Milk-Derived Extracellular Vesicles: Biomedical Applications, Current Challenges, and Future Perspectives.

Extracellular vesicles (EVs) are nano to-micrometer-sized sacs that are released by almost all animal and plant cells and act as intercellular communicators by transferring their cargos between the source and target cells. As a safe and scalable alternative to conditioned medium-derived EVs, milk-derived EVs (miEVs) have recently gained a great deal of popularity. Numerous studies have shown that miEVs have intrinsic therapeutic actions that can treat diseases and enhance human health. Additionally, they can be used as natural drug carriers and novel classes of biomarkers. However, due to the complexity of the milk, the successful translation of miEVs from benchtop to bedside still faces several unfilled gaps, especially a lack of standardized protocols for the isolation of high-purity miEVs. In this work, by comprehensively reviewing the bovine miEVs studies, we provide an overview of current knowledge and research on miEVs while highlighting their challenges and enormous promise as a novel class of theranostics. It is hoped that this study will pave the way for clinical applications of miEVs by addressing their challenges and opportunities.

Angiosarcoma of gallbladder, a literature review.

BACKGROUND: Angiosarcoma of the gallbladder is a rare diagnostic entity rarely encountered by pathologists and has rarely been reported in literature. This review aimed to examine the clinicopathological features, immunohistochemistry, treatment, and outcomes of gallbladder angiosarcoma. METHODS: A search of the PubMed, Science Direct and Google Scholar was done with the search terms ("angiosarcoma" OR "angiosarcomas") AND ("gallbladder" OR "gallbladders"). Based on inclusion and exclusion criteria, only case reports could be used for this review. RESULT: 8 case reports were chosen in the end for analysis. The mean age of the patients at presentation was 65 years. It was most frequently observed in males. Abdominal pain and palpable mass were the most commonly reported symptoms. Cholelithiasis and anemia were also reported. On histopathology morphologically epithelioid appearance of angiosarcoma was evident. Cytokeratin (CK) AE1/AE3, Von willebrand factor, Factor VIII antigen, Vimentin, CD31 were positive. Meanwhile, UEA, CD34, CD117, S-100, Keratin, EMA, and CEA showed negative outcome. Surgery was the preferred method of treatment and a mean 10-months follow-up was done. CONCLUSION: Despite the unavailability of convincing data, histological and immunohistochemical analyses play a major role in the diagnosis of gallbladder angiosarcoma. Nevertheless, more comprehensive clinical studies are required to provide universal guidelines for the treatment and diagnosis of angiosarcoma of the gallbladder.

Primary gallbladder melanoma: A systematic review of literature.

Primary gallbladder melanoma (PGM) is a rare malignancy with only sporadic cases reported in the English literature. We performed a systematic review of the cases published in the PubMed, Science Direct and Google Scholar databases with the aim of describing the reported clinicopathologic features of PGM. Thirty-six articles reporting on 39 patients were reviewed. There was a male predominance, with 23 (64 %) of 36 patients being males. The mean age at presentation was 55 ±16 years. Pain in the right upper quadrant was reported in 20/27 (74 %). The average size of the tumor was 3.5 × 1.9 × 1.4 cm. Gallbladder calculi were reported in 7/27 (26 %). A cholecystectomy was performed in 34/38 (89.5 %). Grossly, the tumor mostly (96.5 %) had polypoid appearances and on microscopic examination, the tumor were predominantly comprised of epithelioid cells 12/17 (70.6 %). Mitotic figures and prominent nucleoli were reportedly found in 8/8 (100 %) and 3/3 (100 %) respectively. Junctional melanocytic components were present in 13/21 (61.9 %). Tumor cells were reportedly immunoreactive for S-100 and HMB-45 in all tested cases. Metastasis were reported in 25/36 (69.4 %), with lymph nodes being the most common site (n = 8), followed by brain (n = 6) and liver (n = 4) for metastasis. At a mean follow-up period of 19 +/- 3 months, 16 (48.5 %) of the 33 patients with available survival data were alive and 17/33 (51.5 %) were dead of disease. There is a lack of unified criteria for the diagnosis of PGM, and future studies should aim to resolve this.

Histiocytic sarcoma in renal transplant patients: a literature review.

