A state-of-the-art review of the recent advances in exosome isolation and detection methods in viral infection.

Proteins, RNA, DNA, lipids, and carbohydrates are only some of the molecular components found in exosomes released by tumor cells. They play an essential role in healthy and diseased cells as messengers of short- and long-distance intercellular communication. However, since exosomes are released by every kind of cell and may be found in blood and other bodily fluids, they may one day serve as biomarkers for a wide range of disorders. In many pathological conditions, including cancer, inflammation, and infection, they play a role. It has been shown that the biogenesis of exosomes is analogous to that of viruses and that the exosomal cargo plays an essential role in the propagation, dissemination, and infection of several viruses. Bidirectional modulation of the immune response is achieved by the ability of exosomes associated with viruses to facilitate immunological escape and stimulate the body's antiviral immune response. Recently, exosomes have received a lot of interest due to their potential therapeutic use as biomarkers for viral infections such as human immunodeficiency virus (HIV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Epstein-Barr virus (EBV), and SARS-CoV-2. This article discusses the purification procedures and detection techniques for exosomes and examines the research on exosomes as a biomarker of viral infection.

Unrevealing the vital role of ncRNAs in Gastric Cancer chemoresistance.

The high incidence of gastric cancer in many nations and poor overall survival rates has remained a serious global health concern. Chemoresistance in gastric cancer is a significant issue that hinders the efficacy of available treatment options. In gastric cancer, non-coding RNAs like microRNAs, long non-coding RNAs, and circular RNAs have become effective regulators of chemoresistance. These non-coding RNAs can influence several mechanisms, including drug efflux transporters, drug metabolism, and detoxification, cancer stem cells and the epithelial-mesenchymal transition, autophagy and apoptosis, and the tumor microenvironment. In this article review, we summarize the key roles non-coding RNAs play in the chemoresistance of gastric cancer and consider how they might be used in clinical settings as markers for diagnosis and prognosis, as well as potential targets and treatment plans. We also emphasize the need for additional study and collaborations in this area and highlight the difficulties and opportunities in non-coding RNA research for gastric cancer chemoresistance. This review offers crucial insights into the intricate relationship between non-coding RNAs and chemoresistance in gastric cancer, with implications for precision oncology and personalized medicine.

Pathological role of inflammation in ocular disease progress and its targeting by mesenchymal stem cells (MSCs) and their exosome; current status and prospect.

Because of their unique capacity for differentiation to a diversity of cell lineages and immunosuppressive properties, mesenchymal stem cells (MSC) are being looked at as a potential new treatment option in ophthalmology. The MSCs derived from all tissue sources possess immunomodulatory attributes through cell-to-cell contact and releasing a myriad of immunomodulatory factors (IL-10, TGF-ß, growth-related oncogene (GRO), indoleamine 2,3 dioxygenase (IDO), nitric oxide (NO), interleukin 1 receptor antagonist (IL-1Ra), prostaglandin E2 (PGE2)). Such mediators, in turn, alter both the phenotype and action of all immune cells that serve a pathogenic role in the progression of inflammation in eye diseases. Exosomes from MSCs, as natural nano-particles, contain the majority of the bioactive components of parental MSCs and can easily by-pass all biological barriers to reach the target epithelial and immune cells in the eye without interfering with nearby parenchymal cells, thus having no serious side effects. We outlined the most recent research on the molecular mechanisms underlying the therapeutic benefits of MSC and MSC-exosome in the treatment of inflammatory eye diseases in the current article.

Advances in natural killer cell therapies for breast cancer.

