Human MutT Homolog 1 (MTH1) Inhibitor Reduces the Biological Activity of Ovarian Carcinoma Cells

This study intends to discuss the mechanism of MTH1 inhibitor (TH588) in the biological activity of ovarian carcinoma cells. A2780 and SKOV-3 cells were treated with different concentrations of TH588 and assigned into AT group (control), BT group (8 μmol/L TH588), CT group (16 μmol/L), DT group (32 μmol/L), ET group (64 μmol/L) and FT group (128 μmol/L) followed by measuring level of Bcl-2 and Bax by Western blot and PCR, and cell biological activities by MTT, FCM and Transwell chamber assay. The cell proliferative rate was not affected in AT group, but was lower in other groups in a reverse dose-dependent manner. There was significant difference on apoptotic rate and cell invasion among groups with increased apoptosis and reduce invasion after TH588 treatment. FT group showed lowest expression of Bcl-2 and Bax compared to other groups. In conclusion, the biological activity of A2780/SKOV3 cells could be reduced by MTH1 inhibitor which was probably through regulation of Bax and Bcl-2 expression.

Transcriptomic analysis of granulosa cell populations proximal and distal to the germinal disc of chicken preovulatory follicles

Within the oocytes of chicken preovulatory follicles, the engulfed yolk constitutes 99% of the oocyte content, while the small germinal disc (GD) (which contains the nucleus and 99% ooplasm) occupies only less than 1%. Relative to the position of the GD, the single granulosa cell layer surrounding the oocyte can be sub-divided into two sub-populations: granulosa cells proximal (named Gp cells) and distal (Gd cells) to the GD. It was reported that Gp cells and Gd cells differ in their morphology, proliferative rate and steroidogenic capacity, however, the underlying mechanism controlling granulosa cell heterogeneity remains unclear. Here we analyzed the transcriptomes of Gd and Gp cells of preovulatory (F5 and F1) follicles in chicken ovaries. We found that: (1) genes associated with cell cycle and DNA replication (CDK1, CCNB3 etc.) have comparatively higher expression levels in Gp cells than in Gd cells, while genes associated with steroidogenesis (CYP51A1, DHCR24) are highly expressed in Gd cells, indicating that Gp cells are likely more mitotic and less steroidogenic than Gd cells; (2) genes associated with extracellular matrix remodeling, cell adhesion and sperm binding (ZP3, ZP2) are differentially expressed in Gp and Gd cells; (3) Furthermore, signaling molecules (WNT4/IHH) and receptors for NGF (NGFR), epidermal growth factor (EGFR), gonadotropins (FSHR/LHR) and prostaglandin (PTGER3) are abundantly but differentially expressed in Gp and Gd cells. Taken together, our data strongly supports the notion that Gp and Gd cells of preovulatory follicles differ in their proliferation rate, steroidogenic activity, ECM organization and sperm binding capacity, which are likely controlled by gonadotropins and local ovarian factors, such as GD-derived factors.

Effect of riboflavin deficiency on development of the cerebral cortex in Slc52a3 knockout mice

Riboflavin transporter 3 (RFVT3), encoded by the SLC52A3 gene, is important for riboflavin homeostasis in the small intestine, kidney, and placenta. Our previous study demonstrated that Slc52a3 knockout (Slc52a3−/−) mice exhibited neonatal lethality and metabolic disorder due to riboflavin deficiency. Here, we investigated the influence of Slc52a3 gene disruption on brain development using Slc52a3−/− embryos. Slc52a3−/− mice at postnatal day 0 showed hypoplasia of the brain and reduced thickness of cortical layers. At embryonic day 13.5, the formation of Tuj1+ neurons and Tbr2+ intermediate neural progenitors was significantly decreased; no significant difference was observed in the total number and proliferative rate of Pax6+ radial glia. Importantly, the hypoplastic phenotype was rescued upon riboflavin supplementation. Thus, it can be concluded that RFVT3 contributes to riboflavin homeostasis in embryos and that riboflavin itself is required during embryonic development of the cerebral cortex in mice.

Apolipoprotein A-I Supports MSCs Survival under Stress Conditions

Clinical trials have shown the safety of mesenchymal stem/stromal cells (MSCs) transplantation, but the effectiveness of these treatments is limited. Since, transplanted MSCs will undergo metabolic disturbances in the bloodstream, we investigated the influence of blood plasmas of type 2 diabetes (T2D) patients on MSCs viability and examined whether apolipoprotein A-I (apoA-I) could protect cells from stressful conditions of serum deprivation (SD), hypoxia, and elevated concentrations of reactive oxygen species (ROS). ApoA-I exhibits anti-inflammatory, immune activities, improves glycemic control, and is suitable for T2D patients but its influence on MSCs remains unknown. For the first time we have shown that apoA-I decreases intracellular ROS and supports proliferative rate of MSCs, thereby increasing cell count in oxidation conditions. ApoA-I did not influence cell cycle when MSCs were predominantly in the G0/G1 phases under conditions of SD/hypoxia, activated proliferation rapidly, and reduced apoptosis during MSCs transition to the oxygenation or oxidation conditions. Finally, it was found that the blood plasma of T2D individuals had a cytotoxic effect on MSCs in 39% of cases and had a wide variability of antioxidant properties. ApoA-I protects cells under all adverse conditions and can increase the efficiency of MSCs transplantation in T2D patients.

