Nanomaterials and Their Impact on the Immune System.

Nanomaterials have been the focus of intensive development and research in the medical and industrial sectors over the past several decades. Some studies have found that these compounds can have a detrimental impact on living organisms, including their cellular components. Despite the obvious advantages of using nanomaterials in a wide range of applications, there is sometimes skepticism caused by the lack of substantial proof that evaluates potential toxicities. The interactions of nanoparticles (NPs) with cells of the immune system and their biomolecule pathways are an area of interest for researchers. It is possible to modify NPs so that they are not recognized by the immune system or so that they suppress or stimulate the immune system in a targeted manner. In this review, we look at the literature on nanomaterials for immunostimulation and immunosuppression and their impact on how changing the physicochemical features of the particles could alter their interactions with immune cells for the better or for the worse (immunotoxicity). We also look into whether the NPs have a unique or unexpected (but desired) effect on the immune system, and whether the surface grafting of polymers or surface coatings makes stealth nanomaterials that the immune system cannot find and get rid of.

Nanomaterials as a Potential Target for Infectious Parasitic Agents.

Despite the technological advancement in the era of personalized medicine and therapeutics development, infectious parasitic causative agents remain one of the most challenging areas of research and development. The disadvantages of conventional parasitic prevention and control are the emergence of multiple drug resistance as well as the non-specific targeting of intracellular parasites, which results in high dose concentration needs and subsequently intolerable cytotoxicity. Nanotechnology has attracted extensive interest to reduce medication therapy adverse effects including poor bioavailability and drug selectivity. Numerous nanomaterials-based delivery systems have previously been shown in animal models to be effective in the treatment of various parasitic infections. This review discusses a variety of nanomaterials-based antiparasitic procedures and techniques as well as the processes that allow them to be targeted to different parasitic infections. This review focuses on the key prerequisites for creating novel nanotechnology-based carriers as a potential option in parasite management, specifically in the context of human-related pathogenic parasitic agents.

Current state of, prospects for, and obstacles to mRNA vaccine development.

Given their superior efficacy, rapid engineering, low-cost manufacturing, and safe delivery prospects, mRNA vaccines offer an intriguing alternative to conventional vaccination technologies. Several mRNA vaccine platforms targeting infectious diseases and various types of cancer have exhibited beneficial results both in vivo and in vitro. Issues related to mRNA stability and immunogenicity have been addressed. Current mRNA vaccines can generate robust immune responses, without being constrained by the major histocompatibility complex (MHC) haplotype of the recipient. Given that mRNA vaccinations are the only transient genetic information carriers, they are also safe. In this review, we provide an update and overview on mRNA vaccines, including their current state, and the problems that have prevented them from being used in more general therapeutic ways.

Reactive Oxygen Species: the Dual Role in Physiological and Pathological Conditions of the Human Body.

Reactive oxygen species (ROS) are well-known for playing a dual role as destructive and constructive species. Indeed, ROS are engaged in many redox-governing activities of the cells for the preservation of cellular homeostasis. However, its overproduction has been reported to result in oxidative stress, which is considered as a deleterious process, and is involved in the damage of cell structures that causes various diseased states. This review provides a concise view on some of the current research published in this topic for an improved understanding of the key roles of ROS in diverse conditions of health and disease. Previous research demonstrated that ROS perform as potential signaling molecules to control several normal physiological functions at the cellular level. Additionally, there is a growing body of evidence supporting the role of ROS in various pathological states. The binary nature of ROS with their profitable and injurious characteristics indicates the complexities of their specific roles at a biological compartment and the difficulties in establishing convenient intervention procedures to treat ROS-related diseases.

Discovery of potent polyphosphate kinase 1 (PPK1) inhibitors using structure-based exploration of PPK1Pharmacophoric space coupled with docking analyses.

Inorganic polyphosphate (polyP) is present in all living forms of life. Studied mainly in prokaryotes, polyP and its associated enzymes are vital in diverse metabolic activities, in some structural functions, and most importantly in stress responses. Bacterial species, including many pathogens, encode a homolog of a major polyP synthesis enzyme, Poly Phosphate Kinase (PPK) with 2 different genes coding for PPK1 and PPK2. Genetic deletion of the ppk1 gene leads to reduced polyP levels and the consequent loss of virulence and stress adaptation responses. This far, no PPK1 homolog has been identified in higher-order eukaryotes, and, therefore, PPK1 represents a novel target for chemotherapy. The aim of the current study is to investigate PPK1 from Escherichia coli with comprehensive understanding of the enzyme's structure and binding sites, which were used to design pharmacophores and screen a library of compounds for potential discovery of selective PPK1 inhibitors. Verification of the resultant inhibitors activities was conducted using a combination of mutagenic and chemical biological approaches. The metabolic phenotypic maps of the wild type E. coli (WT) and ppk1 knockout mutant were generated and compared with the metabolic map of the chemically inhibited WT. In addition, biofilm formation ability was measured in WT, ppk1 knockout mutant, and the chemically inhibited WT. The results demonstrated that chemical inhibition of PPK1, with the designed inhibitors, was equivalent to gene deletion in altering specific metabolic pathways, changing the metabolic fingerprint, and suppressing the ability of E. coli to form a biofilm.

Glucose Deprivation Enhances the Antiproliferative Effects of Oral Hypoglycemic Biguanides in Different Molecular Subtypes of Breast Cancer: an in Vitro Study.

Extensive in vitro studies have been conducted to evaluate the anticancer activity of oral hypoglycemic agents. Many of these studies experienced detrimental limitations, since they were conducted on cancer cells commonly grown in culture media consisting of extremely high concentrations of growth factors and glucose. The present study was aimed at exploring the antiproliferative effects of the commonly studied metformin and the less frequently reported phenformin oral hypoglycemic agents on different molecular subtypes of breast cancer under rich glucose and glucose deprived conditions. Our results indicate that under glucose deprived conditions, which better reflect the factual glucose-starved solid tumors in vivo, biguanides exert more antiproliferative activities against the three molecular subtypes of breast cancer cell lines examined in this study. In addition, the observed antiproliferative activities of biguanides appear to be mediated by apoptosis induction in breast cancer cells. This induction is significantly augmented under glucose deprived conditions.

Studies on the In Vitro Antiproliferative, Antimicrobial, Antioxidant, and Acetylcholinesterase Inhibition Activities Associated with Chrysanthemum coronarium Essential Oil.

The essential oil of the Jordanian Chrysanthemum coronarium L. (garland) was isolated by hydrodistillation from dried flowerheads material. The oil was essayed for its in vitro scavenging activity using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. The results demonstrate that the oil exhibits moderate radical scavenging activity relative to the strong antioxidant ascorbic acid. In addition, cholinesterase inhibitory activity of C. coronarium essential oil was evaluated for the first time. Applying Ellman's colorimetric method, interesting cholinesterase inhibitory activity, which is not dose dependent, was evident for the oil. Furthermore, antimicrobial activities of the oil against both Gram-negative and Gram-positive bacteria were evaluated. While it fails to inhibit Gram-negative bacteria growth, the antibacterial effects demonstrated by the oil were more pronounced against the Gram-positive strains. Moreover, the examined oil was assessed for its in vitro antiproliferative properties where it demonstrated variable activities towards different human cancer cell lines, of which the colon cancer was the most sensitive to the oil treatment.