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Spike proteins on the surface of human corona viruses is important to enhance it’s competency to get transmit into other healthy population. Because of it’s specific spike protein, the virus got its name corona in 1960s. Afterward, it was renamed as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) in 2002 and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012. It was mortal for old population, new born babies and immune-compromised individuals, who didn't have sufficient immunity or defense system. On February 11, 2020, World Health Organization (WHO) gave the names of COVID-19 and SARS-CoV-2. A characteristic of nCoV-19, which is a cause of COVID-19, was identified as major cause of pneumonia. However, the healthcare professionals worked hard to to stop it’s outbreak and transmission all over the world. But, there was no medicines that have been cleared by the FDA to treat COVID-19 successfully. So, the goal of this study is to look at the scientific data that is already available about clinical care and therapy of this disease. Some of the sources that were checked for this study were BioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, WanFang Data, and PubMed. A lot of work went into finding out what medicines could be used to avoid and treat COVID-19 illnesses. Remdesivir, chloroquine, hydroxychloroquine, and immunosuppressant drugs have all been shown to help to fight the virus. Until a treatment for the COVID-19 virus is found, it is best to stay away from other people and follow strict hygiene. Most medicinal treatments still have a lot of unknown effects, and different medicines and vaccines are being trialed and tested succefully to stop prevelance, transmission and develop the symptoms.

Background and objective: Nursing homes are threatened by external and internal threats, effect of which may result in a crisis situation (state of emergency). While managing an already existing emergency, it is necessary to create conditions allowing the elderly to maintain their fundamental human and civil rights. Any interference with human and civil rights is acceptable only in a state of emergency when crisis measures are applied. Social isolation was one of the emergency measures within the Covid-19 pandemics and involuntary social isolation may result in one´s state of depression. To eliminate this prediction, it is necessary to create such conditions that enable the elderly to maintain their basic human needs as well as civil rights. The authors therefore aim to identify and evaluate the effectiveness of possible alternative communication tools and strategies in the nursing homes along with the ways of a potential reduction of negative effects of social contacts restrictions.Methods: On the basis of an online questionnaire, a community of experts evaluated alternative communication tools on a scale from 1 to 5, considering three factors: 1. benefit for the elderly; 2. financial requirements for purchasing/provision for a nursing home; 3. organization requirements for a nursing home. A cost-benefit evaluation was performed to determine a ranking of individual alternative tools.Results: The acquired results of questionnaire survey served as a tool to determine the ranking of importance of individual alternative communication tools that are feasible depending on specific conditions of a nursing home.Conclusion: The research identified useful tools that may help in the nursing homes to mitigate the impacts resulting from restrictions applied in the state of emergency and associated initiatives in the field of mental health.

The purpose of the research consisted of assessing the modification produced by hydrogen peroxide (H₂O₂)-induced oxidative stress (OS) on the ketorolac therapeutic effects in the chickens which are the analgesic, antipyretic, and anti-inflammatory. A significant decrease in the total antioxidant capacity (T-AOC) and subsequent occurrence of OS was observed in the stressed (H₂O₂) group on days 7^th, 10^th, and 14^th by 39, 29, and 41%, respectively in comparison to the control (non-stressed) group. The analgesic effect of ketorolac in the stressed group had more intense in comparison to the non-stressed group, the analgesic effectiveness of ketorolac raised by 16% in that group. In the non-stressed and stressed groups, ketorolac produces its antipyretic effect at 3 and 4 hours after fever induction by baker’s yeast while it shows the effect significantly at 1, 2, and 4 hours. Furthermore, ketorolac has the superiority of antipyretic action in stressed group over the non-stressed group. Ketorolac carries out anti-inflammatory activity in the stressed and non-stressed groups by 61 and 75%, respectively. Ketorolac has a significant anti-inflammatory property in the stressed group through a significant decrease in the delta thickness compared to the non-stressed group. The stressed group was treated with ketorolac for five consecutive days signifi-cantly affect the kidney and liver function concerning the non-stressed group. The net findings proposed the ability of H²O²-induced OS to alter ketorolac’s analgesic, antipyretic, and anti-inflammatory properties in the chickens thus, it is recommended to reduce the dose of ketorolac intended to be given to stressed animals involved.