BACKGROUND: Histiocytic sarcoma (HS) is defined as neoplasm resembling morphological and immunophenotypic characteristics of mature histiocytes. It is a rare form of lymphoid neoplasms. Despite advances in treatment and diagnosis of histiocytic sarcoma, majority of cases had poor prognosis due to progressive nature of the disease. In the following article, all reported cases of histiocytic sarcoma in renal transplant patients are reviewed. METHODS: In our literature review, all relevant reports were collected electronically by entering the necessary keywords. A Boolean approach using Medical Subject Heading (MeSH) keywords was implemented. After establishing the inclusion/exclusion criteria, article titles and abstracts were evaluated by Systematic Reviews and Meta-Analyses (PRISMA) standards for 2020. All cases of histiocytic sarcoma in renal transplant patients were included. RESULT: Based on our inclusion and exclusion criteria 4 case reports were yielded in this review. Two were males and 2 were females with the mean age of 42.25 years. Fever was the most common symptom. Although tumor originated from the native kidney on one patient, the site of the primary tumor was thorax, oropharynx, and transplanted kidney in the rest. Metastasis was detected in all cases. Prednisone was used for all cases. EBV was positive in 2 cases and negative in one of them. Histology was diagnostic and similar in all cases. Immunohistochemistry was done for 3 cases. Although chemotherapy was done for 3 patients, all 4 cases ended in mortality. CONCLUSION: Despite the fact that neoplasms are post renal transplant complications, histiocytic sarcoma is a scarce and fatal entity in such patients. Histological and immunohistochemistry tests are the corner stone in diagnosis of histiocytic sarcoma.

Membranous fat necrosis of gall bladder, a case report and literature review.

INTRODUCTION AND IMPORTANCE: Membranous fat necrosis is a rare histological finding. Despite its low incidence and lack of clinical significance, it can involve various organs. Majority of membranous fat necrosis cases are diagnosed in breast lumps and skin in comparison to intra-abdominal lesions. There has been only one reported case of membranous fat necrosis of gall bladder in literature. CASE PRESENTATION: A 56-year-old female patient with previous history of diabetes mellitus and hypertension was administered due to abdominal pain and fever. Based on her physical exam, lab data, and ultrasonography, she was diagnosed by cholangitis. After primary care, she went under cholecystectomy. The histological finding of gall bladder revealed crenulated fatty membranes phagocytized by macrophages in Hematoxylin and Eosin (H&E) staining. Moreover, necrosis and giant cells were seen on Sudan black staining. Hence, the diagnosis of membranous fat necrosis in gall bladder was made. CLINICAL DISCUSSION: Membranous fat necrosis occurs when peripheral blood circulation is compromised. Ischemia of fat tissue cause fatty membranous material accumulation acting as foreign bodies. Hence, it can attract inflammatory response. Regarding pathology, phagocyted membranous by macrophages and giant cells is diagnostic. Sudan black, Luxol fast blue (LFB), long Ziehl-Neelsen, and D-PAS are positive in membranous fat necrosis. CONCLUSION: Membranous fat necrosis of gall bladder is a rare entity. This is the second reported case of such diagnosis. Nonetheless, further pathological investigations are necessary.

Circulating Tumor Cells as a Promising Tool for Early Detection of Hepatocellular Carcinoma.

Liver cancer is a significant contributor to the cancer burden, and its incidence rates have recently increased in almost all countries. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is the second leading cause of cancer-related deaths worldwide. Because of the late diagnosis and lack of efficient therapeutic modality for advanced stages of HCC, the death rate continues to increase by ~2-3% per year. Circulating tumor cells (CTCs) are promising tools for early diagnosis, precise prognosis, and follow-up of therapeutic responses. They can be considered to be an innovative biomarker for the early detection of tumors and targeted molecular therapy. In this review, we briefly discuss the novel materials and technologies applied for the practical isolation and detection of CTCs in HCC. Also, the clinical value of CTC detection in HCC is highlighted.

QSPR study of viscoplastic properties of peptide-based hydrogels.

