n light of the rapid increase in the number of obesity incidences worldwide, obesity has become an independent risk factor for chronic kidney disease. Obesity-related giomerulopathy （ORG） is ...characterized by glomerulomegaly in the presence or absence of focal and segmental glomerulosclerosis lesions. IgM and complement 3 （C3） nonspeciflcally deposit in lesions without immune-complex-type deposits during ORG immunofluorescence. ORG-associated glomerulomegaly and focal and segmental glomerulosclerosis can superimpose on other renal pathologies. The mechanisms under ORG are complex, especially hemodynamic changes, inflammation, oxidative stress, apoptosis, and reduced functioning nephrons. These mechanisms synergize with obesity to induce end-stage renal disease. A slow increase of subnephrotic proteinuria （ 〈 3.5 g/d） is the most common clinical manifestation of ORG. Several treatment methods for ORG have been developed. Of these methods, renin-angiotensin-aldosterone system blockade and weight loss are proven effective. Targeting mitochondria may offer a novel strategy for ORG therapy. Nevertheless, more research is needed to further understand ORG.
Research about the effects of magnesium (Mg) supplementation on chronic kidney disease-mineral bone disorder (CKD-MBD) among hemodialysis (HD) patients is controversial. Thus, we conducted a ...meta-analysis to examine Mg supplementation's effects on CKD-MBD in patients requiring dialysis.
The PubMed and EMBASE databases were searched for English language studies up to September 2020. The main indicators of our study were changes in serum Mg, calcium (Ca), phosphate, parathyroid hormone (PTH), and C-reactive protein levels, and carotid intima-media thickness (CIMT) after Mg supplementation. Mg efficacy was evaluated by weighted mean difference (WMD) and confidence intervals (CIs), and subgroup analyses of intervention type and intervention duration were also performed.
Eight eligible studies comprising 309 HD patients were included in our meta-analysis. Mg supplementation alone produced a negative effect on serum PTH levels (WMD = -236.56; 95% CI -349.71 to -123.41) and CIMT (WMD = -0.18; 95% CI -0.34 to -0.01). A subgroup analysis based on intervention type showed a significant improvement in serum Mg (WMD = 1.08; 95% CI 0.51-1.64) and Ca (WMD = -0.50; 95% CI -0.77 to -0.23) levels when Mg was administered via dialysate and oral medication, respectively. Different intervention durations had no effect on serum Mg levels. Mg supplementation had no significant effect on serum phosphate (WMD = -0.25; 95% CI -0.64 to 0.14) and C-reactive protein levels (WMD = -0.02; 95% CI -2.80 to 2,76).
Our results showed that Mg supplementation alone could improve CKD-MBD by regulating serum Ca and PTH metabolism and decreasing CIMT among HD patients.
In this methodological brief, we demonstrate the usefulness of the restricted variance (RV) interaction to entrepreneurship research. RV reasoning can help scholars to specify precise roles for ...contextual moderators. This specificity allows for strengthening of arguments and for testing of one of the reasons for an interaction. In some cases, it points to otherwise unexpected interaction patterns. We illustrate the power of RV reasoning with a data set of 503 biotech firms to show how RV explains geographic differences in the relationship between number of alliances and initial public offering value. Finally, we show how these interactions can be tested given typical distributions.
Unraveling the complex regulatory pathways that mediate the effects of phosphate on vascular smooth muscle cells (VSMCs) may provide novel targets and therapies to limit the destructive effects of ...vascular calcification (VC) in patients with chronic kidney disease (CKD). Our previous studies have highlighted several signaling networks associated with VSMC autophagy, but the underlying mechanisms remain poorly understood. Thereafter, the current study was performed to characterize the functional relevance of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in high phosphate-induced VC in CKD settings. We generated VC models in 5/6 nephrectomized rats
in vivo
and VSMC calcification models
in vitro
. Artificial modulation of OGT (knockdown and overexpression) was performed to explore the role of OGT in VSMC autophagy and VC in thoracic aorta, and
in vivo
experiments were used to substantiate
in vitro
findings. Mechanistically, co-immunoprecipitation (Co-IP) assay was performed to examine interaction between OGT and kelch like ECH associated protein 1 (KEAP1), and
in vivo
ubiquitination assay was performed to examine ubiquitination extent of nuclear factor erythroid 2-related factor 2 (NRF2). OGT was highly expressed in high phosphate-induced 5/6 nephrectomized rats and VSMCs. OGT silencing was shown to suppress high phosphate-induced calcification of VSMCs. OGT enhances KEAP1 glycosylation and thereby results in degradation and ubiquitination of NRF2, concurrently inhibiting VSMC autophagy to promote VSMC calcification in 5/6 nephrectomized rats. OGT inhibits VSMC autophagy through the KEAP1/NRF2 axis and thus accelerates high phosphate-induced VC in CKD.
