Telomerase - future drug target enzyme?

Problem pomnoževanja koncev evkariontskih kromosomov (telomer) so uspešno rešili z odkritjem encima telomeraze konec 80. let prejšnjega stoletja, za odkritje so leta 2009 podelili tudi Nobelovo nagrado za medicino in fiziologijo. Izražanje telomeraze pri rakavih boleznih in človeške sanje o večni mladosti so močno pospešile razvoj farmakoloških telomeraznih inhibitorjev in aktivatorjev, vendar pa kljub 15-letnemu raziskovanju zdravila še niso dostopna na trgu. V članku smo glede na podatke v svetovnih medijih in literaturi naredili pregled farmakoloških učinkovin v zgodnjih fazah kliničnih preskušanj, ki specifično uravnavajo aktivnost telomeraze. Načrtovana protitumorska zdravila večinoma ne bodo namenjena samostojni uporabi, saj telomerazne inhibitorje klinično preskušajo v kombinaciji z obstoječimi kemoterapevtskimi sredstvi, protitelomerazna cepiva pa v kombinaciji z imunostimulansi. Poleg raka in staranja v prispevku navajamo ostala bolezenska stanja, ki so povezana s telomerazo/telomerami, hkrati pa opisujemo tudi tehnično-pravne probleme pri razvoju novih zdravil. Glede na dinamiko razvoja lahko prva protitelomerazna zdravila na trgu pričakujemo v naslednjih petih letih.Eucaryotic chromosome endings (telomeres) replication problem was solved in the 1980\u27s by discovery of the telomerase enzyme. The Nobel Prize in Physiology or Medicine was awarded in 2009 for the discovery of telomerase. Altered telomerase expression in cancer, and human dream of eternal youth haveaccelerated the development of pharmacological telomerase inhibitors and activators. However, after 15 years of development they are still not available on the market. In the present article we reviewed pharmacological agents that target telomerase activity, which have entered clinical trials. Current drugs in development are mostly not intended to be used alone, as telomerase inhibitors under clinical trials are used in combination with the existing chemotherapeutics and anti-telomerase vaccines in combination with immuno-stimulants. Apart from cancer and aging, there are other diseases linked to deregulated activity of telomerasežtelomeres and we also discuss technical and legal problems that researchers encounter in developing anti-telomerase therapy. Given the pace of development, first anti-telomerase drugs might appear on the market in the next 5 years

Modulation of Campylobacter jejuni adhesion to biotic model surfaces by fungal lectins and protease inhibitors

Campylobacter jejuni, a Gram-negative bacterium, is one of the most common causes of foodborne illness worldwide. Its adhesion mechanism is mediated by several bacterial factors, including flagellum, protein adhesins, lipooligosaccharides, proteases, and host factors, such as surface glycans on epithelial cells and mucins. Fungal lectins, specialized carbohydrate-binding proteins, can bind to specific glycans on host and bacterial cells and thus influence pathogenesis. In this study, we investigated the effects of fungal lectins and protease inhibitors on the adhesion of C. jejuni to model biotic surfaces (mucin, fibronectin, and collagen) and Caco-2 cells as well as the invasion of Caco-2 cells. The lectins Marasmius oreades agglutinin (MOA) and Laccaria bicolor tectonin 2 (Tec2) showed remarkable efficacy in all experiments. In addition, different pre-incubations of lectins with C. jejuni or Caco-2 cells significantly inhibited the ability of C. jejuni to adhere to and invade Caco-2 cells, but to varying degrees. Pre-incubation of Caco-2 cells with selected lectins reduced the number of invasive C. jejuni cells the most, while simultaneous incubation showed the greatest reduction in adherent C. jejuni cells. These results suggest that fungal lectins are a promising tool for the prevention and treatment of C. jejuni infections. Furthermore, this study highlights the potential of fungi as a rich reservoir for novel anti-adhesive agents

