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Abstract

In this study, the ability of microRNA-1906 (miR-1906) to attenuate bone loss in osteoporosis was evaluated by measuring the effects of a miR-1906 mimic and inhibitor on the cellular toxicity and cell viability of MC3T3‐E1 cells. Bone marrow-derived macrophage (BMM) cells were isolated from female mice, and tartrate-resistant acid phosphatase signalling was performed in miR-1906 mimic-treated, receptor-activated nuclear factor kappa-B (NF-κB) ligand (RANKL)-induced osteoclasts. In-vivo, osteoporosis was induced by ovariectomy (OVX). Rats were treated with 500 nmol/kg of the miR-1906 mimic via intrathecal administration for 10 consecutive days following surgery. The effect of the miR-1906 mimic on bone mineral density (BMD) in OVX rats was observed in the whole body, lumbar vertebrae and femur. Levels of biochemical parameters and cytokines in the serum of miR-1906 mimic-treated OVX rats were analysed. The mRNA expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), p-38 and NF-κB in tibias of osteoporotic rats (induced by ovariectomy) was observed using quantitative reverse-transcription polymerase chain reaction. Treatment with the miR-1906 mimic reduced cellular toxicity and enhanced the cell viability of MC3T3‐E1 cells. Furthermore, osteoclastogenesis in miR-1906 mimic-treated, RANKL-induced osteoclast cells was reduced, whereas the BMD in the miR-1906 mimic-treated group was higher than in the OVX group of rats. Treatment with the miR-1906 mimic also increased levels of biochemical parameters and cytokines in the serum of ovariectomised rats. Finally, mRNA expression levels of TLR4, MyD88, p-38 and NF-κB were lower in the tibias of miR-1906 mimic-treated rats than in those of OVX rats. In conclusion, the miR-1906 mimic reduces bone loss in rats with ovariectomy-induced osteoporosis by regulating the TLR4/MyD88/NF‐κB pathway.

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Abstract

In this study, 14 yeast cultures from 62 isolates from traditional sourdoughs collected from 6 different regions of Turkey were selected by FT-IR identification and characterised to reveal their probiotic properties. Four yeast strains were genotypically identified and compared with FT-IR identification. In all analyses, it was observed that mostly Saccaromyces cerevisiae strain exhibited high hydrophobicity, auto-aggregation feature, and all yeast isolates in this study showed tolerance to 0.3%, even salt concentration. In addition, all yeast strains were susceptible to anti-yeasts agents, although they were resistant to all antibiotics used in the study. All selected yeast isolates exhibited high antimicrobial activity against the Staphylococcus aureus. In conclusion, this study investigated the potential probiotic properties of yeast strains isolated from sourdough.

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Abstract

A validated UHPLC-PDA with an ESI-MS/MS method has been developed for simultaneous estimation of six bioactive alkaloids (magnoflorine, berbamine, columbamine, jatrorrhizine, palmatine and berberine) in the different extracts of the roots of Berberis aristata DC (Family:Berberdiaceae). It is an important medicinal herb native to Northern Himalaya and commonly known as ‘daruharidra’, ‘daruhaldi’, ‘Indian barberry’ or ‘tree turmeric’. An insight into the research literature uncovered reports on isoquinoline alkaloids like magnoflorine, berbamine, columbamine, jatrorrhizine, palmatine, and berberine as major bioactives in B. aristata roots, possessing different pharmacological and therapeutic effects. In the present study, these aforementioned alkaloids were separated on Phenomenex Luna®, 5 µm-C8 analytical column. The HPLC-MS analysis was performed at a flow rate of 0.90 mL min−1. Each alkaloid that is resolved was characterized by precursor ions and fragment ions with electrospray ionization (ESI) source in both positive and negative ionization using scan mode. The limit of detections (LODs) were 0.087, 0.727, 0.035, 0.124, 0.782 and 0.794 μg mL−1 for magnoflorine, berbamine, columbamine, jatrorrhizine, palmatine and berberine, respectively. The proposed UHPLC-PDA method was fully validated according to international (ICH) guidelines and was found to be selective, sensitive and highly accurate for the concomitant estimation of the aforementioned symbolic bio-markers of B. aristata roots.

