Hyperuricemia has been proven to be an independent risk factor for chronic kidney disease (CKD). However, the role of hyperuricemia in the progression of CKD remains unclear. Thus, we performed a ...systematic review and meta-analysis to evaluate the efficacy and safety of febuxostat, a first line urate-lowering agent, in CKD patients with hyperuricemia.
We have systematically searched for randomized controlled trials assessing the efficacy and safety of febuxostat versus control in CKD patients with hyperuricemia through MEDLINE, PubMed, EMBASE, and Cochrane databases. All statistical analyses were conducted by using the statistical package Review Manager, version 5.3.5. Heterogeneity was assessed using the Cochrane Q and I tests and summary statistics were reported with 95% confidence interval. Two-tailed test was used for analysis and a P value of <.05 is considered statistically significant.
Eleven eligible trials with 1317 participants were included in the meta-analysis. A significant reduction in serum uric acid was found in the febuxostat treated group. Also, a significant higher eGFR was found in the febuxostat treated group among CKD stage 3 and 4 patients. No significant difference of major complication or death was identified between treatment and control groups.
The meta-analysis showed that other than its urate-lowering effect, febuxostat presented a reno-protective effect in CKD patients. More studies with larger sample sizes and higher quality are required to clarify the role of febuxostat use in the progression of CKD.
It remains unclear how different uses of angiotensin-converting inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) influence the progression of chronic kidney disease (CKD). This study ...explored CKD progression in a multicentre, longitudinal cohort study that included 2639 patients with CKD stage 1-5 and hypertension. Patients treated with ACEI or ARB for ≥90 days during a 6-mo period comprised the study group, or no treatment, comprised the control group. The study group was subdivided on the basis of treatment: ACEI monotherapy or ARB monotherapy. Progression of renal deterioration was defined by an average eGFR decline of more than 5 mL/min/1.73 m
/yr or the commencement of dialysis. With at least 1-year follow up, a progression of renal deterioration was demonstrated in 29.70% of the control group and 25.09% of the study group. Patients in the study group had significantly reduced progression of CKD with adjusted odds ratio 0.79 (95% confidence interval: 0.63-0.99). However, when ACEI monotherapy and ARB monotherapy were analyzed separately, none of their associations with CKD progression was statistically significant. In conclusion, ACEI or ARB monotherapy may retard the deterioration of renal function among patients with CKD and hypertension.
We examined the characteristics and source apportionment of organic aerosols in ambient PM2.5 samples collected during the late autumn in Changchun, Northeast China. 8 compound classes (>90 ...individual species) were detected in the aerosol samples, including biomass burning tracers, aliphatic lipids (fatty acids and fatty alcohols), secondary oxidation products, polycyclic aromatic hydrocarbons (PAHs), sugar compounds, hopanes and biogenic secondary organic aerosol (SOA) tracers. The concentrations of total quantified organic species ranged from 138.2 to 6.8 × 103 ng m−3, among which levoglucosan was the most abundant compound. Biomass burning tracers (anhydrosugars, lignin and resin acids) were the most abundant compounds, followed by fatty acids, secondary oxidation products, PAHs, sugar compounds and fatty alcohols. Biogenic SOA tracers and hopanes were less abundant. The homohopane index defined as 31abS/(31abS + 31abR) was 0.5, indicating a potential contribution of traffic emission. PAHs showed a dominance of benzo(b)fluoranthene (BbF), and the diagnostic ratios implicated a substantial contribution of petroleum combustion as well as coal combustion. 2-methylglyceric acid to 2-methyltetrols ratio (2.2) indicated that NOx influence isoprene oxidation products formation. Furthermore, the average ratio of cis-pinonic acid plus pinic acid to 3-hydroxyglutaric acid (31.4) revealed the much fresher α/β-pinene oxidation products to some extent. A good correlation was found between β-caryophyllinic acid and levoglucosan (r = 0.61), suggesting that β-caryophyllene can mainly be generated by biomass burning. The biogenic secondary organic carbon (SOC) was underestimated by the tracer-based method, which only occupied 0.4% of the organic carbon (OC). In contrast, PMF model indicated that emissions from fossil fuel combustion and biomass burning were most important, accounting for 42.4% and 33.6%, respectively, followed by biogenic SOA emission (17.0%) and fungal spore derived source (7.0%), suggesting biogenic aerosol is a nonnegative contributor.
Fossil fuel combustion (42.4%) as well as biomass burning (33.6%) were most important contributors of organic aerosols in a typical city in Northeast China.
