Кераміка «terra sigillata» з с. Зимне на Волині

Стаття присвячена публікації чотирьох керамічних посудин типу «terra sigillata», знайдених на дні р. Луги у с. Зимне Володимир-Волинського району Волинської області. Попередній аналіз цих знахідок дозволяє віднести їх до Понтійського центру виробництва такого посуду. Вірогідним шляхом потрапляння цієї колекції на Волинь була готська експансія у Північне Причорномор’я

Additional file 1 of Trend changes and factor analysis of endometrial hyperplasia in patients with polycystic ovarian syndrome based on the Korean National Health Insurance Database

Additional file 1: Supplementary Table 1. List of medications. Supplementary Table 2. Prevalence rates of PCOS and EH from 2009 to 2016 by age distribution. PCOS = polycystic ovary syndrome, EH = endometrial hyperplasia. Supplementary Table 3. Incidence rates of PCOS and EH from 2009 to 2016 by age distribution. PCOS = polycystic ovary syndrome, EH = endometrial hyperplasia

SIRT3 Overexpression Attenuates Palmitate-Induced Pancreatic β-Cell Dysfunction.

Abnormally high levels of circulating free fatty acids can lead to pancreatic islet β-cell dysfunction and apoptosis, contributing to β-cell failure in Type 2 diabetes. The NAD+-dependent protein deacetylase Sirtuin-3 (SIRT3) has been implicated in Type 2 diabetes. In this study, we tested whether SIRT3 overexpression affects palmitate-induced β-cell dysfunction in cells of line NIT1, which are derived from mouse pancreatic β-cells. Two different lengths of SIRT3 were overexpressed: full length SIRT3 (SIRT3LF), which was preferentially targeted to mitochondria and partially to the nucleus, and its N-terminal truncated form (SIRT3SF), which was located in the nucleus and cytoplasm. Overexpression of SIRT3LF and SIRT3SF using an adenoviral system alleviated palmitate-induced lipotoxicity such as reduction of cell viability and mitogen-activated protein kinase (MAPK) activation. Chronic exposure to low concentrations of palmitate suppressed glucose-stimulated insulin secretion, but the suppression was effectively reversed by overexpression of SIRT3LF or SIRT3SF. The mRNA levels of the endoplasmic reticulum (ER) stress responsive genes ATF4, GRP94 and FKBP11 were increased by palmitate treatment, but the increases were completely inhibited by SIRT3LF overexpression and less effectively inhibited by SIRT3SF overexpression. This result suggests that overexpression of SIRT3 inhibits induction of ER stress by palmitate. Collectively, we conclude that overexpression of SIRT3 alleviates palmitate-induced β-cell dysfunction

Contribution of p38 MAPK Pathway to Norcantharidin-Induced Programmed Cell Death in Human Oral Squamous Cell Carcinoma

Norcantharidin (NCTD), a demethylated analog of cantharidin isolated from blister beetles, has been used as a promising anticancer agent; however, the underlying function of NCTD against human oral squamous cell carcinoma (OSCC) has not been fully understood. Here, this study was aimed to investigate the apoptotic effect and molecular targets of NCTD in human OSCC in vitro and in vivo. The anticancer effects of NCTD and its related molecular mechanisms were evaluated by trypan blue exclusion assay, live/dead assay, western blotting, 4-6-Diamidino-2-Phenylindole (DAPI) staining, flow cytometric analysis, Terminal Deoxynucleotidyl Transferase dUTP Nick end Labeling (TUNEL) assay, and immunohistochemistry. NCTD significantly inhibited cell growth and increased the number of dead cells in HSC-3 and HN22 cell lines. It induced the following apoptotic phenomena: (1) the cleavages of poly (ADP-ribose) polymerase and casepase-3; (2) increase in apoptotic morphological changes (nuclear condensation and fragmentation); (3) increase in annexin V-positive cells or sub-G1 population of cells. NCTD significantly activated the p38 mitogen-activated protein kinase (MAPK) pathway but inactivated the signal transducer and activator of transcription (STAT)3 pathway. A p38 MAPK inhibitor (SB203580) partially attenuated NCTD-induced programmed cell death (apoptosis) in both cell lines, whereas ectopic overexpression of STAT3 did not affect it. NCTD strongly suppressed tumor growth in the tumor xenograft bearing HSC-3 cells, and the number of TUNEL-positive cells increased in NCTD-treated tumor tissues. In addition, NCTD did not cause any histopathological changes in the liver nor the kidney. NCTD induced programmed cell death via the activation of p38 MAPK in OSCC. Therefore, these results suggest that NCTD could be a potential anticancer drug candidate for the treatment of OSCC

Direct differentiation of bone marrow mononucleated cells into insulin producing cells using pancreatic β-cell-derived components