Open access

Abstract

Phenolic compounds provide important quality attributes to red wines interacting with the organoleptic impact of wines. Yeast mannoproteins can interact with grape phenolic compounds, responsible for colour and antioxidant activity of wines. The aim of this work was to perform oenological characterisation and specific selection of Calabrian strains of Saccharomyces sensu stricto. Among the considered traits, the aptitude of the yeast to preserve grape pigments and colour intensity was included. Among the best six yeast strains – Sc2731, Sc2742, Sc2756, Sc2773, Sc2774, and Sc2823 – strain Sc2742 exhibits the highest Folin–Ciocalteu index and strain Sc2774 the highest colour intensity. These two selected yeasts may be used as starter for the production of red wines in order to preserve grape pigments and colour intensity.

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Az akadémiai-ipari együttműködések szerepe a gyógyszerfejlesztésben pandémia idején

Drug development collaborations between Academia and Industry in Pandemia

Scientia et Securitas
Author: György Miklós Keserű

Összefoglaló. Egészen az ezredfordulóig a gyógyszeripari kutatás-fejlesztés világszerte hagyományosan nagyvállalati keretek között folyt. Az elmúlt évtizedekben azonban ebben a szegmensben jelentős átrendeződések tapasztalhatók, ugyanis a korai kutatási és fejlesztési projektek sok esetben már az egyetemi-akadémiai, illetve kkv-szektorból indulnak. A szervezeti keretek mellett a fejlesztések szakmai tartalma is változott, a hagyományos kismolekulás gyógyszerek mellett egyre meghatározóbb szerep jut a biológiai terápiáknak, valamint a hatóanyagok fejlesztése mára összekapcsolódott a releváns diagnosztikumok fejlesztésével. A projektek finanszírozásában is fontos változások történtek, egyre jelentősebb szerep jut az állami KFI finanszírozásnak és a (kockázati) tőkebefektetéseknek. A gyógyszeripari K+F szakmai, szervezeti és finanszírozási kereteinek változása jelentősen felértékelte és szélesítette a korábban is meglévő akadémiai-ipari kapcsolatokat. Az együttműködések fontos szerepet játszanak a COVID–19 járványra adott válaszokban is, amit a magyar egyetemek, kutatóintézetek, kis- és középvállalatok, valamint gyógyszeripari nagyvállalatok részvételével indult kutatások igazolnak.

