The distribution of neurotransmitters in the brain circuitry: Mesolimbic pathway and addiction.

Understanding the central nervous system (CNS) circuitry and its different neurotransmitters that underlie reward is essential to improve treatment for many common health issues, such as addiction. Here, we concentrate on understanding how the mesolimbic circuitry and neurotransmitters are organized and function, and how drug exposure affects synaptic and structural changes in this circuitry. While the role of some reward circuits, like the cerebral dopamine (DA)/glutamate (Glu)/gamma aminobutyric acid (GABA)ergic pathways, in drug reward, is well known, new research using molecular-based methods has shown functional alterations throughout the reward circuitry that contribute to various aspects of addiction, including craving and relapse. A new understanding of the fundamental connections between brain regions as well as the molecular alterations within these particular microcircuits, such as neurotrophic factor and molecular signaling or distinct receptor function, that underlie synaptic and structural plasticity evoked by drugs of abuse has been made possible by the ability to observe and manipulate neuronal activity within specific cell types and circuits. It is exciting that these discoveries from preclinical animal research are now being applied in the clinic, where therapies for human drug dependence, such as deep brain stimulation and transcranial magnetic stimulation, are being tested. Therefore, this chapter seeks to summarize the current understanding of the important brain regions (especially, mesolimbic circuitry) and neurotransmitters implicated in drug-related behaviors and the molecular mechanisms that contribute to altered connectivity between these areas, with the postulation that increased knowledge of the plasticity within the drug reward circuit will lead to new and improved treatments for addiction.

Peptide-Membrane Docking and Molecular Dynamic Simulation of In Silico Detected Antimicrobial Peptides from Portulaca oleracea's Transcriptome.

The main issue with clinical infections is multidrug resistance to traditional antibiotics. As they are essential to innate immunity, shielding hosts from pathogenic microbes, traditional herbal remedies are an excellent supplier of antimicrobial peptides (AMPs), vital parts of defensive systems. Nevertheless, little is known about the bioactive peptide components of most ethnobotanical species. Our goal in this study was to find new, likely AMPs from Portulaca oleracea (P. oleracea) using in silico studies. The P. oleracea transcriptome was gained from Sequence Read Archive (SRA) and quality controlled, then adapters and other low-quality reads were trimmed. Afterward, de novo assembled and translated open reading frames (ORFs) were determined. Next, the ORFs were filtered based on AMP physiochemical criteria and deep learning methods. Finally, the five selected putative AMPs docked with E. coli and S. aureus membranes that showed penetration in bilayers. In this step, PO2 was chosen as a candidate AMP to analyze with molecular dynamics (MD) simulations. Our data demonstrated that PO2 is more stable in E. coli than in S. aureus. Moreover, these predicted AMPs can be good candidates for in vitro and in vivo analysis.

Engineered exosomes: a promising vehicle in cancer therapy.

During the past few decades, researchers have attempted to discover an effective treatment for cancer. Exosomes are natural nanovesicles released by various cells and play a role in communication between cells. While natural exosomes have high clinical potential, their inherent limitations have prompted researchers to design exosomes with improved therapeutic properties. To achieve this purpose, researchers have undertaken exosome engineering to modify the surface properties or internal composition of exosomes. After these modifications, engineered exosomes can be used as carriers for delivery of chemotherapeutic agents, targeted drug delivery or development of cancer vaccines. The present study provides an overview of exosomes, including their biogenesis, biological functions, isolation techniques, engineering methods, and potential applications in cancer therapy.

Processing and post-processing of fish skin as a novel material in tissue engineering.

As a natural material, fish skin contains significant amounts of collagen I and III, and due to its biocompatible nature, it can be used to regenerate various tissues and organs. To use fish skin, it is necessary to perform the decellularization process to avoid the immunological response of the host body. In the process of decellularization, it is crucial to conserve the extracellular matrix (ECM) three-dimensional (3D) structure. However, it is known that decellularization methods may also damage ECM strands arrangement and structure. Moreover, after decellularization, the post-processing of fish skin improves its mechanical and biological properties and preserves its 3D design and strength. Also, sterilization, which is one of the post-processing steps, is mandatory in pre-clinical and clinical settings. In this review paper, the fish skin decellularization methods performed and the various post-processes used to increase the performance of the skin have been studied. Moreover, multiple applications of acellular fish skin (AFS) and its extracted collagen have been reviewed.

Nanoparticles as Powerful Tools for Crossing the Blood-brain Barrier.

The blood-brain barrier (BBB) is considered an important protective barrier in the central nervous system (CNS). The barrier is mainly formed by endothelial cells (ECs) interconnected by various junctions such as tight junctions (TJs), gap junctions, and adherent junctions. They collectively constitute an intensive barrier to the transit of different substances into the brain, selectively permitting small molecules to pass through by passive movement but holding off large ones such as peptides and proteins to cross the brain. Hence some molecules selectively transfer across the BBB by active routes via transcytosis. The BBB also forms a barrier against neurotoxins as well as pathogenic agents. Although various CNS disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) could hamper the integrity of the border. Nevertheless, the BBB acts as a barrier for CNS disorders treatment because it prevents the drugs from reaching their target in the CNS. In recent years, different strategies, including osmotic disruption of BBB or chemical modification of drugs, have been used to transfer the chemotherapeutic agents into brain substances. Nowadays, nanoparticles (NPs) have been used as an effective and non-invasive tool for drug delivery and diagnosis of CNS disorders. In this review, we discuss the structural characteristic of BBB, safe passageways to cross the BBB, and the relation of barrier lesions with different CNS disorders. In the end, we explore the progress in drug delivery, diagnosis, imaging, and treatment of CNS disorders using nanoparticles.

Cell penetrating peptide: A potent delivery system in vaccine development.

One of the main obstacles to most medication administrations (such as the vaccine constructs) is the cellular membrane's inadequate permeability, which reduces their efficiency. Cell-penetrating peptides (CPPs) or protein transduction domains (PTDs) are well-known as potent biological nanocarriers to overcome this natural barrier, and to deliver membrane-impermeable substances into cells. The physicochemical properties of CPPs, the attached cargo, concentration, and cell type substantially influence the internalization mechanism. Although the exact mechanism of cellular uptake and the following processing of CPPs are still uncertain; but however, they can facilitate intracellular transfer through both endocytic and non-endocytic pathways. Improved endosomal escape efficiency, selective cell targeting, and improved uptake, processing, and presentation of antigen by antigen-presenting cells (APCs) have been reported by CPPs. Different in vitro and in vivo investigations using CPP conjugates show their potential as therapeutic agents in various medical areas such as infectious and non-infectious disorders. Effective treatments for a variety of diseases may be provided by vaccines that can cooperatively stimulate T cell-mediated immunity (T helper cell activity or cytotoxic T cell function), and immunologic memory. Delivery of antigen epitopes to APCs, and generation of a potent immune response is essential for an efficacious vaccine that can be facilitated by CPPs. The current review describes the delivery of numerous vaccine components by various CPPs and their immunostimulatory properties.