Transcatheter embolization for hemorrhage from aberrant testicular artery after partial nephrectomy: A case report.

BACKGROUND: Arterial bleeding typically involves the renal artery following partial nephrectomy; in this study, we present a case of bleeding originating from the testicular artery that has not been reported in previous studies. CASE SUMMARY: A 52-year-old man suffered hemorrhage from a perinephric branch of the aberrant left testicular artery after an open nephron-sparing surgery for renal cell carcinoma. Clinical signs of bleeding were manifested by the patient, such as fresh blood drainage from the catheter, decreased hemoglobin levels, and significant vital sign changes. Since computed tomography did not show evidence of active bleeding, transcatheter angiography was conducted to identify the bleeding site. Fluoroscopic spot images confirmed bleeding derived from a perinephric branch of the testicular artery originating from the segmental artery of the left renal artery. Using n-butyl-2-cyanoacrylate, successful transcatheter arterial embolization of the affected branch was performed. Immediately after the embolization procedure, the bleeding ceased, and the patient experienced complete recovery devoid of complications. CONCLUSION: In patients with postoperative arterial hemorrhage after partial nephrectomy, the testicular artery can be a rare but notable source of bleeding. Accurate bleeding site localization via angiographic evaluation, followed by transcatheter arterial embolization, can be instrumental for safe, prompt, and effective hemostasis.

Galectin-3 Plays an Important Role in BMP7-Induced Cementoblastic Differentiation of Human Periodontal Ligament Cells by Interacting with Extracellular Components.

Human periodontal ligament stem cells (hPDLSCs) contain multipotent postnatal stem cells that differentiate into PDL progenitors, osteoblasts, and cementoblasts. Previously, we obtained cementoblast-like cells from hPDLSCs using bone morphogenetic protein 7 (BMP7) treatment. Differentiation into appropriate progenitor cells requires interactions and changes between stem or progenitor cells and their so-called environment niches, and cell surface markers play an important role. However, cementoblast-specific cell surface markers have not yet been fully studied. Through decoy immunization with intact cementoblasts, we developed a series of monoclonal antibodies against cementoblast-specific membrane/extracellular matrix (ECM) molecules. One of these antibodies, the anti-CM3 antibody, recognized an approximate 30 kDa protein in a mouse cementoblast cell line, and the CM3 antigenic molecule accumulated in the cementum region of human tooth roots. Using mass spectrometric analysis, we found that the antigenic molecules recognized by the anti-CM3 antibody were galectin-3. As cementoblastic differentiation progressed, the expression of galectin-3 increased, and it localized at the cell surface. Inhibition of galectin-3 via siRNA and a specific inhibitor showed the complete blockage of cementoblastic differentiation and mineralization. In contrast, ectopic expression of galectin-3 induced cementoblastic differentiation. Galectin-3 interacted with laminin α2 and BMP7, and these interactions were diminished by galectin-3 inhibitors. These results suggested that galectin-3 participates in binding to the ECM component and trapping BMP7 to induce, in a sustained fashion, the upregulation of cementoblastic differentiation. Finally, galectin-3 could be a potential cementoblast-specific cell surface marker, with functional importance in cell-to-ECM interactions.

Golgin Subfamily A Member 5 Is Essential for Production of Extracellular Matrix Proteins during TGF-ß1-Induced Periodontal Ligament-Fibroblastic Differentiation.

