UV-Curing Assisted Direct Ink Writing of Dense, Crack-Free, and High-Performance Zirconia-Based Composites With Aligned Alumina Platelets.

Additive manufacturing (AM) of high-performance structural ceramic components with comparative strength and toughness as conventionally manufactured ceramics remains challenging. Here, a UV-curing approach is integrated in direct ink writing (DIW), taking advantage from DIW to enable an easy use of high solid-loading pastes and multi-layered materials with compositional changes; while, avoiding drying problems. UV-curable opaque zirconia-based slurries with a solid loading of 51 vol% are developed to fabricate dense and crack-free alumina-toughened zirconia (ATZ) containing 3 wt% alumina platelets. Importantly, a non-reactive diluent is added to relieve polymerization-induced internal stresses, avoid subsequent warping and cracking, and facilitate the de-binding. For the first time, UV-curing assisted DIW-printed ceramic after sintering reveals even better mechanical properties than that processed by a conventional pressing. This is attributed to the aligned alumina platelets, enhancing crack deflection and improving the fracture toughness from 6.8 ± 0.3 MPa m0.5 (compacted) to 7.4 ± 0.3 MPa m0.5 (DIW). The four-point bending strength of the DIW ATZ (1009 ± 93 MPa) is also higher than that of the conventionally manufactured equivalent (861 ± 68 MPa). Besides homogeneous ceramic, laminate structures are demonstrated. This work provides a valuable hybrid approach to additively manufacture tough and strong ceramic components.

Novel Selective Quantification of Zinpentraxin Alfa Biotherapeutic in the Presence of Endogenous Isomer in Plasma Samples of Idiopathic Pulmonary Fibrosis Patients Using Immunoaffinity LC-MS.

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal interstitial lung disease that affects three million patients worldwide and currently without an effective cure. Zinpentraxin alfa, a recombinant human pentraxin-2 (rhPTX-2) protein, has been evaluated as a potential drug candidate for the treatment of IPF. Clinical pharmacokinetic analysis of zinpentraxin alfa has been challenging historically due to interference from serum amyloid P component (SAP), an endogenous human pentraxin-2 protein. These molecules share an identical primary amino acid sequence and glycan composition; however, zinpentraxin alfa possesses α2,3-linked terminal sialic acid residues while SAP is an α2,6-linked isomer. By taking advantage of this only structural difference, we developed a novel assay strategy where α2,3-sialidase was used to selectively hydrolyze α2,3-linked sialic acid residues, resulting in desialylated zinpentraxin alfa versus unchanged sialylated SAP, following an immunoaffinity capture step. Subsequent tryptic digestion produced a unique surrogate asialo-glycopeptide from zinpentraxin alfa and allowed specific quantification of the biotherapeutic in human plasma. In addition, a common peptide shared by both molecules was selected as a surrogate to determine total hPTX-2 concentrations, i.e., sum of zinpentraxin alfa and SAP. The quantification methods for both zinpentraxin alfa and total hPTX-2 were validated and used in pharmacokinetic assessment in IPF patients. The preliminary results suggest that endogenous SAP levels remained largely constant in IPF patients throughout the treatment with zinpentraxin alfa. Our novel approach provides a general bioanalytical strategy to selectively quantify α2,3-sialylated glycoproteins in the presence of their corresponding α2,6-linked isomers.

Correction: Vu et al. Specific Changes in Arabidopsis thaliana Rosette Lipids during Freezing Can Be Associated with Freezing Tolerance. Metabolites 2022, 12, 385.

There was an error in the original publication [...].

Fracture analysis of one/two-piece clinically failed zirconia dental implants.

