Circular RNAs in tuberculosis: From mechanism of action to potential diagnostic biomarker.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), continues to be a major global health concern. Understanding the molecular intricacies of TB pathogenesis is crucial for developing effective diagnostic and therapeutic approaches. Circular RNAs (circRNAs), a class of single-stranded RNA molecules characterized by covalently closed loops, have recently emerged as potential diagnostic biomarkers in various diseases. CircRNAs have been demonstrated to modulate the host's immunological responses against TB, specifically by reducing monocyte apoptosis, augmenting autophagy, and facilitating macrophage polarization. This review comprehensively explores the roles and mechanisms of circRNAs in TB pathogenesis. We also discuss the growing body of evidence supporting their utility as promising diagnostic biomarkers for TB. By bridging the gap between fundamental circRNA biology and TB diagnostics, this review offers insights into the exciting potential of circRNAs in combatting this infectious disease.

A novel chimeric protein with enhanced cytotoxic effects on breast cancer in vitro and in vivo.

In our previous study, we reported the design and recombinant production of the p28-apoptin as a novel chimeric protein for breast cancer (BC) treatment. This study aimed to evaluate the inhibitory activity of the chimeric protein against BC cells in vitro and in vivo. We developed a novel multifunctional protein, consisting of p28, as a tumor-homing killer peptide fused to apoptin as a tumor-selective killer. The chimeric protein showed significantly higher toxicity in BC cell lines dose-dependently than in non-cancerous control cell lines. IC50 values were 1.41, 1.38, 6.13, and 264.49 µM for 4T1, MDA-MB-468, Vero, and HEK293 cells, respectively. The protein showed significantly enhanced uptake in 4T1 cancer cells compared with non-cancerous Vero cells. We also showed that the p28-apoptin chimeric protein binds significantly higher to human breast cancer tumor sections than the normal human breast tissue section. Also, significant apoptosis induction and tumor growth inhibition were observed in established tumor-bearing mice accompanied by a decreased frequency of metastases. Our results support that the chimeric protein has inhibitory activity in vitro and in vivo, making it a promising choice in targeted cancer therapy.

Immunometabolism in biofilm infection: lessons from cancer.

BACKGROUND: Biofilm is a community of bacteria embedded in an extracellular matrix, which can colonize different human cells and tissues and subvert the host immune reactions by preventing immune detection and polarizing the immune reactions towards an anti-inflammatory state, promoting the persistence of biofilm-embedded bacteria in the host. MAIN BODY OF THE MANUSCRIPT: It is now well established that the function of immune cells is ultimately mediated by cellular metabolism. The immune cells are stimulated to regulate their immune functions upon sensing danger signals. Recent studies have determined that immune cells often display distinct metabolic alterations that impair their immune responses when triggered. Such metabolic reprogramming and its physiological implications are well established in cancer situations. In bacterial infections, immuno-metabolic evaluations have primarily focused on macrophages and neutrophils in the planktonic growth mode. CONCLUSION: Based on differences in inflammatory reactions of macrophages and neutrophils in planktonic- versus biofilm-associated bacterial infections, studies must also consider the metabolic functions of immune cells against biofilm infections. The profound characterization of the metabolic and immune cell reactions could offer exciting novel targets for antibiofilm therapy.

The emerging role of exosomal miRNAs as a diagnostic and therapeutic biomarker in Mycobacterium tuberculosis infection.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), has been the world's driving fatal bacterial contagious disease globally. It continues a public health emergency, and around one-third of the global community has been affected by latent TB infection (LTBI). This is mostly due to the difficulty in diagnosing and treating patients with TB and LTBI. Exosomes are nanovesicles (40-100 nm) released from different cell types, containing proteins, lipids, mRNA, and miRNA, and they allow the transfer of one's cargo to other cells. The functional and diagnostic potential of exosomal miRNAs has been demonstrated in bacterial infections, including TB. Besides, it has been recognized that cells infected by intracellular pathogens such as Mtb can be secreting an exosome, which is implicated in the infection's fate. Exosomes, therefore, open a unique viewpoint on the investigative process of TB pathogenicity. This study explores the possible function of exosomal miRNAs as a diagnostic biomarker. Moreover, we include the latest data on the pathogenic and therapeutic role of exosomal miRNAs in TB.

DLX6-AS1: a putative lncRNA candidate in multiple human cancers.

