Progesterone regulation of endometrial estrogen receptor and cell proliferation during the late proliferative and secretory phase in artificial menstrual cycles in the rhesus monkey

Progesterone (P) down-regulation of uterine estradiol (E) receptor (ER) appears to be a general mechanism by which P modulates E action in the uterus. Our present studies focus on the regulation of ER by P during the changeover from E to P dominance during artificial menstrual cycles in the rhesus monkey. Because of differential cell-type response and the cellular zonation of the primate uterus, we used immunohistochemical analysis in addition to biochemical assays to study the regulation of ER by P. Ki-67 immunoreactivity was used as an index of endometrial proliferation. We performed our analyses on Days 13 (peak of E), 14 (declining E and rising P), 17 (basal E and rising P), and 21 (basal E and peak P). ER immunoreactivity was present throughout the endometrium in luminal and glandular epithelia and stromal fibroblasts on Day 13. As E was withdrawn and P rose on Day 14 there were few distinct changes in ER staining in stromal and epithelial cells. On Day 17, immunoreactive staining showed a distinct reduction for stromal cells in all zones. Although luminal epithelial cells showed a decrease in immunoreactivity on Day 17, zones II, III, and IV retained positive staining for ER in glandular epithelia. ER staining in stromal cells on Day 21 was similar to the pattern observed on Day 17, whereas epithelial cells in zones I, II, and III showed a reduction in staining. Glandular epithelia in zone IV maintained strong positive staining for ER on Day 21.(ABSTRACT TRUNCATED AT 250 WORDS

Measuring State and Trait Anxiety: An Application of Multidimensional Item Response Theory

The State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA) is a widely used measure of state and trait anxiety. Within the Classical Testing Theory model, consistent findings provide support for its multidimensional factor structure, discriminant, convergent, and nomological validity, as well as age and gender invariance, across healthy and clinical samples. Nevertheless, some issues regarding STICSA dimensionality and item-scale composition remain unresolved (e.g., both bifactor and two-factor models were found to fit data equally well). The goal of this study was to investigate the STICSA’s dimensionality within the Item Response Theory, and to assess the tenability of the bifactor model as a plausible model over the multidimensional model. The sample consisted of 3338 Italian participants (58.21% females; 41.79% males) with an average age of 35.65 years (range: 18–99; SD = 20.25). Both bifactor and two-correlated dimensions of the STICSA scales were confirmed to fit data by applying the multidimensional Item Response Theory (mIRT). While the bifactor model showed better fit indices, the multidimensional model was more accurate and precise (0.86–0.88) in estimating state and trait latent anxiety. A further comparison between multidimensional item parameters revealed that the multidimensional and bifactor models were equivalent. Findings showed that the STICSA is an accurate and precise instrument for measuring somatic and cognitive symptomatology dimensions within state and trait anxiety. The use of the state/trait total score requires special attention from the clinicians and researchers to avoid bias in the psychodiagnostic assessment

Isolation of progesterone-dependent complementary deoxyribonucleic acid fragments from rhesus monkey endometrium by sequential subtractive hybridization and polymerase chain reaction amplification

The steroid sex hormone progesterone (P) induces the expression of a variety of genes through a signal transduction pathway mediated by the P receptor, a DNA-binding regulator of transcription. To identify genes and gene networks that are P dependent in the rhesus endometrium, we used a powerful technique employing subtractive hybridization coupled with polymerase chain reaction (PCR). Poly(A)+ RNA was isolated from both P-dominant (days 21-23 of artificial menstrual cycles) and estrogen (E)-dominant (days 9-13) endometrium. The two classes of RNA were converted to cDNA, ligated to EcoRI adaptors, and amplified by PCR using an adaptor-complimentary primer. E-dominant cDNA was labeled with biotin, hybridized in excess to P-dominant cDNA (PcDNA), and complexed with streptavidin. Labeled cross-hybrid sequences common to both populations were subtracted by phenol-chloroform extraction. The remaining cDNA fragments were amplified by PCR. After four rounds of hybridization/amplification, the subtracted PcDNA was analyzed for P-dependent sequences by semiquantitive PCR. Initial analysis revealed that housekeeping genes were undetectable in subtracted cDNA, but a previously characterized P-dependent gene was retained. Three of five clones sequenced at random from the subtracted library exhibited P-inducibility/dependency by PCR analysis of E and PcDNA. One of these, an 835-basepair fragment designated H5, may represent a novel P-dependent gene, as no comparable homology could be found with existing sequences in GenBank and Swissprot databases. We estimate that the procedure described here resulted in highly significant enrichment of up-regulated cDNA fragments from P-dominant tissue

