Kidney ischemia and reperfusion injury could cause microvascular barrier dysfunction, lung inflammatory cascades activation, and programmed cell death of pulmonary endothelium, leading to acute lung injury. Our study aimed at determining whether erythropoietin (EPO) can ameliorate lung dysfunction following renal ischemia and reperfusion (IR) injury and explored the underlying mechanisms. In vivo, C57BL/6 mice received EPO (6000 U/kg) before right renal vascular pedicles clamping for 30 minutes, followed by 24 hours of reperfusion. The lung histopathologic changes and inflammatory cytokines expression were assessed. In vitro, cultured human umbilical vein endothelial cells were treated with EPO, and apoptosis rate, proliferation capacity, and phosphorylation status of the Janus kinase-signal transducer and activator of transcription 3 (Jak-STAT3) pathway were measured respectively in the presence or absence of lipopolysaccharide stimulation. In vivo, EPO remarkably attenuated pulmonary interstitial and alveolar epithelial edema caused by renal IR injury. In vitro, the proliferation capacity of human umbilical vein endothelial cells was significantly increased under EPO stimulation, which correlated with changes in Jak-STAT3 signaling. Our data indicated that EPO is able to ameliorate acute lung tissue damage induced by renal IR, and at least in part, via the Jak-STAT3 pathway.
During a developmental period that extends postnatally in the mouse, proliferating multipotent retinal progenitor cells produce one of 7 major cell types (rod, cone, bipolar, horizontal, amacrine, ganglion, and Müller glial cells) as they exit the cell cycle in consecutive waves. Cell production in the retina is tightly regulated by intrinsic, extrinsic, spatial, and temporal cues, and is coupled to the timing of cell cycle exit. Arsenic-resistance protein 2 (ARS2, also known as SRRT) is a component of the nuclear cap-binding complex involved in RNA Polymerase II transcription, and is required for cell cycle progression. We show that postnatal retinal progenitor cells (RPCs) require ARS2 for proper progression through S phase, and ARS2 disruption leads to early exit from the cell cycle. Furthermore, we observe an increase in the proportion of cells expressing a rod photoreceptor marker, and a loss of Müller glia marker expression, indicating a role for ARS2 in regulating cell fate specification or differentiation. Knockdown of Flice Associated Huge protein (FLASH), which interacts with ARS2 and is required for cell cycle progression and 3'-end processing of replication-dependent histone transcripts, phenocopies ARS2 knockdown. These data implicate ARS2-FLASH-mediated histone mRNA processing in regulating RPC cell cycle kinetics and neuroglial cell fate specification during postnatal retinal development.
Based on barge model tests and full scale barge train trials, formulae for calculating the resistance of a single barge and towing train respectively are presented using multi-variable regression analysis. The influence of the barge numbers, first barge form and the shallow water effect on the resistance of the towing train is analyzed and the energy-saving potential is also discussed.
Gelsolin is an actin-binding protein that under the control of calcium ions and polyphosphoinositide can either sever and cap the actin filaments therefore breakdown the actin networks, or initiate the formation of actin filaments and the actin networks. Studies of gelsolin in mammals have shown that gelsolin is the substrate of various signal cascades and on the other hand it can modulate lipid signaling.
The function of gelsolin during Drosophila development is unclear due to the lack of gelsolin mutants. A previous attempt to generate a gelsolin mutant in an extensive EMS screen failed, which implies that either gelsolin is not easily chemically mutable or loss of gelsolin function is not lethal. A different approach, P-element mediated mutagenesis is employed in the work presented here to generate a gelsolin null mutant. A PCR based screen was developed to identify gelsolin mutants without prior knowledge of their phenotype.
However the screen was not successful despite the fact that the screen was large and sensitive. No gelsolin mutants were found, suggesting that the gelsolin locus can also not be easily mutated by P-element mediated mutagenesis.
(1) Background: Astragaloside IV (AS-IV) is derived from Astragalus membranous (AM), which is used to treat kidney disease. Macrophages significantly affect the whole process of renal ischemia-reperfusion (I/R). The regulation of macrophage polarization in kidneys by AS-IV was the focus. (2) Methods: Renal tubular injury and fibrosis in mice were detected by Hematoxylin and Eosin staining and Masson Trichrome Staining, separately. An ELISA and quantitative real-time polymerase chain reaction were used to explore the cytokine and mRNA expression. Western blot was used to determine protein expression and siRNA technology was used to reveal the crosstalk of signal pathways in RAW 264.7 under hypoxia. (3) Results: In the early stages of I/R injury, AS-IV reduced renal damage and macrophage infiltration. M1-associated markers were decreased, while M2 biomarkers were increased. The NF-κB (p65)/Hif-1α pathway was suppressed by AS-IV in M1. Moreover, p65 dominated the expression of Hif-1α. In the late stages of I/R injury, renal fibrosis was alleviated, and M2 infiltration also decreased after AS-IV treatment. Hif-1α expression was reduced by AS-IV, while Smad7 expression was enhanced. Hif-1α interferes with the expression of Smad7 in M2. (4) Conclusions: AS-IV promoted the differentiation of M1 to M2, relieving the proinflammatory response to alleviate the kidney injury during the early stages. AS-IV attenuated M2 macrophage infiltration to prevent kidney fibrosis during the later stages.
