Inguinal hernia containing the uterus and both adnexa in a full-term infant

We report a case of inguinal hernia that contained the entire uterus and both adnexa, presenting with an irreducible soft mass in the left groin and asymmetric labia majora, in a 2-month-old, full-term girl who visited the emergency department. Ultrasonography was performed immediately, and urgent surgical repair was performed without complications. Although inguinal hernia is a common surgical disease, it is rare that the hernia contains the uterus with its adnexa, and presents as a mass of the labia majora. Unlike the bowel herniation, the entity can be complicated by strangulation of the ovary, leading to infertility. To preserve fertility, rapid and accurate diagnosis using ultrasonography should be considered in an infant with an irreducible inguinal mass and asymmetric labia majora

A transcriptomic analysis of serial-cultured, tonsil-derived mesenchymal stem cells reveals decreased integrin α3 protein as a potential biomarker of senescent cells

Abstract Background Mesenchymal stem cells (MSCs) have been widely used for stem cell therapy, and serial passage of stem cells is often required to obtain sufficient cell numbers for practical applications in regenerative medicine. A long-term serial cell expansion can potentially induce replicative senescence, which leads to a progressive decline in stem cell function and stemness, losing multipotent characteristics. To improve the therapeutic efficiency of stem cell therapy, it would be important to identify specific biomarkers for senescent cells. Methods Tonsil-derived mesenchymal stem cells (TMSCs) with 20–25 passages were designated as culture-aged TMSCs, and their mesodermal differentiation potentials as well as markers of senescence and stemness were compared with the control TMSCs passaged up to 8 times at the most (designated as young). A whole-genome analysis was used to identify novel regulatory factors that distinguish between the culture-aged and control TMSCs. The identified markers of replicative senescence were validated using Western blot analyses. Results The culture-aged TMSCs showed longer doubling time compared to control TMSCs and had higher expression of senescence-associated (SA)-β-gal staining but lower expression of the stemness protein markers, including Nanog, Oct4, and Sox2 with decreased adipogenic, osteogenic, and chondrogenic differentiation potentials. Microarray analyses identified a total of 18,614 differentially expressed genes between the culture-aged and control TMSCs. The differentially expressed genes were classified into the Gene Ontology categories of cellular component (CC), functional component (FC), and biological process (BP) using KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis. This analysis revealed that those genes associated with CC and BP showed the most significant difference between the culture-aged and control TMSCs. The genes related to extracellular matrix-receptor interactions were also shown to be significantly different (p < 0.001). We also found that culture-aged TMSCs had decreased expressions of integrin α3 (ITGA3) and phosphorylated AKT protein (p-AKT-Ser473) compared to the control TMSCs. Conclusions Our data suggest that activation of ECM-receptor signaling, specifically involved with integrin family-mediated activation of the intracellular cell survival-signaling molecule AKT, can regulate stem cell senescence in TMSCs. Among these identified factors, ITGA3 was found to be a representative biomarker of the senescent TMSCs. Exclusion of the TMSCs with the senescent TMSC markers in this study could potentially increase the therapeutic efficacy of TMSCs in clinical applications

Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin

Background Although the major anticancer effect of metformin involves AMPK-dependent or AMPK-independent mTORC1 inhibition, the mechanisms of action are still not fully understood. Methods To investigate the molecular mechanisms underlying the effect of metformin on the mTORC1 inhibition, MTT assay, RT-PCR, and western blot analysis were performed. Results Metformin induced the expression of ATF4, REDD1, and Sestrin2 concomitant with its inhibition of mTORC1 activity. Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment. Moreover, REDD1- and Sestrin2-mediated mTORC1 inhibition in response to metformin was independent of AMPK activation. Additionally, lapatinib enhances cell sensitivity to metformin, and knockdown of REDD1 and Sestrin2 decreased cell sensitivity to metformin and lapatinib. Conclusions ATF4-induced REDD1 and Sestrin2 expression in response to metformin plays an important role in mTORC1 inhibition independent of AMPK activation, and this signalling pathway could have therapeutic value.This research was supported by grants from the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by the Ministry of Science and ICT (MSIT), Republic of Korea (Nos. 50336–2021; 50531–2021; and 50544–2021)

Clinical and Lifestyle Determinants of Continuous Glucose Monitoring Metrics in Insulin-Treated Patients with Type 2 Diabetes Mellitus

Background There was limited evidence to evaluate the association between lifestyle habits and continuous glucose monitoring (CGM) metrics. Thus, we aimed to depict the behavioral and metabolic determinants of CGM metrics in insulin-treated patients with type 2 diabetes mellitus (T2DM). Methods This is a prospective observational study. We analyzed data from 122 insulin-treated patients with T2DM. Participants wore Dexcom G6 and Fitbit, and diet information was identified for 10 days. Multivariate-adjusted logistic regression analysis was performed for the simultaneous achievement of CGM-based targets, defined by the percentage of time in terms of hyper, hypoglycemia and glycemic variability (GV). Intake of macronutrients and fiber, step counts, sleep, postprandial C-peptide-to-glucose ratio (PCGR), information about glucose lowering medications and metabolic factors were added to the analyses. Additionally, we evaluated the impact of the distribution of energy and macronutrient during a day, and snack consumption on CGM metrics. Results Logistic regression analysis revealed that female, participants with high PCGR, low glycosylated hemoglobin (HbA1c) and daytime step count had a higher probability of achieving all targets based on CGM (odds ratios [95% confidence intervals] which were 0.24 [0.09 to 0.65], 1.34 [1.03 to 1.25], 0.95 [0.9 to 0.99], and 1.15 [1.03 to 1.29], respectively). And participants who ate snacks showed a shorter period of hyperglycemia and less GV compared to those without. Conclusion We confirmed that residual insulin secretion, daytime step count, HbA1c, and women were the most relevant determinants of adequate glycemic control in insulin-treated patients with T2DM. In addition, individuals with snack consumption were exposed to lower times of hyperglycemia and GV

