Age-Specific Differences in the Severity of COVID-19 Between Children and Adults: Reality and Reasons.

In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, children experience mild symptoms compared to adults. However, the precise explanations for this disparity are not clear. Thus, we attempted to identify rational explanations about age-related differences as reported in different studies. Given the incomplete data on SARS-CoV-2, some information has been gathered from other studies of earlier coronavirus or influenza outbreaks. Age-related differences in disease severity are important with regard to diagnosis, prognosis, and treatment of SARS-CoV-2 infections. In addition, these differences impact social distancing needs, since pediatric patients with mild or asymptomatic are likely to play a significant role in disease transmission.

Circular RNAs and Glioma: Small Molecule with Big Actions.

Glioma is known as one of very important tumors that is associated with high rate of mortality worldwide. The mean rate of survival of these patients has not changed (approximately 14 months) even with improvements in comprehensive therapeutic approaches, such as chemotherapy, radiation, and surgery. Therefore, it seems that new therapeutic or developed platforms are needed. In this regard, more understanding about genetic and epigenetic modifications in the glioma, could contribute to finding and developing these platforms. Among epigenetic mechanisms, circular RNAs have crucial roles in the glioma pathogenesis. Reported by several studies, some of the abilities of circRNAs include the exhibition of tissue specificity in humans and regulation of genes. Research has also confirmed the participation of circRNAs in different pathological or biological procedures, including migration, invasion, and apoptosis of glioma. Herein, we summarized circular RNAs involved in glioma.

Preparation and Applications of Superparamagnetic Iron Oxide Nanoparticles in Novel Drug Delivery Systems: An Overview.

Nanocarriers, as drug delivery frameworks, have been intended to enhance the pharmacological and restorative properties of traditional medications. The consolidation of medical atoms as nanocarriers can function as the drug that is required against corruption, as well as offer the desired potential outcomes in regards to targeting and controlled discharge. In the present overview article, applications of magnetic nanoparticles (MNPs) in medication conveyance are outlined. The MNPs have increased the excitement due to their biocompatibility - low poisonous quality, and their capacity to be handled in a magnetic field, which enables their applications as drug-bearing vehicles. The simplicity of surface modification of these particles can provide opportunities for targeting the moieties that are linked to the particle surface. We trust that the intriguing particles will gain further attention alongside achievements in the current ones in the near future.

Wnt Network: A Brief Review of Pathways and Multifunctional Components.

The Wnt signaling pathway appears to activate intracellular signaling transduction in embryonic development, cell migration, hematopoiesis, and several diseases. Wnt signaling is basically recognized as a canonical ß-catenin-dependent signaling pathway. However, in recent years, generally three Wnt-mediated pathways have been investigated, which operate independently of ß-catenin and include calcium/calmodulin-dependent kinase II and protein kinase C, planar cell polarity, and a third one recruits hetrotrimeric GTP-binding proteins to stimulate phospholipase C and phosphodiesterase. We provide an overview of the noncanonical Wnt signaling pathway and then will focus on canonical Wnt signaling components, Wnt ligands, agonists, and antagonist. This review will also discuss ß-catenin, both cytoplasmic and nuclear mechanisms, through signaling transduction, and, as a consequence, we have briefly highlighted potential implications of Wnt/ß-catenin in some cancers.

Long non-coding RNA molecules in tuberculosis.

Tuberculosis (TB), a chronic disease caused by Mycobacterium tuberculosis, is one of the deadliest infectious diseases in the world. Despite significant advances in detection techniques and therapeutic approaches for tuberculosis, there is still no suitable solution for early screening and reducing the number of individuals affected and their effective treatment. Various cellular events can disrupt the development of TB. The basis of these events is dysregulating of genes expression patterns related with specific molecules. Long non-coding RNAs (lncRNAs) are molecules discovered to regulate the expression of protein-coding genes and participate in gene silencing, cell cycle regulation and cellular differentiation processes. Dysregulation of lncRNAs has been found to be associated with many diseases, including cancers and infectious diseases. Thus, the recognition of lncRNAs as novel molecular biomarkers and therapeutic targets for tuberculosis is promising. In the present review, we try to summarize the current findings of lncRNA expression patterns and its role in tuberculosis infection process.

Liposome Circulation Time is Prolonged by CD47 Coating.