Abstract Transplantation of stem cell-derived insulin producing cells (IPCs) has been proposed as an alternative to islet transplantation for the treatment of diabetes mellitus. However, current IPC differentiation protocols are focused on generating functional cells from the pluripotent stem cells and tend to rely on multistep, long-term exposure to various exogenous factors. In this study, we addressed the observation that under stress, pancreatic β-cells release essential components that direct the differentiation of the bone marrow nucleated cells (BMNCs) into IPCs. Without any supplementation with known differentiation-inducing factors, IPCs can be generated from BMNCs by in vitro priming for 6 days with conditioned media (CM) from the β-cells. In vitro primed BMNCs expressed the β-cell-specific transcription factors, as well as insulin, and improved hyperglycemia and glucose intolerance after transplantation into the streptozotocin-induced diabetic mice. Furthermore, we have found that components of the CM which trigger the differentiation were enclosed by or integrated into micro particles (MPs), rather than being secreted as soluble factors. Identification of these differentiation-directing factors might enable us to develop novel technologies required for the production of clinically applicable IPCs

SIRT3 overexpression ameliorates reduction of viability by palmitate.

<p>(A) NIT1 cells were incubated with palmitate (Pal) as indicated. After 24 h incubation, SIRT3 mRNA levels were measured by real-time PCR. The mRNA level of untreated cells was expressed 1.0 and the others were as its relative values. Data are the means ± SEM of 5 independent experiments. (B) NIT1 cells were incubated with palmitate for 24h. Cell lysates (50 μg) were loaded on each lane of SDS-PAGE gels and immunoblotted with an anti-SIRT3 antibody. (C) NIT1 cells were infected with Ad-GFP, Ad-SIRT3LF, or Ad-SIRT3SF (all 50 MOI) and treated with palmitate (500 μM) for 24 h. Caspase 3 activity was measured [n = 6]. (D) NIT1 cells were infected with Ad-GFP, Ad-SIRT3LF, or Ad-SIRT3SF (all 50 MOI) and treated with palmitate (500 μM) for 8 h. Cellular ATP levels were determined [n = 4]. Caspase activity and ATP levels of the cells were expressed as percentage of values measured in the cells infected with Ad-GFP without palmitate. Data represent means ± SEM; *<i>P</i> < 0.05 for comparison with Ad-GFP infected cells without palmitate treatment; #<i>P</i> < 0.05 for the comparison with Ad-GFP infected cells treated with palmitate.</p

Extracellular Vesicles from Thapsigargin-Treated Mesenchymal Stem Cells Ameliorated Experimental Colitis via Enhanced Immunomodulatory Properties

Therapeutic applications of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have attracted considerable attention because of their immunomodulatory properties against immune-mediated, inflammatory diseases. Here, we demonstrated enhanced immunomodulatory properties of EVs secreted from endoplasmic reticulum (ER) stress inducer thapsigargin (TSG)-primed human Wharton’s jelly-derived MSCs (WJ-MSCs). EVs from TSG-primed WJ-MSCs (TSG-EV) showed increased yield and expression of immunomodulatory factors, such as transforming growth factor-β1 (TGFβ), cyclooxygenase-2 (COX2), and especially indoleamine 2,3-dioxygenase (IDO), compared to control EVs. TSG-EV showed a significantly enhanced immunosuppressive effect on human peripheral blood-derived T cell proliferation and Th1 and Th17 differentiation, whereas Treg and M2-type macrophage were enriched compared to a control EV-treated group. Furthermore, TSG-EV substantially mitigated mouse experimental colitis by reducing the inflammatory response and maintaining intestinal barrier integrity. A significant increase of Tregs and M2-type macrophages in colitic colons of a TSG-EV-treated mouse suggests an anti-inflammatory effect of TSG-EV in colitis model, possibly mediated by Treg and macrophage polarization. These data indicate that TSG treatment promoted immunomodulatory properties of EVs from WJ-MSCs, and TSG-EV may provide a new therapeutic approach for treatment of colitis

SIRT3 overexpression inhibits palmitate-induced MAPK activation and ER stress.

<p>(A) NIT1 cells were infected with Ad-GFP, Ad-SIRT3LF, or Ad-SIRT3SF (50 MOI) and treated with palmitate (500 μM) for 8 h. The cell lysates were subjected to Western blot analysis. (B and C) NIT1 cells were infected with Ad-GFP, Ad-SIRT3LF, or Ad-SIRT3SF (50 MOI) and treated with palmitate (500 μM) for 24 h. The mRNA levels of ATF4, GRP94, and FKBP11 [n = 6] (B) and the mRNA levels of IL-1β, IL-6 and TXNIP [n = 5] (C) were measured using real-time PCR. The mRNA levels of the cells infected with Ad-GFP without palmitate treatment was set to 1.0 and the others were expressed relative to that value; *<i>P</i> < 0.05 for the comparison with the value of the Ad-GFP-infected cells without palmitate; #<i>P</i> < 0.05 for the comparison with the value of Ad-GFP infected cells in the presence of palmitate.</p