Bone marrow derived mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury.

BACKGROUND: Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI). The main drawbacks of MSCs therapy, including the lack of specific homing after systemic infusion and early cell death in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning of MSCs promotes their therapeutic effect, however, the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO in bone marrow derived mesenchymal stem cells (BMSCs) for AKI treatment. RESULTS: We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in BMSCs, which was decreased by EPO pretreatment, indicating that EPO protected the cells from apoptosis. Further, we showed that EPO up-regulated silent information regulator 1 (SIRT1) and Bcl-2 expression and down-regulated p53 expression. This effect was partially reversed by SIRT1 siRNA intervention. The anti-apoptotic effect of EPO in pretreated BMSCs may be mediated through the SIRT1 pathway. In a rat AKI model, 24 h after intravenous infusion, GFP-BMSCs were predominantly located in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs and increased their distribution in the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1ß and TNF-α, and a significantly higher level of IL-10 as compared to rats infused with untreated BMSCs. The administration of EPO-BMSCs after reperfusion reduced serum creatinine, blood urea nitrogen, and pathological scores in I/R-AKI rats more effectively than BMSCs treatment did. CONCLUSIONS: Our data suggest that EPO pretreatment enhances the efficacy of BMSCs to improve the renal function and pathological presentation of I/R-AKI rats.

[Comparative Characteristics of Optical Absorption in Waters from Yiluo River and Huntai River in Spring].

The absorption characteristics, composition, spatial variability, and relative contribution of optically active constituents over the range of photosynthetically active radiation (PAR, 400-700 nm) were analyzed from samples collected in the Yiluo and Huntai Rivers in May 2017 and 2013, respectively. Results demonstrated that the absorption curves of total suspended particulates[ap(λ)] were similar to those of non-algae particles[ad(λ)]. Significant correlations between ap(λ) and ad(λ) were obtained, especially at 440 nm, with r=0.968 in the Yiluo River and r=0.899 in the Huntai River. Meanwhile, positive correlations between ap(λ) and the absorption of phytoplankton[aph(λ)] were observed at 675 nm. ap(λ) in the two basins was dominated by ad(λ). Moreover, the composition of auxiliary pigments and chloropyhll a concentration[Chla] showed more significant spatial variations based on aph(440)/aph(675) in the Yiluo River than in the Huntai River. In addition, CDOM absorption slopes (SCDOM) indicated that CDOM composition in the Yiluo River was dominated by exogenous substances; in comparison, the Huntai River had more endogenous substances. SCDOM in the Yiluo River was lower than in the Huntai River, indicating that the CDOM composition of the Yiluo River was inclined towards high molecular weights. Furthermore, Mr[aCDOM(250)/aCDOM(365)] showed greater ranges and lower mean values in the Yiluo River than in the Huntai River, confirming that CDOM molecular weight varied greatly in the former. CDOM molecular weight in the Huntai River was also lower than in the Yiluo River, in accordance with SCDOM results.

Bone mesenchymal stem cells pretreated with erythropoietin enhance the effect to ameliorate cyclosporine A-induced nephrotoxicity in rats.

An increasing number of experiments and clinical trials have demonstrated the safety, feasibility, and efficacy of mesenchymal stem cells (MSCs)-based therapies for the treatment of various diseases. The main drawbacks of MSC therapy are the lack of specific homing after systemic infusion and early death of injected cells because of the injury micro-environment. We pretreated bone mesenchymal stem cells (BMSCs) with erythropoietin (EPO) to investigate their positive effect on cyclosporine A (CsA)-induced nephrotoxicity. BMSCs were incubated with different concentrations of EPO (10, 100, 500, and 1000 IU/mL) for 24 and 48 h, and their proliferation rate, cytoskeletal morphology, migration ability, and the expression of CXCR4 were evaluated to determine the optimal pretreatment conditions. To investigate the therapeutic effects of BMSCs pretreated with EPO in CsA-induced nephrotoxicity, we established CsA-induced in vitro and in vivo toxicity models. In our in vitro study, preconditioning of BMSCs with 500 IU/mL EPO for 48 h induced a marked increase in their proliferation rate, cytoskeletal rearrangement, migration in the scrape-healing assay, and migration toward injured HK2 cells. In vivo, EPO-BMSCs showed higher ability to improve renal function than BMSCs, and in CsA-induced rats treated with EPO-BMSCs, interstitial lymphocyte infiltration, tubular swelling, necrosis, and interstitial fibrosis decreased. We demonstrated that pretreatment with 500 IU/mL EPO before infusion markedly increased the homing ability of BMSCs, and obviously ameliorate CsA-induced nephrotoxicity in rats.

Rutin ameliorates kidney interstitial fibrosis in rats with obstructive nephropathy.