Antioxidant Strategy to Prevent Simulated Microgravity-Induced Effects on Bone Osteoblasts

The effects induced by microgravity on human body functions have been widely described, in particular those on skeletal muscle and bone tissues. This study aims to implement information on the possible countermeasures necessary to neutralize the oxidative imbalance induced by microgravity on osteoblastic cells. Using the model of murine MC3T3-E1 osteoblast cells, cellular morphology, proliferation, and metabolism were investigated during exposure to simulated microgravity on a random positioning machine in the absence or presence of an antioxidant—the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Our results confirm that simulated microgravity-induced morphological and metabolic alterations characterized by increased levels of reactive oxygen species and a slowdown of the proliferative rate. Interestingly, the use of Trolox inhibited the simulated microgravity-induced effects. Indeed, the antioxidant-neutralizing oxidants preserved cell cytoskeletal architecture and restored cell proliferation rate and metabolism. The use of appropriate antioxidant countermeasures could prevent the modifications and damage induced by microgravity on osteoblastic cells and consequently on bone homeostasis.

Canine lymphoma: Pathological and clinical characteristics of patients treated at a referral hospital

Non-Hodgkin’s lymphomas are common canine cancers with variable demographic and clinical presentations. Their pathological characterization and treatment lag far behind those of humans. We describe consecutive lymphoma patients detected over a one-year period at the National Autonomous University of Mexico (UNAM). Of 4,512 dogs: 220 (4.9%) had a cancer diagnosis, of which 27 (0.6%) had lymphoma (12% of cancer patients). We found an association with Miniature Schnauzers, which represented 18.5% (5/27) of lymphoma patients, but it was only 6.4% (288/4,512) of the dogs studied in this time period (p < 0.011). Miniature Schnauzers and mongrels together constituted nearly half of lymphoma cases. Mean age at diagnosis was 7.5 years (3-14), with a female to male ratio of 1.7:1. We found no correlation between lymphoma and castration status. Most patients presented nodal involvement (80%), were in advanced stages III/IV (90%) and had B-cell versus T-cell tumors (64%/36%). Only two histopathological patterns were seen, both with diffuse nodal-replacement by large immunoblast and/or centroblast-like cells; one having numerous tingible-body macrophages which are suggestive of a high proliferative rate. Chemotherapy was given to 15 patients (65%) with an overall response of 73% (3 complete responses/8 partial responses) and a mean overall survival of 219 days (4-586; SD±185). One cutaneous lymphoma-patient achieved partial response (PR) with lomustine/prednisone, and treatment was still ongoing at 548 days. Earlier diagnosis, better lymphoma subtype distinction, and specific curative treatments are needed.

Cellular mesoblastic nephroma in infants and children: Report of four cases and review of the literature

Background: Cellular mesoblastic nephroma is rare after infancy, and there are many controversial reports about its clinical presentation and treatment as well as outcome in infants, young children, and adolescents. Objectives: In this report, we will discuss our experience with four cases of cellular mesoblastic nephroma presented from infancy to childhood (from 18 months of age to 11 years of age). Cases: During 10 years, we had the experience of 4 cases of pediatric renal tumor with the diagnosis of cellular mesoblastic nephroma, which have been followed between 1 year and 6 years. There were three male and one female patients with the age of 1.5, 2, 2, and 11 years. These tumors showed variable characteristics according to the number of mitosis, proliferative rate, necrosis, immunohistochemical markers, and metastatic potential; however, despite of all of these variabilities, all of these patients have done well and all have been well at the end of study. Conclusion: Pediatric renal tumors with the histologic diagnosis of cellular mesoblastic nephroma have good outcome even with metastasis, mitosis, and high proliferative rate.

Astragalus Extract Mixture HT042 Increases Longitudinal Bone Growth Rate by Upregulating Circulatory IGF-1 in Rats

Astragalus extract mixture HT042 is a standardized ingredient of health functional food approved by Korean FDA with a claim of “height growth of children.” HT042 stimulates bone growth rate and increases local IGF-1 expression in growth plate of rats which can be considered as direct stimulation of GH and its paracrine/autocrine actions. However, it remains unclear whether HT042 stimulates circulatory IGF-1 which also plays a major role to stimulate bone growth. To determine the effects on circulatory IGF-1, IGF-1 and IGFBP-3 expressions and phosphorylation of JAK2/STAT5 were evaluated in the liver after 10 days of HT042 administration. HT042 upregulated liver IGF-1 and IGFBP-3 mRNA expression, IGF-1 protein expression, and phosphorylation of JAK2/STAT5. HT042 also increased bone growth rate and proliferative zonal height in growth plate. In conclusion, HT042 stimulates bone growth rate via increment of proliferative rate by upregulation of liver IGF-1 and IGFBP-3 mRNA followed by IGF-1 protein expression through phosphorylation of JAK2/STAT5, which can be regarded as normal functioning of GH-dependent endocrine pathway.