SRF depletion in early life contributes to social interaction deficits in the adulthood.

Alterations in social behavior are core symptoms of major developmental neuropsychiatric diseases such as autism spectrum disorders or schizophrenia. Hence, understanding their molecular and cellular underpinnings constitutes the major research task. Dysregulation of the global gene expression program in the developing brain leads to modifications in a number of neuronal connections, synaptic strength and shape, causing unbalanced neuronal plasticity, which may be important substrate in the pathogenesis of neurodevelopmental disorders, contributing to their clinical outcome. Serum response factor (SRF) is a major transcription factor in the brain. The behavioral influence of SRF deletion during neuronal differentiation and maturation has never been studied because previous attempts to knock-out the gene caused premature death. Herein, we generated mice that lacked SRF from early postnatal development to precisely investigate the role of SRF starting in the specific time window before maturation of excitatory synapses that are located on dendritic spine occurs. We show that the time-controlled loss of SRF in neurons alters specific aspects of social behaviors in SRF knock-out mice, and causes deficits in developmental spine maturation at both the structural and functional levels, including downregulated expression of the AMPARs subunits GluA1 and GluA2, and increases the percentage of filopodial/immature dendritic spines. In aggregate, our study uncovers the consequences of postnatal SRF elimination for spine maturation and social interactions revealing novel mechanisms underlying developmental neuropsychiatric diseases.

The gill monogenean Sciadicleithrum variabilum induces histomorphological alterations in the gill tissues of the discus Symphysodon aequifasciatus.

High mortality is among the most serious problems and challenges in the ornamental fish trade. Examination of the discus Symphysodon aequifasciatus from ornamental fish hatchery revealed infestation with the monogenean Sciadicleithrum variabilum. Gill infestation with this monogenean induced serious damage to the gill lamellae, including clavate lamellae, vascular congestion in the peripheral blood vessels, lamellar blood sinus dilation, and other structural anomalies. Light and transmission electron microscopy showed that in all infested hosts the interlamellar cell mass (ILCM) completely filled the interlamellar space. The monogenean-associated damage combined with the ILCM led to severe impairment of respiratory efficiency of the gill. Anti-parasitic treatment was applied during breeding (hatchery), which was followed by almost complete regression of the ILCM seen in the fish. A single point of ILCM hyperplasia was observed in only one specimen at the site of parasite attachment to the gill filament. The ILCM covering the gill lamellae protected the discus against infestation with this monogenean, but considerable reduction in the gaseous exchange surface and serious damage to the gill lamellae contributed to the increased mortality of the fish in the hatchery, which reached 90%.

Aloe arborescens juice prevents EMF-induced oxidative stress and thus protects from pathophysiology in the male reproductive system in vitro.

More and more studies suggest that prolonged exposure to EMF may cause adverse biological effects and point directly to a significantly negative correlation between EMF and human health, especially men fertility. In our previous study, we reported that this could be related to the EMF-induced reactive oxygen species formation, followed by DNA damage, cell cycle arrest and apoptosis induction. In this study, we decided to expand our research by the search for substances which would prevent EMF-induced damage in spermatogenic cells. Such an agent seems to be Aloe arborescens Mill. juice, which was shown to possess a wide range of protective properties. The administration of aloe extract helps among others to prevent the formation of free radicals by various biochemical pathways. Therefore, the main aim of our study was to provide a significant knowledge concerning the mechanism involved in the multi-pathway cytoprotective response of aloe juice against EMF. The study was carried out in an in vitro mouse spermatogenesis pathway cell lines (GC-1 spg and GC-2 spd). Our results suggest that the aloe juice has many positive effects, especially for the cellular antioxidant systems by reducing the intracellular reactive oxygen species pool induced by EMF. In consequence, aloe juice prevents DNA damage, cell cycle arrest and therefore the viability and metabolic activity of both cell line tested are preserved. In conclusion, our study provides new insight into the underlying mechanisms through which aloe juice prevents spermatogenic cells from cytotoxic and genotoxic events.

Cancer on-target: Selective enhancement of 3-bromopyruvate action by an electromagnetic field in vitro.

Cancer is one of the leading causes of death in the modern world. Nowadays, most often treatment methods used in clinical oncology are drug therapies applied as monotherapy or combined therapy. Additionally, recent studies focus on developing approaches with the use of a drug in combination with other factors, not only chemical, to improve the probability and magnitude of therapeutic responses and reduce the possibility of chemoresistance. Such a promising factor seems to be an electromagnetic field (EMF) application. Here, we tested the effect of continuous or pulsed EMF on human cancer cells of different origin treated or not with 3-bromopyruvate, a small and powerful alkylating agent with a broad spectrum of anticancer activities. We provide strong evidence suggesting that ELF-EMF potentiates the anti-cancer activity of 3BP in human cancer cells through inhibition of TNFα secretion leading to irreversible p21/p27-dependent G2/M cell cycle arrest and finally cancer cell death. Our findings suggest a novel approach combining pharmacotherapy with ELF-EMF. In conclusion, electromagnetic field seems to be a potential modulator of anti-cancer efficacy of 3BP while combined therapy offers off-target activity. These features contribute to the development of innovative therapeutic strategies for cancer treatment.

Establishment of two hiPSC lines (IIMCBi001-A and IIMCBi002-A) from dermal fibroblasts of healthy donors and characterization of their cell cycle.

Two human induced pluripotent stem cell (hiPSC) lines (IIMCBi001-A and IIMCBi002-A) were generated from dermal fibroblasts of healthy females 10 and 30 years old, respectively. For the reprogramming lentiviral vector expressing OCT4, SOX2, KLF4 and C-MYC was used. The generated hiPSCs showed typical embryonic stem cell-like morphology and correct diploid karyotype. Characterization of the hiPSC lines confirmed expression of pluripotency markers and demonstrated their ability to differentiate into the three-germ layers. Cell cycle analysis of the hiPSCs allowed to estimate population doubling time (DT), duration time of particular phases of the cell cycle and proportion of cells found at each phase.

Pulsed or continuous electromagnetic field induce p53/p21-mediated apoptotic signaling pathway in mouse spermatogenic cells in vitro and thus may affect male fertility.

The impact of electromagnetic field (EMF) on the human health and surrounding environment is a common topic investigated over the years. A significant increase in the electromagnetic field concentration arouses public concern about the long-term effects of EMF on living organisms associated with many aspects. In the present study, we investigated the effects of pulsed and continuous electromagnetic field (PEMF/CEMF) on mouse spermatogenic cell lines (GC-1 spg and GC-2 spd) in terms of cellular and biochemical features in vitro. We evaluated the effect of EMF on mitochondrial metabolism, morphology, proliferation rate, viability, cell cycle progression, oxidative stress balance and regulatory proteins. Our results strongly suggest that EMF induces oxidative and nitrosative stress-mediated DNA damage, resulting in p53/p21-dependent cell cycle arrest and apoptosis. Therefore, spermatogenic cells due to the lack of antioxidant enzymes undergo oxidative and nitrosative stress-mediated cytotoxic and genotoxic events, which contribute to infertility by reduction in healthy sperm cells pool. In conclusion, electromagnetic field present in surrounding environment impairs male fertility by inducing p53/p21-mediated cell cycle arrest and apoptosis.