Long non-coding RNAs (lncRNAs) have important roles in regulating the expression of genes and act as biomarkers in the initial development of different cancers. Increasing research studies have verified that dysregulation of lncRNAs occurs in various pathological processes including tumorigenesis and cancer progression. Among the different lncRNAs, DLX6-AS1 has been reported to act as an oncogene in the development and prognoses of different cancers, by affecting many different signalling pathways. This review summarises and analyses the recent research studies describing the biological functions of DLX6-AS1, its overall effect on signalling pathways and the molecular mechanisms underlying its action on the expression of genes in multiple human cancers. Our critical analysis suggests that different signalling pathways associated to this lncRNA may be used as a biomarker for diagnosis, or targets of treatment in cancers.

Role of microRNAs in Staphylococcus aureus infection: Potential biomarkers and mechanism.

Staphylococcus aureus is known as a common pathogen that colonizes 30% of healthy humans. Additionally, this bacterium can cause a number of serious infections, that is, endocarditis, bacteremia, pneumonia, wound, skin infections, and tissue abscesses. A variety of cellular and molecular pathways and targets are involved in response against S. aureus. Among them, microRNAs (miRNAs) have crucial roles in response against S. aureus. In this regard, it has been shown that these molecules exert their regulatory roles via modulating a wide range of events, such as inflammatory reactions, host innate, and adaptive immunity. Current works have provided insight into the crucial involvement of miRNAs in immune defense toward Staphylococcal infections. Herein, we highlighted the current findings on the deregulation of different miRNAs in S. aureus-infected cells. Moreover, we summarized the mechanisms and targets of miRNAs in S. aureus infections.

Bacterial biofilm in colorectal cancer: What is the real mechanism of action?

Human colorectal cancer is the third most common cancer around the world. Colorectal cancer has various risk factors, but current works have bolded a significant activity for the microbiota of the human colon in the development of this disease. Bacterial biofilm has been mediated to non-malignant pathologies like inflammatory bowel disease but has not been fully documented in the setting of colorectal cancer. The investigation has currently found that bacterial biofilm is mediated to colon cancer in the human and linked to the location of human cancer, with almost all right-sided adenomas of colon cancers possessing bacterial biofilm, whilst left-sided cancer is rarely biofilm positive. The profound comprehension of the changes in colorectal cancer can provide interesting novel concepts for anticancer treatments. In this review, we will summarize and examine the new knowledge about the links between colorectal cancer and bacterial biofilm.

Dendritic Cells - Winning the Fight against HIV.

HIV is a virus that targets and hijacks the immune cells of the host. It multiplies by attacking the helper T-lymphocytes. HIV has remained one of the most difficult and dangerous infections in the world due to the inability to find a successful treatment and a lack of access to medical care. When the virus reaches the body, dendritic cells are the first cells it encounters. DCs have been identified as one of the most effective mediators of immune responses, implying a promising strategy against viral infection. The current state of knowledge about the function of dendritic cells and their subsets is critical for using their full potential as a candidate for the development of an HIV vaccine. Despite extensive efforts, a reliable vaccine with the fewest side effects has yet to be found, and further research is needed to find a dependable and efficient vaccine. The extent to which dendritic cell-based therapy is used to treat HIV was investigated in this study. As the virus attacks the host immune system, the dendritic cells can trigger an immune response against HIV-1 infection.

Innovative Diagnostic Peptide-Based Technologies for Cancer Diagnosis: Focus on EGFR-Targeting Peptides.

Active targeting using biological ligands has emerged as a novel strategy for the targeted delivery of diagnostic agents to tumor cells. Conjugating functional targeting moieties with diagnostic probes can increase their accumulation in tumor cells and tissues, enhancing signal detection and, thus, the sensitivity of diagnosis. Due to their small size, ease of chemical synthesis and site-specific modification, high tissue penetration, low immunogenicity, rapid blood clearance, low cost, and biosafety, peptides offer several advantages over antibodies and proteins in diagnostic applications. Epidermal growth factor receptor (EGFR) is one of the most promising cancer biomarkers for actively targeting diagnostic and therapeutic agents to tumor cells due to its active involvement and overexpression in various cancers. Several peptides for EGFR-targeting have been identified in the last decades, which have been obtained by multiple means including derivation from natural proteins, phage display screening, positional scanning synthetic combinatorial library, and in silico screening. Many studies have used these peptides as a targeting moiety for diagnosing different cancers in vitro, in vivo, and in clinical trials. This review summarizes the progress of EGFR-targeting peptide-based assays in the molecular diagnosis of cancer.

