Background/Aims: Recent studies suggested the involvement of the Akt/mammalian target of rapamycin (mTOR) pathway in the pathogenesis of diabetic nephropathy. The effect of mTOR blockade by rapamycin in diabetic nephropathy was investigated, but in vivo study of rapamycin treatment in the course of early diabetes is still insufficient. This study was designed to determine the therapeutic effects of rapamycin on diabetic nephropathy at an early stage. Methods: Diabetes was induced in Sprague-Dawley rats with streptozotocin, and rapamycin (1 mg/kg) was administered by daily gavage for 4 weeks. Renal structural changes and some factors involved in the early pathogenesis of diabetic nephropathy were tested. The activation level of the Akt/mTOR pathway was also determined. Results: Rapamycin treatment reduced albuminuria, glomerular enlargement, glomerular basement membrane thickening, renal macrophage recruitment, and levels of renal mRNA expression of proliferating cell nuclear antigen, transforming growth factor-β₁, vascular endothelial growth factor, and monocyte chemoattractant protein-1 without change in blood glucose level and blood pressure in experimental diabetic rats. In addition, treatment with rapamycin also down-regulated the enhanced levels of renal p-Akt, phospho-p70S6 kinase, and phospho-ribosomal S6 protein in diabetic rats. Conclusions: Rapamycin treatment can prevent the early renal structural changes of diabetes in experimental rats, and thus halt the early steps of the development of diabetic nephropathy. mTOR blockade might be beneficial for the treatment of diabetic nephropathy.

Background: NOD-like receptor 3 (NLRP3) inflammasome is necessary to initiate acute sterile inflammation. Increasing evidence indicates the activation of NLRP3 inflammasome induced pyroptosis is closely related to reactive oxygen species (ROS) in the sterile inflammatory response triggered by ischemia/reperfusion (I/R) injury. Nacetylcysteine (NAC) is an antioxidant and plays a protective role in local myocardial I/R injury, while its effect on post-resuscitation myocardial dysfunction, as well as its mechanisms, remain elusive. In this study, we aimed to investigate the effect of NAC on post-resuscitation myocardial dysfunction in a cardiac arrest rat model, and whether its underlying mechanism may be linked to ROS and NLRP3 inflammasome-induced pyroptosis. Methods: The rats were randomized into three groups: (1) sham group, (2) cardiopulmonary resuscitation (CPR) group, and (3) CPR + NAC group. CPR group and CPR + NAC group went through the induction of ventricular fibrillation (VF) and resuscitation. After return of spontaneous circulation (ROSC), rats in the CPR and CPR + NAC groups were again randomly divided into two subgroups, ROSC 6 h and ROSC 72 h, for further analysis. Hemodynamic measurements and myocardial function were measured by echocardiography, and western blot was used to detect the expression of proteins. Results: Results showed that after treatment with NAC, there was significantly better myocardial function and survival duration; protein expression levels of NLRP3, adaptor apoptosis-associated speck-like protein (ASC), Cleaved-Caspase-1 and gasdermin D (GSDMD) in myocardial tissues were significantly decreased; and inflammatory cytokines levels were reduced. The marker of oxidative stress malondialdehyde (MDA) decreased and superoxide dismutase (SOD) increased with NAC treatment.

Rationale:Hypereosinophilic syndrome (HES) is a rare disease characterized by hypereosinophilia and its ensuing organ damage. Cardiac involvement is divided into 3 chronological stages: an acute necrotic stage; a thrombus formation stage; and a fibrotic stage. Infiltration of the myocardium by eosinophilic cells followed by endomyocardial fibrosis is known as “Loeffler endocarditis.”Patient concerns:We report a case of a 60-year-old man diagnosed with left-sided restrictive cardiomyopathy.Diagnosis:The patient experienced heart failure with preserved ejection fraction. The cardiac MRI showed intense, linear, delayed gadolinium enhancement of the endocardium of the lateral wall of the left ventricle, and obliteration of the LV apex. He was ultimately identified as Loeffler endocarditis.Intervention:A bone marrow smear and biopsy revealed the FIP1L1-PDGFRA fusion gene was positive in 82% of segmented nucleated cells.Outcome:Our patient responded well to prednisone at 1 mg/kg/d.Lessons:HES is a rare disease that often afflicts the heart. Cardiac involvement in hypereosinophilia, especially Loeffler endocarditis, carries a poor prognosis and significant mortality. Early detection and treatment of the disease is therefore essential. Further studies are needed to ascertain therapeutic corticosteroid dosages and develop targeted gene therapies, both important steps to ameliorate the effects of Loeffler endocarditis and improve patient outcomes.