The Non-Coding Transcriptome of Prostate Cancer: Implications for Clinical Practice

Prostate cancer (PCa) is the most common type of cancer and the second leading cause of cancer-related death in men. Despite extensive research, the molecular mechanisms underlying PCa initiation and progression remain unclear, and there is increasing need of better biomarkers that can distinguish indolent from aggressive and life-threatening disease. With the advent of advanced genomic technologies in the last decade, it became apparent that the human genome encodes tens of thousands non-protein-coding RNAs (ncRNAs) with yet to be discovered function. It is clear now that the majority of ncRNAs exhibit highly specific expression patterns restricted to certain tissues and organs or developmental stages and that the expression of many ncRNAs is altered in disease and cancer, including cancer of the prostate. Such ncRNAs can serve as important biomarkers for PCa diagnosis, prognosis, or prediction of therapy response. In this review, we give an overview of the different types of ncRNAs and their function, describe ncRNAs relevant for the diagnosis and prognosis of PCa, and present emerging new aspects of ncRNA research that may contribute to the future utilization of ncRNAs as clinically useful therapeutic targets

Age dynamic in the central corneal thickness in children

Цел: Да се установи и анализира съществува ли динамика в биометричния показател централна роговична дебелина при българските деца от различни възрастови групи. Обект: Проучването обхваща 248 пациента/496 очи/, разпределени в четири възрастови групи. Метод: Ултразвукова пахиметрия с PacScanЗ00AP. Изводи: Установи се статистически значимо нарастване на средното ниво на ЦРД с възрастта на децата до 15 години. Средното ниво на ЦРД във втора и трета група е еднакво. С нарастване на възрастта нараства ЦРД и тя е най-голяма в четвърта група.Aim: To identify and analyze the dynamic of central corneal thickness in Bulgarian children in different age groups. Object: The study cover 248 patient / 496 eye / divided into four age groups. Method: Ultrasonic pachimetry with PacScan300AP. Conclusions: Establish a statistically signi? cant increase in the average level of CRD in children to 15 years old. Average CRD in the second and third group is the same. With increasing age increases CRD and it is greatest in the fourth group

Neuroactive steroids in depression and anxiety disorders: Clinical studies

Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3 alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3 alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment, we studied the impact of nonpharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation, nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder, changes in neuroactive steroid composition have been observed opposite to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3 alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(A) receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds. Copyright (c) 2006 S. Karger AG, Basel

Cytokine profile in community-acquired pneumonia in children

Community-acquired pneumonia (CAP) is one of the most common acute infectious diseases. To date, the incidence of CAP among children was decreased significantly worldwide, mainly due to increasing use of effective preventive measures. Nevertheless, CAP remains a common cause of childhood morbidity and mortality. Pneumonia may develop at any age, but most often it occurs in young children, who are more likely to have a more severe course of pneumonia. Currently, early diagnosis and prognosis of the disease severity in children is an urgent issue. It was found that, in most cases, a panel of conventional biomarkers, including the number of leukocytes, procalcitonin, CRP is not sufficient for the diagnosis of pediatric CAP. There is a demand for new biological markers which, along with clinical evaluation, may significantly improve diagnostics and management of CAP in children, thus reducing the risk of adverse outcomes associated with this disease. Such markers could be found among the cytokines, which are active participants in the CAP pathogenesis. The aim of this study was to determine the level of several cytokines in blood serum of children with CAP and to assess changes in the cytokine profile depending on the patient’s age and severity of the disease. The study included 117 children aged 1 to 18 years with a diagnosis of CAP confirmed by X-ray examination. The comparison group included 28 healthy children who did not have CAP or other signs of acute respiratory viral infection at the time of examination, being free of any chronic pathology requiring outpatient observation. A number of cytokines were determined quantitatively in blood serum, i.e., IL-1β, IFNγ, IL-2, IL-4, IL-6, IL-10, TNFα, IFNλ2 (IL-28A), IFNλ3 (IL-28B), IL-8, MCP-1, IL-17AF, GM-CSF using test systems based on the “sandwich” method of solid-phase ELISA using peroxidase labeling. As a result, it was found that the content of IL-6, IL-17AF, IL-1β, IFNγ, MCP-1, IFNλ2 (IL-28A), IFNλ3 (IL-28B), GM-CSF was significantly higher in the group of children with severe community-acquired pneumonia. The levels of certain cytokines, e.g., IL-6, IFNλ2 (IL-28A), IFNλ3 (IL-28B), GM-CSF varied depending on the age of patients, thus, probably, reflecting the degree of immune system activation in the children of different age groups

Strengthening CoViD-19 therapy via combinations of RAS modulators.

