IndexAbstractIntroductionConclusionAbstractSmall membrane-encapsulated transport vesicles known as exosomes present enormous potential in the field of non-invasive biomarker discovery due to their robust integrity in collection from biofluid samples. This minireview briefly discusses their diagnostic and prognostic contributions in three different disease settings of great interest: tumor metastasis/cancer research, neurodegenerative diseases, and drug-induced organ injury. This text also attempts to shed light on important general concerns of the exosomal biomarker approach, including uncertainty in the diagnostic performance, heterogeneity, and isolation protocol of these potential candidate biomarkers. Currently, advances in omics approaches result in a high discovery phase of these biomarkers in high-profile, precision medical applications. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay IntroductionTissue biopsies have remained the gold standard in the diagnosis and screening of various disease states due to the growing number of validated tissue variant biomarkers currently on the horizon. Several studies utilize methods such as endoscopic biopsy that prove effective in collecting and quantifying potential prognostic biomarkers of cancer progression, angiogenesis, and atypical immune behaviors. However, the invasive nature of this procedure has accelerated common interest in cell-free biomarkers that can be selectively obtained through noninvasive means, such as through collection from biofluids and liquid biopsies. Cellular constituents are found in great abundance in serum, plasma, urine, saliva, and other forms of biological fluids. Fluctuations in the expression of intra- and extra-vesicular targets are currently being explored worldwide as potential high-performance candidate biomarkers for global inflammation and disease states. One area of recent interest focuses specifically on exosomes, a subclass of extracellular vesicles (EVs). Exosomes are small organelles (30-200 nm in diameter) produced through cell fission mechanisms from membrane transport vesicles and/or endosomal cells. The loss of these microvesicles allows the release of a number of biomolecules such as lipids, carbohydrates, functional proteins, and subtypes of nucleic RNA including non-coding microRNAs (miRNAs) that are subject to pathological changes in concentration and expression. Many recent studies attempt to validate the use of such targeted profiling in the minimally invasive diagnosis of several common and debilitating diseases, including cancer subtypes, neurodegenerative diseases, and drug-induced organ toxicity. The primary objective of this minireview is to evaluate the progress and effective use of exosomal biomarkers within these three disease domains, while also addressing outstanding concerns related to overall diagnostic performance, heterogeneity, and exosome isolation protocol. A critical analysis of exosomes is extremely essential to promote the validation and widespread use of these novel candidate biomarkers in personalized medicine. Cell fission is a recognizable feature in tumor malignancy. The loss of tumor exosomes appears to occur under the mediation of extracellular signals, releasing enhanced concentrations of tumor antigens responsible for the suppression of T lymphocyte and monocyte activation. Detection of increasing concentrations of tumor-derived exosomes and cellscirculating tumor cells (CTCs) is positively correlated with clinical outcomes, including increased severity of cancer status, increased metastasis, and shorter time to recurrence. Further examining the diagnostic and prognostic sensitivity of tumor-derived exosomes and circulating tumor cells (CTCs). Exosomal biomarkers in lung adenocarcinoma patients reveal a significant increase in the expression of peripheral exosomes in those with lung adenocarcinoma compared to healthy controls. Findings of a similar nature give rise to the future diagnostic potential of these biomarkers, enabling less invasive alternatives for cancer patients. A table obtained from a 2010 review of miRNA biomarkers in cancer research provides an index of circulating serum miRNAs that have been considered candidate biomarkers in the diagnosis of common cancer subtypes. Another feature of exosomes and their derived miRNA profiles is their prognostic capabilities. Identification of miRNA biomarkers of tumorigenesis may further promote screening efforts in asymptomatic patients with a family history of cancer. A recent study aimed to access the prognostic capacity of validated candidate biomarkers in head and cervical cancer patients. Results from a discovery cohort screened before and after radiotherapy treatment indicate 8 plasma-derived miRNAs that discriminate between cancer patients and healthy controls, with miR-186-5p demonstrating the highest sensitivity of therapeutic response. Studies of a similar nature show miRNA profiling results consistent with tumor tissue biopsy results, which further validates the clinical efficacy of biofluid analysis in the future cancer screening protocol. Exosome biogenesis contributes to the transport and intracellular communication of proteins, which can occur under physiological conditions