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•The chemical and source characteristics of organic aerosols in Northeast China was studied.•90 individual species were quantified with biomass burning tracers as most abundant compounds.•NOx influence SOA formation from isoprene.•Fossil combustion (42.4%) and biomass burning (33.6%) were most important contributors of OA.•Biogenic aerosol is a non-negligible contributor.
During neonatal testis development, centrally located gonocytes migrate to basement membrane of the seminiferous cords, where physical contact with a niche established by Sertoli cells is essential ...for transition of gonocytes into spermatogonial stem cells (SSCs). To provide structural support and signaling stimuli for the gonocyte‐to‐SSC transition that occurs at a specific location during a finite phase, temporal‐spatial establishment of the niche is critical. To date, the factors that guide Sertoli cells to establish the initial stem cell niche remain largely unknown. Using the Sertoli cell‐specific Arid4b knockout (Arid4bSCKO) mice, we demonstrated that ablation of AT‐rich interaction domain 4B (ARID4B) resulted in abnormal detachment of Sertoli cells from the basement membrane of seminiferous cords during the gonocyte‐to‐SSC transition phase, suggesting failure to establish a niche for the SSC formation. Without support by a niche environment, gonocytes showed disarranged cell distribution in the Arid4bSCKO testes and underwent apoptosis. The commitment of gonocytes to differentiate into the spermatogonial lineage was broken and the capability of SSCs to self‐renew and differentiate was also impaired. Gene expression profiling revealed the molecular mechanisms responsible for the phenotypic changes in the Arid4bSCKO testes, by identifying genes important for stem cell niche function as downstream effectors of ARID4B, including genes that encode gap junction protein alpha‐1, KIT ligand, anti‐Müllerian hormone, Glial cell‐line derived neurotrophic factor, inhibin alpha, inhibin beta, and cytochrome P450 family 26 subfamily b polypeptide 1. Our results identified ARID4B as a master regulator of a signaling network that governs the establishment of a niche during the critical gonocyte‐to‐SSC transition phase to control the fate of gonocytes and SSCs. Stem Cells 2017;35:1554–1565
During neonatal testis development, centrally located gonocytes migrate to basement membrane of the seminiferous cords, where physical contact with a niche established by Sertoli cells is essential for transition of gonocytes into spermatogonial stem cells (SSCs) to form the primary SSC reservoir. In this study, we show that Sertoli cell‐specific Arid4b knockout in mice resulted in a defect in gonocyte homing. Double immunofluorescent staining of AMH (green, cytoplasmic) and PLZF (red, nuclear) was performed to detect Sertoli cells and gonocytes, respectively, in the control and Arid4bSCKO testes at postnatal day 2.5 of age. Nuclear DNA was stained by DAPI (blue). In the control testes, gonocytes (red, nuclear) had migrated to the basement membrane of the seminiferous cords. In the Arid4bSCKO testes, some gonocytes remained in the center of the seminiferous cords (white arrows) and some gonocytes escaped from the cord structure (yellow arrows), while some Sertoli cells (green, cytoplasmic) broke away from the seminiferous cords (orange arrows). Further study identified ARID4B as a master regulator of a signaling network that governs the establishment of the initial SSC niche in testes. Scale bar = 20mm.
We have previously demonstrated calcimimetics optimize the balance between osteoclastic bone resorption and osteoblastic mineralization through upregulating Wingless and int-1 (Wnt) signaling ...pathways in the mouse and cell model. Nonetheless, definitive human data are unavailable concerning therapeutic effects of Cinacalcet on chronic kidney disease and mineral bone disease (CKD-MBD) and osteoclast-osteoblast interaction. We aim to investigate whether Cinacalcet therapy improves bone mineral density (BMD) through optimizing osteocytic homeostasis in a human model. Hemodialysis patients with persistently high intact parathyroid hormone (iPTH) levels > 300 pg/mL for more than 3 months were included and received fixed dose Cinacalcet (25 mg/day, orally) for 6 months. Bone markers presenting osteoclast-osteoblast communication were evaluated at baseline, the 3rd and the 6th month. Eighty percent of study patients were responding to Cinacalcet treatment, capable of improving BMD, T score and Z score (16.4%, 20.7% and 11.1%, respectively). A significant correlation between BMD improvement and iPTH changes was noted (
= -0.26,
< 0.01). Nonetheless, baseline lower iPTH level was associated with better responsiveness to Cinacalcet therapy. Sclerostin, an inhibitor of canonical Wnt/β-catenin signaling, was decreased from 127.3 ± 102.3 pg/mL to 57.9 ± 33.6 pg/mL. Furthermore, Wnt-10b/Wnt 16 expressions were increased from 12.4 ± 24.2/166.6 ± 73.3 pg/mL to 33.8 ± 2.1/217.3 ± 62.6 pg/mL. Notably, procollagen type I amino-terminal propeptide (PINP), a marker of bone formation and osteoblastic activity, was increased from baseline 0.9 ± 0.4 pg/mL to 91.4 ± 42.3 pg/mL. In contrast, tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), a marker of osteoclast activity, was decreased from baseline 16.5 ± 0.4 mIU/mL to 7.7 ± 2.2 mIU/mL. Moreover, C-reactive protein levels were suppressed from 2.5 ± 0.6 to 0.8 ± 0.5 mg/L, suggesting the systemic inflammatory burden may be benefited after optimizing the parathyroid-bone axis. In conclusion, beyond iPTH suppression, our human model suggests Cinacalcet intensifies BMD through inhibiting sclerostin expression and upregulating Wnt-10b/Wnt 16 signaling that activates osteoblastic bone formation and inhibits osteoclastic bone resorption and inflammation. From the perspective of translation to humans, this research trial brings a meaningful insight into the osteoblast-osteoclast homeostasis in Cinacalcet therapy for CKD-MBD.