Summary. Until the turn of the millennium, pharmaceutical research and development worldwide had traditionally taken place in pharmaceutical companies. In recent decades, however, significant rearrangements have been witnessed, as early-stage research and development projects often start at the universities or the academic and SME sectors. In addition to the organizational framework, the professional content has also changed: in addition to traditional small molecule drugs, biological therapies are playing an increasingly important role, and the development of active ingredients is now linked to the development of relevant diagnostics. Important changes have also taken place in the financing of projects, with public RDI financing and (venture) capital investments playing an increasing role. Changes in the professional, organizational and funding frameworks for pharmaceutical R&D have significantly enhanced and broadened existing academic-industrial relations. Collaborations also play an important role in the responses to the COVID-19 epidemic, as evidenced by research involving Hungarian universities, research institutes, small and medium-sized enterprises, and large pharmaceutical companies. The first example is a collaboration of an academic research group and a spin-off company formed from this environment. Researchers of the Eötvös University (ELTE) and others working at the Research Centre for Natural Sciences (RCNS) applied phage display technology to discover new protease inhibitors. They established EvolVeritas Ltd, a spin-off company developing high affinity and high specificity inhibitors of the TMPRSS2 protease that is involved in the SARS-CoV-2 viral entry to host cells. In a parallel research program, the same consortium is working on new inhibitors of the MASP2 protease contributing to the coronavirus mediated activation of innate immunity, particularly the complement system. This latter approach would result in the effective control of microthrombosis events associated with serious COVID-19 infections. Both of the approaches are in the early preclinical phase and further investment would be needed to push these projects into clinical testing. The second example is a collaboration between an academic research group and an SME to reposition of azelastine, an approved antihistamine drug that was found to be effective in blocking SARS-CoV-2 mediated pathogenesis. After successful preclinical studies, the partners have now initiated clinical trials to demonstrate the efficacy of azelastine nasal drops in the prevention and treatment of COVID-19 infections. The third example is a collaboration of academic research groups, a SME and a pharmaceutical company. This consortium develops an antibody-like fusion protein therapeutics that can neutralize the SARS-CoV-2 virus. One component of the ACE2-Fc fusion protein is the relevant portion of angiotensin-converting enzyme 2 (ACE2) produced by recombinant technologies, which binds to the spike protein of the pathogen. The virus thus binds to the fusion protein instead of the ACE2 receptors in human cells. Another component is responsible for the long half-life of IgG, the so-called Fc region. The consortium confirmed that the ACE2-Fc fusion protein inhibits SARS-CoV-2 infection in cell culture, and prevents disease in experimental animals. Preclinical development and the preparation of the core documentation is ongoing, which will soon be submitted to the European Medicines Agency (EMA) to initiate clinical trials. The final example is a joint development project that involved a research group, an SME and two pharmaceutical companies. The objective of this program is process development and pharmaceutical formulation of favipiravir, a broad-spectrum antiviral with a treatment potential against COVID-19. The consortium completed the process development of the active pharmaceutical ingredient (API) and developed finished dosage formulations available for clinical testing. Clinical trials are ongoing that aim investigating safety and efficacy of favipiravir in COVID-19 infected patients. All of the examples described here demonstrate the power of collaborations that helped the participants to give diverse and effective responses to the unprecedented pandemic challenge of COVID-19. We believe that these experiences would encourage the members of the academic and industry community to formulate further collaborations to tackle the unmet medical need in our societies.

Open access

COVID–19 járvány hatása a pszichiátriai megbetegedések gyakoriságára – PTSD

Effects of the COVID-19 pandemic on the incidence of psychiatric illnesses – PTSD

Scientia et Securitas
Authors: Mária Zsóka Bellavics, Zsombor Hermann, and József Haller

Összefoglaló. A poszttraumás stressz zavar (PTSD) egy súlyos mentális állapot, amely nehezen gyógyítható, és évtizedeken keresztül fennállhat. Gyakorisága 1–3%-ról világszerte 20% körülire emelkedett a COVID–19 járvány után. Az észlelt gyakoriság nem függött a vizsgált populációk érintettségétől: a gyakoriság közel azonos volt fertőzöttek, karanténba kerültek, pusztán életmódváltozást elszenvedők és egészségügyi szakemberek körében. Ez vetekszik a háborús helyzetekben tapasztaltakkal, azzal a különbséggel, hogy a modern háborúk a világ népességének kis részét, míg a járvány az emberiség tekintélyes részét érintette. A COVID–19 járvány lecsengése után tehát számolnunk kell azokkal a pszichiátriai jellegű károkkal is, amelyeket maga mögött hagy, köztük a PTSD áldozataival.

