The Roles of Exosomal microRNAs in Diffuse Large B-Cell Lymphoma: Diagnosis, Prognosis, Clinical Application, and Biomolecular Mechanisms.

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous neoplasm and is characterized as the most common subtype of non-Hodgkin lymphoma (NHL). Despite 60-70% of all patients being cured with R-CHOP therapeutic regimen (Cyclophosphamide, doxorubicin, vincristine, and prednisone, combined with rituximab), remaining patients display aggressive disease. Therefore, there is an urgent need to develop novel diagnostic, prognostic, and predictive biomarkers. Recently, exosomal miRNAs have been approved as novel biomarkers in DLBCL due to their potential involvement in lymphomagenesis. Material and Methods: We conducted an investigation on the potential role of exosomal miRNAs as diagnostic, prognostic, and predictive biomarkers in DLBCL in the PubMed, Scopus, and Web of Science search engines. We searched by using a combination of keywords, such as diffuse large B-cell lymphoma, DLBCL, miRNA, microRNA, miR, exosome, exosomes, exosomal, extracellular vesicles, EVs, and secretome. Then, search results were narrowed based on specific inclusion and exclusion criteria. Results: Twelve articles were eligible for our systematic reviews. Among them, nine discussed diagnostic biomarkers, three considered prognostic significance, four evaluated therapeutic efficacy, two studies were conducted in vitro, and three assessed molecular pathways associated with these exosomal miRNAs in DLBCL. Discussion: According to our systematic review, exosomal miRNAs are not only useful for diagnosis and prognosis in DLBCL but are also promising therapeutic tools and predictors of response to therapy. Although promising results so far, more research is required to develop innovative biomarkers.

The Potential Role of Exosomes in the Treatment of Brain Tumors, Recent Updates and Advances.

Exosomes are small endosomal derived membrane extracellular vesicles that contain cell-specific cargos such as lipid, protein, DNA, RNA, miRNA, long non-coding RNA, and some other cell components that are released into surrounding body fluids upon the fusion of multivesicular bodies (MVB) and the plasma membrane. Exosomes are a one-of-a-kind cell-to-cell communication mechanism that might pave the way for target therapy. The use of exosomes as a therapeutic potential in a variety of cancers has been and is still being investigated. One of the most important of these has been the use of exosomes in brain tumors therapy. Exosome contents play a crucial role in brain tumor progression by providing a favorable niche for tumor cell proliferation. Also, exosomes that are secreted from tumor cells, lead to the protection of tumor cells and their proliferation in the tumor environment by reducing the inflammatory response and suppression of the immune system. Although some treatment protocols such as surgery, chemotherapy, and radiotherapy are common in brain tumors, they do not result in complete remission in the treatment of some malignant and metastatic brain tumors. Identifying, targeting, and blocking exosomes involved in the progression of brain tumors could be a promising way to reduce brain tumor progression. On the other way, brain tumor therapy with effective therapeutic components such as siRNAs, mRNAs, proteins, could be developed. Finally, our research suggested that exosomes of nanoscale sizes might be a useful tool for crossing the blood-brain barrier and delivering effective content. However, further research is needed to fully comprehend the potential involvement of the exosome in brain tumor therapy protocols.

Assessment of T helper 17-associated cytokines in thromboangiitis obliterans.

BACKGROUND: The management of thromboangiitis obliterans (TAO) remains a medical challenge because of its unknown etiology. It is also not known whether it is a systemic or localized disease or a type of autoimmune vasculitis. METHODS: In this study, we evaluated the serum level of IL-17 and IL-23 which increase in both systemic inflammation and autoimmunity, in 60 TAO patients and 30 age- and smoking habit-matched controls. Also, IL-22, which has reported high level during infection but not in autoimmunity, was evaluated. RESULTS: The serum levels of IL-17, IL-22 and IL-23 were significantly higher in the TAO patients in comparison with the controls (P<0.001). Notably, the serum levels of IL-17, IL-22 and IL-23 were highest in the patients with the chief complaint of chronic ulcer and lowest in the patients with gangrene (P<0.05). Also, the serum level of IL-22 was significantly higher in the anemic patients in comparison with the non-anemic patients (P=0.03). CONCLUSION: Owing to our findings, TAO appears more likely to be a systemic disorder rather than a localized vasculopathy. Therefore, treatment protocols based on systemic treatment of TAO patients may be more helpful than localized treatment, such as bypass surgery and endovascular procedures. Also, according to our findings regarding the high level of IL-22, the trigger of TAO development may be an infectious pathogen. However, additional research is highly recommended to investigate whether TAO is an infectious disease or an infectious-induced autoimmunity.