Adolescent social isolation affects parvalbumin expression in the medial prefrontal cortex in the MAM-E17 model of schizophrenia

Altered parvalbumin (PV) expression is observed in the prefrontal cortex of subjects with schizophrenia. Environmental context, particularly during adolescence, might regulate PV expression. In the present study, we investigated the effect of adolescent social isolation (SI) on PV expression in the medial prefrontal cortex in a neurodevelopmental model (MAM-E17) of schizophrenia. SI exposure occurred from postnatal day 30 to 40, followed by resocialization until late adolescence or early adulthood. PV mRNA and protein levels, as well as the number of PV cells, were analysed at these ages. Moreover, epigenetic regulation of PV expression by histone methylation was examined by measuring the total and PV gene-bound H3K4me3 levels. MAM only decreased levels of the PV mRNA and protein in adulthood. Decreases in total H3K4me3 levels and its level at the PV gene were also observed at this age. In contrast, in late adolescence, SI induced a decrease in the expression of the PV mRNA in the MAM group that was related to the reduction in total and PV gene-bound H3K4me3 levels. However, at this age, SI increased the levels of the PV protein in both the control and MAM groups. In adulthood, SI did not affect PV mRNA or H3K4me3 levels but decreased levels of the PV protein in both groups. Both MAM and SI failed to change the number of PV cells at any age. The results indicate that adolescent SI accelerated epigenetic impairments of PV expression in MAM-E17 rats; however, subsequent resocialization abolished this dysfunction, but failed to prevent alterations in PV protein.

     

Ovarian steroid cell tumor as an example of severe hyperandrogenism in 45-year-old woman

Abstract

Approximately, 5% of ovarian tumors have hormonal activity. Steroid cell tumors (SCTs) represent about 0.1% of all ovarian tumors. They cause hyperandrogenism associated with typical virilization. In this case report, we present 45-year-old women with unmalignant ovarian SCT-producing androgens which cause severe virilization and secondary amenorrhea lasting two years. Transvaginal ultrasound, computed tomography of adrenal glands, magnetic resonance imaging of small pelvis, laboratory tests (including serum concentration of FSH, LH, testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEA-S), as well as ROMA index) were performed. During hormonal evaluation, elevated concentrations of serum T – on admission 1.72?ng/ml and one month later 3.75?ng/ml (normal range 0.08–0.82?ng/ml) and A – 24.90?ng/ml (normal range 0.40–3.40?ng/ml) were found. The ROMA index was within the normal range. Enlargement of the left ovary by solid mass 56?×?43?mm was found during ultrasound examination. Based on small pelvis MRI scan and hormonal finding, patient was qualified for laparotomy. During this procedure, the left salpingo-oophorectomy with removal of the tumor was performed. The histopathological examination identified SCT. During follow-up examination, one day after surgery, we found serum testosterone levels within normal ranges – 0.74?ng/ml (normal range 0.08–0.82?ng/ml). This case shows that hormone-producing ovarian tumors are rare but very important clinical causes of severe hyperandrogenism.     

Role of WNT/β-Catenin Pathway as Potential Prognostic and Predictive Factors in Renal Cell Cancer Patients Treated With Everolimus in the Second and Subsequent Lines

Background

The aim of the present study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of the WNT/β-catenin pathway.

Characterization of a complex rearrangement with interstitial deletions and inversion on human chromosome 1

Deletion of the distal band of the short arm of chromosome 1 (monosomy 1p36) is the most common terminal deletion syndrome, occurring in about 1 in 5000 newborns. Of the 121 subjects ascertained for our study to date, 12 (9.9%) have interstitial deletions, three of which are complex rearrangements showing more than one deletion. Herein we report the characterization of a complex rearrangement with two interstitial deletions in the same chromosome 1p36.33-p36.23. We narrowed and analyzed the breakpoints and junctions between the sequence fragments involved in the rearrangement to determine the structure of this deleted chromosome 1. The analyses of the DNA sequence at the junctions showed additional complexity: an inversion and a third de-novo interstitial deletion. We reconstructed this complex rearrangement of 1p36 to understand the mechanism of formation. Analysis of the breakpoint junctions revealed that three of the four breakpoints each interrupted a gene. Alignments of the junctions showed the lack of any sequence similarity between the breakpoints, suggesting the involvement of non-homologous end joining (NHEJ) in the ligation of broken ends following deletion. The identification of translin recognition sites in the breakpoints suggests translin involvement in the repair of broken chromosomes. This report is one of the first to examine constitutional chromosomal rearrangements at the DNA sequence level. The discovery of cryptic events in seemingly simple chromosome rearrangements may provide the basis for proposing mechanisms of formation.     

Myocardial volume and organization are changed by failure of addition of secondary heart field myocardium to the cardiac outflow tract.