Summary. Almost 20 years ago McNally (2003) wrote a paper on the Vietnam War with the title “Psychiatric Casualties of War”, outlining that people may suffer psychological injuries in war beyond those that harm them physically. Like wars, epidemics also have “psychiatric casualties” e.g., people who avoid the dangers of the epidemic per se but do not survive the situation without harm. One possible form of impairment is psychiatric in nature; this category includes among others post-traumatic stress disorder (PTSD). This study addresses the question of how how much concern the COVID-19 epidemic raises in the long run for an increased incidence of PTSD. PTSD is a severe and difficult-to-treat mental disorder caused by traumatic stress i.e., an event that threatens life and/or physical integrity. It is usually attributed to disasters, war, and interpersonal violence, but it can also be caused by serious illness such as AIDS and cancer. The COVID-19 epidemic conforms to the concept of trauma in the Diagnostic and Statistical Manual of Mental Disorders, as the disease it causes is potentially life threatening. Thus, even a purely logical approach suggests that the epidemic may increase the incidence of PTSD, an assumption that is confirmed by numerous targeted studies. The pre-epidemic PTSD morbidity rate of 1-3% has risen to around 20% globally over the past year due to the COVID-19 epidemic. PTSD affected not only those who fell victim to the disease, but also those who have “merely” witnessed the development and spread of the disease, those who have been placed in preventive quarantine, and healthcare workers who have had the burden of treating the epidemic. Behind the global 20%, an uneven picture emerges. In certain populations and at certain times, the frequency was reported to be much lower (e.g., 8%) or much higher (e.g., 96%), depending on the specifics of the study participants, as well as the place and time of the investigation. Overall, however, the post-epidemic prevalence of PTSD appears to rival that observed in war situations, such as the Vietnam War. The difference is that modern wars mostly affect a small portion of the world’s population, while the COVID-19 epidemic affects almost the entire humanity. Recent events suggest that the epidemic will soon recede. However, the epidemic leaves behind a large number of people who have sustained long-lasting and severe mental injuries - including those who have developed PTSD. Tackling this problem is the task for the future, but it must be prepared in advance. To this end, the study also briefly maps the factors of inborn and acquired resilience in a new network science approach.

Open access

Demencia prevenció: A korai diagnózistól a személyre szabott intervencióig

Dementia Prevention: From Early Diagnosis to Personalised Intervention

Scientia et Securitas
Authors: Annamária Manga, Menta Havadi-Nagy, Orsolya Székely, and Zoltán Vidnyánszky

Összefoglaló. Az elmúlt évtizedekben a várható élettartam emelkedésével drámai mértékben nőtt a demencia előfordulásának gyakorisága, melynek hátterében leggyakrabban az Alzheimer-kór áll. A rendkívül ígéretes, biomarkereken, agyi képalkotáson és mesterséges intelligencián alapuló megközelítéseknek köszönhetően egyre szélesebb körű információink vannak a betegség kialakulásáról és lefolyásáról, új kapukat nyitva ezzel a demencia korai diagnózisa és a személyre szabott terápia felé. Míg az új kutatási irányzatok előnye vitathatatlan, a nagy mennyiségű kutatási adat kezelése, illetve a betegség korai szakaszban történő azonosítása több biztonsági kérdést felvet. A korai diagnózis mellett egyre nagyobb hangsúly helyeződik az intervencióra, a demenciára hajlamosító tényezőkbe történő beavatkozás által.

Summary. As a consequence of increasing life expectancy, the number of those living with dementia is rising. While Alzheimer’s disease (AD) constitutes the most common cause of dementia, the origin of AD is unknown. Furthermore, in the absence of effective treatment, therapy focuses on the cognitive and behavioural symptoms of the disease, and the wellbeing of the patient. AD is characterised by a pronounced impairment experienced in one or more cognitive domains, and the criterion of the diagnosis is the presence of aggregated proteins in the brain leading to neuron death, and eventually to the loss of cognitive abilities.

As a result of the latest technological advances, several biological markers (biomarkers) of AD pathology were identified. The biomarkers can be obtained using positron emission tomography or measured from cerebrospinal fluid, and lately from blood serum and plasma as well. Magnetic resonance imaging provides an important measure of brain atrophy, a biomarker of neurodegeneration and neuronal injury. The structure of the brain shows significant alterations as a function of neuronal loss, with cortical thinning and tissue density changes, mainly starting from the medial temporal lobes (also including the hippocampus playing a prominent role in memory functions), and extending to the temporoparietal regions, with observed changes in the activity of the different functional brain networks as well.