OBJECTIVES: Analyzing factors that may have led to fracture of zirconia implants by macro/micro-fractography. METHODS: Six one-piece and ten two-piece full-ceramic zirconia implants from two manufacturers, Z-Systems and CeraRoot, were retrieved after clinical failure. The time-to-failure ranged from 3 to 49 months. Optical and scanning electron microscopy (SEM) were used to analyze the fracture planes at the macro- and microscopic level. Treatment planning, surgical protocol, fracture-origin location and characteristic fracture features were assessed. RESULTS: The fracture of all implants seemed to have been primarily due to overload in bending mode, while the fracture-initiation sites varied for the one- and two-piece implants. The fracture of all one-piece implants originated in the constriction region between two threads in the endosseous implant part. For two-piece implants, the abutment neck, internal abutment-implant connections and inner threads were found to be the main fracture-initiation sites. Surface defects at the root area for one-piece implants and damages at the abutment surface for two-piece implants were connected to the fracture origins. Importantly, the clinical failures of implants were often found to result from combined effects related to patient aspects, treatment planning/protocols, a high bending moment at the weakest link, implant-surface conditions and specific implant designs. SIGNIFICANCE: This study provided information to be considered for future optimization of treatment planning and the surgical protocol for zirconia implants. Optimization of the surface conditions and the zirconia-starting powder were also suggested.

Specific Changes in Arabidopsis thaliana Rosette Lipids during Freezing Can Be Associated with Freezing Tolerance.

While the roles of a few specific lipids in plant freezing tolerance are understood, the effect of many plant lipids remains to be determined. Acclimation of plants to non-freezing cold before exposure to freezing temperatures improves the outcome of plants, compared to plants exposed to freezing without acclimation. Arabidopsis thaliana plants were subjected to one of three treatments: (1) "control", i.e., growth at 21 °C, (2) "non-acclimated", i.e., 3 days at 21 °C, 2 h at -8 °C, and 24 h recovery at 21 °C, and (3) "acclimated", i.e., 3 days at 4 °C, 2 h at -8 °C, and 24 h recovery at 21 °C. Plants were harvested at seven time points during the treatments, and lipid levels were measured by direct-infusion electrospray ionization tandem mass spectrometry. Ion leakage was measured at the same time points. To examine the function of lipid species in relation to freezing tolerance, the lipid levels in plants immediately following the freezing treatment were correlated with the outcome, i.e., ion leakage 24-h post-freezing. Based on the correlations, hypotheses about the functions of specific lipids were generated. Additionally, analysis of the lipid levels in plants with mutations in genes encoding patatin-like phospholipases, lipoxygenases, and 12-oxophytodienoic acid reductase 3 (opr3), under the same treatments as the wild-type plants, identified only the opr3-2 mutant as having major lipid compositional differences compared to wild-type plants.

Nonspecific phospholipase C4 hydrolyzes phosphosphingolipids and sustains plant root growth during phosphate deficiency.

Phosphate is a vital macronutrient for plant growth, and its availability in soil is critical for agricultural sustainability and productivity. A substantial amount of cellular phosphate is used to synthesize phospholipids for cell membranes. Here, we identify a key enzyme, nonspecific phospholipase C4 (NPC4) that is involved in phosphosphingolipid hydrolysis and remodeling in Arabidopsis during phosphate starvation. The level of glycosylinositolphosphorylceramide (GIPC), the most abundant sphingolipid in Arabidopsis thaliana, decreased upon phosphate starvation. NPC4 was highly induced by phosphate deficiency, and NPC4 knockouts in Arabidopsis decreased the loss of GIPC and impeded root growth during phosphate starvation. Enzymatic analysis showed that NPC4 hydrolyzed GIPC and displayed a higher activity toward GIPC as a substrate than toward the common glycerophospholipid phosphatidylcholine. NPC4 was associated with the plasma membrane lipid rafts in which GIPC is highly enriched. These results indicate that NPC4 uses GIPC as a substrate in planta and the NPC4-mediated sphingolipid remodeling plays a positive role in root growth in Arabidopsis response to phosphate deficiency.

Reliability and aging behavior of three different zirconia grades used for monolithic four-unit fixed dental prostheses.