Osnovna mikrobiologija

Bridging the gap between the theoretical and the practical application of what students are learning is the first step towards understanding the central roles of microorganisms in nature and in our daily lives. Our goal for these instructions on laboratory exercises is to provide a bridge that helps our foreign students, who choose the Microbiology course (Erasmus exchange program), to integrate lectures with laboratory experience.Znanje študentov sloni na gradnji mostu med teoretično osnovo in praktičnimi vajami ter ponazarja prvi korak na poti do razumevanja poglavitne vloge mikroorganizmov v naravi in našem vsakdanjiku. Namen navodil za laboratorijske vaje pri predmetu Mikrobiologija v angleškem jeziku je omogočiti gradnjo tega mostu ter tako naše tuje študente, ki si v okviru programa Erasmus izberejo učni predmet Mikrobiologija, naučiti povezovanja teoretičnih osnov s praktičnimi prvinami

Food risk analysis

For risk communication, it is important to understand the difference between “hazard” and “risk”. Definitions can be found in Codex Alimentarius and the European Union (EU) General Food Regulation (EC) No. 178/2002. The use of these terms as synonyms or their interchange is a recurrent issue in the area of food safety, despite awareness-raising messages sent by EFSA (European Food Safety Authority) and other interested entities. A quick screening of the EU’s food regulations revealed several inconsistencies. Hence, it was considered necessary to further investigate if regulations could act as a source for this problem. A software tool was developed to support the detection and listing of inconsistent translations of “hazard” and “risk” in certain EU food regulations. Subsequently, native-speaking experts working in food safety from each EU country were asked to provide their individual scientific opinion on the prepared list. All data were statistically analysed after applying numerical scores (1–5) describing different levels of consistency. Results showed that the most common problem was the interchange of “hazard” with “risk” and vice versa. This lack of consistency can create confusion that can further translate into misjudgments at food risk assessment and communication levels

Probiotic Mechanisms Affecting Glucose Homeostasis: A Scoping Review

The maintenance of a healthy status depends on the coexistence between the host organism and the microbiota. Early studies have already focused on the nutritional properties of probiotics, which may also contribute to the structural changes in the gut microbiota, thereby affecting host metabolism and homeostasis. Maintaining homeostasis in the body is therefore crucial and is reflected at all levels, including that of glucose, a simple sugar molecule that is an essential fuel for normal cellular function. Despite numerous clinical studies that have shown the effect of various probiotics on glucose and its homeostasis, knowledge about the exact function of their mechanism is still scarce. The aim of our review was to select in vivo and in vitro studies in English published in the last eleven years dealing with the effects of probiotics on glucose metabolism and its homeostasis. In this context, diverse probiotic effects at different organ levels were highlighted, summarizing their potential mechanisms to influence glucose metabolism and its homeostasis. Variations in results due to different methodological approaches were discussed, as well as limitations, especially in in vivo studies. Further studies on the interactions between probiotics, host microorganisms and their immunity are needed

Activité biologique de certaines souches roumaines et turques de <i>Trichoderma</i> Pers

