Repeated PTZ Treatment at 25-Day Intervals Leads to a Highly Efficient Accumulation of Doublecortin in the Dorsal Hippocampus of Rats

BACKGROUND: Neurogenesis persists throughout life in the adult mammalian brain. Because neurogenesis can only be assessed in postmortem tissue, its functional significance remains undetermined, and identifying an in vivo correlate of neurogenesis has become an important goal. By studying pentylenetetrazole-induced brain stimulation in a rat model of kindling we accidentally discovered that 25±1 days periodic stimulation of Sprague-Dawley rats led to a highly efficient increase in seizure susceptibility. METHODOLOGY/PRINCIPAL FINDINGS: By EEG, RT-PCR, western blotting and immunohistochemistry, we show that repeated convulsive seizures with a periodicity of 25±1 days led to an enrichment of newly generated neurons, that were BrdU-positive in the dentate gyrus at day 25±1 post-seizure. At the same time, there was a massive increase in the number of neurons expressing the migratory marker, doublecortin, at the boundary between the granule cell layer and the polymorphic layer in the dorsal hippocampus. Some of these migrating neurons were also positive for NeuN, a marker for adult neurons. CONCLUSION/SIGNIFICANCE: Our results suggest that the increased susceptibility to seizure at day 25±1 post-treatment is coincident with a critical time required for newborn neurons to differentiate and integrate into the existing hippocampal network, and outlines the importance of the dorsal hippocampus for seizure-related neurogenesis. This model can be used as an in vivo correlate of neurogenesis to study basic questions related to neurogenesis and to the neurogenic mechanisms that contribute to the development of epilepsy

Two Worlds Colliding: The Interplay Between Natural Compounds and Non-Coding Transcripts in Cancer Therapy

Cancer is a devastating disease and has recently become the leading cause of death in western countries, representing an immense public health burden. When it comes to cancer treatment, chemotherapy is one of the main pillars, especially for advanced stage tumors. Over the years, natural compounds have emerged as one of the most valuable resources for new chemotherapies. It is estimated that more than half of the currently used chemotherapeutic agents are derived from natural compounds. Usually, natural compounds are discovered empirically and an important limitation of introducing new anti-cancer natural products is lack of knowledge with regard to their mechanism of action. Recent data has proven that several natural compounds may function via modulating the expression and function of non-coding RNAs (ncRNAs). NcRNAs are a heterogenous class of RNA molecules which are usually not translated into proteins but have an important role in gene expression regulation and are involved in multiple tumorigenic processes, including response/resistance to pharmacotherapy. In this review, we will discuss how natural compounds function via ncRNAs while summarizing the available data regarding their effects on over 15 types of cancer. Moreover, we will critically analyze the current advances and limitations in understanding the way natural compounds exert these health-promoting effects by acting on ncRNAs. Finally, we will propose several hypotheses that may open new avenues and perspectives regarding the interaction between natural compounds and ncRNAs, which could lead to improved natural compound-based therapeutic strategies in cancer.Peer Reviewe

Biological and Histological Assessment of the Hepatoportoenterostomy Role in Biliary Atresia as a Stand-Alone Procedure or as a Bridge toward Liver Transplantation

Background and objectives: In patients with biliary atresia (BA), hepatoportoenterostomy (HPE) is still a valuable therapeutic tool for prolonged survival or a safer transition to liver transplantation. The main focus today is towards efficient screening programs, a faster diagnostic, and prompt treatment. However, the limited information on BA pathophysiology makes valuable any experience in disease management. This study aimed to analyze the evolution and survival of patients with BA referred for HPE (Kasai operation) in our department. Materials and Methods: A retrospective analysis was performed on fourteen patients with BA, diagnosed in the pediatric department and further referred for HPE in our surgical department between 2010 and 2016. After HPE, the need for transplantation was assessed according to patients cytomegalovirus (CMV) status, and histological and biochemical analysis. Follow-up results at 1–4 years and long term survival were assessed. Results: Mean age at surgery was 70 days. Surgery in patients younger than 60 days was correlated with survival. Jaundice’s clearance rate at three months was 36%. Total and direct bilirubin values had a significant variation between patients with liver transplants and native liver (p = 0.02). CMV was positive in eight patients, half with transplant need and half with native liver survival. Smooth muscle actin (SMA) positivity was proof of advanced fibrosis. The overall survival rate was 79%, with 75% for native liver patients and an 83% survival rate for those with liver transplantation. Transplantation was performed in six patients (43%), with a mean of 10 months between HPE and transplantation. Transplanted patients had better survival. Complications were diagnosed in 63% of patients. The mean follow-up period was six years. Conclusions: HPE, even performed in advanced cirrhosis, allows a significant survival, and ensures an essential time gain for patients requiring liver transplantation. A younger age at surgery is correlated with a better outcome, despite early CMV infection

High potential for CH₄ emission mitigation from oil infrastructure in one of EU's major production regions

Ambitious methane (CH4) emission mitigation represents one of the most effective opportunities to slow the rate of global warming over the next decades. The oil and gas (O&amp;G) sector is a significant source of methane emissions, with technically feasible and cost-effective emission mitigation options. Romania, a key O&amp;G producer within the EU, with the second highest reported annual CH4 emissions from the energy sector in the year 2020 (Greenhouse Gas Inventory Data - Comparison by Category, 2022), can play an important role towards the EU's emission reduction targets. In this study, we quantify CH4 emissions from onshore oil production sites in Romania at source and facility level using a combination of ground- and drone-based measurement techniques. Measured emissions were characterized by heavily skewed distributions, with 10 % of the sites accounting for more than 70 % of total emissions. Integrating the results from all site-level quantifications with different approaches, we derive a central estimate of 5.4 kg h−1 per site of CH4 (3.6 %–8.4 %, 95 % confidence interval) for oil production sites. This estimate represents the third highest when compared to measurement-based estimates of similar facilities from other production regions. Based on our results, we estimate a total of 120 kt CH4 yr−1 (range: 79–180 kt yr−1) from oil production sites in our studied areas in Romania. This is approximately 2.5 times higher than the reported emissions from the entire Romanian oil production sector for 2020. Based on the source-level characterization, up to three-quarters of the detected emissions from oil production sites are related to operational venting. Our results suggest that O&amp;G production infrastructure in Romania holds a massive mitigation potential, specifically by implementing measures to capture the gas and minimize operational venting and leaks.</p