Recent advances in artificial intelligence (AI) have introduced powerful tools for machine translation (MT) and automated language proofreading (ALP) into academic publishing. However, their evaluation in highly specialized fields such as medicine and pharmacy remains methodologically underexplored. This study presents a multidimensional evaluation framework that integrates human expert judgment with AI-based replication to assess the quality of AI-generated translations and proofreading outputs. The framework covers three quality dimensions applicable to both MT and ALP: semantic fidelity, terminological accuracy and consistency, and grammatical correctness and fluency, as well as a fourth dimension specific to ALP, the appropriateness of edits.In the pilot phase of the research, five machine translation systems were compared using the multidimensional evaluation framework, with DeepL serving as a strong baseline; under advanced idiomatic prompting, the Large Language Model (LLM) systems achieved performance levels comparable to this baseline. The semantic fidelity dimension was further evaluated through an AI simulation of human judgment using ChatGPT-5. The agreement between human and AI evaluators reached κ = 0.81 (95% CI = 0.73–0.88), indicating high consistency and no observed hallucinations within this pilot sample.These preliminary results demonstrate that large language models have promising potential to reproduce human expert quality reasoning when guided by structured prompts. Beyond its technical contribution, our ongoing research represents a step toward transparent and reproducible evaluation for AI-generated academic writing and its automated quality assessment.

Juvenil, a nontoxic extract of bovine blood, is registered as a dietary supplement having no side effects. It contains a broad spectrum of free amino acids, as well as small proteins and oligopeptides (molecular weights up to 10 kDa), various nucleotides, and small amounts of phospholipids. The complex of these exclusively natural components has been shown to support physiological responses of supplemented organisms.Juvenil has been studied for several decades using a wide range of both experimental and clinical studies. Analyses have shown that it acts directly neither on individual functional systems of the body nor on individual metabolic processes. Current findings indicate that modulatory effects of Juvenil occur through modulation of gut microbiota composition, which is associated with the modulation of microbiota–gut–brain axis signaling. In murine model that modulatory effect is reflected in the expression of an early activation c-Fos marker in specific parts of the brain.In this review we present a set of findings about Juvenil, which has a wide range of positive effects on the functional systems of organisms. These effects can be used to strenghten the resistance, immunity, and regeneration of human beings. According to its effects Juvenil can be classified as a psychobiotics.

The rapid growth of microbiome research is hindered by significant challenges in data management, including data fragmentation across disparate silos, a lack of methodological standardization, and barriers to advanced privacy-preserving analysis. To address these issues, this article proposes a conceptual architectural blueprint for a resilient, scalable, and integrated platform for microbiome data. Our proposed architecture is a modular, cloud-native system designed to support the entire research lifecycle. Key attributes include a multi-layered microservices framework to ensure scalability, adherence to FAIR (Findable, Accessible, Interoperable, Reusable) data principles, and native support for longitudinal data tracking. Crucially, the platform incorporates integrated services for advanced AI/ML analysis and a coordinator for federated learning, enabling collaborative model development without centralizing sensitive data. By providing a robust infrastructure that combines standardized data management with powerful, privacy-aware analytical tools, our proposed model aims to empower researchers, enhance reproducibility, and accelerate discoveries into the complex relationship between the microbiome and human health.

Growing evidence of antibiotic-resistant pathogens is a serious medical issue that has to be addressed. Our antimicrobial research is focused on searching for novel small molecules that differ from the most clinically used antibiotics by chemical structure and mechanism. However, this fundamental research is like looking for a needle in a haystack. In addition, in vitro methods are time-consuming and expensive to screen large number of compounds in reasonable time. Off-target screening can represent a solution to find novel and effective antimicrobial agents that can eliminate these problems. Accordingly, molecular docking in the family of selected frentizole derivatives predicted their potential to inhibit bacterial nicotinate mononucleotide adenylyltransferase (NadD). This bacterial-essential specific enzyme has an important role in NAD metabolism. Thus, underlying mechanism of antimicrobials derived from frentizole would be interference with this biochemical process. Unfortunately, broth microdilution assay did not display any antimicrobial activity of tested compounds. On the other hand, herein we propose that off-target screening can facilitate searching for new drugs and that NadD could be a relevant target for antimicrobials.