INTRODUCTION: Bio-degradable nano-particles have many applications as drug delivery vehicles because of their good bio-availability, controlled release, low toxicity and potential for encapsulation. However, the most important obstacle to nanoparticulate drug delivery is elimination by macrophages which reduces the residence time of nanoparticles in the blood. To overcome this problem, the surface of the nanoparticle can be passivated by coating with Polyethylene glycol (PEG). However, the use of PEG has its own disadvantages. CD47 receptor acts as a self marker on the surface of many cells and inhibits phagocytosis. This study used a CD47 mimicry peptide as a substitute for PEG to fabricate "stealth" nanoliposome with reduced macrophage clearance. METHODS: Doxorubibin was used as a model drug because of its inherent fluorescence. Doxorubicin- containing liposomes were coated with different percentages of CD47 mimicry peptide (0.5% and 1%). PEG-functionalized doxorubicin-containing liposomes, were used as a comparator. The liposomal formulations were intravenously injected into mice. Serum was collected at pre-defined time points and tissue samples were taken at 24 hours. Fluorescence was used to determine the concentration doxorubicin in serum, heart, spleen, kidney, liver and lung tissues. RESULTS: Tissue biodistribution and serum kinetic studies indicated that compared with PEG, the use of CD47 mimicry peptide increased the circulation time of doxorubicin in the circulation. Moreover, unwanted accumulation of doxorubicin in the reticuloendothelial tissues (liver and spleen), kidney and heart was significantly decreased by the CD47 mimicry peptide. CONCLUSION: The use of a CD47 mimicry peptide on the surface of nanoliposomes improved the residence time of liposomal doxorubicin in the circulation. The accumulation of drug in non-target tissues was reduced, thereby potentially reducing toxicity.

Harnessing CRISPR/Cas9 technology in cardiovascular disease.

The CRISPR/Cas9 system is a precisely targeted bacterial defense system, used to control invading viruses. This technology has many potential applications including genetic changes in somatic and germ cells and the creation of knockout animals. Compared to other genome editing techniques such as zinc-finger nucleases and transcription activator-like effector nucleases (TALENS), the CRISPR/Cas9 system is much easier and more efficient. Most importantly, the multifunctional capacity of this technology allows simultaneous editing of several genes. The CRISPR/Cas9 system also potentially has the ability to prevent and treat human diseases. The present article addresses some key points related to the use of the CRISPR/Cas9 system as a powerful tool in cardiovascular research and as a new strategy for the treatment of cardiovascular disease (CVD).

CD47: role in the immune system and application to cancer therapy.

BACKGROUND: CD47 is a widely expressed cellular receptor well known for its immunoregulatory functions. By interacting with its ligands, including thrombospondin-1 (TSP-1), signal regulatory protein α (SIRPα), integrins, and SH2-domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1), it modulates cellular phagocytosis by macrophages, transmigration of neutrophils and activation of dendritic cells, T cells and B cells. Ample studies have shown that various types of cancer express high levels of CD47 to escape from the immune system. Based on this observation, CD47 is currently considered as a prominent target in cancer therapy. CONCLUSIONS: Here, we review the role of CD47 in the maintenance of immune system homeostasis. We also depict three emerging CD47-targeting strategies for cancer therapy, including the use of mimicry peptides, antibodies, and gene silencing strategies. Among these approaches, the most advanced one is the use of anti-CD47 antibodies, which enhances cancer cell phagocytosis via inhibition of the CD47-SIRPα axis. These antibodies can also achieve higher anti-cancer efficacies when combined with chemotherapy and immunotherapy and hold promise for improving the survival of patients with cancer.

Gene Delivery Using Lipoplexes and Polyplexes: Principles, Limitations and Solutions.

Gene therapy has attracted considerable attention for the treatment of genetic and acquired diseases. Successful gene therapy occurs when the therapeutic genes penetrate targeted cells and become available to the intracellular active site. Currently, a promising approach in gene delivery is the use of nonviral gene delivery vectors that lack immunogenicity but have low toxicity and potential tissue specificity. The widely used, existing nonviral gene vectors are cationic lipids and polymers that can pass across extracellular and intracellular barriers. However, the toxicity of these vectors is a barrier to their use. Currently, the disadvantages of nonviral vectors have been minimized by several modifications. The main purpose of this review is to describe the pros and cons of gene delivery using cationic lipids and polymers.

Cellular and Molecular Aspects of Parkinson Treatment: Future Therapeutic Perspectives.

