Exosomes are one type of membrane vesicles secreted into extracellular space by most types of cells. In addition to performing many biological functions particularly in cell-cell communication, cumulative evidence has suggested that several biological entities in exosomes like proteins and microRNAs are closely associated with the pathogenesis of most human malignancies and they may serve as invaluable biomarkers for disease diagnosis, prognosis, and therapy. This provides a commanding impetus and growing demands for simple, efficient, and affordable techniques to isolate exosomes. Capitalizing on the physicochemical and biochemical properties of exosomes, a number of techniques have been developed for the isolation of exosomes. This article summarizes the advances in exosome isolation techniques with an emphasis on their isolation mechanism, performance, challenges, and prospects. We hope that this article will provide an overview of exosome isolation techniques, opening up new perspectives towards the development more innovative strategies and devices for more time saving, cost effective, and efficient isolations of exosomes from a wide range of biological matrices.

The gut microbiota possesses diverse metabolic activities, but its contribution toward heterogeneous toxicological responses is poorly understood. In this study, we investigated the role of the liver-gut microbiota axis in underpinning the hepatotoxicity of tacrine. We employed an integrated strategy combining pharmacokinetics, toxicology, metabonomics, genomics, and metagenomics to elucidate and validate the mechanism of tacrine-induced hepatotoxicity in Lister hooded rats. Pharmacokinetic studies in rats demonstrated 3.3-fold higher systemic exposure to tacrine in strong responders that experienced transaminitis, revealing enhanced enterohepatic recycling of deglucuronidated tacrine in this subgroup, not attributable to variation in hepatic disposition gene expression. Metabonomic studies implicated variations in gut microbial activities that mapped onto tacrine-induced transaminitis. Metagenomics delineated greater deglucuronidation capabilities in strong responders, based on differential gut microbial composition (e.g., Lactobacillus, Bacteroides, and Enterobacteriaceae) and approximately 9% higher b-glucuronidase gene abundance compared with nonresponders. In the validation study, coadministration with oral b-glucuronidase derived from Escherichia coli and pretreatment with vancomycin and imipenem significantly modulated the susceptibility to tacrine-induced transaminitis in vivo. Conclusion: This study establishes pertinent gut microbial influences in modifying the hepatotoxicity of tacrine, providing insights for personalized medicine initiatives. (HEPATOLOGY 2018;67:282-295). SEE EDITORIAL ON PAGE 18E lucidating the mechanisms underlying interindividual responses to pharmacotherapy is paramount in personalized medicine research. The superorganismic nature of the human host means that not all variations in therapeutic outcome can be attributed to host genetics. (1)(2)(3) Indeed, the gut microbiota possesses vast metabolic activities that can either complement or oppose the host's enzymatic actions, thereby modulating drug disposition and therapeutic outcomes. (3)(4)(5) To date, only a small fraction of marketed drugs are known to be metabolically influenced by the microbiota, (3) and the contribution of gut microbiota toward interindividual variation in pharmacology remains poorly understood.

Polyphenol-rich curry intake can improve postprandial glucose homeostasis. The longer term effects remain to be established.

Objectives To investigate plasma and urinary kynurenine (KYN)–tryptophan (TRP) ratios in bladder cancer, expression of indoleamine 2,3‐dioxygenase 1 (IDO1) in relation to tryptophan 2,3‐dioxygenase (TDO2) in bladder tumour, and the correlation of KYN–TRP ratio with bladder tumour burden. Methods Metabotyping of the TRP–KYN metabolic axis was performed via a clinical case–control study. Expression of IDO1 and TDO2 was measured in human biopsied tissues. Correlational experiments between KYN–TRP ratio and bladder tumour were performed using a murine orthotopic prostate‐specific antigen (PSA)‐secreting MB49 bladder cancer model. Results We established for the first time that plasma TRP level was significantly decreased, while both plasma and urinary KYN–TRP ratios were significantly higher in bladder cancer patients, and expression level of IDO1 but not TDO2 was increased in human bladder tumour. We reported the positive correlation between IDO1 expression, KYN–TRP ratio, normalized PSA to creatinine, and bladder tumour burden in the murine model. Conclusion Kynurenine–tryptophan ratio is a promising surveillance biomarker for bladder cancer, but would require further validation before clinical translation.

Spices that are rich in polyphenols are metabolized to a convergent group of phenolic/aromatic acids. We conducted a dose-exposure nutrikinetic study to investigate associations between mixed spices intake and plasma concentrations of selected, unconjugated phenolic/aromatic acids. In a randomized crossover study, 17 Chinese males consumed a curry meal containing 0 g, 6 g, and 12 g of mixed spices. Postprandial blood was drawn up to 7 h at regular intervals and plasma phenolic/aromatic acids were quantified via liquid chromatography tandem mass spectrometry (LC-MS/MS). Cinnamic acid (CNA, p < 0.0001) and phenylacetic acid (PAA, p < 0.0005) concentrations were significantly increased with mixed spices consumption, although none of the other measured phenolic/aromatic acids differ significantly between treatments. CNA displayed a high dose-exposure association (R2 > 0.8, p < 0.0001). The adjusted mean area under the plasma concentration-time curve until 7 h (AUC0–7 h) for CNA during the 3 increasing doses were 8.4 ± 3.4, 376.1 ± 104.7 and 875.7 ± 291.9 nM.h respectively. Plasma CNA concentration may be used as a biomarker of spice intake.