In this study, the power of machine learning was harnessed to probe the link between molecular structures of peptide-based hydrogels and their viscoplastic properties. The selection of compounds was attempted in accordance with the prescribed full list of peptide-based materials exhibiting hydrogel functionality in the literature. In this pursuit, a complete set of molecular descriptors and fingerprints was considered - accounting for an entry of size 17,968 for each peptide-based structure analyzed. The elastic and viscous moduli response of materials were mapped over a wide frequency spectrum in the range [0.1-100] (rad/s). In general, the results indicate that the frequency-dependent mechanical response of peptide-based hydrogels is statistically correlated with its (inter)molecular attributes, such as charge, first ionization potential (or equivalently electronegativity), surface area, number of chemical substrates, bond type, and intermolecular interactions. The performance of several (supervised) soft computing techniques was measured, for our quantitative structure property relationships model. In addition, the hypothesis of mapping our databank to a new system of principal components was tested, by using an unsupervised methodology, which resulted in enhancement of the prediction accuracy. In terms of significance, the present article provides the first report of frequency-dependent elastic and viscous moduli, for a set of 70 peptide-based formulations with hydrogel functionality.Communicated by Ramaswamy H. Sarma.

Splenogonadal fusion: A rare case report and literature review.

INTRODUCTION AND IMPORTANCE: Splenogonadal fusion is a rare congenital anomaly occurs when splenic tissue presents near or within a gonad. It mostly involves male children. Although it is benign and rare, making a pre-operation precise diagnosis is challenging which can lead to unnecessary invasive treatments. CASE PRESENTATION: A 3-year-old boy was presented by the chief complaint of a painless mass on the left testis and left inguinal hernia. He had a previous history of bilateral cryptorchidism and orchiopexy. Ultrasonography showed a small mass on the inferior pole of left testis and left reducible inguinal hernia. He went under left orchiectomy and hernia repair. Pathological investigation of the specimen resembled normal splenic tissue next to testicular tissue and the diagnosis of splenogonadal fusion was made. CLINICAL DISCUSSION: Splenogodal fusion cases can be challenging. Pain and sensation of mass in the scrotal sac are the most common presentation of splenogonadal fusion. Testicular malignancies can be considered as their main differential diagnosis, despite the fact that imaging and intra-operation frozen section can be helpful in making a definite diagnosis in some cases. It is mostly diagnosed incidentally during other procedures such as hernia repair or orchiopexy. Since it is benign, removal of tumor without orchiectomy is curative. CONCLUSION: In dealing with testicular mass in children, raising awareness of splenogonadal fusion have utmost importance to prevent unnecessary radical surgical interventions.

Utero-ovarian low grade endometrial stromal sarcoma, a case report.

INTRODUCTION: Endometrial stromal sarcoma (ESS) is a rare malignancy of uterine in middle aged women. There are numerous subtypes for ESS which share the same clinical picture of uterine bleeding and pelvic pain. Consequently, diagnosis and treatment modalities of LG-ESS with metastasis are challenging. However, both molecular and immunological study of samples can be useful. CASE PRESENTATION: In this case study, we report a 52-year-old woman presenting with the chief complaint of unusual uterine bleeding. There was no specific finding in her past medical history. The CT study revealed enlarged bilateral ovary with a significantly large left ovarian mass and suspicious mass in uterus. By the diagnosis of ovarian mass, patient went under total abdominal hysterectomy with bilateral salpingo-oophorectomy (BSO), greater omentectomy, and appendectomy followed by post-op hormone therapy. Her follow-up was uneventful. The IHC and pathological study of samples revealed incidental LG-ESS uterus mass with metastasis to ovaries despite her primary diagnosis. DISCUSSION: LG-ESS has low metastasis rate. Surgical modalities and neoadjuvant therapies are recommended base on the stage of ESS. In the following study, we represent a case of incidental LG-ESS with bilateral ovarian invasion who was initially diagnosed as an ovarian mass. CONCLUSION: Our patient was successfully managed by surgical intervention. Despite scarcity of LG-ESS, it is advised to consider LG-ESS as a differential diagnosis in management of patients with a uterus mass with bilateral ovarian involvement.

Effects of intracerebroventricular injection of apelin-13 on food intake in broiler chicks.

