Immethridine, histamine H 3 -receptor (H 3 R) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells Immethridine, histamine H3-receptor (H3R) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells

FKBP10, a member of the FK506-binding protein (FKBP) family, has been implicated in cancer development, although its prognostic function remains controversial. In this study, we analyzed the expression of FKBP10 in tumor tissues using online databases (TCGA) as well as our CRC cohort, and investigated the relationship between its subcellular expression pattern and patient outcomes. Cox regression analysis was used to determine the associations between different subcellular expression patterns of FKBP10 and clinical features of patients. We also discussed the expression level of FKBP10 based on different subcellular expression patterns. Our results showed that FKBP10 was significantly elevated in CRC tissues and exhibited three different subcellular expression patterns which were defined as ‘FKBP10-C’ (concentrated), ‘FKBP10-T’ (transitional) and ‘FKBP10-D’ (dispersive). The FKBP10-D expression pattern was only found in tumor tissues and was associated with unfavorable disease-free survival in CRC patients. High expression levels of FKBP10-C predicted an unfavorable prognosis of recurrence of CRC, while FKBP10-D did not. Our findings suggest that the subcellular expression patterns and expression level of FKBP10 play crucial prognostic roles in CRC, which revealed that FKBP10 may be a viable prognostic and therapeutic target for the diagnosis and treatment of CRC.

Zebrafish is broadly used as a model organism in gene loss-of-function studies in vivo, but its employment in vitro is greatly limited by the lack of efficient gene knockdown approaches in zebrafish cell lines such as ZF4. In this article, we attempt to induce silencing of telomere associated genes in ZF4 by applying the frequently-used siRNA transfection technology and a novel moiety-linked morpholino(vivo-MO). By proceeding with integrated optimization of siRNAs transfection and vivo-MOs treatment, we compared five transfection reagents and vivo-MOs simultaneously to evaluate the efficiency of terfa silencing in ZF4. 48 hours after siRNAs transfection, Lipofectamine™ 3000 and X-tremeGENE™ HP leaded to knockdown in 35% and 43% of terfa mRNA, respectively, while vivo-MO-terfa modulated 58% down-expression of zfTRF2 in contrast to vivo-MO-ctrl 72 hours after treatment. Further siRNA transfection targeting telomere associated genes by X-tremeGENE™ HP showed silencing in 40-68% of these genes without significant cytotoxicity and off-target effect. Our results confirmed the feasibility of gene loss-of-function studies in a zebrafish cell line, offered a systematic optimizing strategy to employ gene silencing experiments, and presented Lipofectamine™ 3000, X-tremeGENE™ HP and vivo-morpholinos as candidate gene silencing approaches for zebrafish in vitro gene loss-of-function studies. Successfully knockdown of shelterin genes further opened a new field for telomeric study in zebrafish.

Background: The gut microbiota is closely related to exercise, but the interrelationship between the two remains elusive. In this study, we aimed to explore differences in the gut microbiota between young adults with exercise and sedentary lifestyles. In addition, we evaluated the effects of gut microbiota from these different lifestyle populations on endurance exercise capacity. Methods: The exercise status and nutritional characteristics of young adults were evaluated by PARS-3 and food frequency questionnaires. The gut microbiota of young adults from exercise and sedentary lifestyle groups was analyzed by 16S rRNA analysis. Subsequently, we performed fecal bacteria transplantation (FMT) from the human donors into mice and evaluated the effects on their endurance exercise capacity. Results: The exercise group exhibited significantly higher gut microbiota diversity compared to the sedentary group. Several beneficial bacteria, including Veillonella, Faecalibacterium, and Bacteroides, were enriched in the exercise group. The FMT experiment confirmed that mice receiving microbiota from the exercise group showed significantly improved endurance exercise capacity. Conclusion: Young people who exercise regularly possess a more diverse gut microbiota enriched with beneficial bacteria. This exercise-associated microbiota has the potential to directly improve exercise capacity.