NMRK2 is an efficient diagnostic indicator for Xp11.2 translocation renal cell carcinoma.

Xp11.2 translocation renal cell carcinomas (tRCC) are a rare and highly malignant type of renal cancer, lacking efficient diagnostic indicators and therapeutic targets. Through the analysis of public databases and our cohort, we identified NMRK2 as a potential diagnostic marker for distinguishing Xp11.2 tRCC from kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) due to its specific upregulation in Xp11.2 tRCC tissues. Mechanistically, we discovered that TFE3 fusion protein binds to the promoter of the NMRK2 gene, leading to its upregulation. Importantly, we established RNA- and protein-based diagnostic methods for identifying Xp11.2 tRCC based on NMRK2 expression levels, and the diagnostic performance of our methods was comparable to a dual-color break-apart fluorescence in situ hybridization assay. Moreover, we successfully identified fresh Xp11.2 tRCC tissues after surgical excision using our diagnostic methods and established an immortalized Xp11.2 tRCC cell line for further research purposes. Functional studies revealed that NMRK2 promotes the progression of Xp11.2 tRCC by upregulating the NAD+/NADH ratio, and supplementation with ß-nicotinamide mononucleotide (NMN) or nicotinamide riboside chloride (NR), effectively rescued the phenotypes induced by the knockdown of NMRK2 in Xp11.2 tRCC. Taken together, these data introduce a new diagnostic indicator capable of accurately distinguishing Xp11.2 tRCC and highlight the possibility of developing novel targeted therapeutics. © 2024 The Pathological Society of Great Britain and Ireland.

Effect of D-ribose supplementation on delayed onset muscle soreness induced by plyometric exercise in college students.

OBJECTIVE: Previous investigations suggest that appropriate nutritional interventions may reduce delayed onset muscle soreness (DOMS). This study examined the effect of D-ribose supplementation on DOMS induced by plyometric exercise. METHODS: For the purpose of inducing DOMS, 21 untrained male college students performed a lower-limb plyometric exercise session that involved 7 sets of 20 consecutive frog hops with 90-s of rest between each set. Muscle soreness was measured with a visual analogue scale 1-h before, 24-h after, and 48-h after exercise. Subjects were then randomly placed into the D-ribose group (DRIB, n = 11) and the placebo group (PLAC, n = 10) to assure equivalent BMI and muscle soreness. After a 14-d washout/recovery period, subjects performed the same exercise session, with DRIB ingesting a 200 ml solution containing 15 g D-ribose 1-h before, 1-h, 12-h, 24-h, and 36-h after exercise, and PLAC ingesting a calorically equivalent placebo of the same volume and taste containing sorbitol and ß-cyclodextrin. Muscle soreness and isokinetic muscle strength were measured, and venous blood was assessed for markers of muscle damage and oxidative stress 1-h before, 24-h and 48-h after exercise. RESULTS: In DRIB, muscle soreness after 24-h and 48-h in the second exercise session were significantly lower (p < 0.01) than was experienced in the first exercise session. In the second exercise, blood-related markers of muscle soreness, including creatine kinase, lactate dehydrogenase (LDH), myoglobin and malondialdehyde (MDA) in DRIB after 24-h were lower in DRIB after 24-h than in PLAC (MDA, p < 0.05; rest outcomes, p < 0.01). In addition, LDH and MDA in DRIB were significantly lower (p < 0.01) after 24-h in DRIB than in PLAC. No difference was found in isokinetic muscle strength and oxidative stress markers, including superoxide dismutase and total antioxidant capacity, between DRIB and PLAC after 24-h and 48-h. CONCLUSION: D-ribose supplementation reduces muscle soreness, improves recovery of muscle damage, and inhibits the formation of lipid peroxides. Young adult males performing plyometric exercise are likely to realize a DOMS reduction through consumption of D-ribose in 15 g/doses both before (1-h) and after (1-h, 12-h, 24-h, 36-h) exercise. These results suggest that appropriately timed consumption of D-ribose may induce a similar alleviation of exercise-induced DOMS in the general public.