Abstract Purpose We investigated the role of farnesoid X receptor (FXR), a ligand‐dependent transcription factor, in renal ischaemia‐reperfusion (I/R) injury. Materials and Methods We performed unilateral renal I/R model in FXR knockout ( Fxr −/− ) and wild‐type (WT) mice in vivo and a hypoxia‐reoxygenation (H/R) model in vitro. The pathways by which FXR induces apoptosis were detected using a proteome profiler array. The effects of FXR on apoptosis were evaluated using immunoblotting, TUNEL assays and flow cytometry. Results Compared with WT mice, Fxr −/− mice showed improved renal function and reduced tubular injury scores and apoptosis. Consistent with the in vivo results, the silencing of FXR decreased the number of apoptotic HK‐2 cells after H/R, while FXR overexpression aggravated apoptosis. Notably, bone marrow transplantation (BMT) and immunohistochemistry experiments revealed the involvement of FXR in the tubular epithelium rather than in inflammatory cells. Furthermore, in vivo and in vitro studies demonstrated that FXR deficiency increased phosphorylated Bcl‐2 agonist of cell death (p‐Bad) expression levels and the ratio of Bcl‐2/Bcl‐xL to Bax expression in the kidney. Treatment with wortmannin, which reduced p‐Bad expression, inhibited the effects of FXR deficiency and eliminated the tolerance of Fxr −/− mouse kidneys to I/R injury. Conclusions These results established the pivotal importance of FXR inactivation in tubular epithelial cells after I/R injury. FXR may promote the apoptosis of renal tubular epithelial cells by inhibiting PI3k/Akt‐mediated Bad phosphorylation to cause renal I/R damage.
Wind power utilization is attracting worldwide attention in the renewable energy field, and as wind power develops from land to sea, the size of the blades is becoming incredibly larger. The fatigue test, especially the biaxial synchronous fatigue test for the blades, is becoming an indispensable step to ensure the blade’s quality before mass production, which means the biaxial independent test presently used may have difficulty reproducing the real damage for large-sized blades that oscillate simultaneously in flap-wise and edgewise directions in service conditions. The main point of the fatigue test is to carry out accelerated and reinforced oscillations on blades in the experimental plan. The target moments of critical blade sections are reached or not during the test are treated as one significant evaluation criterion. For independent tests, it is not hard to realize moment matching using additional masses fixed on certain critical blade sections, which may be not easy to put into effect for biaxial synchronous tests, since the mechanical properties and target moments in the flap-wise and edgewise directions are widely varied. To realize the mechanical decoupling for loading force or additional mass inertia force in two directions is becoming one of the key issues for blade biaxial synchronous fatigue testing. For this problem, the present paper proposed one mechanical decoupling design concept after a related literature review. After that, the blade moment design and target matching approach are also proposed, using the Transfer Matrix Method (TMM) for moment quick calculation and Particle Swarm Optimization (PSO) for case optimization.
Abstract Background: Posttransplantation diabetes mellitus (PTDM) constitutes one of the most important complications associated with kidney transplantation and is associated with significant morbidity and mortality. Methods: This study was a single-centred prospective observational study that included 310 consecutive renal transplant recipients. The primary end point was graft failure, including death-censored graft failure and mortality. The secondary endpoints include estimated glomerular filtration rate (eGFR) at 12 months and adverse events after transplantation. The prevalence rate of PTDM and relevant risk factors for PTDM were also explored. Results: The incidence of PTDM was 16.4% within one year. Death-censored graft loss rate differed significantly between recipients without PTDM and those with PTDM(0.77% versus 12%, p<0.001). Compared with non-PTDM group, the mean eGFR was significantly lower in the PTDM group(70.55±20.54 ml/min·1.73 m² versus 63.04±21.92 ml/min·1.73 m², P=0.03). Additionally, compared with the other group, the PTDM group was more easily infected by bacteria(16.2% versus 40%, P<0.001). Multi-factor analysis indicated that higher preoperative fasting plasma glucose (FPG), increased age and use of tacrolimus after transplantation were independent risk factors for PTDM. Conclusion: The incidence rate of PTDM is 16.4% 1 year after surgery. Our study suggests that patients with PTDM are at higher risk of death-censored graft loss and bacterial infection, and worse kidney function. Independent risk factors of PTDM include preoperative FPG level, increased age, and tacrolimus. The PTDM group is more vulnerable to worse graft function, postoperative graft loss and bacterial infection.
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