Les infections causées par des champignons et des bactéries envahissants comptent parmi les principales causes de pertes agricoles et de contamination des aliments. Les infections fongiques humaines diminuent la qualité de vie et, dans les cas graves, elles peuvent entraîner une morbidité, voire une mortalité. Dans le domaine agricole, des traitements préventifs doivent être fournis pour contrôler les maladies des plantes, tandis que dans le système de santé, pour supprimer les infections par des agents pathogènes humains, des mesures curatives peuvent également être appliquées, mais avec des coûts importants dans n’importe quelle partie du monde. Pour pallier ces carences, trois souches de Trichoderma spp. ont été étudiées pour leurs activités antimicrobiennes et antibiofilm. L’effet antifongique de ces souches a été évalué contre huit champignons phytopathogènes communs : Alternaria sp. Nees, Botrytis cinerea Pers., Fusarium culmorum (Wm.G.Sm.) Sacc., F. graminearum Schwabe, F. oxysporum Schltdl., F. proliferatum (Matsush.) Nirenberg ex Gerlach &amp; Nirenberg, Macrophomina phaseolina (Tassi) Goid. et Sclerotinia sclerotiorum (Lib.) de Bary. Les souches testées de Trichoderma spp. ont réduit la croissance des pathogènes d’au moins 50 %, et elles ont été le plus efficace contre B. cinerea, avec jusqu’à 92,1 ± 2,0 % d’inhibition. L’activité antibactérienne de l’extrait brut de cultures liquides du Trichoderma spp. a été aussi examinée contre six pathogènes humains opportunistes et contaminants alimentaires : Enterococcus faecalis (Andrewes &amp; Horder) Schleifer &amp; Kilpper-Bälz, Escherichia coli (Migula) Castellani &amp; Chalmers, Listeria monocytogenes (Murray et al.) Pirie, Pseudomonas aeruginosa (Schroeter) Migula, Salmonella typhimurium (Loeffler) Castellani &amp; Chalmers et Staphylococcus aureus Rosenbach. L’activité antibactérienne a été déterminée par la méthode du disque de diffusion. Les souches testées de Trichoderma spp. se sont révélé avoir une activité inhibitrice particulièrement élevée contre les bactéries Gram positives. De plus, l’activité antibiofilm de ces trois souches de biocontrôle a également été examinée par le kit XTT Assay. La souche turque Trichoderma sp. Ș4 a montré une activité inhibitrice significative contre les agents pathogènes testés.Disease infections caused by invasive fungi and bacteria, are some of the major causes of agricultural losses and food contamination. Human pathogenic infections are diminishing the quality of life, and in severe cases, they can trigger morbidity or even mortality. In the agricultural field, preventive treatments should be provided to control plant diseases, while in the healthcare system, for suppressing human pathogens infections, curative measures can also be applied, but with enormous costs in many parts of the world. To diminish these shortcomings, three Trichoderma spp. strains were screened in this study for antimicrobial and antibiofilm activities. The antifungal effect of these strains was evaluated against eight common plant pathogenic fungi: Alternaria sp. Nees, Botrytis cinerea Pers., Fusarium culmorum (Wm.G.Sm.) Sacc., F. graminearum Schwabe, F. oxysporum Schltdl., F. proliferatum (Matsush.) Nirenberg ex Gerlach &amp; Nirenberg, Macrophomina phaseolina (Tassi) Goid. and Sclerotinia sclerotiorum (Lib.) de Bary. Tested Trichoderma spp. strains reduced the pathogenic growth with at least 50% inhibition; however, they were most effective against B. cinerea, with up to 92.1 ± 2.0% inhibition. The antibacterial activity of the crude extract obtained from liquid cultures of tested Trichoderma spp. strains was also screened against six opportunistic human pathogens and food contaminants: Enterococcus faecalis (Andrewes &amp; Horder) Schleifer &amp; Kilpper-Bälz, Escherichia coli (Migula) Castellani &amp; Chalmers, Listeria monocytogenes (Murray et al.) Pirie, Pseudomonas aeruginosa (Schroeter) Migula, Salmonella typhimurium (Loeffler) Castellani &amp; Chalmers and Staphylococcus aureus Rosenbach. Antibacterial activity was determined by disc diffusion assay, and tested Trichoderma spp. strains revealed particularly high inhibitory activity against gram positive bacteria. Moreover, the antibiofilm activity of these three biocontrol strains was also screened by XTT Assay kit. Turkish Trichoderma sp. Ș4 strain showed significant inhibitory activity against the tested pathogens.</p

In vitro selection and characterization of new probiotic candidates from table olive microbiota