and/or pathogenic conditions. When conditions for fusion of the multivesicular body with lysosomes are unfavorable or limited, the release of exosomal contents into the extracellular space serves as a secondary and alternative pathway to protein degradation, promoting greater modulation of function in nearby recipient cells. This presents an opportunistic and non-selective process. function of exosomes whereby amyloid precursors can be engulfed within an exosome and released extracellularly in pathogenic cellular conditions such as amyloid deposits or plaques. This feature of non-selectivity is observed in Alzheimer's disease (AD), where the global spread of amyloid deposits in the brain is not specific to a particular set of cells or area of interest, while in Parkinson's disease (PD), on the contrary , is a highly specific disease that depends on the type of brain tissue affected and the amyloid protein. In both neurodegenerative states, there is a growing body of evidence suggesting an intrinsic link between exosomal miRNA responses and pathogenesis. A study published in 2015 examines the diagnostic potential of an exosomal miRNA profile in cerebrospinal fluid (CSF), determining its association with and discriminative ability of neurodegenerative diseases, PD and AD. This particular study uses flow cytometric analysis and electron microscopy to identify and observe exosomal structures by monitoring the presence of the phenotypic surface protein CD63 within the sample. 16 exosomal miRNAs from cerebrospinal fluid are significantly upregulated while 11 are suppressed in Parkinson's disease patients compared to age- and sex-matched healthy controls. From this panel,analysis of 6 specific miRNAs reveals the high diagnostic sensitivity of miR-409-3p, miR-153, miR-10a-5p in Parkinson's disease patients with values of 0.97, 0.92 and 0.90 respectively obtained through receiver operator characteristic (ROC) analysis. Another publication published in the same year focuses its attention on the role of exosome-derived proteins in AD, evaluating their sensitivity to biomarkers and association with clinical severity in a case-control study. Blood exosomal proteins are isolated from case group (AD) and control group (AC) patients, revealing higher levels of tau and A proteins that are significant in AD cohorts. Sensitivity evaluation via ROC analysis and area under the curve (AUC) determines that P-T181-tau protein shows the highest diagnostic performance (AUC = 0.991) followed by P-S396-tau (AUC = 0.988), A1- 42 (AUC = 0.987) and total tau protein (AUC = 0.731). Evaluation of these proteins at the time of diagnosis and times 1 to 10 years after diagnosis reveal that A1-42 levels are significantly elevated in Alzheimer's patients in their second blood test compared to the time of diagnosis. The results of this study allude to the possibility that exosomes are directly involved in the pathogenesis of neurodegenerative development, correlating the severity and development of the AD state to the presence of exosome-derived amyloid-beta concentrations. Drug-induced organ damage can be described as damage to organ tissue or its functional integrity attributable to the use of diagnosable drugs. The damage is highly variable and depends on the organ, patients' heterogeneous lifestyles and concomitant medical histories. One particular subtype, drug-induced liver injury (DILI), is currently of interest in the context of biomarker discovery as the era of metabolomics and proteomics technology advances. DILI is a potentially adverse outcome of the use of hepatotoxic agents – carbon tetrachloride, d-galactosamine – as well as active agents – acetaminophen, isoniazid – in commonly diagnosed medications. Progression of DILI after drug administration is concerning for reasons other than clinical outcome; Drugs that are suspected causative agents of hepatotoxicity are often stripped of their approval by the FDA until their efficacy in the patient's therapeutic intervention is demonstrated and, in this case, under strict review conditions. Therefore, the development of prognostic biomarkers for DILI is essential for both early screening protocol and treatments of other liver diseases in guiding heterogeneous dose adjustments and effective utility of common drugs including acetaminophen in patients. In a recent clinical study using animal models exposed to acetaminophen, the evaluation of a selective panel of exosomal miRNAs as biomarkers in DILI is one of several endpoints of this study. MiRNAs, miR-122, miR-155, and miR-192, are selected based on prior performance in organ injury studies as candidate liver-specific biomarkers. qPCR results reveal altered panel expressions both in the presence and absence of antioxidant N-acetyl cysteine treatment (NAC treatment). No NAC treatment shows significant increases in panel expression, whereas NAC treatment results in downregulated expression of these liver-specific exosomal microRNAs. These results demonstrate that the profile of liver-associated miRNAs showed high and independent expression changes related to increased hepatocyte damage in the absence of treatment. The presence of therapeutic interventions.
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