Cardiac neural crest ablation results in primary myocardial dysfunction and failure of the secondary heart field to add the definitive myocardium to the cardiac outflow tract. The current study was undertaken to understand the changes in myocardial characteristics in the heart tube, including volume, proliferation, and cell size when the myocardium from the secondary heart field fails to be added to the primary heart tube. We used magnetic resonance and confocal microscopy to determine that the volume of myocardium in the looped heart was dramatically reduced and the compact layer of myocardium was thinner after neural crest ablation, especially in the outflow tract and ventricular regions. Proliferation measured by 5-bromo-2'-deoxyuridine incorporation was elevated at only one stage during looping, cell death was normal and myocardial cell size was increased. Taken together, these results indicate that there are fewer myocytes in the heart. By incubation day 8 when the heart would have normally completed septation, the anterior (ventral) wall of the right ventricle and right ventricular outflow tract was significantly thinner in the neural crest-ablated embryos than normal, but the thickness of the compact myocardium was normal in all other regions of the heart. The decreased volume and number of myocardial cells in the heart tube after neural crest ablation most likely reflects the amount of myocardium added by the secondary heart field.     

NETs in cancer

Many aspects of neutrophil hyperactivity and its role in numerous immune responses still remain a mystery. A new neutrophil mechanism was discovered recently, i.e., the formation of neutrophil extracellular traps (NETs). These structures, composed of DNA strands and neutrophil granule proteins, are an element of the non-specific immune response and bind pathogens to prevent their spread and ensure increased local concentrations of toxic factors. Research on this phenomenon shows that tumor-associated neutrophils (TANs) also form and release NETs. Reports on the role of NETs in the course of cancer are scarce, and the opinions on the involvement of extracellular traps in the disease are divided, indicating a dual function. There is speculation about the anti-cancer properties of NETs connected with direct killing of cancer cells or stimulation of the immune system. On the other hand, the trap structures might promote migration and immune escape of cancer cells or constitute a physical barrier between cancer cells and immune-competent cells. This article summarizes our knowledge about the proven roles of NETs in the course of cancer with particular focus on the significance of NETs as prognosis biomarkers in the course of the neoplastic process and their potential use in therapy.     

A preliminary study of apoptosis induction in glioma cells via alteration of the Bax/Bcl-2-p53 axis by transformed and non-transformed root extracts of Leonurus sibiricus L.

Tumor Biology - Leonurus sibiricus L. is a traditional medicinal plant which occurs in southern Siberia, China, Korea, Japan, and Vietnam. The plant shows several pharmacological effects, but the...     

Expression of extracellular matrix metalloproteinase (MMP-9), E-cadherin and proliferation-associated antigen Ki-67 and their reciprocal correlation in canine mammary adenocarcinomas

BACKGROUND: The purpose of the present study was to determine the expression of the proteins related to tumour metastatic potential, including matrix metalloproteinase (MMP)-9 and E-cadherin, in correlation with the expression of proliferation-associated antigen (Ki-67) in canine mammary adenocarcinomas. MATERIALS AND METHODS: Material for the studies was obtained during surgery from 35 dogs of various breeds, aged 7 to 16 years. Neoplastic tumours were verified by a pathologist. The studied proteins were detected by immunohistochemical reactions. The microphotographs of the studied tumours were subjected to computer-assisted image analysis using MultiScaneBase V 14.02 software. RESULTS: Expression of MMP-9 was noted in almost 83% of the tumours, expression of E-cadherin in 77% of tumours, while expression of Ki-67 antigen was detected in fewer than 26% of studied tumours. CONCLUSION: The positive correlation (r=0.375) between expressions of MMP-9 and Ki-67 and negative correlations between E-cadherin and Ki-67 (r=-0.383) as well as between MMP-9 and E-cadherin (r=-0.45) could suggest that expression and biological significance of the studied markers in mammary adenocarcinomas in dogs resembles the pattern noted in ductal carcinoma, i.e. in the most frequent histological type of malignant tumour in humans. This may point to suitability of the animal model in studies on mechanism of neoplasia and metastases in humans.     

Curcumin in Metabolic Health and Disease

In recent years, epidemiological studies have suggested that metabolic disorders are nutritionally dependent. A healthy diet that is rich in polyphenols may be beneficial in the treatment of metabolic diseases such as polycystic ovary syndrome, metabolic syndrome, non-alcoholic fatty liver disease, cardiovascular disease, and, in particular, atherosclerosis. Curcumin is a polyphenol found in turmeric and has been reported to have antioxidant, anti-inflammatory, hepatoprotective, anti-atherosclerotic, and antidiabetic properties, among others. This review summarizes the influence of supplementation with curcumin on metabolic parameters in selected metabolic disorders.