Urine has the potential to become a better source of biomarkers. Urinary proteins are affected by many factors; therefore, differentiating between the variables associated with any particular pathophysiological condition in clinical samples is challenging. To circumvent these problems, simpler systems, such as animal models, should be used to establish a direct relationship between disease progression and urine changes. In this study, a unilateral ureteral obstruction (UUO) model was used to observe tubular injury and the eventual development of renal fibrosis, as well as to identify differential urinary proteins in this process. Urine samples were collected from the residuary ureter linked to the kidney at 1 and 3 weeks after UUO. Five hundred proteins were identified and quantified by LC-MS/MS, out of which 7 and 19 significantly changed in the UUO 1- and 3-week groups, respectively, compared with the sham-operation group. Validation by western blot showed increased levels of Alpha-actinin-1 and Moesin in the UUO 1-week group, indicating that they may serve as candidate biomarkers of renal tubular injury, and significantly increased levels of Vimentin, Annexin A1 and Clusterin in the UUO 3-week group, indicating that they may serve as candidate biomarkers of interstitial fibrosis.

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Background TP53 mutations are the most prevalent mutations detected in non‐small‐cell lung cancer (NSCLC) and have been revealed as a negative prognostic biomarker of outcome. The impact of concomitant TP53 mutations in ALK‐rearranged NSCLC remains uncertain. Methods Tumor samples from 64 ALK‐rearranged NSCLC patients receiving crizotinib treatment were subjected to next‐generation sequencing (NGS) to identify TP53 mutational status. The clinicopathologic features of the TP53 mutations and its impact on the effect of crizotinib treatment were analyzed. Results Among the 64 ALK‐rearranged patients, 15 (23.4%) patients showed a TP53 mutation. Of these, six cases had disruptive mutations and nine with nondisruptive mutations. The objective response rate (ORR) and disease control rate (DCR) for TP53 mutated patients were both significantly lower compared with those for TP53 wild‐type patients (p = 0.003 and 0.023, respectively). A significantly shorter progression‐free survival (PFS) was found in TP53 mutated patients compared with TP53 wild‐type patients (p = 0.045). Nondisruptive TP53 mutations were associated with a shorter PFS in comparison with disruptive TP53 mutations in ALK‐rearranged patients (p = 0.069). When nondisruptive TP53 mutated patients were in comparison with TP53 wild‐type patients, nondisruptive TP53 mutations were associated with a significant reduced PFS (p = 0.003). Conclusions TP53 mutations, especially nondisruptive mutations, negatively affected the response to crizotinib and correlated with shorter PFS in ALK‐rearranged NSCLC patients.

Alzheimer's disease (AD) is an incurable age-associated neurodegenerative disorder that is characterized by irreversible progressive cognitive deficits and extensive brain damage. The identification of candidate biomarkers before beta amyloid plaque deposition occurs is therefore of great importance for the early intervention of AD. Urine, which is not regulated by homeostatic mechanisms, theoretically accumulates changes associated with AD earlier than cerebrospinal fluid and blood. In this study, an APP (swe)/PSEN1dE9 transgenic mouse model was used to identify candidate biomarkers for early AD. Urine samples were collected from 4-, 6-, and 8-month-old transgenic mouse models, and the urinary proteomes were profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The levels of 33 proteins differed significantly between wild-type and 4-month-old mice, which had not started to deposit beta amyloid plaque. Among these proteins, 16 have been associated with the mechanisms of AD, while 9 have been suggested as AD biomarkers. Our

Biomarker is the change associated with the disease. Blood is relatively stable because of the homeostatic mechanisms of the body. However, urine accumulates changes of the body, which makes it a better early biomarker source. Liver fibrosis is a reversible pathological condition, whereas cirrhosis, the end-stage of liver fibrosis, is irreversible. Consequently, noninvasive early biomarkers for fibrosis are desperately needed. In this study, differential urinary proteins were identified in the thioacetamide liver fibrosis rat model using tandem mass tagging and two-dimensional liquid chromatography tandem mass spectrometry. A total of 766 urinary proteins were identified, 143 and 118 of which were significantly changed in the TAA 1-week and 3-week groups, respectively. Multiple reaction monitoring (MRM)-targeted proteomics was used to further validate the abundant differentially expressed proteins. A total of 40 urinary proteins were statistically significant, 15 of which had been previously reported as biomarkers of liver fibrosis, cirrhosis or other related diseases and 10 of which had been reported to be associated with the pathology and mechanism of liver fibrosis. These differential proteins were detected in urine before the alanine aminotransferase and aspartate transaminase changes in the serum and before fibrosis was observed upon hematoxylin and eosin (HE) and Masson's staining.