A major challenge in defeating AD is that in most cases, the disease is recognised subsequent to the appearance of the decline in cognitive abilities, hampering everyday life. Previous studies identified a preclinical stage of AD, where the biomarkers indicative of the disease are present in the absence of detectable cognitive symptoms. This early, preclinical stage – with the use of artificial intelligence-based techniques – has been suggested to be a promising window for the early detection of the disease, and also for the prediction of individual disease trajectories, allowing for the thorough planning of patient management. While the benefit of the early diagnosis is unequivocal, it raises a number of important ethical and safety issues.

Besides the tremendous effort of developing effective medical treatments, the importance of intervention stands in the centre of scientific interest. The proposed prevention and intervention methods target the potentially modifiable risk factors of dementia, encouraging engagement in stimulating everyday activities and healthy lifestyle, to preserve longevity.

Open access

Előszó

Foreword

Scientia et Securitas
Author: Valéria Csépe
Open access

Erőművek életciklus-elemzése a fajlagos anyagfelhasználás tükrében

Life-cycle analysis of power plants in the light of specific material use

Scientia et Securitas
Author: Zoltán Korényi

Összefoglaló. A dolgozat témája a különböző erőműfajták életciklusra vonatkozó fajlagos anyagigényének a vizsgálata. Az elemzések a nemzetközi szakirodalmi források felhasználásával történtek. Módszere, a bázisadatok elemzése, majd az anyagigényeknek az erőmű beépített teljesítményére és az életciklus alatt megtermelt villamosenergiára vonatkoztatott fajlagos értékek meghatározása. Az eredmények azt mutatják, hogy a nap- és szélerőművek elterjedésével a hagyományos erőművek által felhasznált fosszilis energiaforrások (pl. a szén) bent maradnak ugyan a földben, de cserébe az új technológia legyártásához a hagyományos anyagokból (beton, acél, alumínium, réz stb.) fajlagosan jóval nagyobb mennyiségekre lesz szükség. Emellett megnő a ritkán előforduló fémek (gallium, indium stb.) felhasználása, ami Európában, a lelőhelyek hiányában, új kockázatokkal jár.

Summary. The topic of the study is to determine the material use of different power plant types. This is a part of the known life cycle analysis (LCA). The aim of LCA is to determine the impact of human activity on nature. The procedure is described in the standards (ISO 14040/41/42/42). Under environmental impact we mean changes in our natural environment, air, water, soil pollution, noise and impacts on human health. In the LCA, the environmental impact begins with the opening of the mine, continues with the extraction and processing of raw materials, and then with the production of equipment, construction and installation of the power plant. This is followed by the commissioning and then operation of the power plants for 20-60 years, including maintenance. The cycle ends with demolition, which is followed by recycling of materials. The remaining waste is disposed of. This is the complex content of life cycle analysis. Its purpose is to determine the ecological footprint of man.

The method of the present study is to isolate a limited area from the complex LCA process. This means determining the amount of material needed to build different power plants, excluding mining and processing of raw materials. Commercially available basic materials are built into the power plant’s components.

The research is based on the literature available in the international area. The author studied these sources, analysed the data, and checked the authenticity. It was not easy because the sources from different times, for different power plants showed a lot of uncertainty. In overcoming the uncertainties, it was a help that the author has decades of experience in the realisation of power plants. It was considered the material consumption related to the installed electricity capacity of the power plant (tons/MW) as basic data.

The author then determined the specific material consumptions, allocated to the electric energy generated during the lifetime, in different power plants.

The calculation is carried out with the help of the usual annual peak load duration hours and the usual lifetime of the power plants.