OBJECTIVE: To investigate the fracture resistance and phase composition of tooth supported four-unit fixed dental prostheses (FDPs) made from three different zirconia grades after loading and aging. METHODS: Seventy-two FDPs were fabricated from 3Y-TZP, 4Y-PSZ and 5Y-PSZ. This resulted in 24 FDPs per grade, subdivided into three groups (n = 8): a control group (C), a hydrothermally aged (H2O, 85 °C, 90 days) group (A) and a group subjected to loading (2.5M cycles, 98N) with simultaneous thermal cycling (H2O, 5-55 °C) subsequent to treatment A (AL). Subsequently, FDPs were statically loaded to fracture. Phase composition was quantified by X-ray diffraction (XRD) and µ-Raman spectroscopy. Focused ion beam (FIB) - Scanning electron microscopy (SEM) was used for visualization in-depth. RESULTS: Compared to 3Y-C FDPs (1233 ± 165N), reduced fracture load was found for 5Y-C FDPs (889 ± 80 N; p < .001). This did not apply for 4Y-C samples (1065 ± 111N). Treatments (A, AL) did not negatively affect the fracture load for the three grades of zirconia (p > .645). Both A and AL increased monoclinic phase content for 3Y and 4Y FDPs, whereas FIB-SEM suggests no transformability of 5Y-PSZ. 5Y-AL FDPs showed cracks and fractures at the abutment walls and restoration margins after dynamic loading. Reduced fracture load of 5Y samples as compared to 3Y and 4Y was associated with deficient transformability in the fracture zone. SIGNIFICANCE: Aging and loading did not negatively affect the fracture resistance of monolithic four-unit FDPs made from three grades of zirconia. Due to cracks after dynamic loading, 5Y-PSZ cannot be recommended for the clinical application of four-unit FDPs.

Leaf Lipid Alterations in Response to Heat Stress of Arabidopsis thaliana.

In response to elevated temperatures, plants alter the activities of enzymes that affect lipid composition. While it has long been known that plant leaf membrane lipids become less unsaturated in response to heat, other changes, including polygalactosylation of galactolipids, head group acylation of galactolipids, increases in phosphatidic acid and triacylglycerols, and formation of sterol glucosides and acyl sterol glucosides, have been observed more recently. In this work, by measuring lipid levels with mass spectrometry, we confirm the previously observed changes in Arabidopsis thaliana leaf lipids under three heat stress regimens. Additionally, in response to heat, increased oxidation of the fatty acyl chains of leaf galactolipids, sulfoquinovosyldiacylglycerols, and phosphatidylglycerols, and incorporation of oxidized acyl chains into acylated monogalactosyldiacylglycerols are shown. We also observed increased levels of digalactosylmonoacylglycerols and monogalactosylmonoacylglycerols. The hypothesis that a defect in sterol glycosylation would adversely affect regrowth of plants after a severe heat stress regimen was tested, but differences between wild-type and sterol glycosylation-defective plants were not detected.

Mechanical properties, aging stability and translucency of speed-sintered zirconia for chairside restorations.