Human periodontal ligament stem cells (hPDLSCs) can be differentiated into periodontal ligament- (PDL-) fibroblastic progenitors by treatment with low concentrations of transforming growth factor beta 1 (TGF-ß1). Although much is known about the profibrotic effects of TGF-ß1, the molecular mechanisms mediating the activation of fibroblasts in periodontal ligament-fibroblastic differentiation are not well known. Our study was to investigate the mechanism of the fibroblastic process in the periodontal ligament differentiation of hPDLSCs through the discovery of novel markers. One of the monoclonal antibodies previously established through decoy immunization was the anti-LG11 antibody, which recognized Golgi subfamily A member 5 (GOLGA5) as a PDL-fibroblastic progenitor-specific antigen. GOLGA5/LG11 was significantly upregulated in TGF-ß1-induced PDL-fibroblastic progenitors and accumulated in the PDL region of the tooth root. GOLGA5 plays a role in vesicle tethering and docking between the endoplasmic reticulum and the Golgi apparatus. siRNA-mediated depletion of endogenous GOLGA5 upregulated in TGF-ß1-induced PDL-fibroblastic progenitors resulted in downregulation of representative PDL-fibroblastic markers and upregulation of osteoblast markers. When the TGF-ß1 signaling pathway was blocked or GOLGA5 was depleted by siRNA, the levels of extracellular matrix (ECM) proteins, such as type I collagen and fibronectin, decreased in PDL-fibroblastic progenitors. In addition, Golgi structures in the perinuclear region underwent fragmentation under these conditions. These results suggest that GOLGA5/LG11 is a PDL-fibroblastic marker with functional importance in ECM protein production and secretion, which are important processes in PDL-fibroblastic differentiation.

Cell Surface Accumulation of Intracellular Leucine Proline-Enriched Proteoglycan 1 Enhances Odontogenic Potential of Human Dental Pulp Stem Cells.

Primary dental pulp cells can be differentiated into odontoblast-like cells, which are responsible for dentin formation and mineralization. Successful differentiation of primary dental pulp cells can be verified using a few markers. However, odontoblast-specific cell surface markers have not been fully studied yet. LEucine PRoline-Enriched Proteoglycan 1 (LEPRE1) is a basement membrane-associated proteoglycan. LEPRE1 protein levels are increased during odontoblastic differentiation of human dental pulp cells (hDPCs). Intracellular and cell surface accumulation of this protein completely disappeared during dentin maturation and mineralization. Cell surface binding of an anti-LEPRE1 monoclonal antibody that could recognize an extracellular region was gradually increased in the odontoblastic stage. Overexpression and knockdown experiments showed that accumulation of intracellular LEPRE1 could lead to inefficient odontoblastic differentiation and that the movement of LEPRE1 from intracellular region to the cell surface was required for odontoblastic differentiation. Indeed, when LEPRE1 already located on the cell surface was blocked by the anti-LEPRE1 monoclonal antibody, odontoblastic differentiation of hDPCs was inhibited. In this study, we looked at other aspects of LEPRE1 function as a cell surface molecule rather than its known intracellular hydroxylase activity. Our results indicate that this protein has potential as a specific cell surface marker in odontoblastic differentiation.

Transcriptome Profile of Membrane and Extracellular Matrix Components in Ligament-Fibroblastic Progenitors and Cementoblasts Differentiated from Human Periodontal Ligament Cells.

Ligament-fibroblastic cells and cementoblasts, two types of progenitor cells that differentiate from periodontal ligament stem cells (hPDLSCs), are responsible for the formation of the adhesive tissues in the tooth root. Since one of the factors that determines the fate of stem cell differentiation is the change in the microenvironment of the stem/progenitor cells, this study attempted to compare and analyze the molecular differences in the membrane and ECM of the two progenitor cells. Single cells derived from hPDLSCs were treated with TGF-ß1 and BMP7 to obtain ligament-fibroblastic and cementoblastic cells, respectively. The transcriptome profiles of three independent replicates of each progenitor were evaluated using next-generation sequencing. The representative differentially expressed genes (DEGs) were verified by qRT-PCR, Western blot analysis, and immunohistochemistry. Among a total of 2245 DEGs identified, 142 and 114 DEGs related to ECM and cell membrane molecules were upregulated in ligament-fibroblastic and cementoblast-like cells, respectively. The major types of integrin and cadherin were found to be different between the two progenitor cells. In addition, the representative core proteins for each glycosaminoglycan-specific proteoglycan class were different between the two progenitors. This study provides a detailed understanding of cell-cell and cell-ECM interactions through the specific components of the membrane and ECM for ligament-fibroblastic and cementoblastic differentiation of hPDLSCs.