Rutin reportedly conveys many beneficial effects, including renoprotection; however, it has not yet been demonstrated to have a renoprotective effect against obstructive nephropathy. The present study is the first to show a protective effect of rutin against obstructive renal injury induced by unilateral ureteral obstruction (UUO). A total of 24 male Wistar rats were randomly divided into four groups of six rats each, including vehicle- or rutin-treated sham operated groups, and vehicle- or rutin-treated UUO groups. Rats received daily oral gavage of rutin (100mg/kg) for 2weeks. All rats were euthanized on postoperative day 14. Histological findings showed that rutin administration significantly reduced renal interstitial injury and suppressed interstitial collagen deposits in UUO rats. Moreover, rutin decreased macrophage infiltration, proinflammatory cytokine expression and phosphorylation of nuclear factor-κB p65. Furthermore, rutin inhibited extracellular matrix accumulation by reducing expression of type I/III collagen and fibronectin. Rutin also prevented the epithelial-mesenchymal transition processes of renal tubular cells by decreasing α-smooth muscle actin expression and retaining E-cadherin expression. These effects of rutin were in parallel with the reductions in Smad3 activity and pivotal to the fibrogenic potential of TGF-ß1. Taken together, the renoprotective effects of rutin in obstructive nephropathy were likely due to anti-inflammatory effects and inhibition of TGF-ß1/Smad3 signaling.

Ghrelin attenuates renal fibrosis and inflammation of obstructive nephropathy.

PURPOSE: Ghrelin is a gastric peptide that modulates multiple biological functions, of which the stimulation of food intake is the most well-known function. Ghrelin also exerts potential anti-inflammatory and antifibrotic properties in different organs but to our knowledge whether ghrelin inhibits the progression of renal fibrosis is unknown. Thus, we investigated the effect and underlying mechanisms of ghrelin in a rat model of renal fibrosis. MATERIALS AND METHODS: Male Sprague Dawley® rats were divided into 4 groups, including vehicle or ghrelin treated sham operated groups and vehicle or ghrelin treated unilateral ureteral obstruction groups. Kidneys harvested on postoperative day 7 or 14 were evaluated for renal inflammation, fibrosis and apoptosis, and the expression of profibrotic and proinflammatory factors. RESULTS: Ghrelin inhibited renal fibrosis by attenuating collagen production, extracellular matrix deposition, and α-smooth muscle actin and fibronectin expression. Ghrelin administration decreased macrophage infiltration and several proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß and monocyte chemotactic protein-1, as well as phosphorylated nuclear factor-κB p65. Ghrelin also inhibited myofibroblast accumulation by blocking the transforming growth factor-ß1/Smad3 signaling pathway. Furthermore, ghrelin attenuated renal tubular cell apoptosis and epithelial-mesenchymal transition processes induced by unilateral ureteral obstruction injury. CONCLUSIONS: These findings indicate that ghrelin is a potent antifibrotic agent that may have therapeutic potential in patients with obstructive nephropathy.

[Photosensitizer nanoparticles photodynamic therapy on LOVO human colon cancer xenografts in athymic mice].

OBJECTIVE: To evaluate the inhibitory of profrin II nanoparticles photodynamic therapy on Lovo human colon cancer xenografts in athymic mice. METHODS: Profrin II nanoparticles were obtained from hypersound emulsification method. LOVO human colon cancer xenograft were established in athymic mice. Athymic mice were divided into four groups:normal control group, profrin II nanoparticles control group, profrin II PDT group and profrin II nanoparticles PDT group. The animals bearing xenografts were treated 30 mg/kg body weight profrin II nanoparticles and 3 h later were irradiated with 9 J/cm(2) light from a diode laser. After Profrin II nanoparticles PDT, the anti-tumor effect was assessed by measuring tumor volume over a 3-4 weeks period, the morphologic changes were observed by microscopy and microscopy via the histological examination. RESULTS: Compared with the control groups, profrin II nanoparticles control group, profrin II PDT group and profrin II nanoparticles-PDT treated tumors had regressed significantly in earlier period with the inhibiting rate being 87.9% (P<0.05), 87.5% (P<0.05) and 56.0% respectively (P<0.05). In the later period post-PDT, tumors growth resumed with a slower rate. Profrin II nanoparticles-PDT prolonged the survival time in the treated group with (38.0+/-6.0) days (P<0.05). Extensive damage to tumor tissue was found in the earlier period (7d) post-PDT, whereas in the later period (21d) post-PDT, islands of vital-looking tumor cells were observed around the damaged tissue. CONCLUSION: Profrin II nanoparticles-PDT results in inhibition Lovo colon carcinoma growth in post-PDT earlier period in vivo, and can prolong the survival time of nude mice bearing xenografts significantly, whereas profrin II-PDT could not inhibit the growth of colon tumor completely.

[Risk factors of acute rejection in sensitized kidney transplant recipients].