Marital Satisfaction in Relation to Age and Number of Children

Previous research on marital satisfaction has shown that while children help to stabilize marriages, they have a negative impact on the satisfaction within the marriage. To understand whether this finding coincides with the rural areas of Northeast Georgia, the authors studied the impact of number and ages of children, as well as stress level of the parents on happiness within the marriage. All three of these factors predicted a diminished marital satisfaction in the couple. Results found that the more children a couple has, the higher their level of parental stress. Age and number of children as well as parental stress levels negatively impacted marital satisfaction. In addition, couples who were younger when they started having kids also seem to have a higher parental stress level, compared to couples who were older when they started having kids. This suggests that marital satisfaction is impacted by children in the same basic ways, regardless of the couples’ location

A new measure for trait and state anxiety: The state trait inventory of cognitive and somatic anxiety (STICSA). standardization in an Italian population

The Italian version of the STICSA has exhibited good psychometric properties in a sample of middle-aged and older adults (Balsamo et al., 2015).The aim of the current project is to investigate psychometric properties of the STICSA in a large Italian population

A new measure for trait and state anxiety: The state trait inventory of cognitive and somatic anxiety (STICSA). standardization in an Italian population

The Italian version of the STICSA has exhibited good psychometric properties in a sample of middle-aged and older adults (Balsamo et al., 2015).The aim of the current project is to investigate psychometric properties of the STICSA in a large Italian population

Frontiers in Anti-Cancer Drug Discovery: Challenges and Perspectives of Metformin as Anti-Angiogenic Add-On Therapy in Glioblastoma

Glioblastoma is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. Glioblastoma shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), has demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including glioblastoma. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss metformin’s potential antitumoral effects on glioblastoma, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of glioblastoma patients

Effects of Metformin as Add-On Therapy against Glioblastoma: An Old Medicine for Novel Oncology Therapeutics

Background: Glioblastoma is the most aggressive primary brain malignancy in adults, with a poor prognosis of about 14 months. Recent evidence ascribed to metformin (MET), an antihyperglycemic drug, the potential to reduce cancer incidence and progression, but the molecular mechanisms underlying these effects need to be better investigated. Methods: Here, we tested the efficacy of MET on n = 10 primary glioblastoma endothelial cells (GECs), by viability and proliferation tests, as MTT and Live/Dead assays, apoptosis tests, as annexin V assay and caspase 3/7 activity, functional tests as tube-like structure formation and migration assay and by mRNA and protein expression performed by quantitative real-time PCR analysis (qRT-PCR) and Western Blot, respectively. Results: Data resulting revealed a time- and μ-dependent ability of MET to decrease cell viability and proliferation, increasing pro-apoptotic mechanisms mediated by caspases 3/7. Also, MET impacted GEC functionality with a significant decrease of angiogenesis and invasiveness potential. Mechanistically, MET was able to interfere with sphingolipid metabolism, weakening the oncopromoter signaling promoted by sphingosine-1-phosphate (S1P) and shifting the balance toward the production of the pro-apoptotic ceramide. Conclusions: These observations ascribed to MET the potential to serve as add-on therapy against glioblastoma, suggesting a repurposing of an old, totally safe and tolerable drug for novel oncology therapeutics

Microgravity and the intervertebral disc: The impact of space conditions on the biomechanics of the spine

The environmental conditions to which astronauts and other military pilots are subjected represent a unique example for understanding and studying the biomechanical events that regulate the functioning of the human body. In particular, microgravity has shown a significant impact on various biological systems, such as the cardiovascular system, immune system, endocrine system, and, last but not least, musculoskeletal system. Among the potential risks of flying, low back pain (LBP) has a high incidence among astronauts and military pilots, and it is often associated with intervertebral disc degeneration events. The mechanisms of degeneration determine the loss of structural and functional integrity and are accompanied by the aberrant production of pro-inflammatory mediators that exacerbate the degenerative environment, contributing to the onset of pain. In the present work, the mechanisms of disc degeneration, the conditions of microgravity, and their association have been discussed in order to identify possible molecular mechanisms underlying disc degeneration and the related clinical manifestations in order to develop a model of prevention to maintain health and performance of air- and space-travelers. The focus on microgravity also allows the development of new proofs of concept with potential therapeutic implications