The <Emphasis Type="Italic">defH9-iaaM</Emphasis> auxin-synthesizing gene increases plant fecundity and fruit production in strawberry and raspberry

Background  

The DefH9-iaaM gene fusion which is expressed specifically in placenta/ovules and promotes auxin-synthesis confers parthenocarpic fruit development to eggplant, tomato and tobacco. Transgenic DefH9-iaaM eggplants and tomatoes show increased fruit production due mainly to an improved fruit set. However, the weight of the fruits is also frequently increased.     

Endometrial caspase 1 and interleukin-18 expression during the estrous cycle and peri-implantation period of porcine pregnancy and response to early exogenous estrogen administration

Background  

The role for endometrial secretion of cytokines during the establishment of pregnancy in a number of mammals is well established. The current study determined endometrial expression of caspase 1 (CASP1) and interleukin-18 (IL18) during the estrous cycle and early pregnancy, and following early estrogen administration, which induces conceptus loss during early development in pigs.     

Progesterone receptor A and c-Met mediates spheroids-endometrium attachment

Background  

Implantation in humans involves cross talk between an active blastocyst and receptive endometrium. The role of the endometrial receptors in this complex embryo-maternal interaction is still unclear. We tested gene and protein expression of endometrial receptors (Progesterone receptor (PR) and c-Met) and the effect of theses receptors in endometrial receptivity.     

Mesenteric resistance arteries in type 2 diabetic db/db mice undergo outward remodeling

Objective

Resistance vessel remodeling is controlled by myriad of hemodynamic and neurohormonal factors. This study characterized structural and molecular remodeling in mesenteric resistance arteries (MRAs) in diabetic (db/db) and control (Db/db) mice.

Methods

Structural properties were assessed in isolated MRAs from 12 and 16 wk-old db/db and Db/db mice by pressure myography. Matrix regulatory proteins were measured by Western blot analysis. Mean arterial pressure and superior mesenteric blood flow were measured in 12 wk-old mice by telemetry and a Doppler flow nanoprobe, respectively.

Results

Blood pressure was similar between groups. Lumen diameter and medial cross-sectional area were significantly increased in 16 wk-old db/db MRA compared to control, indicating outward hypertrophic remodeling. Moreover, wall stress and cross-sectional compliance were significantly larger in diabetic arteries. These remodeling indices were associated with increased expression of matrix regulatory proteins matrix metalloproteinase (MMP)-9, MMP-12, tissue inhibitors of matrix metalloproteinase (TIMP)-1, TIMP-2, and plasminogen activator inhibitor-1 (PAI-1) in db/db arteries. Finally, superior mesenteric artery blood flow was increased by 46% in 12 wk-old db/db mice, a finding that preceded mesenteric resistance artery remodeling.

Conclusions

These data suggest that flow-induced hemodynamic changes may supersede the local neurohormonal and metabolic milieu to culminate in hypertrophic outward remodeling of type 2 DM mesenteric resistance arteries.     

Protective Effects of Astragaloside IV on db/db Mice with Diabetic Retinopathy

Objectives

Diabetic retinopathy (DR) is a common diabetic eye disease which is well-known as the result of microvascular retinal changes. Although the potential biological functions of astragaloside IV (AS IV) have long been described in traditional system of medicine, its protective effect on DR remains unclear. This study aims to investigate the function and mechanism of AS IV on type 2 diabetic db/db mice.

Methods

Db/db mice were treated with AS IV (4.5 mg/kg or 9 mg/kg) or physiological saline by oral gavage for 20 weeks along with db/m mice. In each group, retinal ganglion cell (RGC) function was measured by pattern electroretinogram (ERG) and apoptosis was determined by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Blood and retina aldose reductase (AR) activity were quantified by chemiluminescence analysis. The expressions of phosporylated-ERK1/2, NF-κB were determined by Western blot analysis. Furthermore, the expression of related downstream proteins were quantified by Label-based Mouse Antibody Array.