Phytic acid (IP6) is the most abundant inositol phosphate in nature present in plants as well as in mammalian cells, thus, IP6 is common part of human diet. IP6 has been considered for a long time as an antinutritional component due to its ability to bound minerals and affect their bioavailability in gastrointestinal tract (1). On the other hand, the protective effects of IP6 have been reported in pathological conditions including neurodegenerative diseases, cardiovascular diseases and cancer, likewise, a hepatoprotective effect has been observed (2). Cytochromes P450 (CYPs) are key enzymes involved in the metabolism of 70-80% of all clinically used drugs and they are responsible for variability in drug response. Expression of CYPs is affected by many factors and can be regulated by specific nuclear receptors such as aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR). To date, variety of diet-derived metabolites, have been identified as ligands of these receptors showing that different diet habits may contribute to interindividual differences in CYP activity.
In our study, the effect of IP6 on CYPs expression and enzymatic activity was assessed using different hepatic cell models. We have found that mRNA expression of CYP2B6, CYP2E1 and CYP3A4 was significantly downregulated by 10μM IP6 in primary human hepatocytes.
Therefore, further studies are needed to evaluate the complex functions of IP6 and its possible interaction with drug metabolism in order to translate its promising therapeutic potential to clinical practice.

The thyroid hormone regulation is a vital and complex process for proper organism function that involves multiple organs across species. A disruption of the thyroid hormone system (THS) by endocrine disruptors (EDs) can be linked with adverse effects such as developmental and autoimmune disorders. However, THS has been rather neglected, even though EDs have been gaining attention recently. Currently, the H2020 ERGO project aims to develop a battery of high-throughput in vitro bioassays based on molecular initiating events (MIEs) in the adverse outcome pathway network connected to THS disruption (tAOP) to narrow the knowledge gap.
The thyroid hormone (TH) activity may be disrupted on several levels including synthesis, transport, metabolism, and receptor (trans)activation. To evaluate the suitability of various in vitro models for studying different endpoints, these have been characterized regarding the expression of the set of genes corresponding to MIEs in tAOP. Moreover, we developed a set of in vitro transfected HEK-293T cell lines overexpressing genes of major interest, i.e., deiodinases type 1-3 (DIO1-3), natrium-iodide symporter (SLC5A5; NIS) and thyroid peroxidase (TPO). Next to this, we adopted and optimized bioassays for thyroxine/transthyretin (T4/TTR) displacement, aryl hydrocarbon receptor (AhR), and thyroid receptor (TR) activation and characterized the potential of selected human exposure-relevant compounds to disrupt prioritized MIEs.

Bisphenol A (BPA), a widely used plastic additive with proven endocrine disrupting properties, has been previously linked to reproductive system disorders and tumors. Due to such harmful effects, its use has become restricted but other bisphenol (BP) analogs have been introduced as replacements for BPA usage in many applications. However, little is known about their biological actions or about similarities with the actions of the prototype BPA. The present study used the human prostate cell lines: androgen-unresponsive PC3 cells and androgen-responsive LNCaP cells, to examine effects of bisphenols AF, S, F and B, in comparison to BPA. We focused on BP effects on cell viability, proliferation, and oxidative stress (concentrations 10^-10–10^-4M) at several time points. We observed different sensitivity of both cell lines to toxic effects of the individual analogs. Although the highest concentration of each of the five BPs inhibited cell proliferation (BrdU incorporation) in both cell lines, this resulted in viability decrease only in LNCaP cells while in PC3 cells, the viability remained unaffected (MTS assay). The exception was observed in the presence of the BPAF analog with the profound cytotoxic effects, which seem to be caused by the early apopotic actions and increase in caspase activity (fluorescent assay). In addition, the highest concentration of each BP analog elevated reactive oxygen species production by the prostate cells. The results show that high concentrations of BPs can affect prostate cancer cell status and that androgen-responsive LNCaP cells are significantly more sensitive than the unresponsive PC3 cells, what indicates possible involvement of androgen receptors in the action of BP derivatives, and will be a subject of further elucidation.

Harman is a heterocyclic aromatic amine discovered in coffee, cigarette smoke, roasted meat, or fish (1). However, carcinogenic properties of harmane were proved - partly explained by its interaction via the AhR receptor and induction of CYP1A1 (2). Cytochrome P450 (CYP) enzymes are responsible for the metabolism of 75 % of drugs used in clinical practice (3). Our study aimed to determine the effects of harman on the most important CYP variants in a preclinical experiment.
Harman was administered to Wistar Albino rats intragastrically at the doses of 25, 40, and 64 mg/kg/day for 8 days (control group - 66% propylene-glycol). Microsomes were prepared from liver samples via differential ultracentrifugation. The content of total protein and CYP was measured in isolated microsomes. To evaluate the metabolic activity, the microsomes were incubated in vitro with CYP specific substrates: diclofenac (CYP2C6), dextromethorphan (CYP2D1/2), phenacetin (CYP1A2), testosterone (CYP2A, CYP3A, CYP2C).
Harman significantly decreased the metabolic activity of rat CYP2B, CYP3A, CYP2D1/2 (40 and 64 mg/kg/day) and CYP2C11 (25, 40 and 64 mg/kg/day). The metabolic activity of CYP1A2, CYP2A or CYP2C6 was not affected. Our results did not confirm the potential of harmane to induce liver CYP450 in rat. Nevertheless, significant inhibition of various CYP enzymes was proved. To exclude the risk of serious interactions, the effect of harmane on CYP in humans should be studied.