The current paper was motivated by previous results (Meyer et al. Journal of Management, 40, 1010–1041, 2014) that appeared to contradict the popular idea that “strong” situations weaken the impact ...of personality on job performance. We extend situational strength theory by contending that, when a strong situation blocks one outlet for poor performance (e.g., low task performance), employees predisposed toward such behavior experience negative affect. They then displace their negative behavior to a second outlet (e.g., counterproductive work behavior), thereby strengthening their predispositions, unless that second outlet, too, is blocked by a strong situation. We then test this assertion using a two-wave survey (N = 369), analyzed using dual-stage moderated mediation. Results indicate strong support for this assertion vis-à-vis the personality traits of conscientiousness and agreeableness, thereby replicating and extending Meyer et al.’s (Journal of Management, 40, 1010–1041, 2014) seemingly anomalous results. However, results indicate weaker support vis-à-vis a third personality trait, emotional stability, which has a weaker bivariate relationship with counterproductive work behavior. The extended situational strength theory suggests important avenues for future research as well as practical guidelines for avoiding unintended consequences when applying strong situations in organizations.
Macrophages are the most abundant infiltrating immune-related stromal cells present in and around tumors, showing different phenotypes and functions. M2 macrophages mainly exert immunosuppressive ...functions and promote tumor growth. Exosomes are emerging as important mediators of cross-talk between tumor cells and the microenvironment. CircRNAs are novel members of non-coding RNAs that regulate cancer proliferation and progression. However, the mechanism by which exosomal circRNA regulates macrophage polarization in renal cell carcinoma (RCC) is still largely unknown.
RCC-derived exosomes were characterized using transmission electron microscopy and nanoparticle tracking analysis (NTA). CCK-8, wound healing, and Transwell assays were performed to assess whether exosomes would affect the proliferation, migration, and invasion of RCC. Furthermore, we performed a bioinformatics analysis to identify circRNAs in RCC serum-derived exosomes from the GEO database. The fluorescence
hybridization (FISH) assay was used to detect the cellular distribution of circSAFB2. Bioinformatics analyses (StarBase 2.0) were used to pool the miRNA targets of circSAFB2. Luciferase assays were performed to verify the direct interactions. Western blotting was used to detect markers of macrophage M2 polarization. Lastly, mouse xenograft and bioluminescence imaging were used to examine the clinical relevance of exosomal circSAFB2
.
We report the circRNA derived from SAFB2 and evaluate its biological function in promoting the immune escape of RCC. We found that circSAFB2 was highly expressed in RCC tissues and RCC-derived exosomes. Furthermore, we demonstrated that exosomal circSAFB2 mediates the polarization of M2 macrophages through the miR-620/JAK1/STAT3 axis to promote RCC metastasis.
Our data first demonstrated that circSAFB2 leads to immune escape from RCC by mediating M2 macrophage polarization
the miR-620/JAK1/STAT3 axis. These findings indicate a novel molecular mechanism of exosomal circSAFB2 in the progression of RCC and implicate circSAFB2 as a target for exosome-mediated tumor immune evasion.
It is controversial for the effect and safety between cinacalcet and other treatments in treating secondary hyperparathyroidism for patients with chronic kidney disease (CKD) or end-stage renal ...disease (ESRD).
Embase, PubMed, and Cochrane Library were searched through Feb 2017. 21 randomized controlled trials were included. We calculated the pooled mean difference (MD), relative risk (RR) and corresponding 95% confidence interval (CI).
Patients received calcimimetic agents had significantly decreased serum parathyroid hormone (MD = - 259.24 pg/mL, 95% CI: - 336.23 to - 182.25), calcium (MD = - 0.92 mg/dL, 95% CI: - 0.98 to - 0.85) and calcium phosphorus product (MD = - 5.97 mg
/dL
, 95% CI: - 9.77 to - 2.16) concentration compared with control treatment. However, the differences in cardiovascular mortality and all-cause mortality between calcimimetics agents and control group were not statistically significant. The incidence of nausea (RR = 2.13, 95% CI: 1.62 to 2.79), vomiting (RR = 1.99, 95% CI: 1.78 to 2.23) and hypocalcemia (RR = 10.10, 95% CI: 7.60 to 13.43) in CKD patients with calcimimetics agents was significantly higher than that with control treatment.