OBJECTIVE: To identify the risk factors of acute rejection in sensitized recipients undergoing kidney transplantation. METHODS: The clinical data of 102 sensitized kidney transplant recipients were retrospectively analyzed to evaluate the incidence of acute rejection in relation to panel reactive antibodies (PRA), amino acid residual match, postoperative elevation of PRA level and cytokine genotypes. RESULTS: During the follow-up, acute rejection occurred in totally 33 patients, and the incidence was higher in the recipients with high tumor necrosis factor (TNF)-alpha or high interleukin (IL)-10 producer genotype than in those with low TNF-alpha or low/intermediate IL-10 producer genotype (53.1%, 55.0% vs 22.8%, 20.9%, P(18)0.01 respectively). Acute rejection was even more frequent in the recipients with both high TNF-alpha and high/intermediate IL-10 producer genotypes than in those with low TNF-alpha and IL-10 producer genotype (66.7% vs 10.2%, P<0.01). No relations were found between TGF-beta1, IL-6, IFN-gamma gene polymorphisms and the incidence of acute rejection. The incidence in the recipients with PRA level of more than 40% was also higher than those with lower PRA level (<20%, 53.3% vs 22.7%, P<0.05), and the amino acid residual mismatch with 3-4 MM was responsible for a higher incidence in comparison with a mismatch with 0-1 MM (75.0% vs 24.1%, P<0.01). Postoperative elevation of PRA level also increased the risk of acute rejection (45.4% vs 22.4%, P<0.01). CONCLUSION: TNF-alpha, IL-10 gene polymorphism, PRA, amino acid residual mismatch, and increased postoperative PRA level may significantly influence acute rejection in sensitized kidney transplantation recipient, and preoperative evaluation of these factors may benefit the designing of immunosuppressive protocols for these patients.

Risk factors for graft survival in sensitized recipients of kidney transplantation.

OBJECTIVE: To investigate the independent prognostic factors for graft survival in sensitized recipients undergoing kidney transplantation, so as to identify the individuals at high risk of graft loss before transplantation. METHODS: A retrospective investigation was conducted in 102 sensitized kidney transplant recipients and 31 relative variables were analyzed with SPSS10.0 software. Using log-rank method, the influence of these variables on short- and long-term graft survivals was evaluated, and Kaplan-Meier analysis was performed to estimate the 1-, 3- and 5-year graft survival rates and half-life. Proportional hazards regression analysis (Cox model) was used to assess the relative risks of the potential variables. RESULTS: In the recipients with a mean half-life of 8.9 years, the 1-, 3- and 5-year graft survival rates were 90%, 85%, and 75%, respectively. By log-rank analysis, the factors affecting short- and long-term graft survivals were identified, namely the recipient age, times of transplantation, levels of panel reactive antibody and the post-operative anti-HLA-IgG antibody, HLA mismatch, renal function, time needing for graft function recovery, presence of acute rejection, delay of graft function recovery and infection, which affected the graft survival demonstrated by Cox model multivariate analysis. CONCLUSION: High-quality donor kidney and minimization of the risk factors for graft survival may insure successful kidney transplantation in sensitized recipients.

[Cytokine gene polymorphism in sensitized kidney transplant recipients and its association with acute rejection episodes].

OBJECTIVE: To investigate the relationship between cytokine gene polymorphism in sensitized kidney transplant recipients and acute rejection episodes. METHODS: PCR using sequence-specific primer (PCR-SSP) was performed to determine the cytokine genotypes of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), transforming growth factor-beta1 (TGF-beta1), interleukin-6 (IL-6), interferon-gamma (IFN-gamma) in 97 sensitized kidney transplant recipients. The association of cytokine genotypes with early graft rejection was explored. RESULTS: Acute rejection occurred in 23 of the 97 patients during the first three months after operation. The incidence of acute rejection was higher in the recipients with high TNF-alpha or high IL-10 producer genotype (51.9% and 55.5% respectively) than in the recipients with low TNF-alpha or low to intermediate IL-10 producer genotype (12.9% and 13.3% respectively, P<0.01). The incidence of acute rejection was even higher in the recipients with high TNF-alpha in combination with intermediate to high IL-10 producer genotype than in the recipients with low TNF-alpha combined with low IL-10 producer genotype (62.5% vs 8.5%, P

[Association between aldosterone synthase gene polymorphism and hypertrophic cardiomyopathy].

OBJECTIVE: To investigate the relationship between aldosterone synthase (CYP11B2) gene polymorphism and hypertrophic cardiomyopathy (HCM). METHODS: Fifteen HCM patients and 18 healthy subjects were enrolled in this study. Peripheral blood samples were collected from these subjects to exact genome DNA. PCR and Hae III restriction endonuclease digestion were employed to study -344C/T polymorphism of CYP11B2 gene. RESULTS: CYP11B2 gene showed a significant difference in CT genotype distribution in HCM groups as compared with that in the control groups (P<0.05). CONCLUSION: CT genotype of CYP11B2 gene may be one of factors responsible for the pathogenesis of HCM in a proportion of patients.