A Novel Hyperthermostable Recombinant Protein Nanocage

Background: Background: Ferritin has an important role in iron storage in the cells, and due to its nanocage structure and self-assembly properties, it has wide application prospects in nanobiotechnology. Methods: Methods: The maize (Zea mays) ferritin gene ZmFer1 was cloned and expressed in Escherichia coli BL21 (DE3) for the first time. Change in macromolecular structure of ZmFer1 ferritin due to heat treatment was investigated using native PAGE electrophoresis, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Change in the secondary structures of the protein was evaluated using circular dichroism spectroscopy. Moreover, alteration in the conformation of the protein was evaluated using UV-absorption spectra and intrinsic fluorescence spectra. The melting temperature (Tm) of ZmFer1 was obtained using differential scanning calorimetry (DSC). Finally, the effect of heat on the function of ZmFer1 was assessed by iron loading ability. Results: Results: The purified ZmFer1 protein showed a homopolymer nanocage structure. The results of native PAGE electrophoresis, DLS, and TEM techniques showed that ZmFer1 protein nanocage is stable to heat treatment up to 90 °C, and some of the protein nanocages retain their macromolecular structures even at 100 °C in liquid aqueous solution. Based on the DSC results, ZmFer1 protein nanocage had a Tm of 81.9 °C. After treatment at 100 °C, stable ZmFer1 protein nanocages were able to store iron atoms. Conclusion: Conclusion: Recombinant ZmFer1 ferritin with a Tm > 80°C is a hyperthermostable protein nanocage. The results of this study are beneficial for the development of protein nanocages that are stable under extreme temperature conditions, as well as application of ZmFer1 in nanobiotechnology, biomaterials, and biomedical fields.

Engineered cells along with smart scaffolds: critical factors for improving tissue engineering approaches.

In this review, gene delivery and its applications are discussed in tissue engineering (TE); also, new techniques such as the CRISPR-Cas9 system, synthetics biology and molecular dynamics simulation to improve the efficiency of the scaffolds have been studied. CRISPR-Cas9 is expected to make significant advances in TE in the future. The fundamentals of synthetic biology have developed powerful and flexible methods for programming cells via artificial genetic circuits. The combination of regenerative medicine and artificial biology allows the engineering of cells and organisms for use in TE, biomaterials, bioprocessing and scaffold development. The dynamics of protein adsorption at the scaffold surface at the atomic level can provide valuable guidelines for the future design of TE scaffolds /implants.

Role of microbiota-derived short-chain fatty acids in nervous system disorders.

During the past decade, accumulating evidence from the research highlights the suggested effects of bacterial communities of the human gut microbiota and their metabolites on health and disease. In this regard, microbiota-derived metabolites and their receptors, beyond the immune system, maintain metabolism homeostasis, which is essential to maintain the host's health by balancing the utilization and intake of nutrients. It has been shown that gut bacterial dysbiosis can cause pathology and altered bacterial metabolites' formation, resulting in dysregulation of the immune system and metabolism. The short-chain fatty acids (SCFAs), such as butyrate, acetate, and succinate, are produced due to the fermentation process of bacteria in the gut. It has been noted remodeling in the gut microbiota metabolites associated with the pathophysiology of several neurological disorders, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, stress, anxiety, depression, autism, vascular dementia, schizophrenia, stroke, and neuromyelitis optica spectrum disorders, among others. This review will discuss the current evidence from the most significant studies dealing with some SCFAs from gut microbial metabolism with selected neurological disorders.

A brief review on DNA vaccines in the era of COVID-19.

This article provides a brief overview of DNA vaccines. First, the basic DNA vaccine design strategies are described, then specific issues related to the industrial production of DNA vaccines are discussed, including the production and purification of DNA products such as plasmid DNA, minicircle DNA, minimalistic, immunologically defined gene expression (MIDGE) and Doggybone™. The use of adjuvants to enhance the immunogenicity of DNA vaccines is then discussed. In addition, different delivery routes and several physical and chemical methods to increase the efficacy of DNA delivery into cells are explained. Recent preclinical and clinical trials of DNA vaccines for COVID-19 are then summarized. Lastly, the advantages and obstacles of DNA vaccines are discussed.

Nucleic acid aptamers in diagnosis of colorectal cancer.

Nucleic acid aptamers are promising recognition ligands for diagnostic applications. They are short DNA or RNA molecules isolated from large random libraries through the Systematic Evolution of Ligands by EXponential enrichment (SELEX) procedure. These molecules, with a particular three-dimensional shape, bind to a wide range of targets from small molecules to whole cells with high affinity and specificity. The unique properties of nucleic acid aptamers including high binding affinity and specificity, thermostability, ease of chemical production, ease of chemical modification, target adaptability, simple storage, resistance to denaturation, low immunogenicity, and low cost make them potential diagnostic tools for clinical use. Colorectal cancer is one of the most common types of cancer in humans and the third leading cause of cancer deaths in the world. Due to low response rate to current therapies in advanced stages of the disease, early detection of CRC can be useful in disease management. This review highlights recent advances in the development of nucleic acid aptamer-based methods for diagnosis, prognosis, and theranosis of colorectal cancer.