Results

Administration of AS IV significantly improved the amplitude in pattern ERG and reduced the apoptosis of RGCs.in db/db mice. Furthermore, downregulation of AR activity, ERK1/2 phosphorylation, NF-κB and related cytokine were observed in AS IV treatment group.

Conclusions

Our study indicated that AS IV, as an inhibitor of AR, could prevent the activation of ERK1/2 phosporylation and NF-kB and further relieve the RGCs disfunction in db/db mice with DR. It has provided a basis for investigating the clinical efficacy of AR inhibitors in preventing DR.     

Physiological effects of superoxide dismutase on altered visual function of retinal ganglion cells in db/db mice

Background

The C57BLKS/J db/db (db/db) mouse is a widely used type 2 diabetic animal model, and this model develops early inner retinal neuronal dysfunction beginning at 24 weeks. The neural mechanisms that mediate early stage retinal dysfunction in this model are unknown. We evaluated visual response properties of retinal ganglion cells (RGCs) during the early stage of diabetic insult (8, 12, and 20 wk) in db/db mice and determined if increased oxidative stress plays a role in impaired visual functions of RGCs in 20 wk old db/db mice.

Methodology/Principal Findings

In vitro extracellular single-unit recordings from RGCs in wholemount retinas were performed. The receptive field size, luminance threshold, and contrast gain of the RGCs were investigated. Although ON- and OFF-RGCs showed a different time course of RF size reduction, by 20 wk, the RF of ON- and OFF-RGCs were similarly affected. The LT of ON-RGCs was significantly elevated in 12 and 20 wk db/db mice compared to the LT of OFF-RGCs. The diabetic injury also affected contrast gains of ON- and OFF-RGCs differently. The generation of reactive oxidative species (ROS) in fresh retina was estimated by dihydroethidium. Superoxide dismutase (SOD) (300 unit/ml) was applied in Ames medium to the retina, and visual responses of RGCs were recorded for five hours. ROS generation in the retinas of db/db mice increased at 8wk and continued to progress at 20 wk of ages. In vitro application of SOD improved visual functions in 20 wk db/db mice but the SOD treatment affected ON- and OFF-RGCs differently in db/m retina.

Conclusions/Significance

The altered visual functions of RGCs were characterized by the reduced RF center size, elevated LT, and attenuated contrast gain in 12 and 20 wk db/db mice, respectively. These altered visual functions could, at least partly, be due to oxidative stress since in vitro application of SOD effectively improves visual functions.     

Phospholipase D promotes <Emphasis Type="Italic">Arcanobacterium haemolyticum</Emphasis> adhesion via lipid raft remodeling and host cell death following bacterial invasion

Background  

Arcanobacterium haemolyticum is an emerging bacterial pathogen, causing pharyngitis and more invasive infections. This organism expresses an unusual phospholipase D (PLD), which we propose promotes bacterial pathogenesis through its action on host cell membranes. The pld gene is found on a genomic region of reduced %G + C, suggesting recent horizontal acquisition.     

Combined analysis of endometrial thickness and pattern in predicting outcome of in vitro fertilization and embryo transfer: a retrospective cohort study

Objective  

To evaluate the combined effect of endometrial thickness and pattern on clinical outcome in patients undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET).     

Genomic modulation of diabetes (<Emphasis Type="Italic">db/db)</Emphasis> and obese (<Emphasis Type="Italic">ob/ob</Emphasis>) mutation-induced hypercytolipidemia: cytochemical basis of female reproductive tract involution