OBJECTIVE: To evaluate the performance of zirconia ceramics sintered in a speed sintering induction furnace by comprehensive understanding of their optical and mechanical properties, microstructure, phase composition and aging stability, in comparison to ceramics sintered in a conventional furnace. METHODS: Speed sintered (SS) Katana STMLSS (Kuraray Noritake) (total thermal cycle/sintering time/dwell temperature: 30min/16min/1560°C) and CEREC Zirconia (CEREC ZrSS) (Dentsply Sirona) (15min/2min/1578°C) were compared to conventionally sintered (CS) Katana STMLCS (6.8h/2h/1550°C) and inCoris TZICS (4h/2h/1510°C). The translucency parameter (TP) and contrast ratio (CR) were measured with a spectrophotometer. The chemical composition of the materials was determined by XRF and phase composition was characterized using XRD. Hydrothermal aging behavior was evaluated by measuring the tetragonal-to-monoclinic ZrO2 phase transformation after accelerated hydrothermal aging in steam at 134°C. The indentation fracture toughness, Vickers hardness and biaxial strength of the sintered ceramics were assessed. RESULTS: Speed and conventionally sintered zirconia revealed similar density, microstructure, average strength and hydrothermal aging stability. Both Katana STMLSS/CS 5Y-PSZ ceramics were characterized with a higher content of cubic phase (≈53wt%), which resulted in a higher amount of Y2O3 in the remaining tetragonal ZrO2 phases compared to the 3Y-TZP CEREC ZrSS and inCoris TZICS (8 and 20wt%, respectively). The sintering program did not affect the hydrothermal aging behavior of Katana STMLSS and CEREC ZrSS. TP of Katana STMLSS (TP≈32) was not affected by speed sintering, while the translucency of CEREC ZrSS (TP=14) was significantly reduced. Hardness, fracture toughness and Weibull characteristic strength of Katana STMLSS and CEREC ZrSS also reached the optimal level, but speed sintering substantially lowered their mechanical reliability. SIGNIFICANCE: Speed sintering of 3Y-TZP and 5Y-PSZ in a speed sintering induction oven appeared suitable for clinical applications. However, further studies should focus on improving of translucency and mechanical reliability of the speed-sintered zirconia ceramics.

Patatin-Related Phospholipase pPLAIIIγ Involved in Osmotic and Salt Tolerance in Arabidopsis.

Patatinrelated phospholipases (pPLAs) are acylhydrolyzing enzymes implicated in various processes, including lipid metabolism, signal transduction, plant growth and stress responses, but the function for many specific pPLAs in plants remains unknown. Here we determine the effect of patatinrelated phospholipase A pPLAIIIγ on Arabidopsis response to abiotic stress. Knockout of pPLAIIIγ rendered plants more sensitive whereas overexpression of pPLAIIIγ enhanced plant tolerance to NaCl and drought in seed germination and seedling growth. The pPLAIIIγknockout and overexpressing seedlings displayed a lower and higher level of lysolipids and free fatty acids than that of wildtype plants in response to NaCl stress, respectively. These results indicate that pPLAIIIγ acts a positive regulator of salt and osmatic stress tolerance in Arabidopsis.

RankProd Combined with Genetic Algorithm Optimized Artificial Neural Network Establishes a Diagnostic and Prognostic Prediction Model that Revealed C1QTNF3 as a Biomarker for Prostate Cancer.

Prostate cancer (PCa) is the most commonly diagnosed cancer in males in the Western world. Although prostate-specific antigen (PSA) has been widely used as a biomarker for PCa diagnosis, its results can be controversial. Therefore, new biomarkers are needed to enhance the clinical management of PCa. From publicly available microarray data, differentially expressed genes (DEGs) were identified by meta-analysis with RankProd. Genetic algorithm optimized artificial neural network (GA-ANN) was introduced to establish a diagnostic prediction model and to filter candidate genes. The diagnostic and prognostic capability of the prediction model and candidate genes were investigated in both GEO and TCGA datasets. Candidate genes were further validated by qPCR, Western Blot and Tissue microarray. By RankProd meta-analyses, 2306 significantly up- and 1311 down-regulated probes were found in 133 cases and 30 controls microarray data. The overall accuracy rate of the PCa diagnostic prediction model, consisting of a 15-gene signature, reached up to 100% in both the training and test dataset. The prediction model also showed good results for the diagnosis (AUC = 0.953) and prognosis (AUC of 5 years overall survival time = 0.808) of PCa in the TCGA database. The expression levels of three genes, FABP5, C1QTNF3 and LPHN3, were validated by qPCR. C1QTNF3 high expression was further validated in PCa tissue by Western Blot and Tissue microarray. In the GEO datasets, C1QTNF3 was a good predictor for the diagnosis of PCa (GSE6956: AUC = 0.791; GSE8218: AUC = 0.868; GSE26910: AUC = 0.972). In the TCGA database, C1QTNF3 was significantly associated with PCa patient recurrence free survival (P < .001, AUC = 0.57). In this study, we have developed a diagnostic and prognostic prediction model for PCa. C1QTNF3 was revealed as a promising biomarker for PCa. This approach can be applied to other high-throughput data from different platforms for the discovery of oncogenes or biomarkers in different kinds of diseases.

