proposed leads to PV system sizes of 160, 320 and 480 Wp for reduced, mean and extended families, respectively, enjoying a level of comfort similar to grid-conneced systems.     

Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs

The cerebral synthesis of cholesterol is mainly handled by astrocytes, which are also responsible for apoproteins’ synthesis and lipoproteins’ assembly required for the cholesterol transport in the brain parenchyma. In Alzheimer disease (AD), these processes are impaired, likely because of the astrogliosis, a process characterized by morphological and functional changes in astrocytes. Several ATP-binding cassette transporters expressed by brain cells are involved in the formation of nascent discoidal lipoproteins, but the effect of beta-amyloid (Aβ) assemblies on this process is not fully understood. In this study, we investigated how of Aβ_1-42-induced astrogliosis affects the metabolism of cholesterol in vitro. We detected an impairment in the cholesterol efflux of reactive astrocytes attributable to reduced levels of ABCA1 transporters that could explain the decreased lipoproteins’ levels detected in AD patients. To approach this issue, we designed biomimetic HDLs and evaluated their performance as cholesterol acceptors. The results demonstrated the ability of apoA-I nanodiscs to cross the blood–brain barrier in vitro and to promote the cholesterol efflux from astrocytes, making them suitable as a potential supportive treatment for AD to compensate the depletion of cerebral HDLs.     

OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions

The Novel Organic Cation Transporter, OCTN1, is the first member of the OCTN subfamily; it belongs to the wider Solute Carrier family SLC22, which counts many members including cation and anion organic transporters. The tertiary structure has not been resolved for any cation organic transporter. The functional role of OCNT1 is still not well assessed despite the many functional studies so far conducted. The lack of a definitive identification of OCTN1 function can be attributed to the different experimental systems and methodologies adopted for studying each of the proposed ligands. Apart from the contradictory data, the international scientific community agrees on a role of OCTN1 in protecting cells and tissues from oxidative and/or inflammatory damage. Moreover, the involvement of this transporter in drug interactions and delivery has been well clarified, even though the exact profile of the transported/interacting molecules is still somehow confusing. Therefore, OCTN1 continues to be a hot topic in terms of its functional role and structure. This review focuses on the most recent advances on OCTN1 in terms of functional aspects, physiological roles, substrate specificity, drug interactions, tissue expression, and relationships with pathology.     

A note on polymeric inner-layered single fiber interfacial strength determination

The role of inner-layer (interphase) in fiber-reinforced composites is often assessed by measuring the interfacial shear strength of single fibers embedded in matrix blocks. Interfacial shear strength is calculated using simple shear lag analyses (Kelly and Tyson model). This paper shows that application of Kelly and Tyson's equation may result in gross overprediction of interfacial shear strengths if the thickness of the inner-layer is not negligible in comparison with the fiber diameter.     

The influence of processing conditions on the mechanical properties of poly(aryl-ether-ketone)/polybenzimidazole blends

Interest in developing high-performance blends for niche applications has grown significantly in efforts to meet ever-increasing harsh environment demands. In this work, four model poly(aryl-ether-ketone)/polybenzimidazole (PAEK/PBI) blends were chosen to study the influence of premixing methods, processing, and matrix polymers, on their mechanical properties. Among the model poly(ether ether ketone) (PEEK) and PBI blends, mechanical properties are greatly enhanced by melt premixing. The molding process mainly affects the matrix crystallinity, which in turn greatly influences fracture toughness of the blend. Poly(ether ketone ketone) (PEKK) and PBI blend exhibits a slightly lower tensile strength and fracture toughness than PEEK/PBI due to the differences in inherent properties of PEEK and PEKK matrices and their interfacial interaction with PBI. The processing−structure–property relationship of PAEK/PBI blends is established to help guide optimal design of high-performance polymer blends for structural applications. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48966.