Breast cancer (BC) is the most common cause of cancer death in women. According to the American Cancer Society's yearly cancer statistics, BC constituted almost 15% of all the newly diagnosed cancer cases in 2022 for both sexes. Metastatic disease occurs in 30% of patients with BC. The currently available treatments fail to cure metastatic BC, and the average survival time for patients with metastatic BC is approximately 2 years. Developing a treatment method that terminates cancer stem cells without harming healthy cells is the primary objective of novel therapeutics. Adoptive cell therapy is a branch of cancer immunotherapy that utilizes the immune cells to attack cancer cells. Natural killer (NK) cells are an essential component of innate immunity and are critical in destroying tumor cells without prior stimulation with antigens. With the advent of chimeric antigen receptors (CARs), the autologous or allogeneic use of NK/CAR-NK cell therapy has raised new hopes for treating patients with cancer. Here, we describe recent developments in NK and CAR-NK cell immunotherapy, including the biology and function of NK cells, clinical trials, different sources of NK cells and their future perspectives on BC.

Spotlight on the impact of viral infections on Hematopoietic Stem Cells (HSCs) with a focus on COVID-19 effects.

Hematopoietic stem cells (HSCs) are known for their significant capability to reconstitute and preserve a functional hematopoietic system in long-term periods after transplantation into conditioned hosts. HSCs are thus crucial cellular targets for the continual repair of inherited hematologic, metabolic, and immunologic disorders. In addition, HSCs can undergo various fates, such as apoptosis, quiescence, migration, differentiation, and self-renewal. Viruses continuously pose a remarkable health risk and request an appropriate, balanced reaction from our immune system, which as well as affects the bone marrow (BM). Therefore, disruption of the hematopoietic system due to viral infection is essential. In addition, patients for whom the risk-to-benefit ratio of HSC transplantation (HSCT) is acceptable have seen an increase in the use of HSCT in recent years. Hematopoietic suppression, BM failure, and HSC exhaustion are all linked to chronic viral infections. Virus infections continue to be a leading cause of morbidity and mortality in HSCT recipients, despite recent advancements in the field. Furthermore, whereas COVID-19 manifests initially as an infection of the respiratory tract, it is now understood to be a systemic illness that significantly impacts the hematological system. Patients with advanced COVID-19 often have thrombocytopenia and blood hypercoagulability. In the era of COVID-19, Hematological manifestations of COVID-19 (i.e., thrombocytopenia and lymphopenia), the immune response, and HSCT may all be affected by the SARS-CoV-2 virus in various ways. Therefore, it is important to determine whether exposure to viral infections may affect HSCs used for HSCT, as this, in turn, may affect engraftment efficiency. In this article, we reviewed the features of HSCs, and the effects of viral infections on HSCs and HSCT, such as SARS-CoV-2, HIV, cytomegalovirus, Epstein-Barr virus, HIV, etc. Video Abstract.

Synthesis and electrochemical study of enzymatic graphene oxide-based nanocomposite as stable biosensor for determination of bevacizumab as a medicine in colorectal cancer in human serum and wastewater fluids.

This work's goal was the fabrication of a graphene oxide-based nanocomposite biosensor for the determination of bevacizumab (BVZ) as a medicine for colorectal cancer in human serum and wastewater fluids. For the fabrication electrode, graphene oxide was electrodeposited on GCE (GO/GCE), and then DNA and monoclonal anti-bevacizumab antibodies were immobilized on the GO/GCE surface, respectively (Ab/DNA/GO/GCE). Structural characterization using XRD, SEM, and Raman spectroscopy confirmed the binding of DNA to GO nanosheets and the interaction of Ab with the DNA/GO array. Electrochemical characterization of Ab/DNA/GO/GCE using CV and DPV indicated immobilization of antibodies on DNA/GO/GCE and sensitive and selective behavior of modified electrodes for determination of BVZ. The linear range was obtained 10-1100 µg/mL, and the sensitivity and detection limit values were determined to be 0.14575 µA/µg.mL-1 and 0.02 µg/mL, respectively. To verify the applicability of the planned sensor for determination of BVZ in human serum and wastewater fluid specimens, the outcomes of DPV measurements using Ab, DNA, GO, and GCE and the results of the Bevacizumab ELISA Kit for determination of BVZ in prepared real specimens showed good conformity between the outcomes of both analyses. Moreover, the proposed sensor showed considerable assay precision with recoveries ranging from 96.00% to 98.90% and acceptable relative standard deviations (RSDs) below 5.11%, illustrating sufficiently good sensor accuracy and validity in the determination of BVZ in prepared real specimens of human serum and wastewater fluids. These outcomes demonstrated the feasibility of the proposed BVZ sensor in clinical and environmental assay applications.

miR-122 dysregulation is associated with type 2 diabetes mellitus-induced dyslipidemia and hyperglycemia independently of its rs17669 variant.