Parkinson's disease is a neurodegenerative disorder accompanied by depletion of dopamine and loss of dopaminergic neurons in the brain that is believed to be responsible for the motor and non-motor symptoms in this disease. The main drug prescribed for Parkinsonian patients is L-dopa, which can be converted to dopamine by passing through the blood-brain barrier. Although L-dopa is able to improve motor function and improve the quality of life in the patients, there is inter-individual variability and some patients do not achieve the therapeutic effect. Variations in treatment response and side effects of current drugs have convinced scientists to think of treating Parkinson's disease at the cellular and molecular level. Molecular and cellular therapy for Parkinson's disease include (i) cell transplantation therapy with human embryonic stem (ES) cells, human induced pluripotent stem (iPS) cells and human fetal mesencephalic tissue, (ii) immunological and inflammatory therapy which is done using antibodies, and (iii) gene therapy with AADC-TH-GCH gene therapy, viral vector-mediated gene delivery, RNA interference-based therapy, CRISPR-Cas9 gene editing system, and alternative methods such as optogenetics and chemogenetics. Although these methods currently have a series of challenges, they seem to be promising techniques for Parkinson's treatment in future. In this study, these prospective therapeutic approaches are reviewed.

Molecular mechanisms, prevalence, and molecular methods for familial combined hyperlipidemia disease: A review.

Familial combined hyperlipidemia (FCHL) is the most common genetic dyslipidemia disorder which is accompanied by increasing of triglyceride and cholesterol. This disorder is a complex genetic disease although it also has monogenic forms. The familial form has several criteria for diagnosis that can be distinguished of nonfamilial position. It has been shown that a variety of internal and external risk factors are involved in the pathogenesis of FCHL. Environmental factors and the genetic background also play an important role in the FCHL pathogenesis. Many mechanisms and pathways are involved in lipid metabolism (ie, dysfunctional adipose tissue, hepatic fat and very low-density lipoprotein overproduction, triglyceride-rich lipoproteins, and clearance of low-density lipoprotein particles) that could lead to FCHL. Individuals with a positive family history like those who have a positive family history of cardiovascular diseases are more predispositions for this disorder. To date several methods have been used to identify the genetic background of the FCHL. In the current review, we summarized the prevalence and the molecular mechanisms involved in the FCHL disease. Moreover, we highlighted the used molecular methods for determining the genes involved in the FCHL.

Berberine: A potential adjunct for the treatment of gastrointestinal cancers?

Gastrointestinal cancers are among the most prevalent cancers in the general population. Despite effective early diagnostics and intervention, the gastrointestinal cancer-related mortality still remains elevated. Berberine (BBR) is a benzyl tetra isoquinoline alkaloid exracted from several plants. BBR is nontoxic to human normal cells, but suppresses the growth of different tumor cells: melanoma, epidermoid carcinoma, hepatoma, oral carcinoma, glioblastoma, prostatic carcinoma, and gastric carcinoma. In particular, BBR seems to suppress the proliferation of gastrointestinal cancers in a number of preclinical models. Several mechanisms of action have been hypothesized and demonstrated: immunomodulation, inhibition of topoisomerase enzymes, suppression of the EGF receptor, Her2/neu, and the VEGF receptor, induction of p53, Cip1/p21, Kip1/p27, Rb expression, induction of apoptosis (by regulation of MMPs pathway, caspases, Bax, and Smac/DIABLO), inhibition of arylamin N-acetyltransferase activity, and regulation of microRNAs expression. The aim of this review is to summarize the pharmacological effects of BBR on animal and human gastrointestinal cancers.

Recombinant Protein Expression in Escherichia coli (E.coli): What We Need to Know.

BACKGROUND: Host, vector, and culture conditions (including cultivation media) are considered among the three main elements contributing to a successful production of recombinant proteins. Accordingly, one of the most common hosts to produce recombinant therapeutic proteins is Escherichia coli. METHODOLOGY: A comprehensive literature review was performed to identify important factors affecting production of recombinant proteins in Escherichia coli. RESULTS: Escherichia coli is taken into account as the easiest, quickest, and cheapest host with a fully known genome. Thus, numerous modifications have been carried out on Escherichia coli to optimize it as a good candidate for protein expression and; as a result, several engineered strains of Escherichia coli have been designed. In general; host strain, vector, and cultivation parameters are recognized as crucial ones determining success of recombinant protein expression in Escherichia coli. In this review, the role of host, vector, and culture conditions along with current pros and cons of different types of these factors leading to success of recombinant protein expression in Escherichia coli were discussed. CONCLUSION: Successful protein expression in Escherichia coli necessitates a broad knowledge about physicochemical properties of recombinant proteins, selection among common strains of Escherichia coli and vectors, as well as factors related to media including time, temperature, and inducer.