Different effects of phospholipase Dζ2 and non-specific phospholipase C4 on lipid remodeling and root hair growth in Arabidopsis response to phosphate deficiency.

Phosphate (Pi) deficiency in soils is a major limiting factor for plant growth. In response to Pi deprivation, one prominent metabolic adaptation in plants is the decrease in membrane phospholipids that consume approximately one-third cellular Pi. The level of two phospholipid-hydrolyzing enzymes, phospholipase Dζ2 (PLDζ2) and non-specific phospholipase C4 (NPC4), is highly induced in Pi-deprived Arabidopsis. To determine the role of PLDζ2 and NPC4 in plant growth under Pi limitation, Arabidopsis plants deficient in both PLDζ2 and NPC4 (npc4pldζ2) were generated and characterized. Lipid remodeling in leaves and roots was analyzed at three different durations of Pi deficiency. NPC4 affected lipid changes mainly in roots at an early stage of Pi deprivation, whereas PLDζ2 exhibited a more overt effect on lipid remodeling in leaves at a later stage of Pi deprivation. Pi deficiency-induced galactolipid increase and phospholipid decrease were impeded in pldζ2 and npc4pldζ2 plants. In addition, seedlings of npc4pldζ2 had the same root hair density as pldζ2 but shorter root hair length than pldζ2 in response to Pi deficiency. The loss of NPC4 decreased root hair length but had no effect on root hair density. These data suggest that PLDζ2 and NPC4 mediate the Pi deprivation-induced lipid remodeling in a tissue- and time-specific manner. PLDζ2 and NPC4 have distinctively different roles in root hair growth and development in response to Pi deprivation; PLDζ2 negatively modulates root hair density and length, whereas NPC4 promotes root hair elongation.

A Novel Modification of Transurethral Enucleation and Resection of the Prostate in Patients With Prostate Glands Larger than 80 mL: Surgical Procedures and Clinical Outcomes.

OBJECTIVE: To evaluate the efficacy and safety of the modified transurethral enucleation and resection of the prostate (M-TUERP) vs the conventional bipolar transurethral resection of the prostate (B-TURP) for the treatment of prostates larger than 80 mL. METHODS: From April 2012 to May 2014, 86 patients with a prostate volume of >80 mL were divided into 2 groups to undergo M-TUERP and B-TURP. In the M-TUERP group, we proposed combining the 12-mm trocar suprapubic cystostomy and using the techniques of "umbrella-shaped resection," "point resection," and "segmental enucleation" to modify the transurethral enucleation and resection of the prostate procedure. The perioperative clinical data were recorded and analyzed. RESULTS: There were no significant differences in preoperative characteristics between the 2 groups. Both groups were similar with the operative time. The M-TUERP group was significantly superior to the B-TURP group in terms of the weight of the resected tissue, the mean intraoperative bladder pressure, hemoglobin decrease, bladder irrigation duration, and urethral catheterization time. No transurethral resection syndrome and incontinence occurred in either group. Compared with the B-TURP group, none of the patients in the M-TUERP group suffered blood transfusion, clot retention, recatheterization, dysuria and reoperation. At the 3-year follow-up, patients who underwent M-TUERP had better international prostate symptom scores, maximum urinary flow rates, and quality of life scores. CONCLUSION: Our modification of the transurethral enucleation and resection of the prostate procedure is a safe and effective method for the surgical treatment of large-volume benign prostatic hyperplasia. It can simplify the surgical procedures, reduce complications, lower difficulties and shorten the learning curve. At 3-year follow-up, the M-TUERP shows a superior and durable clinical outcome than the B-TURP.

