Development and characterization of Polycaprolactone/chitosan-based scaffolds for tissue engineering of various organs: A review.

Research in creating 3D structures mirroring the extracellular matrix (ECM) with accurate environmental cues holds paramount significance in biological applications.Biomaterials that replicate ECM properties-mechanical, physicochemical, and biological-emerge as pivotal tools in mimicking ECM behavior.Incorporating synthetic and natural biomaterials is widely used to produce scaffolds suitable for the intended organs.Polycaprolactone (PCL), a synthetic biomaterial, boasts commendable mechanical properties, albeit with relatively modest biological attributes due to its hydrophobic nature.Chitosan (CTS) exhibits strong biological traits but lacks mechanical resilience for complex tissue regeneration.Notably, both PCL and CTS have demonstrated their application in tissue engineering for diverse types of tissues.Their combination across varying PCL:CTS ratios has increased the likelihood of fabricating scaffolds to address defects in sturdy and pliable tissues.This comprehensive analysis aspires to accentuate their distinct attributes within tissue engineering across different organs.The central focus resides in the role of PCL:CTS-based scaffolds, elucidating their contribution to the evolution of advanced functional 3D frameworks tailored for tissue engineering across diverse organs.Moreover, this discourse delves into the considerations pertinent to each organ.

Anti-CTLA-4 nanobody as a promising approach in cancer immunotherapy.

Cancer is one of the most common diseases and causes of death worldwide. Since common treatment approaches do not yield acceptable results in many patients, developing innovative strategies for effective treatment is necessary. Immunotherapy is one of the promising approaches that has been highly regarded for preventing tumor recurrence and new metastases. Meanwhile, inhibiting immune checkpoints is one of the most attractive methods of cancer immunotherapy. Cytotoxic T lymphocyte-associated protein-4 (CTLA-4) is an essential immune molecule that plays a vital role in cell cycle modulation, regulation of T cell proliferation, and cytokine production. This molecule is classically expressed by stimulated T cells. Inhibition of overexpression of immune checkpoints such as CTLA-4 receptors has been confirmed as an effective strategy. In cancer immunotherapy, immune checkpoint-blocking drugs can be enhanced with nanobodies that target immune checkpoint molecules. Nanobodies are derived from the variable domain of heavy antibody chains. These small protein fragments have evolved entirely without a light chain and can be used as a powerful tool in imaging and treating diseases with their unique structure. They have a low molecular weight, which makes them smaller than conventional antibodies while still being able to bind to specific antigens. In addition to low molecular weight, specific binding to targets, resistance to temperature, pH, and enzymes, high ability to penetrate tumor tissues, and low toxicity make nanobodies an ideal approach to overcome the disadvantages of monoclonal antibody-based immunotherapy. In this article, while reviewing the cellular and molecular functions of CTLA-4, the structure and mechanisms of nanobodies' activity, and their delivery methods, we will explain the advantages and challenges of using nanobodies, emphasizing immunotherapy treatments based on anti-CTLA-4 nanobodies.

circGFRA1: A circular RNA with important roles in human carcinogenesis.

Circular RNAs (circRNAs) are a type of covalently closed RNA molecules, which are mainly formed by back splicing of a precursor mRNA upstream exon into a downstream exon. Abnormally expressed circRNAs can modulate gene transcription by indirectly interacting with microRNAs (miRNAs). According to the current studies, circGFRA1 has been suggested to be upregulated in various cancers. circGFRA1 (hsa_circ_005239) is a type of cancer-related circRNA, which is predicted to be originated from the GFRA1 on chromosome 10. circGFRA1 can act as a sponge for several miRNAs, including miR-34a, miR-1228, miR-361-5p, miR-149, miR-498, miR-188-3p, miR-3064-5p, miR-449a. Additionally, it can regulate signaling pathways such as TGF-ß and PI3K/ AKT. circGFRA1 upregulation has been correlated with patients' poor overall survival in diverse cancers. In the present review, we have summarized the oncogenic effect of circGFRA1 in various cancers according to the adopted criteria from in vitro, in vivo, and clinical research. Moreover, functional enrichment analysis was performed on the circGFRA1 host gene and its protein interaction network to detect gene ontology and related pathways.

Cellular Conversations in Glioblastoma Progression, Diagnosis and Treatment.

Glioblastoma (GBM) is the most frequent malignancy among primary brain tumors in adults and one of the worst 5-year survival rates (< 7%) among all human cancers. Till now, treatments that target particular cell or intracellular metabolism have not improved patients' survival. GBM recruits healthy brain cells and subverts their processes to create a microenvironment that contributes to supporting tumor progression. This microenvironment encompasses a complex network in which malignant cells interact with each other and with normal and immune cells to promote tumor proliferation, angiogenesis, metastasis, immune suppression, and treatment resistance. Communication can be direct via cell-to-cell contact, mainly through adhesion molecules, tunneling nanotubes, gap junctions, or indirect by conventional paracrine signaling by cytokine, neurotransmitter, and extracellular vesicles. Understanding these communication routes could open up new avenues for the treatment of this lethal tumor. Hence, therapeutic approaches based on glioma cells` communication have recently drawn attention. This review summarizes recent findings on the crosstalk between glioblastoma cells and their tumor microenvironment, and the impact of this conversation on glioblastoma progression. We also discuss the mechanism of communication of glioma cells and their importance as therapeutic targets and diagnostic and prognostic biomarkers. Overall, understanding the biological mechanism of specific interactions in the tumor microenvironment may help in predicting patient prognosis and developing novel therapeutic strategies to target GBM.

The emerging role of regulatory cell-based therapy in autoimmune disease.

Autoimmune disease, caused by unwanted immune responses to self-antigens, affects millions of people each year and poses a great social and economic burden to individuals and communities. In the course of autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, and multiple sclerosis, disturbances in the balance between the immune response against harmful agents and tolerance towards self-antigens lead to an immune response against self-tissues. In recent years, various regulatory immune cells have been identified. Disruptions in the quality, quantity, and function of these cells have been implicated in autoimmune disease development. Therefore, targeting or engineering these cells is a promising therapeutic for different autoimmune diseases. Regulatory T cells, regulatory B cells, regulatory dendritic cells, myeloid suppressor cells, and some subsets of innate lymphoid cells are arising as important players among this class of cells. Here, we review the roles of each suppressive cell type in the immune system during homeostasis and in the development of autoimmunity. Moreover, we discuss the current and future therapeutic potential of each one of these cell types for autoimmune diseases.

Engineered Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as New Generations of Blood-Brain Barrier Transmitters.

The blood-brain barrier (BBB) is considered as the most challenging barrier in brain drug delivery. Indeed, there is a definite link between the BBB integrity defects and central nervous systems (CNS) disorders, such as neurodegenerative diseases and brain cancers, increasing concerns in the contemporary era because of the inability of most therapeutic approaches. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have already been identified as having several advantages in facilitating the transportation of hydrophilic and hydrophobic agents across the BBB. This review first explains BBB functions and its challenges in brain drug delivery, followed by a brief description of nanoparticle-based drug delivery for brain diseases. A detailed presentation of recent progressions in optimizing SLNs and NLCs for controlled release drug delivery, gene therapy, targeted drug delivery, and diagnosis of neurodegenerative diseases and brain cancers is approached. Finally, the problems, challenges, and future perspectives in optimizing these carriers for potential clinical application were described briefly.