Apelin is an endogenous peptide ligand for G protein coupled apelin receptors (APJ orphan receptors) which are very similar to angiotensin II receptors. Apelin is expressed in most tissues of the body including hypothalamus that is responsible for regulating water and food intake, the gastrointestinal tract, the circulatory system, adipose and muscle tissues, and the immune system. The physiological actions of apelin, including food intake, has not yet been reported in birds. In this study, the effect of intracerebroventricular injection of different doses of apelin-13 was investigated on food intake in neonatal broilers at the age of five and seven days. The chicks had access to food immediately after injection and cumulative food intake was measured at half, 1, 2, 3, 4, 8 and 21 hr after injection. The 2-way ANOVA analyzed data showed that apelin-13 at dose of 1.00 µg significantly reduced food intake at 21 hr after injection in five-day old chicks. In addition, in dose of 1.50 µg, it could significantly reduce food intake at 2, 3, 4, 8 and 21 hr after injection. In seven-day-old chicks, the doses of 1.00 and 4.00 µg of apelin-13 had no effect on food intake compared to the control group. Apelin-13 at dose of 2.00 µg significantly reduced food intake at 8 and 21 hr after injection. The results of this study showed that apelin-13 had a reducing effect on food consumption in neonatal broiler chicks.

Dermatofibrosarcoma protuberans challenges: a case series and review of the literature.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare variant of skin sarcoma which is characterized by proliferation of spindle cells in a storiform pattern. Although it is mostly benign in its primary stages, it can cause a high burden of morbidity unless it is thoroughly excised. CASE PRESENTATION: Here, we review six cases of DFSP which were characterized by skin lesions in various parts of the body. Patients were from 26 to 51 years old; four were Asian men and two were Asian women. Wide surgical excision was performed for all these patients and no extra treatment was considered. Samples were studied by hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) tests. Only one of our patients experienced recurrence after the initial surgery. CONCLUSION: Determining the best surgical method is still a dilemma in the treatment of DFSP lesions. There are numerous studies to prove the efficacy of various surgical interventions. Although DFSP is not commonly known as a malignant skin lesion, delay in treatment will have a catastrophic impact on patients' lives. Thus, applying an in-time surgical method (wide local excision in our cases) in treating DFSP is crucial in preventing recurrence as well as decreasing the morbidity burden of DFSP.

Exosomal microRNAs and long noncoding RNAs: Novel mediators of drug resistance in lung cancer.

Lung cancer therapeutic resistance, especially chemoresistance, is a key issue in the management of this malignancy. Despite the development of novel molecularly targeted drugs to promote therapeutic efficacy, 5-year survival of lung cancer patients is still dismal. Molecular studies through the recent years have fortunately presented multiple genes and signaling pathways, which contribute to lung cancer chemoresistance, providing a better perception of the biology of tumor cells, as well as the molecular mechanisms involved in their resistance to chemotherapeutic agents. Among those mechanisms, transfer of extracellular vesicles, such as exosomes, between cancer cells and the surrounding noncancerous ones is considered as an emerging route. Exosomes can desirably function as signaling vesicles to transmit multiple molecules from normal cells to cancer cells and their microenvironment, or vice versa. Using this ability, exosomes may affect the cancer cells' chemoresistance/chemosensitivity. Recently, noncoding RNAs (esp. microRNAs and long noncoding RNAs), as key molecules transferred by exosomes, have been reported to play a substantial role in the process of drug resistance, through modulation of various proteins and their corresponding genes. Accordingly, the current review principally aims to highlight exosomal micro- and long noncoding RNAs involved in lung cancer chemoresistance. Moreover, major molecular mechanisms, which connect corresponding RNA molecules to drug resistance, will briefly be addressed, for better clarifying of possible roles of exosomal noncoding RNAs in promoting the effectiveness of lung cancer therapy.

Gastrointestinal cancer drug resistance: the role of exosomal miRNAs.

Resistance of gastrointestinal (GI) cancer cells to therapeutic agents are one of the major problems in treating this type of cancer. Although the exact mechanism of drug resistance has not yet been fully elucidated, various factors have been identified as contributing factors involved in this process. Several studies have revealed the role of exosomes, especially exosomal microRNAs (miRNAs), in GI tumorigenesis, invasion, angiogenesis, and drug resistance. Exosomes, a type of small extracellular vesicles (EVs), are originated from endosomes and are released into the extracellular environment and body fluids by different cell types. Exosomes mediate cell-cell communication by transferring different cargos, including miRNAs, between parent and recipient cells. Therefore, identifying these exosomal miRNAs and their functions in GI cancers might provide new clues to further explore the secret of this process and thus help in drug-resistance management. This review article will discuss the roles of exosomal miRNAs and their mechanisms of action in drug resistance of different types of GI cancer cells (e.g., stomach, esophagus, liver, pancreas, and colon) to therapeutic agents.

Exosomal noncoding RNAs: key players in glioblastoma drug resistance.