Association between three VEGF polymorphisms and renal cell carcinoma susceptibility: a meta-analysis.

Several studies have reported an association between vascular endothelial growth factor (VEGF) gene polymorphisms rs2010963, rs3025039 and rs699947 and renal cell carcinoma (RCC). However, the results remain inconclusive and controversial. We therefore conducted a meta-analysis to evaluate this association. Electronic databases were searched for relevant case-control studies up to November 2016. RevMan 5.2 software and STATA version 12.0 were used for statistical analysis in our meta-analysis. Heterogeneity was assessed using the I2 value. Nine eligible studies were retrieved for detailed evaluation. The pooled estimates indicated that the GG genotype of VEGF rs2010963 polymorphism significantly decreased RCC risk [GG vs. GC+CC; GG vs. GC]. There was also a significant association between VEGF rs3025039 polymorphism and RCC susceptibility [CC+CT vs. TT; CC vs. TT]. Furthermore, a significant association between VEGF rs699947 polymorphism and RCC susceptibility was detected [A vs. C; AA+AC vs. CC; AA vs. AC+CC; AA vs. CC; AA vs. AC; AC vs. CC]. Subgroup analysis revealed that these associations held true especially for Asians. Our meta-analysis suggested that there may be a relationship between the VEGF rs2010963, rs3025039 and rs699947 polymorphisms and RCC susceptibility.

The association between hepatitis B mutants and hepatocellular carcinoma: A meta-analysis.

BACKGROUND: More and more studies focus on the relationship between hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations, but it remains controvercial, we conducted a meta-analysis to investigate the features of hepatitis B virus basal core promoter/precore mutations on the progression of hepatocellular carcinoma (HCC). METHODS: A comprehensive search was conducted for articles published between January 1, 2005 and December 31, 2015 using the following databases: PubMed, Embase, Cochrane Library, Wanfang, and China National Knowledge Infrastructure. Medical subject heading terms were prioritized in setting the search strategy. Search terms included ("hepatitis B virus"), ("mutation or mutations or mutant"), and ("hepatocellular carcinoma" or "liver cancer" or hepatoma). A meta-analysis of pooled results from case-control studies examined the association between mutations G1896A, A1762T, G1764A, and A1762T/G1764A and the risk of HCC. RESULTS: We included 29 articles for analysis and found that G1896A (summary odds ratios [OR] = 2.04, 95% confidence interval [CI] = 1.41-2.95), A1762T (summary OR = 3.96, 95% CI = 1.98-7.92), G1764A (summary OR = 3.48, 95% CI = 1.99-6.09), and A1762T/G1764A (summary OR = 3.96, 95% CI = 2.77-5.65) are each associated with a statistically significant increase in the risk of HCC. CONCLUSION: In summary, we found that G1896A, A1762T, G1764A, and A1762T/G1764A are associated with an increased risk of HCC.

The phospholipase iPLA2γ is a major mediator releasing oxidized aliphatic chains from cardiolipin, integrating mitochondrial bioenergetics and signaling.

