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The accumulation of uric acid (UA) in the body can lead to the occurrence of hyperuricemia or uric acid nephropathy. Mast cells (MCs) increase oxidative stress and release renin to promote the production of Ang II. The aim of this study was to investigate the effect of UA on MCs in rat kidneys and the association between MCs and renal injury. Our results show that UA accumulation in the kidney stimulated the degranulation of MCs and the release of renin to promote Ang II production, resulting in renal oxidative stress, mitochondrial structural damage, and microvascular system damage. The expression of urate-related transporters was regulated by the UA level and serum urinary toxins levels were substantially elevated in hyperuricemia. Administration of the MCs membrane stabilizer sodium cromoglycate (SCG) or the angiotensin receptor antagonist Valsartan decreased the production of renin and Ang II and relieved renal oxidative stress, mitigated mitochondrial structural damage and microvascular system damage, and promoted the excretion of UA and urinary toxins by increasing the expression of urate-related transporters. These results demonstrate that the accumulation of UA in the kidney can trigger the degranulation of MCs and promote the development of renal oxidative stress. Administration of SCG and Valsartan ameliorated UA-induced renal injury by inhibiting MCs degranulation and reducing renal oxidative stress by inhibiting renin and Ang II production and accelerating renal clearance of UA and uremic toxins.

Iron plays an essential role in biological system. An approach for in vivo imaging of this metal ion is needed to investigate its complex contributions to physiological and pathological processes. Herein, we present a bioluminescent probe FP-1 as a powerful tool for targeting Fe2+ detection in vitro and in vivo. The turn-on sensing scheme is based on the caged strategy of luciferin-luciferase system. FP-1 not only can detect accumulations of exogenous Fe2+ in living animal, but also has the capability of monitoring labile endogenous Fe2+ levels in animal model of sepsis. Implementation of this technique provides a valuable opportunity for understanding underlying mechanisms of Fe2+ in biological processes and disease states.

Objectives Monoacylglycerol lipase participates in organ protection by regulating the hydrolysis of the endocannabinoid 2-arachidonoylglycerol. This study investigated whether blocking monoacylglycerol lipase protects against postresuscitation myocardial injury and improves survival in a rat model of cardiac arrest and cardiopulmonary resuscitation. Design Prospective randomized laboratory study. Setting University research laboratory. Subjects Male Sprague-Dawley rat (n = 96). Interventions Rats underwent 8-minute asphyxia-based cardiac arrest and resuscitation. Surviving rats were randomly divided into cardiopulmonary resuscitation + URB602 group, cardiopulmonary resuscitation group, and sham group. One minute after successful resuscitation, rats in the cardiopulmonary resuscitation + URB602 group received a single dose of URB602 (5 mg/kg), a small-molecule monoacylglycerol lipase inhibitor, whereas rats in the cardiopulmonary resuscitation group received an equivalent volume of vehicle solution. The sham rats underwent all of the procedures performed on rats in the cardiopulmonary resuscitation and cardiopulmonary resuscitation + URB602 groups minus cardiac arrest and asphyxia. Measurements and main results Survival was recorded 168 hours after the return of spontaneous circulation (n = 22 in each group). Compared with vehicle treatment (31.8%), URB602 treatment markedly improved survival (63.6%) 168 hours after cardiopulmonary resuscitation. Next, we used additional surviving rats to evaluate myocardial and mitochondrial injury 6 hours after return of spontaneous circulation, and we found that URB602 significantly reduced myocardial injury and prevented myocardial mitochondrial damage. In addition, URB602 attenuated the dysregulation of endocannabinoid and eicosanoid metabolism 6 hours after return of spontaneous circulation and prevented the acceleration of mitochondrial permeability transition 15 minutes after return of spontaneous circulation. Conclusions Monoacylglycerol lipase blockade may reduce myocardial and mitochondrial injury and significantly improve the resuscitation effect after cardiac arrest and cardiopulmonary resuscitation.

As a trace element nutrient, cobalt is critical for both prokaryotes and eukaryotes. In the current study, a turn-on Cobalt Bioluminescent Probe 1 (CBP-1) for the detection of cobalt has been successfully developed based on oxidative C–O bond cleavage. This probe exhibited high selectivity and sensitivity toward cobalt over other analytes. By using CBP-1, the successful in vivo imaging of cobalt accumulation was carried out in a mouse model. Such an ability to determine cobalt in living animals provides a powerful technology for studying the system distribution, toxic potency, and biological effect of Co2+.