Th2 Cytokines Increase the Expression of Fibroblast Growth Factor 21 in the Liver.

Interleukin-4 (IL-4) and IL-13 are the major T helper 2 (Th2) cytokines, and they are involved in the regulation of metabolism in the adipose tissue. The liver contains diverse innate and adaptive immune cells, but it remains to be determined whether Th2 cytokines modulate energy metabolism in the liver. Here, using gene expression data from the Gene Expression Omnibus (GEO) and the BXD mouse reference population, we determined that the Th2 cytokines IL-4 and IL-13 increase the secretion of fibroblast growth factor 21 (FGF21) in the liver. In vitro experiments confirmed that FGF21 was highly expressed in response to IL-4 and IL-13, and this response was abolished by the Janus kinase (JAK)-signal transducer and activator of transcription 6 (STAT6) blockade. Moreover, FGF21 expression in response to Th2 cytokines was augmented by selective peroxisome proliferator-activated receptor α (PPARα) inhibition. In vivo administration of IL-4 increased FGF21 protein levels in the liver in a STAT6-dependent manner, but FGF21 secretion in response to IL-4 was not observed in the epididymal white adipose tissue (eWAT) despite the activation of STAT6. Intraperitoneal administration of IL-33, an activator of type 2 immune responses, significantly increased the level of FGF21 in the serum and liver after 24 h, but repeated administration of IL-33 attenuated this effect. Taken together, these data demonstrate that the IL-4/IL-13-STAT6 axis regulates metabolic homeostasis through the induction of FGF21 in the liver.

Discovery and Biochemical Characterization of a Methanol Dehydrogenase From Lysinibacillus xylanilyticus.

Bioconversion of C1 chemicals such as methane and methanol into higher carbon-chain chemicals has been widely studied. Methanol oxidation catalyzed by methanol dehydrogenase (Mdh) is one of the key steps in methanol utilization in bacterial methylotrophy. In bacteria, few NAD+-dependent Mdhs have been reported that convert methanol to formaldehyde. In this study, an uncharacterized Mdh gene from Lysinibacillus xylanilyticus (Lxmdh) was cloned and expressed in Escherichia coli. The maximum alcohol oxidation activity of the recombinant enzyme was observed at pH 9.5 and 55°C in the presence of 10 mM Mg2+. To improve oxidation activity, rational approach-based, site-directed mutagenesis of 16 residues in the putative active site and NAD+-binding region was performed. The mutations S101V, T141S, and A164F improved the enzyme's specific activity toward methanol compared to that of the wild-type enzyme. These mutants show a slightly higher turnover rate than that of wild-type, although their K M values were increased compared to that of wild-type. Consequently, according the kinetic results, S101, T141, and A164 positions may related to the catalytic activity in the active site for methanol dehydrogenation. It should be further studied other mutant variants with high activity for methanol. In conclusion, we characterized a new Lxmdh and its variants that may be potentially useful for the development of synthetic methylotrophy in the future.

Anion Extraction-Induced Polymorph Control of Transition Metal Dichalcogenides.

Controlled phase conversion in polymorphic transition metal dichalcogenides (TMDs) provides a new synthetic route for realizing tunable nanomaterials. Most conversion methods from the stable 2H to metastable 1T phase are limited to kinetically slow cation insertion into atomically thin layered TMDs for charge transfer from intercalated ions. Here, we report that anion extraction by the selective reaction between carbon monoxide (CO) and chalcogen atoms enables predictive and scalable TMD polymorph control. Sulfur vacancy, induced by anion extraction, is a key factor in molybdenum disulfide (MoS2) polymorph conversion without cation insertion. Thermodynamic MoS2-CO-CO2 ternary phase diagram offers a processing window for efficient sulfur vacancy formation with precisely controlled MoS2 structures from single layer to multilayer. To utilize our efficient phase conversion, we synthesize vertically stacked 1T-MoS2 layers in carbon nanofibers, which exhibit highly efficient hydrogen evolution reaction catalytic activity. Anion extraction induces the polymorph conversion of tungsten disulfide (WS2) from 2H to 1T. This reveals that our method can be utilized as a general polymorph control platform. The versatility of the gas-solid reaction-based polymorphic control will enable the engineering of metastable phases in 2D TMDs for further applications.