Glioma, as one of the most severe human malignancies, is defined as the Central Nervous System's (CNS) tumors. Glioblastoma (GBM) in this regard, is the most malignant type of gliomas. There are multiple therapeutic strategies to cure GBM, for which chemotherapy is often the first-line treatment. Still, various cellular processes, such as uncontrolled proliferation, invasion and metastasis, may disturb the treatment efficacy. Drug resistance is another process in this way, which can also cause undesirable effects. Thereupon, identifying the mechanisms, involved in developing drug resistance and the relevant mechanisms can be very helpful in GBM management. The discovery of exosomal non-coding RNAs (ncRNAs), RNA molecules that can be transferred between the cells and different tissues using the exosomes, was a milestone in this regard. It has been revealed that the key exosomal ncRNAs, including circular RNAs, microRNAs, and long ncRNAs, are able to modulate GBM drug resistance through different signaling pathways or by affecting regulatory proteins and their corresponding genes. Nowadays, researchers are trying to overcome the limitations of chemotherapy by targeting these RNA molecules. Accordingly, this review aims to clarify the substantial roles of exosomal ncRNAs in GBM drug resistance and involved mechanisms.

Case series: Delayed diagnoses of Acanthamoeba keratitis.

PURPOSE: To describe two cases of Acanthamoeba keratitis in contact lens wearers misdiagnosed as Herpes simplex keratitis. OBSERVATIONS: Case 1 is a 54-year-old male that was misdiagnosed with Herpes simplex keratitis who developed advanced Acanthamoeba keratitis. His treatment course was complex and involved both medical therapy and surgical intervention with poor resolution. Case 2 is an 18-year-old male who was also initially misdiagnosed and treated for Herpes simplex keratitis, but ultimately treated with polyhexamethylene biguanide and chlorhexidine with complete resolution. CONCLUSIONS AND IMPORTANCE: The clinical presentation of Acanthamoeba keratitis may closely resemble other causes of keratitis and continues to be misdiagnosed, leading to delayed diagnosis and treatment. However, given the significant morbidity and challenging treatment course for Acanthamoeba keratitis, it is important for clinicians to maintain a high suspicion for Acanthamoeba and to consider obtaining cultures in contact lens wearers with atypical keratitis prior to making a diagnosis of Herpes simplex keratitis.

Therapeutic potentials of curcumin in the treatment of non-small-cell lung carcinoma.

Non-small-cell lung carcinoma (NSCLC) is one of the most lethal malignancies that include more than 80% of lung cancer cases worldwide. During the past decades, plants and plant-derived products have attracted great interest in the treatment of various human diseases. Curcumin, the turmeric isolated natural phenolic compound, has shown a promising chemo-preventive and anticancer agent. Numerous studies have shown that curcumin delays the initiation and progression of NSCLC by affecting a wide range of molecular targets and cell signalling pathways including NF-kB, Akt, MAPKS, BCL-2, ROS and microRNAs (miRNAs). However, the poor oral bioavailability and low chemical stability of curcumin remain as major challenges in the utilisation of this compound as a therapeutic agent. Different analogs of curcumin and new delivery systems (e.g., micelles, nanoparticles and liposomes) provided promising solutions to overcome these obstacles and improve curcumin pharmacokinetic profile. The present review focuses on current reported studies about anti-NSCLC effects of curcumin. NSCLC involved miRNAs whose expression is regulated by curcumin has also been discussed. Furthermore, recent researches on the use of curcumin analogs and delivery systems to enhance the curcumin benefits in NSCLC are also described.

Investigation of platinum recovery from a spent refinery catalyst with a hybrid of oxalic acid produced by Aspergillus niger and mineral acids.

The capability of oxalic acid produced by Aspergillus niger was investigated for bioleaching of platinum from a refinery reforming catalyst. The spent medium mode was selected for bioleaching because of its higher efficiency at favorable pH and temperature conditions. The effects of several important factors such as the pulp density, pH and temperature on platinum recovery were optimized using Box-Behnken design of response surface methodology. The results indicated that pH adjustment during the bioleaching process increases the final platinum recovery significantly. The obtained optimum conditions were 1% for the pulp density, 0.5 for the medium pH, and 70 °C for the temperature which led to 37% platinum recovery. The significance of oxalic acid as the leaching agent in platinum bioleaching was highlighted by investigating the recovery of a blank medium without oxalic acid at the optimum conditions which was just about 13%. The presented method can be utilized in an environmentally friendly process to recover platinum from industrial catalysts.

