Hypoxia preconditioning has been confirmed as an effective strategy to enhance the therapeutic potentials of mesenchymal stem cells (MSCs), such as for myocardial ischemia. However, whether hypoxia preconditioning would produce beneficial effects on MSC-based renal repair has not been demonstrated. In the study, we aimed to determine the feasibility and efficacy of hypoxia preconditioning to enhance MSC-based therapy of acute kidney injury (AKI). MSCs were isolated from human adipose tissues. The paracrine effects of MSCs under normoxia and hypoxia were determined in vitro. Rats of AKI were induced by kidney I/R surgery and randomly divided into three groups: I/R control receiving PBS injection; MSC group receiving normal MSC injection; hypoMSC group receiving hypoxia-preconditioned MSC injection. It was demonstrated in vitro that paracrine effects of MSCs were significantly enhanced, especially angiogenic factors. Dihydroethidium (DHE) staining showed that antioxidative activities of MSCs were significantly enhanced by hypoxia stimulation. Vascularization, apoptosis, and histological injury were all significantly improved in hypoMSC injected group compared with that in control and MSC injected groups. Finally, the renal function was also significantly improved in hypoMSC injected group compared with that in the other two groups as assessed by the serum creatinine and BUN levels.
In plants, the vesicle fusion process plays a vital role in pathogen defence. However, the importance of the vesicle fusion process in apple ring rot has not been studied. Here, we isolated and characterised the apple syntaxin gene MdSYP121. Silencing the MdSYP121 gene in transgenic apple calli increased tolerance to Botryosphaeria dothidea infection; this increased tolerance was correlated with salicylic acid (SA) synthesis-related and signalling-related gene transcription. In contrast, overexpressing MdSYP121 in apple calli resulted in the opposite phenotypes. In addition, the results of RNA sequencing (RNA-Seq) and quantitative real-time PCR (qRT-PCR) assays suggested that MdSYP121 plays an important role in responses to oxidation–reduction reactions. Silencing MdSYP121 in apple calli enhanced the expression levels of reactive oxygen species (ROS)-related genes and the activity of ROS-related enzymes. The enhanced defence response status in MdSYP121-RNAi lines suggests that syntaxins are involved in the defence response to B. dothidea. More importantly, we showed that MdSYP121 forms a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex with MdSNAP33, and the complex may participate in regulating resistance to B. dothidea. In conclusion, by regulating the interaction of SA pathway and oxidation–reduction process, MdSYP121 can influence the pathogen infection process in apple.
The differentiation rate of adipose-derived mesenchymal stem cells (Ad-MSCs) into endothelial cells is always lower under normal condition, which limits further clinical application of Ad-MSCs for angiogenesis regenerative medicine and needs to be enhanced. In the present study, the tissue-specific-derived decellularized ovine arteries matrix (DCS) was used as scaffold to investigate the pro-endothelial differentiation ability of decellularized ovine arteries matrix as well as the underlying mechanisms. The prepared decellularized ovine arteries matrix by the combination of enzymatic and chemical decellularization approaches preserved macroscopic 3D architecture, native composition and ultrastructure of natural ovine arteries. The RT-PCR, histopathological and immunofluorescence assay results suggested that DCS could increase the proliferation ability of MSC. What's more, the DCS could also induce the endothelial differentiation of MSC, which was further enhanced by adding VEGF. Our results showed that natural 3D matrix from decellularized ovine arteries could induce the endothelial differentiation of AD-MSCs alone or with the combination of VEGF. Our results indicated that the decellularized ovine arteries matrix would serve as an efficient culture system for promoting endothelial differentiation of Ad-MSCs.
Central venous catheters (CVC) are widely used in clinics to gain vascular access, but the risk and prevalence of catheter-related complications remains a serious issue. We report a long-term dialysis catheter accidentally inserted into the mediastinum via the right jugular vein in a hemodialysis patient. We also review complications associated with vascular catheterization and propose immediate therapeutic interventions for such cases.
Introduction: We here evaluated the efficacy of piceatannol (PIC) in high glucose (HG)-induced injury of renal tubular epithelial cells HK-2.
Methods: After the establishment of HG-induced cell injury model and the treatment with PIC at both high and low concentrations and/or Acetazolamide (ACZ, the inhibitor of carbonic anhydrase 2 (CA2)), MTT and flow cytometry assays were carried out to confirm the viability and apoptosis of HK-2 cells. The levels of oxidative stress markers lactate dehydrogenase (LDH), malondialdehyde (MDA), and reactive oxygen species (ROS), the ratio of glutathione/oxidized glutathione (GSH/GSSG), and the CA2 activity were determined. Both quantitative reverse-transcription polymerase chain reaction and Western blot were used to calculate the expressions of CA2 (the predicted target gene of PIC via intersecting the data from bioinformatic analyses), and AKT pathway- (Phosphatase and tensin homolog (PTEN), phosphorylated (p)-AKT, AKT) and apoptosis-related proteins (Bcl-2 and cleaved caspase-3).
Results: HG suppressed cell viability and the levels of GSH/GSSG ratio, CA2, pThr308-AKT/AKT, pSer473-AKT/AKT, and Bcl-2, while promoting cell apoptosis, the levels of LDH, MDA, and ROS and the expressions of PTEN and cleaved caspase-3. All effects of HG were reversed by PIC at a high concentration. CA2 was predicted and identified as the target of PIC. In HG-treated HK-2 cells, additionally, ACZ reversed the effects of PIC on the viability, apoptosis, and the levels of both oxidative stress markers and AKT pathway- and apoptosis-related factors.
Conclusion: PIC protects against HG-induced injury of HK-2 cells via regulating CA2.
Background
IgA nephropathy is the most common glomerular disease and a common cause of progression to end-stage renal disease in patients with kidney diseases. Proteinuria levels are critical to the prognosis of patients with IgA nephropathy, but many patients are still unable to effectively control proteinuria levels after receiving adequate RAAS blockers. Antimalarial drugs have shown good efficacy in the treatment of kidney disease in previous studies; however, there have been no strict designed randomized controlled trials to confirm the clinical efficacy of artesunate in IgA nephropathy patients. Therefore, we designed this clinical trial to compare the effect of artesunate versus placebo in patients with IgA nephropathy.
Methods
This study was a randomized, double-blind, three-group-parallel, placebo-controlled clinical trial. One hundred and twenty eligible IgA nephropathy patients at risk of progression were randomly divided into artesunate 100mg group, artesunate 50 mg group, and placebo group. Changes in proteinuria and renal function were measured after 6 months of intervention. The levels of Gd-IgA1, Anti-Gd-IgA1 in the patient's blood will also be tested to further understand possible immune mechanisms.
Discussion
Clinical evidence for artesunate treatment of IgA nephropathy is currently lacking, and we expect that the results of this trial will provide high-quality clinical evidence for artesunate as a treatment option for IgA nephropathy in the future.
Trial registration:
Chinese Clinical Trial Registry: ChiCTR2000038104, registration date: 10 September 2020. http://www.chictr.org.cn/edit.aspx?pid=61338&htm=4.
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