Erythropoietin decreases renal fibrosis in mice with ureteral obstruction: role of inhibiting TGF-beta-induced epithelial-to-mesenchymal transition.

The inhibitory effects of recombinant human erythropoietin (rhEPO) were examined against (1) the progression of renal fibrosis in mice with complete unilateral ureteral obstruction and (2) the TGF-beta1-induced epithelial-to-mesenchymal transition (EMT) in MDCK cells. Unilateral ureteral obstruction was induced in BALB/c mice and rhEPO (100 or 1000 U/kg, intraperitoneally, every other day) or vehicle was administered from day 3 to day 14. Immunoblotting and immunohistochemistry revealed increased expressions of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), and fibronectin and decreased expression of E-cadherin in the obstructed kidneys. In contrast, rhEPO treatment significantly attenuated the upregulation of TGF-beta1 and alpha-SMA and the downregulation of E-cadherin. MDCK cells were treated with TGF-beta1 (5 ng/ml) for 48 h to induce EMT, and the cells were then co-treated with TGF-beta1 and rhEPO for another 48 h. Increased expressions of alpha-SMA and vimentin and decreased expressions of zona occludens-1 and E-cadherin were observed after TGF-beta1 treatment, and these changes were markedly attenuated by rhEPO co-treatment. TGF-beta1 increased phosphorylated Smad-2 expression in MDCK cells, which was decreased by rhEPO co-treatment. In conclusion, rhEPO treatment inhibits the progression of renal fibrosis in obstructed kidney and attenuates the TGF-beta1-induced EMT. It is suggested that the renoprotective effects of rhEPO could be mediated, at least partly, by inhibition of TGF-beta1-induced EMT.

Effects of low glucose degradation products peritoneal dialysis fluid on the peritoneal fibrosis and vascularization in a chronic rat model.

In the present study, we examined the effects of a new peritoneal dialysis fluid (PDF) with a low level of low glucose degradation products (GDP) on the functional and structural stability of the peritoneal membrane (PM). Male Sprague-Dawley rats were divided into three groups: group C (n = 8), without dialysate infusion; group P (n = 12), infused with low-level GDP solution (4.25% Physioneal, pH 7.0-7.4); and group D (n = 12), infused with conventional solution (4.25% Dianeal, pH 5.2, adjusted to pH 7.0). In groups D and P, animals were infused through a permanent catheter with 25 mL of PDF, twice daily for 8 weeks. Lipopolysaccharide was added into the PDF immediately before infusion on days 8, 9 and 10 in the two dialysis groups. When compared with group P, group D showed a higher glucose mass transfer at weeks 6 and 8, D/P urea at week 8, TGF-beta1 at weeks 4 and 8, and VEGF level at week 8. The submesothelial matrix layer of the parietal peritoneum was significantly thickened in group D and the lectin-stained blood vessels in this layer were well-visualized in group D compared with group P. There were significantly more peritoneal blood vessels in group D than group P. The transforming growth factor-beta induced gene-h3 (betaig-h3) and TGF-beta1 levels in the peritoneal effluent correlated with the submesothelial thickness, which correlated with the dialysate-to-plasma ratio (D/P) of protein and, inversely, with the rate of glucose transport (D/D(0) glucose, where D is glucose concentration in the dialysate and D(0) is glucose concentration in the dialysis solution before it is infused into the peritoneal cavity). The present study showed that low-GDP PDF effectively attenuated the peritoneal vascularization and fibrosis related to conventional solution.