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Anion‐Dependent Polarization and Piezoelectric Power Generation in Hybrid Halide MAPbX3 (X = I, Br, and Cl) Thin Films with Out‐of‐Plane Structural Adjustments

Abstract Anion‐dependent differences in the electromechanical energy harvesting capability of perovskite halides have not been experimentally demonstrated thus far. Herein, anion‐dependent piezoelectricity and bending‐driven power generation in high‐quality methylammonium lead halide MAPbX3 (X = I, Br, and Cl) thin films are explored; additionally, anisotropic in situ strain is imposed to improve energy harvesting under tensile bending. After applying the maximum in situ strain of −0.73% for all the halide thin films, the MAPbI3 thin‐film harvester exhibited a peak voltage/current of ≈23.1 V/≈1703 nA as the best values, whereas MAPbBr3 and MAPbCl3 demonstrated ≈5.6 V/≈176 nA and ≈3.3 V/≈141 nA, respectively, under identical bending conditions. Apart from apparent ferroelectricity of tetragonal MAPbI3, origin of the piezoelectricity in both cubic MAPbBr3 and MAPbCl3 is explored as being related to organic–inorganic hydrogen bonding, lattice distortion, and ionic migration, with experimental supports of effective piezoelectric coefficient and grain boundary potential. Conclusively, piezoelectricity of the cubic halides is assumed to be due to their soft polarity modes and relatively low elastic modulus with vacancies contributing to space‐charge polarization. In the case of ferroelectric MAPbI3, the distortion of PbI6 octahedra and atomic displacement within each octahedron are quantitatively estimated

Cell-Permeable Oct4 Gene Delivery Enhances Stem Cell-like Properties of Mouse Embryonic Fibroblasts

Direct conversion of one cell type into another is a trans-differentiation process. Recent advances in fibroblast research revealed that epithelial cells can give rise to fibroblasts by epithelial-mesenchymal transition. Conversely, fibroblasts can also give rise to epithelia by undergoing a mesenchymal to epithelial transition. To elicit stem cell-like properties in fibroblasts, the Oct4 transcription factor acts as a master transcriptional regulator for reprogramming somatic cells. Notably, the production of gene complexes with cell-permeable peptides, such as low-molecular-weight protamine (LMWP), was proposed to induce reprogramming without cytotoxicity and genomic mutation. We designed a complex with non-cytotoxic LMWP to prevent the degradation of Oct4 and revealed that the positively charged cell-permeable LMWP helped condense the size of the Oct4-LMWP complexes (1:5 N:P ratio). When the Oct4-LMWP complex was delivered into mouse embryonic fibroblasts (MEFs), stemness-related gene expression increased while fibroblast intrinsic properties decreased. We believe that the Oct4-LMWP complex developed in this study can be used to reprogram terminally differentiated somatic cells or convert them into stem cell-like cells without risk of cell death, improving the stemness level and stability of existing direct conversion techniques

A Synthetic Cell-Penetrating Heparin-Binding Peptide Derived from BMP4 with Anti-Inflammatory and Chondrogenic Functions for the Treatment of Arthritis

We report dual therapeutic effects of a synthetic heparin-binding peptide (HBP) corresponding to residues 15&ndash;24 of the heparin binding site in BMP4 in a collagen-induced rheumatic arthritis model (CIA) for the first time. The cell penetrating capacity of HBP led to improved cartilage recovery and anti-inflammatory effects via down-regulation of the iNOS-IFN&gamma;-IL6 signaling pathway in inflamed RAW264.7 cells. Both arthritis and paw swelling scores were significantly improved following HBP injection into CIA model mice. Anti-rheumatic effects were accelerated upon combined treatment with Enbrel&reg; and HBP. Serum IFN&gamma; and IL6 concentrations were markedly reduced following intraperitoneal HBP injection in CIA mice. The anti-rheumatic effects of HBP in mice were similar to those of Enbrel&reg;. Furthermore, the combination of Enbrel&reg; and HBP induced similar anti-rheumatic and anti-inflammatory effects as Enbrel&reg;. We further investigated the effect of HBP on damaged chondrocytes in CIA mice. Regenerative capacity of HBP was confirmed based on increased expression of chondrocyte biomarker genes, including aggrecan, collagen type II and TNF&alpha;, in adult human knee chondrocytes. These findings collectively support the utility of our cell-permeable bifunctional HBP with anti-inflammatory and chondrogenic properties as a potential source of therapeutic agents for degenerative inflammatory diseases