Objective
To explore the function of circular RNA IQ motif‐containing GTPase‐activating protein 1 (circ‐IQGAP1) in interleukin (IL)‐1β‐induced osteoarthritis (OA) model and to explore whether ...circ‐IQGAP1 can modulate microRNA‐671‐5p (miR‐671‐5p) and transcription factor 4 (TCF4) to regulate chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation.
Methods
The cartilage tissues were collected from 32 OA patients or normal subjects. Human chondrocyte CHON‐001 cells were challenged via different doses of IL‐1β for 24 hours. CHON‐001 cells were transfected with circ‐IQGAP1 overexpression vector, TCF4 overexpression vector, small interfering RNA (siRNA) for circ‐IQGAP1, miR‐671‐5p mimic, miR‐671‐5p inhibitor or corresponding negative controls. Circ‐IQGAP1, miR‐671‐5p and TCF4 abundances in cartilage tissues or CHON‐001 cells were examined via quantitative reverse transcription polymerase chain reaction (qRT‐PCR) or western blot. Cell viability was investigated by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide (MTT). Cell apoptosis was measured by flow cytometry. The inflammatory injury was analyzed by the secretion levels of inflammatory cytokines (IL‐6, IL‐8 and tumor necrosis factor‐α TNF‐α) by enzyme‐linked immunosorbent assay (ELISA). The extracellular matrix degradation was evaluated by expression of aggrecan and matrix metalloproteinase 13 (MMP13) via western blot. The target relationship of miR‐671‐5p and circ‐IQGAP1 or TCF4 was analyzed via dual‐luciferase reporter and RNA immunoprecipitation (RIP) analyses.
Results
Circ‐IQGAP1 abundance was enhanced in the cartilage tissues from OA patients compared with normal subjects (n = 32), and its expression was increased in CHON‐001 cells after treatment of IL‐1β in a dose‐dependent pattern. MiR‐671‐5p expression was decreased in the cartilage tissues from OA patients (n = 32) and IL‐1β‐challenged CHON‐001 cells. MiR‐671‐5p expression was negatively associated with circ‐IQGAP1 level in OA patients. Circ‐IQGAP1 silence mitigated IL‐1β‐caused chondrocyte viability reduction, apoptosis promotion, secretion of inflammatory cytokine (IL‐6, IL‐8 and TNF‐α), and extracellular matrix degradation (reduction of aggrecan and increase of MMP13). MiR‐671‐5p was targeted and inhibited via circ‐IQGAP1. MiR‐671‐5p knockdown attenuated the influence of circ‐IQGAP1 interference on IL‐1β‐caused chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation. TCF4 was targeted via miR‐671‐5p, and TCF4 expression was increased in the cartilage tissues from OA patients (n = 32) and IL‐1β‐challenged CHON‐001 cells. TCF4 abundance in OA patients was negatively correlated with miR‐671‐5p expression. MiR‐671‐5p overexpression alleviated IL‐1β‐mediated chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation via decreasing TCF4 expression. Circ‐IQGAP1 silence reduced TCF4 expression via regulating miR‐671‐5p in IL‐1β‐challenged CHON‐001 cells.
