The ubiquitin-specific protease ( USP) inhibitors influence many crucial cellular activities and some immune processes, such as anti-inflammatory, anti-infection and anti-tumor by silencing the functions of USP.The main USP inhibitors, which potency and specificity are underlined and current methods for detecting and identifying USP inhibitors are discussed of in this review.

Objective:To document any effect of environmental enrichment on nerve regeneration in a mouse model of sciatic nerve compression and explore its mechanism.Methods:A crushed sciatic nerve model was successfully established in 22 C57BL/6 mice, and they were then randomly divided into an intervention group and a control group. The mice of the intervention group were raised in a cage with an enriched environment, while those of the control group were kept in a standard cage. Two weeks later, both groups′ gait was analyzed and the compound muscle action potential (CMAP) of the sciatic nerve was measured. The proportion of myelinated sciatic nerve fibers was examined using toluidine blue staining, and the expression of myelin basic protein (MBP), growth associated protein-43 (GAP43) and p75 neurotrophin receptor (p75 NTR) was measured using immunofluorescence intensity. Results:①The latency of the CMAP [(1.05±0.04)ms] was significantly shortened in the intervention group compared with the control group and the amplitude was significantly higher. ②Gait analysis showed a significant increase in the average contact intensity, stride length and stride rate of the intervention group compared with the control group. However, the step axis angle of the intervention group was significantly smaller than in the control group on average. ③The stained nerve fibers in the intervention group were orderly and dense, and the average number of myelinated fibers was significantly greater than in the control group. ④Quantitative analysis of the immunofluorescence showed that the levels of MBP, GAP43 and p75 NTR in the sciatic nerves of the intervention group were, on average, significantly higher than in the control group. Conclusion:An enriched environmental can promote the regeneration and functional recovery of crushed sciatic nerves by promoting the proliferation and myelination of Schwann cells.

OBJECTIVETo learn about the effects of psychological counseling intervention on reducing heroin use, increasing methadone dosage and improving compliance rate of methadone maintenance treatment (MMT).

METHODSSubjects who had had at least one positive result for regular urine morphine tests during the past three months were recruited from 16 MMT clinics. During the three-month intervention period, the subjects received regular psychological counseling provided by doctors (once every other week) and peer education (once a week). Positive rates of urine morphine tests, average days receiving MMT during three months before the intervention and during the intervention, and average daily dosage of methadone during the last week before intervention and during the last week of the intervention programs conducted were recorded and compared.

RESULTSA total of 492 patients receiving MMT were surveyed. There were significant changes in positive rates for urine morphine tests, average daily dosage, and average days on MMT before and during the intervention programs. The positive rate for urine morphine tests dropped from 50.1% to 27.1%; the average daily dosage of methadone increased from 63.0 mg to 72.6 mg; the average days receiving MMT increased from 69.4 days to 73.9 days.

CONCLUSIONIntensive psychological counseling intervention was effective in reducing heroin use, increasing methadone dosage and improving compliance rate of MMT among patients receiving MMT.

Counseling ; Heroin Dependence ; drug therapy ; psychology ; Humans ; Methadone ; therapeutic use ; Opiate Substitution Treatment ; psychology ; Patient Compliance ; Surveys and Questionnaires

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.