Cardiolipin (CL) is a dimeric phospholipid with critical roles in mitochondrial bioenergetics and signaling. Recently, inhibition of the release of oxidized fatty acyl chains from CL by the calcium-independent phospholipase A2γ (iPLA2γ)-selective inhibitor (R)-BEL suggested that iPLA2γ is responsible for the hydrolysis of oxidized CL and subsequent signaling mediated by the released oxidized fatty acids. However, chemical inhibition by BEL is subject to off-target pharmacologic effects. Accordingly, to unambiguously determine the role of iPLA2γ in the hydrolysis of oxidized CL, we compared alterations in oxidized CLs and the release of oxidized aliphatic chains from CL in experiments with purified recombinant iPLA2γ, germ-line iPLA2γ-/- mice, cardiac myocyte-specific iPLA2γ transgenic mice, and wild-type mice. Using charge-switch high mass accuracy LC-MS/MS with selected reaction monitoring and product ion accurate masses, we demonstrated that iPLA2γ is the major enzyme responsible for the release of oxidized aliphatic chains from CL. Our results also indicated that iPLA2γ selectively hydrolyzes 9-hydroxy-octadecenoic acid in comparison to 13-hydroxy-octadecenoic acid from oxidized CLs. Moreover, oxidative stress (ADP, NADPH, and Fe3+) resulted in the robust production of oxidized CLs in intact mitochondria from iPLA2γ-/- mice. In sharp contrast, oxidized CLs were readily hydrolyzed in mitochondria from wild-type mice during oxidative stress. Finally, we demonstrated that CL activates the iPLA2γ-mediated hydrolysis of arachidonic acid from phosphatidylcholine, thereby integrating the production of lipid messengers from different lipid classes in mitochondria. Collectively, these results demonstrate the integrated roles of CL and iPLA2γ in lipid second-messenger production and mitochondrial bioenergetics during oxidative stress.

Plant phospholipases D and C and their diverse functions in stress responses.

Phospholipases D (PLD) and C (PLC) hydrolyze the phosphodiesteric linkages of the head group of membrane phospholipids. PLDs and PLCs in plants occur in different forms: the calcium-dependent phospholipid binding domain-containing PLDs (C2-PLDs), the plekstrin homology and phox homology domain-containing PLDs (PX/PH-PLDs), phosphoinositide-specific PLC (PI-PLC), and non-specific PLC (NPC). They differ in structures, substrate selectivities, cofactor requirements, and/or reaction conditions. These enzymes and their reaction products, such as phosphatidic acid (PA), diacylglycerol (DAG), and inositol polyphosphates, play important, multifaceted roles in plant response to abiotic and biotic stresses. Here, we review biochemical properties, cellular effects, and physiological functions of PLDs and PLCs, particularly in the context of their roles in stress response along with advances made on the role of PA and DAG in cell signaling in plants. The mechanism of actions, including those common and distinguishable among different PLDs and PLCs, will also be discussed.

CTRP3 Stimulates Proliferation and Anti-Apoptosis of Prostate Cells through PKC Signaling Pathways.

C1q/TNF-related protein-3 (CTRP3) is a novel adipokine with roles in multiple cellular processes. However, little is known about its function in prostate cells. This study investigated the effects and mechanisms of CTRP3 in prostate cells. We first generated and purified CTRP3 protein in HEK 293T cells. Proliferation of RWPE-1 prostate cells was evaluated by MTT analyses under treatment with different concentrations of CTRP3 for various exposure times. The results revealed maximum enhancement of proliferation with 10 µg/mL CTRP3 for 72 h. Cell apoptosis and cell cycle were determined by TUNEL staining and flow cytometry analysis. TUNEL assay showed decreased TUNEL-positive cells in RWPE-1 prostate cells treated with CTRP3, and flow cytometry showed significantly decreased apoptotic cells upon CTRP3 treatment (treated cells, 8.34±1.175 vs. controls, 20.163±0.35) (P < 0.01). Moreover, flow cytometry analysis also showed a significant decrease of cells in the G1 phase and an increase of cells in the S and G2 phase upon CTRP3 treatment (treated cells, 42.85±1.40 vs. control, 52.77±0.90; 28.41±0.57 vs. 23.49±1.13; 27.08±1.97 vs. 22.20±1.32, respectively) (all P < 0.05). Two-dimensional gel electrophoresis and mass spectrometry identified differentially expressed proteins, including cytokeratin-19, GLRX3 and DDAH1, which were upregulated in CTRP3 treated cells, and cytokeratin-17 and 14-3-3 sigma, which were downregulated. GLRX3, DDAH1 and 14-3-3 sigma were confirmed using western blot analysis. A PKC inhibitor, staurosporine, was used to inhibit PKC activity in CTRP3 treated RWPE-1 cells. Staurosporine completely abolished the CTRP3-induced increased phosphorylation of intracellular PKC substrates and CTRP3-stimulated effect by RWPE-1 cells. Our results provide the first evidence for a physiological role of the novel adipokine, CTRP3, in prostate cells. Our findings suggest that CTRP3 could improve proliferation and anti-apoptosis of prostate cells through protein kinase C signaling pathways.