Infertility and hypercytolipidemic utero-ovarian involution are recognized consequences of the diabetes-obesity syndrome (DOS) in C57BL mice with either obese (ob/ob) or diabetes (db/db) single gene mutations. We have evaluated the interdependent deleterious influences of both mutation types and differences in the genomic background on utero-ovarian dysfunction in C57BL mice. Control (+/?) C57BL mice were matched with littermate ob/ob and db/db mutants expressed on either the /KsJ or /6 background. Both ob/ob and db/db mutations increased body weights of /KsJ and /6 background strains relative to +/? groups. In contrast, uterine and ovarian weights were depressed by ob/ob and db/dbmutations relative to +/?, regardless of the background strain, but especially when expressed on the /KsJ background. Functionally, both ob/ob and db/db mutations induced hyperglycemic-hyperinsulinemic states coupled with depressed serum estradiol-17-β and progesterone concentrations when expressed on a /KsJ background. Microscopic analysis of utero-ovarian tissue samples revealed marked hypercytolipidemia in the follicular granulosa and endometrial epithelial tissue layers of both ob/oband db/db mutant groups relative to normal +/? cytoarchitecture. The db/db mutation consistently promoted more severe hypercytolipidemic profiles than the ob/obmutation, regardless of background strain. Thus, the severity of utero-ovarian hypercytolipidemia following the expression ofob/ob and db/db mutations in C57BL mice is influenced, or moderated, by the genomic background on which the mutation is expressed.     

Inactivation of NMD increases viability of <Emphasis Type="Italic">sup45</Emphasis> nonsense mutants in <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis>

Background  

The nonsense-mediated mRNA decay (NMD) pathway promotes the rapid degradation of mRNAs containing premature termination codons (PTCs). In yeast Saccharomyces cerevisiae, the activity of the NMD pathway depends on the recognition of the PTC by the translational machinery. Translation termination factors eRF1 (Sup45) and eRF3 (Sup35) participate not only in the last step of protein synthesis but also in mRNA degradation and translation initiation via interaction with such proteins as Pab1, Upf1, Upf2 and Upf3.     

Resistin Production from Adipose Tissue Is Decreased in db/db Obese Mice,and Is Reversed by Rosiglitazone

Objective

This study was designed to (1) investigate the expression profiles of resistin in db/db mice and its dynamic association with metabolic parameters; and (2) evaluate the effects of Rosiglitazone on production of resistin.

Methods

Db/db mice and their lean litter mates were used for this study. Epididymal fat tissue was excised from mice of different age (from 5 to 12 weeks) for ex vivo incubation. Resistin,along with adiponectin,in serum and conditioned culture medium of epididymal fat pads were measured with immunoassays. The gene expression of resistin was determined by real-time PCR. Rosiglitazone or the vehicle (PBS) was administered into db/db mice by daily intra-gastric gavage. Differentiated 3T3-L1 adipocytes were used for in vitro evaluation.

Results

The secretion of resistin from the fat pads in db/db mice was significantly lower than that in lean mice (P<0.01). The mRNA expression of the resistin gene in fat tissue of db/db mice at the age of 5 weeks was decreased by 60.5% compared to lean controls (p<0.05). Serum levels of resistin were comparable between the obese and lean groups, perhaps due to the increased total fat mass in db/db mice. Correlation analysis showed that serum resistin levels were positively correlated to resistin secretion from fat pads(r = 0.844,P = 0.000), while negatively associated with the body weight (r = −0.515, P = 0.000) and fasting glucose level (r = −0.357, P = 0.002). Notably, treatment with rosiglitazone increased the serum resistin levels by 66.4%(P<0.05)in db/db mice. In 3T3-L1 adipocytes, Rosiglitazone (10 uM) markedly enhanced the secretion of resistin by 120% (P<0.01) and its gene expression by 78.1% (P<0.05).

Conclusion

Both resistin gene expression and its secretion from the epididymal adipose tissue were decreased in db/db obese mice, while the insulin-sensitizing drug rosiglitazone increased resistin production. Our results do not support the role of resistin as an etiological link between obesity and diabetes.     

MicroRNA array and microarray evaluation of endometrial receptivity in patients with high serum progesterone levels on the day of hCG administration

Background  

To determine the effect of higher progesterone (P) level on endometrial receptivity.     

GOLD.db: genomics of lipid-associated disorders database

Background  

The GOLD.db (Genomics of Lipid-Associated Disorders Database) was developed to address the need for integrating disparate information on the function and properties of genes and their products that are particularly relevant to the biology, diagnosis management, treatment, and prevention of lipid-associated disorders.     