The results show that with the spread of solar and wind energy, the fossil energy sources previously needed for conventional power plants will remain inside the Earth, but in exchange for the production of new technological equipment from traditional structural materials (concrete, steel, aluminium, copper and plastic), the special need multiplies. If we compare the power plants using renewable energy with the electric energy produced during the life cycle of a nuclear power plant, the specific installed material requirement of a river hydropower plant is 37 times, that of an onshore wind farm it is 9.6 times, and that of an outdoor solar power park is 6.6 times higher.

Another important difference is that wind turbines, solar panels and batteries also require rare materials that do not occur in Europe (e.g. gallium, indium, yttrium, neodymium, cobalt, etc.). This can lead to security risks in Europe in the long run.

Open access

A glikációs index lehetséges magyarázata a hemoglobinglikáció biokinetikus modellje alapján

Possible explanation of the hemoglobin glycation index by the biokinetic model of glycation

Orvosi Hetilap
Authors: Olivér Rácz, László Barkai, György Eigner, Levente Kovács, Melinda Bicsák, Katalin Muriová, and Péter Dombrovsky

Összefoglaló. Bevezetés: A HbA1c integrált retrospektív mutatója az elmúlt időszak vércukrának, rendszeres vizsgálata a cukorbetegek anyagcserekontrolljának megítélésében elengedhetetlen. Helyes értékelése azonban nem egyszerű, mert a HbA1c és a vércukor közötti összefüggés nem lineáris. A mérést közvetlenül megelőző hyperglykaemiás epizódok hatása a HbA1c szintjére nagyobb, mint azoké, amelyek régebben történtek. A jelenségre a glikáció biokinetikus modellje ad magyarázatot. Célkitűzés: A mért és a biokinetikus modell alapján számított HbA1c közötti egyezés, illetve diszkordancia vizsgálata. Módszer: A vizsgálatokat 157, 1-es és 2-es típusú cukorbeteg 1793, laboratóriumban mért éhomi vércukor- és 511 HbA1c-adatából végeztük. A különbséget a glikációs index segítségével számítottuk, amely a mért és a számított HbA1c-érték aránya. Eredmények: Egyezést mindössze a vizsgált betegek kevesebb mint egyötödödében találtunk, 60%-ban az index értéke alacsony (<0,95) és 21%-ban magas (>1,05) volt. Az adatok részletes analízise szerint jó anyagcserekontroll esetében gyakoribb a vártnál magasabb, mért HbA1c-érték, mint a biokinetikus egyenlet által számítotté, és rosszabb kontroll (magasabb átlagos vércukor) esetében ez fordítva van. Egyezés esetén a regressziós egyenlet együtthatói gyakorlatilag azonosak a modell alapján számított értékekkel. Következtetés: Vizsgálataink felvetik azt a lehetőséget, hogy a biokinetikus modell magyarázatot adhat a vércukor és a HbA1c közötti diszkordanciára. Orv Hetil. 2021; 162(41): 1652–1657.

Summary. Introduction: HbA1c is an integrated retrospective marker of previous blood glucose concentrations and its regular measurement is indispensable in the assessment of glycaemic compensation of diabetic patients. However, its proper interpretation is not simple becasuse the relationship between HbA1c and average glycemia is not a linear one. Hyperglycemic episodes occuring immediately before the measurement have greater impact on the HbA1c level as compared with those taking place earlier. Objective: Assessment of concordance and discordance between measured and according to the biokinetic model calculated values of HbA1c. Method: The calculations were made from averages of 1793 fasting blood glucose and 511 HbA1c of 157, type 1 and 2 diabetic patients. The glycation index is the quotient between measured and calculated HbA1c. Results: Agreement was found in less than one fifth of the 157 patients; in 60% the value of glycation was low (<0.95) and in 21% high (>1.05). Analysis of the glycation index according to the level of glycemic compensation revealed that in patients with good compensation, the measured HbA1c value was more often higher than the expected and in patients with unsatisfactory compensation the opposite was true. Conclusion: These results raise the possibility that the discordance between average glycemia and measured HbA1c can be explained by the biokinetic model. Orv Hetil. 2021; 162(41): 1652–1657.

Open access