Repair of urethral defects with polylactid acid fibrous membrane seeded with adipose-derived stem cells in a rabbit model.

AIM: The aim of this study is to evaluate the capacity of polylactid acid (PLA) fibrous membrane seeded with allogeneic rabbit adipose tissue-derived stem cells (ADSCs) to repair urethral defects in a rabbit model. MATERIALS AND METHODS: Rabbit ADSCs were harvested and phenotypically characterized. Twenty-four New Zealand male rabbits with 5-mm urethral mucosal defects were randomly divided into two groups. They underwent urethroplasty either with PLA fibrous membrane seeded with ADSCs (group A) or blank PLA fibrous membrane (group B). At 4 and 6 weeks after urethroplasty, the urethral grafts were collected and analyzed grossly and histologically. The incidence rate of urethrostenosis was measured. RESULTS: The adipose tissue-derived cells in monolayer culture showed a typical morphology of mesenchymal stem cells (MSCs). They were positive for the MSC marker CD44 but negative for lineage markers CD45 and CD105. Six weeks after surgery, the incidence rate of urethrostenosis in group A was significantly lower than that in group B (p < 0.05). In group A, the ADSC-seeded grafts showed a normal urethral architecture with a thickened muscle layer. In contrast, the newly developed urethra in group B demonstrated a fewer number of urothelial layers and scarce or no smooth muscle cells. CONCLUSION: The PLA scaffold seeded with ADSCs is effective in urethral regeneration in a rabbit model. ADSCs may represent a promising source of seed cells for urethral tissue engineering.

Endoscopic enucleation versus open prostatectomy for treating large benign prostatic hyperplasia: a meta-analysis of randomized controlled trials.

OBJECTIVES: To evaluate the overall efficacy and safety of endoscopic enucleation of the prostate (EP) vs open prostatectomy (OP) for large benign prostatic hyperplasia (BPH). METHODS: We conducted an electronic search of PubMed/Medline, EMBASE, The Cochrane Library, and Web of Science to detect all relevant randomized controlled trials (RCTs) comparing EP with OP. A meta-analysis was performed using Review Manager 5.3. RESULTS: Seven RCTs (735 patients) were included. At the 3-, 6- and 12-month follow-up, there were no significant differences in the International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), quality of life (QoL) score and post-void residual urine volume (PVR) between EP and OP. The International Index of Erectile Function (IIEF-5) was higher with EP (weighted mean difference [WMD]: 1.00, 95% confidence interval [CI]: 0.21 to 1.78, p=0.01) at the 12-month follow-up. The catheterization time (WMD: 3.80 d, 95%CI: -5.11 to -2.48, P<0.00001) and hospital stay (WMD: 4.93 d, 95%CI: -5.96 to -3.89, P<0.00001) were shorter with EP. The duration of operation was longer for EP compared with OP (WMD: 16.21 min, 95%CI: 3.72 to 28.70, P=0.01). The resected tissue weight (WMD: -9.63 g, 95%CI: -14.46 to -4.81, P<0.0001) and decrease in hemoglobin (WMD: -1.14 g/dL, 95%CI: -1.81 to -0.47, P=0.0008) were less with EP. EP was associated with fewer blood transfusions (risk ratio: 0.22, 95%CI: 0.10 to 0.47, P=0.0001). There were no significant differences between EP and OP when comparing other complications. CONCLUSIONS: Although only a limited number of RCTs with relatively limited follow-up are available, EP is shown to have a similar postoperative profile and comparable safety to OP. By contrast, EP may have a more desirable perioperative profile. EP appears to be an effective and safe minimally invasive option for treating large prostates that requires only brief convalescence.