Knockdown of Long Noncoding RNA Plasmacytoma Variant Translocation 1 with Antisense Locked Nucleic Acid GapmeRs Exerts Tumor-Suppressive Functions in Human Acute Erythroleukemia Cells Through Downregulation of C-MYC Expression.

Objective: Acute erythroleukemia (AEL) is a subtype of acute myeloid leukemia (AML), with no specific treatment. Up- or downregulation of long noncoding RNAs (lncRNAs) is strongly associated with the formation and progression of many malignancies. Plasmacytoma variant translocation 1 (PVT1) is a significantly upregulated lncRNA in AML. Antisense locked nucleic acid (LNA) GapmeRs oligonucleotides are the novel tools for targeting lncRNAs. The purpose of the current study was to investigate the functional role of PVT1 antisense LNA GapmeRs on AEL cell line (KG-1). Materials and Methods: AEL cells were transfected with PVT1 antisense LNA GapmeRs at three different time points. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was accomplished to evaluate the PVT1 expression by PVT1 antisense LNA GapmeRs. The viability was evaluated by MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay, and the apoptosis and necrosis were assessed by Annexin V/propidium iodide staining assay. The C-MYC expression level, the target gene of PVT1, was also quantified by qRT-PCR. Results: The results indicated that PVT1 inhibition could significantly decrease the viability of AEL cells, due to induction of apoptosis and necrosis, probably through the downregulation of C-MYC. Conclusions: Their findings suggest that the inhibition of lncRNA PVT1 could serve as a novel approach for controlling the proliferation of AEL cells and could open up a path for treatment of AEL.

Induction of apoptosis and necrosis in human acute erythroleukemia cells by inhibition of long non-coding RNA PVT1.

Recent advances in molecular medicine have proposed new therapeutic strategies for cancer. One of the molecular research lines for the diagnosis and treatment of cancer is the use of long non-coding RNAs (LncRNAs) which are a class of non-coding RNA molecules longer than 200 base pairs in length that act as the key regulator of gene expression. Different aspects of cellular activities like cell growth, proliferation, differentiation, apoptosis and migration are regulated by lncRNAs. In various cancers, aberrant expression of lncRNAs has been reported. One of the lncRNAs that showed upregulation in human acute myeloid leukemia (AML) is lncRNA plasmacytoma variant translocation 1 (PVT1). Here, we performed blockage of lncRNA PVT1 in human acute erythroleukemia (AEL) cell line (KG1) using antisense LNA GapmeRs. Then, at different time points (24, 48 and 72 hours) after transfection, qRT­real­time PCR and AnnexinV/Propidium Iodide staining assay were performed. The data were processed using the ANOVA test. At all three time points, the ratio of apoptotic cells in the PVT1 antisense LNA GapmeRs treated group was higher than the other groups. The ratio of necrotic cells in the antisense LNA GapmeRs group was also higher than the other groups. These assessments show that inhibition of lncRNA PVT1 could significantly induce apoptosis and necrosis in KG1 cells. Our findings can be used in translational medicine for future investigation in acute erythroleukemia and treatment approach based on antisense therapy.

Exosomal miRNAs as novel cancer biomarkers: Challenges and opportunities.

A biomarker with high specificity and sensitivity, is a basic requirement for non-invasive cancer diagnosis. Exosomes are a type of lipid bilayer extracellular vesicles (EVs), containing different components, including proteins, lipids, DNA, messenger RNA (mRNA), and non-coding RNAs. Increasing evidence indicates that nucleic acids are protected by exosome lipid membrane. These vesicles are almost released from all cell types, into biological fluids. In cancer, the expression of microRNAs (miRNAs), located in the tumor cell-derived exosomes, is deregulated and it could be led to metastasis and therapy resistance. Due to the presence of exosomes in various body fluids and the stability of miRNAs in exosomes, exosomal miRNAs can provide a new class of biomarkers for early and minimally invasive cancer diagnosis. In this article, we review the miRNAs and their roles in cancer. Furthermore, we explain the different types of EVs, especially exosomes, and their functional roles in cancer. At the end, we discuss about the importance of exosomal miRNAs for cancer diagnosis. As well as, we briefly summarize the exosome isolation techniques and obstacles, limiting the clinical applications of exosomal miRNAs.