Conclusion
Circ‐IQGAP1 knockdown attenuated IL‐1β‐caused chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation. Circ‐IQGAP1 could regulate miR‐671‐5p/TCF4 axis to modulate IL‐1β‐caused chondrocyte damage. Circ‐IQGAP1 might act as a new target for the treatment of OA.
Circ‐IQGAP1 promotes IL‐1β‐induced chondrocyte apoptosis, inflammation, and extracellular matrix degradation by miR‐671‐5p/TCF4 axis in osteoarthritis.
Vascular smooth muscle cells (VSMCs) are commonly used as seed cells in tissue-engineered vascular constructions. However, their variable phenotypes and difficult to control functions pose ...challenges. This study aimed to overcome these obstacles using a three-dimensional culture system.
Calf VSMCs were administered tumor necrosis factor-alpha (TNF-α) before culturing in two- and three-dimensional well plates and polyglycolic acid (PGA) scaffolds, respectively. The phenotypic markers of VSMCs were detected by immunofluorescence staining and western blotting, and the proliferation and migration abilities of VSMCs were detected by CCK-8, EDU, cell counting, scratch, and Transwell assays.
TNF-α rapidly decreased the contractile phenotypic markers and elevated the synthetic phenotypic markers of VSMCs, as well as markedly increasing the proliferation and migration ability of VSMCs under two- and three-dimensional culture conditions.
TNF-α can rapidly induce a phenotypic shift in VSMCs and change their viability on PGA scaffolds.
An influenza vaccination might reduce the risk of incident peripheral arterial occlusive disease (PAOD) in patients with chronic kidney disease (CKD), but supporting evidence is limited. This ...case-crossover study analyzed data from Taiwan's real-world National Health Insurance Research Database. This study included elderly (≥ 67 years old) patients with CKD having incident PAOD from January 1, 2006, to June 30, 2015. We defined 1 year before PAOD onset as the index date for the self-control group. A conditional logistic regression model was used to investigate exposure to an influenza vaccination for estimating the risk for incident PAOD following vaccination. In total, this study included 46,782 elderly patients with CKD having incident PAOD. The odds ratios for incident PAOD were 0.85 (95% confidence interval 0.77-0.94), 0.85 (0.79-0.92), 0.84 (0.79-0.90), and 0.85 (0.81-0.90) at 1, 2, 3, and 4 months after an influenza vaccination, respectively. We observed consistent results for the subgroups of patients with CKD and concomitant diabetes. However, we did not observe any beneficial effects of influenza vaccination in patients with advanced CKD or end-stage renal disease. This study demonstrated that influenza vaccination may be associated with a reduced risk of incident PAOD among patients with early-stage CKD.
Mechanical tension is widely applied on the suture to modulate the growth of craniofacial bones. Deeply understanding the features of bone formation in expanding sutures could help us to improve the ...outcomes of clinical treatment and avoid some side effects. Although there are reports that have uncovered some biological characteristics, the regular pattern of sutural bone formation in response to expansion forces is still unknown. Our study was to investigate the shape, arrangement and orientation of new bone formation in expanding sutures and explore related clinical implications. The premaxillary sutures of rat, which histologically resembles the sutures of human beings, became wider progressively under stretch force. Micro-CT detected new bones at day 3. Morphologically, these bones were forming in a finger-like pattern, projecting from the maxillae into the expanded sutures. There were about 4 finger-like bones appearing on the selected micro-CT sections at day 3 and this number increased to about 18 at day 7. The average length of these projections increased from 0.14 mm at day 3 to 0.81 mm at day 7. The volume of these bony protuberances increased to the highest level of 0.12 mm3 at day 7. HE staining demonstrated that these finger-like bones had thick bases connecting with the maxillae and thin fronts stretching into the expanded suture. Nasal sections had a higher frequency of finger-like bones occuring than the oral sections at day 3 and day 5. Masson-stained sections showed stretched fibers embedding into maxillary margins. Osteocalcin-positive osteoblasts changed their shapes from cuboidal to spindle and covered the surfaces of finger-like bones continuously. Alizarin red S and calcein deposited in the inner and outer layers of finger-like bones respectively, which showed that longer and larger bones formed on the nasal side of expanded sutures compared with the oral side. Interestingly, these finger-like bones were almost paralleling with the direction of stretch force. Inclined force led to inclined finger-like bones formation and deflection of bilateral maxillae. Additionally, heavily compressive force caused fracture of finger-like bones in the sutures. These data together proposed the special finger-like pattern of bone formation in sutures guided by stretch force, providing important implications for maxillary expansion.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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