Interleukin 11 is upregulated in uterine lavage and endometrial cancer cells in women with endometrial carcinoma

Background  

Interleukin (IL) 11 is produced by human endometrium and endometrial cancer tissue. It has roles in endometrial epithelial cell adhesion and trophoblast cell invasion, two important processes in cancer progression. This study aimed to determine the levels of IL11 in uterine lavage fluid in women with endometrial cancer and postmenopausal women. It further aimed to determine the levels of IL11 protein and its signaling molecules in human endometrial cancer of varying grades, and endometrium from postmenopausal women and IL11 signalling mechanisms in endometrial cancer cell lines.     

Involvement of cyclin B1 in progesterone-mediated cell growth inhibition, G2/M cell cycle arrest, and apoptosis in human endometrial cell

Background  

Progesterone plays an important role in the proliferation and differentiation of human endometrial cells (hECs). Large-dose treatment with progesterone has been used for treatment of endometrial proliferative disorders. However, the mechanisms behind remain unknown.     

A novel hydroxyfuroic acid compound as an insulin receptor activator - structure and activity relationship of a prenylindole moiety to insulin receptor activation

Background  

Diabetes Mellitus is a chronic disease and many patients of which require frequent subcutaneous insulin injection to maintain proper blood glucose levels. Due to the inconvenience of insulin administration, an orally active insulin replacement has long been a prime target for many pharmaceutical companies. Demethylasterriquinone (DMAQ) B1, extracted from tropical fungus, Pseudomassaria sp., has been reported to be an orally effective agent at lowering circulating glucose levels in diabetic (db/db) mice; however, the cytotoxicity associated with the quinone moiety has not been addressed thus far.     

Ultrastructural analysis of progressive endometrial hypercytolipidemia induced by obese (ob/ob) and diabetes (db/db) genotype mutations: structural basis of female reproductive tract involution

The diabetes (db/db) and obese (ob/ob) genotype mutations induce a progressive, hypercytolipidemic condition within the endometrium of the female reproductive tract that promotes sterility and premature organ involution in C57BL/KsJ mice. The current studies focus on the ultrastructural changes that occur within the epithelial and stromal layers of the uterine endometrium during the progressive expression of these mutations, which induce a hyperglycemic-hyperinsulinemic metabolic state and promote tissue cytolipidemia and organoinvolution. Control (normal: +/-), diabetes (db/db) and obese (ob/ob) genotype groups were prepared for high resolution light (LM) and transmission (TEM) microscopic analysis of endometrial tissue samples collected from 4 (young)- to 20 (aged)-week-old mice, allowing for the progressive influences of the mutational aberrations on uterine structure to be evaluated. Compared to controls, both (ob/ob) and (db/db) mutations induced a dramatic increase in endometrial epithelial cytolipid vacuole accumulation, which increased in density between 4 and 20 weeks of age. Lipid vacuoles aggregated at the baso-polar regions of epithelial cells in response to the hyperglycemic-hyperlipidemic conditions typical of both (ob/ob) and (db/db) groups. Progressive cytoplasmic movement of the lipid pools induced a perinuclear isolation from surrounding cytoplasmic organelles. Apical lipid accumulations forced cytoplasmic organelles into peripheral cell compartments and altered the periepithelial stromal cell profile relative to controls. These studies define the progressive, intracellular accumulation of hypercytolipidemic pools which induce a transformation of normal endometrial cell types into adipocyte-like entities. The lipidemia-induced alterations in cell structure disrupt normal tissue continuity and function, culminating in organoinvolution and overt female reproductive sterility.     

Effect of a povidone-iodine intrauterine infusion on progesterone levels and endometrial steroid receptor expression in mares

Background  

Intrauterine infusions have been widely used for the treatment of endometritis in the mare. Nevertheless, their consequences on endocrine and endometrial molecular aspects are unknown. We studied the effect of a 1% povidone-iodine solution intrauterine infusion on progesterone levels, endometrial histology and estrogen (ERα) and progesterone (PR) receptor distribution by immunohistochemistry.