To date, only a few studies have investigated the complex microbiota of table olives in order to identify new probiotic microorganisms, even though this food matrix has been shown to be a suitable source of beneficial lactic acid bacteria (LAB). Two hundred and thirty eight LAB, belonging to Lactobacillus plantarum, Lactobacillus pentosus and Leuconostoc mesenteroides species, and isolated from Nocellara Etnea table olives, have been screened in this survey through an in vitro approach. A simulation of transit tolerance in the upper human gastrointestinal tract, together with autoaggregation and hydrophobicity, have been decisive in reducing the number of LAB to 17 promising probiotics. None of the selected strains showed intrinsic resistances towards a broad spectrum of antibiotics and were therefore accurately characterized on an undifferentiated and 3D functional model of the human intestinal tract made up of H4-1 epithelial cells. As far as the potential colonization of the intestinal tract is concerned, a high adhesion ratio was observed for Lb. plantarum O2T60C (over 9%) when tested in the 3D functional model, which closely mimics real intestinal conditions. The stimulation properties towards the epithelial barrier integrity and the in vitro inhibition of L. monocytogenes adhesion and invasion have also been assessed. Lb. plantarum S1T10A and S11T3E enhanced trans-epithelial electrical resistance (TEER) and therefore the integrity of the polarized epithelium in the 3D model. Moreover, S11T3E showed the ability to inhibit L. monocytogenes invasion in the undifferentiated epithelial model. The reduction in L. monocytogenes infection, together with the potential enhancement of barrier integrity and an adhesion ratio that was above the average in the 3D functional model (6.9%) would seem to suggest the Lb. plantarum S11T3E strain as the most interesting candidate for possible in vivo animal and human trials

Uporabnost maščobnih kislin omega-3 pri obravnavi ran na koži

Uvod: Namen članka je prikazati analizo podatkov o učinkih maščobnih kislin omega-3 na celjenje ran ter njihovo uporabnost pri obravnavi ran na koži. Metode: Za pregled literature ter analizo dobljenih virov so bile uporabljene podatkovne baze: PubMed, CINAHL, Medline in ScienceDirect. Iskanje je bilo izvedeno s ključnimi besedami v angleščini: omega-3, fish oil, polyunsaturated fatty acid (PUFA), wound, wound healing, in Boolovim operatorjem AND. V analizo so bile vključene eksperimentalne ali randomizirane klinične raziskave, objavljene v angleškem jeziku in izdane od 1993 do januarja 2014, ki so vključevale preprečevanje ali zdravljenje akutnih ali kroničnih ran na koži z uporabo maščobnih kislin omega-3. Izključitveni kriterij je bil obravnava uporabe maščobnih kislin omega-3 pri opeklinah. Iz iskalnega nabora 1151 zadetkov je bilo v podrobno analizo vključenih 15 raziskav. Rezultati: Rezultati analize literature so pokazali, da so maščobne kisline omega-3 večinoma neučinkovite pri obravnavi travmatskih in kirurških ran na koži, potencialno učinkovite pri obravnavi diabetičnih ran in učinkovite pri obravnavi razjed zaradi pritiska. Diskusija in zaključek: Protivnetni učinek maščobnih kislin omega-3 upočasnjuje in moti celjenje akutnih ran na koži, vendar lahko z njimi obvladujemo lokalne vnetne odzive in pospešujemo reepitelizacijo pri kroničnih ranah. Za oblikovanje natančnih smernic uporabe bodo potrebna nadaljnja raziskovanja

Potential role of probiotics for sustainability in rural India

Probiotics (greek "for life") have been recognized and explored for over a century, Metchnikoff\u27s pioneering work was converted into commercial reality in the 1950s, and since then many probiotics\u27 benefits have been described. Nowadays they have already found place as a food supplement and as a preventive or curative drug. The term probiotics describes a variety of microorganisms which can colonize the host and have health improving effects on it. Since it is a natural and comparably affordable product even for people with low incomes, it could be introduced into the diet of people living in the Indian rural areas. The biggest obstacles for this are education about their use and technology to prepare them in a convenient form for domestic use. Regular use could improve the quality of live and reduce the dependence on drugs and medical expenses