Cinacalcet improved the biochemical parameters in CKD patients, but did not improve all-cause mortality and cardiovascular mortality. Moreover, cinacalcet can cause some adverse events.
ABSTRACT
Background and Objectives:
Vascular stenosis and angiogenesis are the major causes of short expectancy of arteriovenous fistula (AVF). Increased expression of vascular endothelial growth ...factor-A (VEGF-A) has been suggested to play an important role in the pathophysiologic process. Anti-VEGF has been proved to be effective on anti-angiogenesis and applied in clinical practice, but its effect on anti-stenosis remains to be verified before it could be applied to prevent stenosis of AVF. This study was aimed to evaluate the effect of local anti-VEGF therapy to prevent the formation of stenosis in the outflow vein in AVF and its mechanism.
Methods:
Bioinformatics of VEGF-A and its downstream-regulated molecules from the STRING PPI database were analyzed in this study. The biopsy samples from outflow veins of AVF in patients and C57BL/6 mouse models were analyzed to examine the mechanisms of pathologic vascular stenosis associated with VEGF pathways and their potential therapeutic targets.
Results:
We found that the reduction of VEGF-A could downregulate downstream molecules and subsequently reduce the intimal hyperplasia and abnormal vascular remodeling by analyzing the STRING PPI database. Venous wall thickening, intimal neointima formation, and apoptosis of vascular endothelial cells in the proliferative outflow vein of the AVF were significantly more obvious, and upregulation of expression of VEGF was observed in dysfunctional AVF in patients. In mouse models, the expression of VEGF, Ephrin receptor B4 (EphB4), matrix metalloproteinase (MMP)2, MMP9, tissue inhibitor of metalloproteinase (TIMP)1, TIMP2, and caspase 3 in the control-shRNA surgical group was significantly higher than in the sham group (
P
< 0.05), and all of these indicators were significantly lower in lentiviral transfection group and Avastin group than in control-shRNA surgical group (
P
< 0.05) on the 14th day after AVF operation.
Conclusion:
VEGF expression is significantly increased in vascular endothelial cells in stenosed or occluded outflow veins of dysfunctional AVF. Local injection of Avastin into the adventitia of the proximal outflow vein in autologous AVF procedure has an excellent potential to prevent the subsequent local stenosis of the proximal outflow vein.
Situational strength is considered one of the most important situational forces at work because it can attenuate the personality-performance relationship. Although organizational scholars have ...studied the consequences of situational strength, they have paid little attention to its antecedents. To address this gap, the current study focused on situational strength cues from different social sources as antecedents of overall situational strength at work. Specifically, we examined how employees combine situational strength cues emanating from three social sources (i.e., coworkers, the immediate supervisor, and top management). Based on field theory, we hypothesized that the effect of situational strength from coworkers and immediate supervisors (i.e., proximal sources of situational strength) on employees' perceptions of overall situational strength on the job would be greater than the effect of situational strength from the top management (i.e., the distal source of situational strength). We also hypothesized that the effect of situational strength from the distal source would be mediated by the effects of situational strength from the proximal sources. Data from 363 full-time employees were collected at two time points with a cross-lagged panel design. The former hypothesis was supported for one of the two situational strength facets studied. The latter hypothesis was fully supported.
Summary
Previous research on the motivational factors of safety performance has predominantly focused on one's willingness to directly enact safety behaviors or safety‐specific motivation. The ...current study extends beyond this view and examines an additional motivational force, altruistic motivation, as a main predictor of employees' safety performance at both individual and team levels. Further, we provide that servant leadership serves as a critical precursor of employee altruistic motivation. A sample of 416 nurses in 42 workgroups and their respective supervisors from a hospital in China completed a two‐wave survey. Hierarchical linear modeling was used to analyze the data. The results indicated that altruistic motivation was positively related to safety performance at both individual and team levels, with a stronger effect at the team level, supporting a proportional theory of homology. Multilevel mediation results showed that servant leadership was positively related to altruistic motivation, which in turn positively led to safety performance at both individual and team levels. These findings highlight both the theoretical and practical importance of encouraging altruistic motivation to improve workplace safety.
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