Evidence has accumulated that the pathology of CoViD-19 is strongly related to the renin-angiotensin system (RAS). The blockage of the angiotensin converting enzyme 2 (ACE2) by the SARS-CoV-2 virus leads to downstream consequences such as increased vascular tone, extensive fibrosis and pronounced immune reactions. Different approaches to tackle the adverse viral effects by compensating the lost ACE2 function have been suggested. Here, we use an unequal-arm lever model to describe a simplified version of the biased regulation exercised by the angiotensin II and angiotensin-(1-7) hormones, which are the substrate and the product of ACE2, respectively. We reason upon the lever dynamics and its disruptions caused by the virus, and propose that a combination of RAS modulators will most efficiently compensate the imbalance due to the excess of angiotensin II and the scarcity of angiotensin-(1-7). Specifically, we focus on the possible benefits of the simultaneous application of two agents, a MAS-receptor agonist and an angiotensin-II-type-2-receptor agonist. We conjecture that this combination has the potential to introduce a beneficial synergistic action that promotes anti-hypoxic, anti-fibrotic and anti-proliferative effects, thereby improving the clinical management of acute and chronic CoViD-19 pathologies

Aspergillus as a multi-purpose cell factory: current status and perspectives

Aspergilli have a long history in biotechnology as expression platforms for the production of food ingredients, pharmaceuticals and enzymes. The achievements made during the last years, however, have the potential to revolutionize Aspergillus biotechnology and to assure Aspergillus a dominant place among microbial cell factories. This mini-review will highlight most recent breakthroughs in fundamental and applied Aspergillus research with a focus on new molecular tools, techniques and products. New trends and concepts related to Aspergillus genomics and systems biology will be discussed as well as the challenges that have to be met to integrate omics data with metabolic engineering attempts

Assessing the effectiveness of the Ramsar Convention in preserving wintering waterbirds in the Mediterranean

lthough biological conservation is based on international agreements, its effectiveness depends on how countries implement such recommendations as effective conservation tools. The Ramsar Convention is the oldest international treaty for wetland and waterbird conservation, establishing the world's largest network of protected areas. However, since it does not constitute any binding measure, its effectiveness in protecting wintering waterbird populations at an international scale has been questioned. Here, we use long-term (1991–2012) count data to assess the effectiveness of the Ramsar Convention in the Mediterranean Basin. We compared abundance and temporal trends of 114 waterbird species between 251 Ramsar wetlands and 3486 non-Ramsar wetlands. We found that the Ramsar network is critical for wintering waterbirds, concentrating nearly half of all waterbirds counted in the Mediterranean Basin in only 7% of monitored wetlands. Waterbird trends followed a northwestsoutheast gradient, with a population decrease in the East. A significant and positive Ramsar effect on population trends was only found for the species of higher conservation concern in the Maghreb, particularly when a management plan was implemented. The Ramsar Convention was previously used on very important wetlands for waterbirds in Southern Europe, but is now an underused conservation tool. Our study suggests weaknesses in the use of Ramsar as an effective conservation tool in most of the Mediterranean Basin. However, the Ramsar Convention effectiveness to enhance waterbird populations in the Maghreb should encourage strengthening the Ramsar Convention. It should be done particularly in countries with limited environmental agreements and by systematic implementation of management plans. Conservation measures International conventions Protected areas Protection status Monitoring WetlandsacceptedVersio

Identification of Genes Affecting the Toxicity of Anti-Cancer Drug Bortezomib by Genome-Wide Screening in S. pombe

Bortezomib/PS-341/Velcade, a proteasome inhibitor, is widely used to treat multiple myeloma. While several mechanisms of the cytotoxicity of the drug were proposed, the actual mechanism remains elusive. We aimed to identify genes affecting the cytotoxicity of Bortezomib in the fission yeast S.pombe as the drug inhibits this organism's cell division cycle like proteasome mutants. Among the 2815 genes screened (covering 56% of total ORFs), 19 genes, whose deletions induce strong synthetic lethality with Bortezomib, were identified. The products of the 19 genes included four ubiquitin enzymes and one nuclear proteasome factor, and 13 of them are conserved in humans. Our results will provide useful information for understanding the actions of Bortezomib within cells