BACKGROUND: miR-122 is a liver specific micro-RNA that participates in the regulation of carbohydrate and lipid metabolism. The rs17669 variant of miR-122 is positioned at the flanking region of miR-122 and may affect its stability and maturation. Therefore, this study was aimed to investigate the association of the rs17669 polymorphism with the miR-122 circulating level, risk of type 2 diabetes mellitus (T2DM) development, and biochemical parameters in T2DM patients and matched healthy controls. METHODS AND RESULTS: This study involved 295 subjects (controls: n = 145 and T2DM: n = 150). The rs17669 variant genotyping was done by ARMS-PCR. Serum biochemical parameters including lipid profile, small-dense low density lipoprotein (sdLDL) and glucose were measured by colorimetric kits. Insulin and Glycated hemoglobin (HbA1c) were assayed using ELISA and capillary electrophoresis methods, respectively. miR-122 expression was measured by real-time PCR. There was no significant difference between study groups in terms of allele and genotype distribution (P > 0.05). The rs17669 variant did not have any significant association with miR-122 gene expression and biochemical parameters (P > 0.05). miR-122 expression level in T2DM patients was significantly higher than that in control subjects (5.7 ± 2.4 vs. 1.4 ± 0.78) (P < 0.001). Furthermore, miR-122 fold change had a positive and significant correlation with low-density lipoprotein cholesterol (LDL-C), sdLDL, fasting blood sugar (FBS), and insulin resistance (P < 0.05). CONCLUSION: It can be concluded that the rs17669 variant of miR-122 is not associated with the miR-122 expression and T2DM-associated serum parameters. Furthermore, it can be suggested that miR-122 dysregulation is involved in T2DM development through inducing dyslipidemia, hyperglycemia, and resistance to insulin.

The Diagnostic Value of Neutrophil to Lymphocyte Ratio as an Effective Biomarker for Eye Disorders: A Meta-Analysis.

The neutrophil to lymphocyte ratio (NLR) reflects a dynamic relationship between the innate (neutrophils) and adaptive (lymphocytes) cellular immune response. This systematic review and meta-analysis was conducted to critically evaluate the literature regarding the use of the NLR as a reliable means to detect several ocular disorders. Our study was registered with the PROSPERO (ID: CRD42022314850). Three databases, including PubMed, Embase, Scopus, and the Web of Science, were searched on September 9, 2022, with no restrictions on the article's language. Finally, 32 articles were recognized as eligible for our meta-analysis. We found that patients with eye diseases had significantly elevated levels of NLR in comparison to healthy controls (SMD =0.53, 95% CI =0.35-0.71, P < 0.001). In subgroup analysis, patients with keratoconus (SMD =0.69; 95% CI =0.33-1.05, P < 0.001), glaucoma (SMD =0.56, 95% CI =0.25-0.87, P < 0.001), pterygium (SMD =0.14; 95% CI =0.01-0.26, P < 0.001), and idiopathic epiretinal membrane (SMD =0.14; 95% CI =0.01-0.26, P < 0.001) had higher levels of NLR compared to healthy controls. However, NLR levels of patients with dry eye disease were similar to healthy controls (SMD =0.32, 95% CI = -0.49-1.13, P = 0.435). It can be said that NLR is a valuable marker of systemic inflammation, which is significantly increased in many eye disorders, suggesting that inflammation plays a key role in the pathophysiology of these diseases.