β-Catenin Preserves the Stem State of Murine Bone Marrow Stromal Cells Through Activation of EZH2

During bone marrow stromal cell (BMSC) differentiation, both Wnt signaling and the development of a rigid cytoskeleton promote commitment to the osteoblastic over adipogenic lineage. β-catenin plays a critical role in the Wnt signaling pathway to facilitate downstream effects on gene expression. We show that β-catenin was additive with cytoskeletal signals to prevent adipogenesis, and β-catenin knockdown promoted adipogenesis even when the actin cytoskeleton was depolymerized. β-catenin also prevented osteoblast commitment in a cytoskeletal-independent manner, with β-catenin knockdown enhancing lineage commitment. Chromatin immunoprecipitation (ChIP)-sequencing demonstrated binding of β-catenin to the promoter of enhancer of zeste homolog 2 (EZH2), a key component of the polycomb repressive complex 2 (PRC2) complex that catalyzes histone methylation. Knockdown of β-catenin reduced EZH2 protein levels and decreased methylated histone 3 (H3K27me3) at osteogenic loci. Further, when EZH2 was inhibited, β-catenin's anti-differentiation effects were lost. These results indicate that regulating EZH2 activity is key to β-catenin's effects on BMSCs to preserve multipotentiality. © 2020 American Society for Bone and Mineral Research.     

Effect of Topical Tetracycline on Seroma Formation in the Lichtenstein Technique: A Prospective Randomized Study

We sought to investigate whether application of topical tetracycline has a limiting effect on seroma formation in patients undergoing hernia repair using a polypropylene mesh. This study was conducted in 96 patients undergoing an elective groin hernia repair. Patients were randomized and divided into 2 groups. After the graft was placed, and before external oblique muscle aponeurosis was closed, 5 mL tetracycline was administered on the graft in the tetracycline group (tetra group, n = 50), and 5 mL isotonic saline was administered in the control group (n = 46) without putting in a drain. Seroma checks via surface ultrasonography were done. Seroma amounts measured on the first day were significantly higher in the tetra group (P = 0.04). There were no significant differences regarding seroma measurements on the seventh day or in the first and second months. Topical tetracycline application has no limiting effect on seroma formation after a groin hernia operation.Key words: Lichtenstein technique, Polypropylene mesh, Topical tetracycline, Seroma, UltrasonographyHernia operations are among the most frequently performed surgical operations. Graft use to repair the defect is commonplace because graft use decreases recurrence rate, and defect closure in large abdominal hernias is easier with a mesh.¹ The most commonly used and least expensive mesh is the polypropylene mesh. This mesh causes a foreign-body reaction where it is placed, which leads to seroma formation.² Repeat aspirations of seromas cause infection, and recurrence is seen on follow-up, especially in large hernias.² While drain use is not recommended in groin hernias, drain use in other abdominal-wall hernias is left to the physician''s discretion. The biggest problem with drain use is transport of the infection by an ascending route.³Tetracycline is an antibiotic, the solution form of which is topically used for pleurodesis in chest surgery.⁴ Some researchers also report successful topical use of its solution in seroma treatment, taking advantage of its sclerosing effect in cases with breast carcinoma.^5,6 Tetracycline has demonstrated increased growth factor–like activity in mesothelial cells exposed to tetracycline leading to fibroblast proliferation.⁷ This study sought to investigate whether tetracycline has a reducing effect on seroma development in cases undergoing elective groin hernia repair using a polypropylene mesh.     

Effect of fish oil, olive oil, and vitamin E on liver pathology, cell proliferation, and antioxidant defense system in rats subjected to partial hepatectomy

The high capacity of liver regeneration after partial hepatectomy (PH) is well known. This study investigated the role of the antioxidant defense system in regeneration among Wistar-albino male rats subjected to 70% partial hepatectomy after a pretreatment period of 2 weeks with eicosapentanoic acid (EPA) rich fish oil (FO), first pressed virgin olive oil (OO), or vitamin E. The control group of 10 rats underwent PH only. On postoperative day 3, all rats were humanely killed. Liver sections of animals treated with FO or vitamin E showed significant increases in regeneration within both liver parenchyma and cut surface compared with the control group (P < .05). Liver sections of OO displayed an insignificant increase in liver regeneration (P > .05), with less increase in parenchyma than of the cut surface. The enhancement of the liver parenchymal regeneration in the FO group was significantly greater than that of the vitamin E group. Concerning liver function tests (LFT), there was no significant difference among the groups. When the treatment groups were compared to the control group glutathione (GSH) levels were increased and content of malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) were decreased. Based on these results, we concluded that after 70% PH in rats, the liver parenchyma and cut surface regeneration were greatest with FO and least with OO treatment. Both FO and vitamin E served to improve the antioxidant defense system more than OO treatment.     

Heterozygous CTNNB1 and TBX4 variants in a patient with abnormal lung growth,pulmonary hypertension,microcephaly, and spasticity

The canonical wingless (Wnt) and fibroblast growth factor (FGF) signaling pathways involving CTNNB1 and TBX4, respectively, are crucial for the regulation of human development. Perturbations of these pathways and disruptions from biological homeostasis have been associated with abnormal morphogenesis of multiple organs, including the lung. The aim of this study was to identify the underlying genetic cause of abnormal lung growth, pulmonary hypertension (PAH), severe microcephaly, and muscle spasticity in a full-term newborn, who died at 4 months of age due to progressively worsening PAH and respiratory failure. Family trio exome sequencing showed a de novo heterozygous nonsense c.1603C>T (p.Arg535*) variant in CTNNB1 and a paternally inherited heterozygous missense c.1198G>A (p.Glu400Lys) variant in TBX4, both predicted to be likely deleterious. We expand the phenotypic spectrum associated with CTNNB1 and TBX4 variants and indicate that they could act synergistically to produce a distinct more severe phenotype. Our findings further support a recently proposed complex compound inheritance model in lethal lung developmental diseases and the contention that dual molecular diagnoses can parsimoniously explain blended phenotypes.     

Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells

Toll-like receptors (TLRs) recognize distinct microbial components and induce innate immune responses. TLR5 is triggered by bacterial flagellin. Here we generated Tlr5-/- mice and assessed TLR5 function in vivo. Unlike other TLRs, TLR5 was not expressed on conventional dendritic cells or macrophages. In contrast, TLR5 was expressed mainly on intestinal CD11c+ lamina propria cells (LPCs). CD11c+ LPCs detected pathogenic bacteria and secreted proinflammatory cytokines in a TLR5-dependent way. However, CD11c+ LPCs do not express TLR4 and did not secrete proinflammatory cytokines after exposure to a commensal bacterium. Notably, transport of pathogenic Salmonella typhimurium from the intestinal tract to mesenteric lymph nodes was impaired in Tlr5-/- mice. These data suggest that CD11c+ LPCs, via TLR5, detect and are used by pathogenic bacteria in the intestinal lumen.     

Relationship between cord blood levels of IGF-I and ferritin in healthy term neonates

OBJECTIVE: We hypothesize that the balance of maternal and fetal insulin-like growth factor-I (IGF-I) concentrations contributes to the regulation of substrate distribution between mother and fetus, and may thus mediate the maintenance of blood ferritin concentration in the fetus. Therefore, the relationship between cord blood IGF-I to ferritin concentration was investigated. INFANTS AND METHODS: Twenty-six term neonates were recruited. Anthropometric measures were recorded and umbilical cord blood samples were collected at birth. We studied serum concentrations of IGF-I in relation to blood ferritin and anthropometric data in term neonates. To assess the importance of the correlation of ferritin with both IGF-I and all other parameters, multiple linear regression analysis was carried out, with ferritin as the dependent variable and IGF-I and anthropometric parameters as independent variables. RESULTS: The mean concentrations of cord blood IGF-I and ferritin levels were 45.2 +/- 36.8 ng/ml and 225.5 +/- 124.2 ng/ml, respectively, at birth. A positive correlation was observed between IGF-I and ferritin concentrations of term neonates (r = 0.53, p = 0.005). IGF-I emerged as a significant predictor of ferritin concentration (beta = 1.79, p = 0.005) contributing to 28% of its variability. CONCLUSIONS: We showed a relationship between cord blood IGF-I and ferritin levels in term neonates, suggesting that even within an unremarkable population, fetal ferritin level may be influenced by IGF-I. Moreover, we speculated that IGF-I might also be important in the regulation of placental transport of ferritin.     

Anterior urethral valves: an uncommon cause of obstructive uropathy in children

PurposeAnterior urethral valves (AUV) are rare entities generally described in case reports. They are an uncommon cause of lower urinary tract obstruction in children and can be difficult to diagnose. In the present study, we present our experience in four children with AUV along with a literature review.Materials and methodsWe retrospectively identified four children with AUV presented between 1998 and 2005 at age 4–9 years.ResultsHematuria, urinary tract infection and weak voiding stream were the most common symptoms. Voiding cystourethrography (VCUG) confirmed the diagnosis of AUV. On cystourethroscopy, cusp-like valves in the anterior urethra were seen in all children. Transurethral endoscopic resection of the valves was carried out in three children using a pediatric resectoscope. In one child with a massive anterior urethral diverticulum, open resection of the valve, diverticulectomy and urethroplasty were performed. All patients were cured, none had complications as a result of surgery, and all reported a normal urinary stream at follow-up.ConclusionsChildren with poor stream and recurrent infections should be evaluated carefully and anterior urethral valves should be considered in differential diagnosis of obstructive lesions.     

Diagnostic tools of metabolic and structural brain disturbances in neonatal non‐ketotic hyperglycinemia

Non‐ketotic hyperglycinemia (NKH) is a rare autosomal recessive disorder of glycine metabolism. We report a newborn case of NKH and discuss the effects of this rare disease on brain metabolism and structure together with amplitude‐integrated electroencephalography, cranial magnetic resonance and magnetic resonance spectroscopy findings which are very rarely reported together so far.     

An in vivo database model for pharmacological and physiological dosage for experimental animals

We developed a database compiling in vivo doses of compounds for various activities in certain animal species. The related database covers almost 100 years of experiments. The conceptual scheme of the database was created using concepts of the entity-relationship modeling principles. Using published references, dosages and their effects on laboratory animals were entered as data. As the next stage of our work, we have started to examine the available literature to information about the experimental dosages of various drugs used in other studies.The database provides various interfaces, including graphical-user interfaces and interfaces for Internet access. The database will be useful as a knowledge infrastructure for researchers who have to perform dose-scan experiments for a specific pharmacological activity. The basic benefit of that knowledge infrastructure is that it will enable virtual pharmacological experiments that will be considerably less expensive than conventional laboratory experiments, because the number of animals used and the number of dose-scan experiments will be greatly reduced. The developed database will also be helpful for new drug development studies and for responding to queries about animal types, drugs used, drug interactions, and results.