Safety and effectiveness of recombinant human erythropoietin coupled with different doses of Roxadustat for treatment of renal anemia in patients on maintenance hemodialysis.

OBJECTIVE: To investigate the safety and efficacy of recombinant human erythropoietin (rHuEPO) in combination with different doses of Roxadustat in treating renal anemia in patients on maintenance hemodialysis. METHODS: Eighty patients with renal anemia on maintenance hemodialysis treated in Shuyang Hospital of Traditional Chinese Medicine from January 2020 to December 2021 were selected as study subjects, and they were divided into a study group (n=40, high-dose Roxadustat + rHuEPO therapy) and a control group (Con) (n=40, low-dose Roxadustat + rHuEPO therapy) in accordance with different therapies. The effects of anemia therapy, changes in anemia indicators (hemoglobin (Hb), hematocrit (Hct)), changes in iron metabolism indicators (transferrin saturation (TSAT), serum ferritin (SF)), changes in oxidative stress indicators Malondialdehyde (MDA), Superoxide Dismutase (SOD), and changes in microinflammatory indicators IL6, CRP were compared between the two groups. The occurrences of adverse effects during therapy were counted and compared between the two groups. RESULTS: The therapy efficiency of the study group was 97.50% (39/40), which was higher than 85.00% (34/40) in the control group (P=0.048). The contents of Hb, Hct, TSAT, and SF were higher in the study group than the Con after therapy (all P<0.001 or P=0.001). The contents of MDA, IL6, and CRP were significantly lower in the study group than the Con after therapy (all P<0.001). The occurrence of adverse effects was 10.00% in the study group, which was higher than 5.00% in the Con, but the difference was not significant (P=0.396). CONCLUSION: The combination of rHuEPO and high-dose Roxadustat (120 mg/time) has a better effect on improving anemia symptoms in maintenance hemodialysis patients than in those who take low dose Roxadustat (100 mg/time). It can significantly improve anemia and iron metabolism indicators and alleviate patients' inflammation and oxidative stress levels.

Losartan Attenuates Atherosclerosis in Uremic Mice by Regulating Treg/Th17 Balance via Mediating PTEN/PI3K/Akt Pathway.

INTRODUCTION: Uremia could accelerate atherosclerosis (AS) formation involving Treg/Th17 imbalance. Losartan regulates the imbalance between regulatory T cells (Treg cells) and T helper 17 cells (Th17 cells). However, their interactions in uremia accelerated AS (UAAS) remained poorly understood. METHODS: UAAS mice model was established, and after losartan and VO-OHpic (VO, phosphatase and tensin homolog [PTEN] inhibitor) injection, biological indexes, and inflammatory cytokines (transforming growth factor-ß1, TGF-ß1; interleukin-10 [IL-10]; IL-17 and IL-6) levels were determined using enzyme-linked immunosorbent assay. Pathological changes on aorta were observed using hematoxylin-eosin staining. Percentages of Treg cells (CD4+CD25+Foxp3+) and Th17 cells (CD4+IL-17+) in total CD4+ T cells were determined using flow cytometry. PTEN expressions were measured using Western blot, quantitative real-time polymerase chain reaction, and immunohistochemistry staining as needed. RESULTS: After UAAS mice model construction, biological indexes (urea, cholesterol, and triglycerides) levels were increased, and aortic atherosclerotic plaque was formed. In UAAS mice, in total CD4+ T cells, Treg cells percentage was decreased yet Th17 cells percentage was increased, and TGF-ß1 and IL-10 levels were downregulated yet IL-17 and IL-6 levels were upregulated. An opposite effect was found after losartan treatment. PTEN was downregulated in UAAS mice, and suppressing PTEN reversed the alleviating effects of losartan in UAAS mice. CONCLUSION: Losartan attenuated UAAS in mice by regulating Treg/Th17 cells balance via mediating PTEN/PI3K/Akt pathway, providing possible therapeutic method for UAAS in clinical practice.

Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury.

OBJECTIVE: To explore the protective roles of Astragalus polysaccharide (APS) on acute renal injury (AKI) induced by sepsis. METHODS: Firstly, an animal model of sepsis-induced AKI was established by injecting lipopolysaccharide (LPS) into mice. The mice were pretreated with an intraperitoneal injection of 1, 3, and 5 mg/(kg·d) APS for 3 consecutive days. The severity of kidney injury was then scored by histopathological analysis, and the concentrations of serum urea nitrogen (BUN) and serum creatinine (SCr) and the levels of tumor necrosis factor α (TNF-α) and interleukin-1ß (IL-1ß) were determined as well. In in vitro experiments, lipopolysaccharide (LPS) was used to induce HK-2 cell injury to establish a sepsis-induced AKI cell model, and the cell counting kit-8 (CCK-8) method was performed to determine the cytotoxicity and appropriate experimental concentration of APS. Then, cells were divided into the control, LPS, and APS+LPS groups. Cell apoptosis and inflammation-related TNF-α, IL-1ß, IL-6, and IL-8 were determined by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The microscope was used to observe the morphological changes of cells, and the cell migration ability was measured by wound healing assay. RT-qPCR and Western blot assay were used to determine the mRNA and protein levels of apoptosis-related factors including caspase-3, caspase-9, Bax, and Bcl-2; endoplasmic reticulum stress- (ERS-) related biomarkers including C/EBP homologous protein (CHOP) and glucose-regulated protein78 (GRP78); and epithelial-mesenchymal transition- (EMT-) related biomarkers including E-cadherin, Snail, α-smooth muscle actin (α-SMΑ), and Vimentin. RESULTS: In vivo experiments in mice showed that APS can reverse LPS-induced kidney damage in a concentration-dependent manner (P < 0.05); the concentrations of BUN and Scr were increased (all P < 0.05); similarly, the levels of TNF-α and IL-1ß were increased as well (all P < 0.05). In in vitro experiments, the results showed that LPS can significantly cause HK-2 cell damage and induce apoptosis, inflammation, ERS, and EMT. When APS concentration was in the range of 0-200 µg/mL, it had no cytotoxicity in HK-2 cells, and 100 µg/mL APS pretreatment could significantly mitigate the decrease of cell activity induced by LPS (P < 0.05). Compared with the LPS group, APS pretreatment could inhibit the expression of inflammatory factors including TNF-α, IL-1 ß, IL-6, and IL-8 (all P < 0.05), reducing the number of apoptotic cells (P < 0.05), suppressing the expression of caspase-3, caspase-9, and Bax, but upregulating the expression levels of Bcl-2. In ERS, APS pretreatment inhibited LPS-induced upregulation of CHOP and GRP78. Moreover, in EMT, APS pretreatment could inhibit the morphological changes of cells, downregulate the migration, decrease the expression of EMT biomarkers, and inhibit the process of EMT. CONCLUSION: APS could alleviate sepsis-induced AKI by regulating inflammation, apoptosis, ERS, and EMT.