Cold atmospheric plasma applications in dermatology: A systematic review

Cold atmospheric plasma (CAP) applications can potentially lead to effective therapy for numerous skin diseases. Our aim is to systematically review the available data and map the use of CAP in dermatology. PubMed, Embase and Web of science were explored before 2020 for studies regarding the use of CAP in dermatology. A total of 166 studies were finally included. 74.1% of these studies used indirect CAP sources. Most studies used plasma jet (67.5%). Argon was the mostly used working gas (48.2%). Plasma application itself could be direct (89.2%) and indirect (16.3%). The proportion of studies with in vivo results remained 57.2%, of which most concerned direct plasma treatment (97.9%). Analyses performed indicate that CAP has been beneficial in many skin disorders. While, most CAP applications were focused on wound healing and melanoma treatment. This study provides a brief overview of CAP sources and relative medical applications in dermatology.     

The birth pangs of monoclonal antibody therapeutics

This paper examines the development and termination of nebacumab (Centoxin®), a human IgM monoclonal antibody (mAb) drug frequently cited as one of the notable failures of the early biopharmaceutical industry. The non-approval of Centoxin in the United States in 1992 generated major concerns at the time about the future viability of any mAb therapeutics. For Centocor, the biotechnology company that developed Centoxin, the drug posed formidable challenges in terms of safety, clinical efficacy, patient selection, the overall economic costs of health care, as well as financial backing. Indeed, Centocor's development of the drug brought it to the brink of bankruptcy. This article shows how many of the experiences learned with Centoxin paved the way for the current successes in therapeutic mAb development.     

Simulation of Steady State and Transient Polymer Growth Kinetics. Application to PEEK

Abstract

A simple two-dimensional rate-theory model demonstrates the principal effects of the Sadler/Gilmer theory of isothermal polymer crystallization. In addition it can be used to describe specific polymers by setting its parameters accordingly. We report on recent results of modelling the aromatic thermoplastic poly(aryl-ether-ether-ketone) (PEEK), in particular its isothermal growth rates, lamellar thicknesses and melting point. An extension of this model has made possible for the first time the study of transient processes such as heating scans and annealing. We report on first results.     

COVID-19 one year later: a retrospect of CRISPR-Cas system in combating COVID-19

Coronavirus disease 2019 (COVID-19), an infectious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a persistent global threat. The transmission of SARS-CoV-2 is wide and swift. Rapid detection of the viral RNA and effective therapy are imperative to prevent the worldwide spread of the new infectious disease. Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR)- CRISPR-associated protein (Cas) system is an RNA-directed adaptive immune system, and it has been transformed into a gene editing tool. Applications of CRISPR-Cas system involves in many fields, such as human gene therapy, drug discovery and disease diagnosis. Under the background of COVID-19 pandemic, CRISPR-Cas system shows hidden capacity to fight the emergency in many aspects. This review will focus on the role of gene editing in COVID-19 diagnosis and treatment. We will describe the potential use of CRISPR-Cas-based system in combating COVID-19, from diagnosis to treatment. Furthermore, the limitation and perspectives of this novel technology are also evaluated.     

Red blood cell rouleaux formation in dextran solution: dependence on polymer conformation

The velocity of rouleaux formation (RF), as previously shown, increases with increasing dextran concentration up to a critical concentration (C_a), beyond which the addition of dextran reduces the RF velocity (RFV). de Gennes' model for polymer solutions suggests that dextrans exist in two conformations: a coil structure at low concentrations, which changes to a network beyond a critical concentration (C^*). In the present study we examined the relation between C_a and C^* for dextrans of different molecular weight, and found that they coincide. This suggests that the change in dextran behavior, from increasing to decreasing RFV, occurs when their conformation changes from coil to network. In addition, it has been reported that in dilute dextran solutions the intercellular distance (D) between RBC in rouleaux increases with the molecular weight of the dextran. We found that D correlates with R_f, the end-to-end distance of the polymer molecule, and for all dextrans D ≤ 1.5 R_f. In accord with de Gennes' Model for polymers between surfaces, this corresponds to intercellular interaction with two overlapping surface-associated polymer layers, which may extend “tails” to interact with the opposing cells. Received: 8 August 1997 / Accepted: 28 November 1997     

Dynamic asymmetry and why chromatin defies simple physical definitions

Recent experiments have demonstrated a nucleus where chromatin is molded into stable, interwoven loops. Yet, many of the proteins, which shape chromatin structure, bind only transiently. In those brief encounters, these dynamic proteins temporarily crosslink chromatin loops. While, on the average, individual crosslinks do not persist, in the aggregate, they are sufficient to create and maintain stable chromatin domains. Owing to the asymmetry in size and speed of molecules involved, this type of organization imparts unique biophysical properties—the slow (chromatin) component can exhibit gel-like behaviors, whereas the fast (protein) component allows domains to respond with liquid-like characteristics.     

Design of Crotoxin-Based Peptides with Potentiator Activity Targeting the ΔF508NBD1 Cystic Fibrosis Transmembrane Conductance Regulator

We have previously shown that the CBb subunit of crotoxin, a β-neurotoxin with phospholipase A₂ (PLA₂) activity, targets the human ΔF508CFTR chloride channel implicated in cystic fibrosis (CF). By direct binding to the nucleotide binding domain 1 (NBD1) of ΔF508CFTR, this neurotoxic PLA₂ acts as a potentiator increasing chloride channel current and corrects the trafficking defect of misfolded ΔF508CFTR inside the cell.Here, for a therapeutics development of new anti-cystic fibrosis agents, we use a structure-based in silico approach to design peptides mimicking the CBb-ΔF508NBD1 interface. Combining biophysical and electrophysiological methods, we identify several peptides that interact with the ΔF508NBD1 domain and reveal their effects as potentiators on phosphorylated ΔF508CFTR. Moreover, protein-peptide interactions and electrophysiological studies allowed us to identify key residues of ΔF508NBD1 governing the interactions with the novel potentiators. The designed peptides bind to the same region as CBb phospholipase A₂ on ΔF508NBD1 and potentiate chloride channel activity. Certain peptides also show an additive effect towards the clinically approved VX-770 potentiator. The identified CF therapeutics peptides represent a novel class of CFTR potentiators and illustrate a strategy leading to reproducing the effect of specific protein–protein interactions.