Activation of the renin angiotensin system and renal oxidative stress (OS) are critical contributors in the progression of chronic kidney disease(CKD). Recent studies have confirmed that the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas(ACE2/Ang(1-7)/Mas) axis, the important components of renin angiotensin system, protected kidneys against damage by antagonizing angiotensin II and attenuating OS in rats with several nephropathy models, but its effect needs to be further evaluated in clinic. In this study, we aimed to detected serum ACE2/Ang (1-7)/Mas axis, OS conditions and described its clinical associations in patients with CKD at different stages.
A total of 48 patients with CKD and 6 healthy controls (CT) were enrolled, and serum angiotensin converting enzyme (ACE), ACE2, Ang (1-7), 8-hydroxy-2’-deoxyguanosine (8-OHdG) were determined by ELISA. Serum extracellular glutathione peroxidase(eGSH-Px) activity and renal functions were determined by the biochemical method.
Serum ACE and ACE2 levels in CKD stages 3 to 5 and serum Ang(1-7) levels in CKD stages 4 to 5 without Ang II receptor blockers treatment significantly increased compared to those in the CT group. However, ACE2 was decreased and Ang(1-7) level increased in early CKD stage with Ang II receptor blockers treatment. Higher serum 8-OHdG levels and lower eGSH-Px activity were noted in CKD stages 4 to 5. Serum 8-OHdG level was correlated with serum ACE2, Ang(1-7) expression. Estimated glomerular filtration rate (eGFR) was correlated with serum ACE, ACE2, Ang(1-7), 8-OHdG, Hcy levels and serum eGSH-Px activity. Multiple-regression analysis eGFR was predicted by ACE, Hcy, eGSH-Px, and also can be predicted by ACE2, Ang(1-7), Hcy in CT subgroup.
The ACE2/Ang(1-7)/Mas axis is associated with OS, and both them were associated with eGFR in the progression of CKD. Activation of ACE2/Ang(1-7)/Mas axis may have renoprotective effect and can be a potential therapeutic target in patients with early CKD stages.
TCM therapy for detoxification, removing stasis, and nourishing yin can effectively regulate the levels of serum lipids and lipoproteins in preventing and treating SLE patients with corticosteroid-induced hyperlipemia.
Objectives
Platelet clumps present in anticoagulant specimens may generate a falsely decreased platelet count and lead to an incorrect diagnosis. A clear understanding of the ability of a haematology analyser (HA) to detect platelet clumps is important for routine work in the clinical laboratory.
Methods
Citrate-anticoagulated whole-blood samples were collected from various patients as a negative group. Adenosine diphosphate (ADP)-induced platelet aggregation was performed on those negative samples to mimic platelet-clump-containing (positive) samples. The ‘platelet clumps’ and ‘platelet abnormal’ flags generated by the Sysmex XN-10 instrument were used to assess the flagging performance of this HA and demonstrate its flagging features. The complete blood count (CBC) results of paired negative and positive samples were compared to evaluate the impact of platelet clumps on the CBC parameters.
Results
A total of 187 samples were eligible for this study. The total accuracy, sensitivity, and specificity of the platelet clumps flag were 0.786, 0.626, and 0.947, respectively. The total accuracy, sensitivity, and specificity of the platelet abnormal flag were 0.631, 0.348, and 0.914, respectively. A separate assessment focusing on the positive samples with low platelet counts showed that the total sensitivities of the platelet clumps and platelet abnormal flags were 0.801 and 1.000, respectively. Platelet clumps may interfere with the leukocyte count and with platelet and erythrocyte indices.
Conclusions
Platelet clumps can influence not only platelet indices but also leukocyte and erythrocyte counts. The Sysmex XN-10 instrument is sensitive to positive samples with low platelet counts but insensitive to those with high platelet counts.
Objectives:
Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus. This study investigated the mechanism of triptolide (TP) in podocyte injury in DN.
Methods:
DN mouse models were established by feeding with a high-fat diet and injecting with streptozocin and MPC5 podocyte injury models were induced by high-glucose (HG), followed by TP treatment. Fasting blood glucose and renal function indicators, such as 24 h urine albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and kidney/body weight ratio of mice were examined. H&E and TUNEL staining were performed for evaluating pathological changes and apoptosis in renal tissue. The podocyte markers, reactive oxygen species (ROS), oxidative stress (OS), serum inflammatory cytokines, nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway-related proteins, and pyroptosis were detected by Western blotting and corresponding kits. MPC5 cell viability and pyroptosis were evaluated by MTT and Hoechst 33342/PI double-fluorescence staining. Nrf2 inhibitor ML385 was used to verify the regulation of TP on Nrf2.
Results:
TP improved renal function and histopathological injury of DN mice, alleviated podocytes injury, reduced OS and ROS by activating the Nrf2/heme oxygenase-1 (HO-1) pathway, and weakened pyroptosis by inhibiting the nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome pathway.
In vitro
experiments further verified the inhibition of TP on OS and pyroptosis by mediating the Nrf2/HO-1 and NLRP3 inflammasome pathways. Inhibition of Nrf2 reversed the protective effect of TP on MPC5 cells.
Conclusions:
Overall, TP alleviated podocyte injury in DN by inhibiting OS and pyroptosis
via
Nrf2/ROS/NLRP3 axis.
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