Oxysterols are 27-carbon derivatives of cholesterol formed by enzymatic, as well as non-enzymatic, oxidation of cholesterol. They participate in cholesterol metabolism and influence many cellular processes, but they are also involved in the etiology of different diseases, including cancer. Previous studies found that oxysterols influence anti-cancer treatment in vitro, e.g., the presence of different oxysterols modulates the activity of doxorubicin, 5-fluorouracil, docetaxel, or cisplatin.
The aim of this study is the analysis of the role of nine oxysterols in pancreatic cancer in vitro. Two human pancreatic cell lines, Paca-44 (mutated in KRAS gene) and BxPC3 (wild-type) are included in this study. To study the effect of different oxysterols, both cell lines were seeded on a 96-well plate and incubated with a medium containing one of the oxysterols. After 72 hours, the cell viability was measured using a CellTiter-Blue^® Cell Viability Assay, and the IC₅₀ of each oxysterol was counted.
The IC₅₀ of some oxysterols was very similar in both cell lines, yet 25-hydroxycholesterol and 5α,6α-epoxycholestanol efficacy varied between Paca-44 and BxPC3 cells. Moreover, two oxysterols, 27-hydroxycholesterol and 4β-hydroxycholesterol, showed no or very low effect on cell viability in both cell lines. In future studies, we would like to analyze the role of oxysterols on the effect of gemcitabine in pancreatic cancer in vitro.

Benchmark dose (BMD) approach, as an advanced statistical methodology for dose-effect analysis in toxicological research (1) was used to quantitatively characterize in vivo efficacy of two experimental bispyridinium oximes K203 and K027, following promising findings on their low acute toxicity and potential to reactivate acetylcholinesterase (AChE) inhibited by organophosphorus (OP) pesticides and nerve agents in vitro and in vivo (2). Immediately after DDVP challenge (75% LD₅₀, s.c.), male Wistar rats were treated with oxime (0/1.25/2.5/5/25/50% LD₅₀, i.m.). Erythrocyte and diaphragm AChE activity was determined by Ellman's method 60 min after the treatment. Benchmark analysis was done in PROAST software ver. 65.5 (RIVM, The Netherlands). Derived BMD_er were K203 = 194 (153, 243) and K027 = 100 (81, 125) µmol/kg bw, BMD_diaph were K203 = 117 (56, 209) and K027 = 21 (10, 37) µmol/kg bw, indicating that oxime K027 induces the same effect size with 2 and 5.5-times lower dose compared to oxime K203 in erythrocites and diaphragm, respectively. Quantification of equieffective doses of oxime reactivators would enable more reliable definition of their therapeutic widths, which further contributes to better determination of therapeutic dosage regimens and, finally, increases the relevance of results obtained in animal models for the human population.

Uridine diphosphate sugar-utilizing glycosyltransferases (UGTs) are an enzyme superfamily that catalyzes glycosyl residues transfer from activated nucleotide sugars to acceptor molecules. In addition to various endogenous compounds, numerous xenobiotics are substrates of UGTs. As the glycosides formed are generally less active/toxic and more hydrophilic than aglycones, UGTs effectively protect organisms from potentially harmful xenobiotics. Therefore, increased UGTs expression and/or activity improves the protection of the organism and may contribute to the development of individuals that become more resistant to certain xenobiotics. While the function of UGTs in the resistance of human cancer cells to chemotherapy is now well known, other organisms and other xenobiotics have attracted much less attention. UGTs play an important role in defense against xenobiotics not only in humans, but in countless other organisms such as parasites, insects, and plants. Moreover, many recent studies clearly show the participation of UGTs in the resistance of nematodes to anthelmintics, insects to insecticides, weeds to herbicides as well as humans to various drugs (not only those used in cancer therapy but also in the treatment of epilepsy, psychiatric disorders, hypertension, hypercholesterolemia, and HIV infection). Nevertheless, although the contribution of UGTs to xenobiotic resistance in diverse organisms has become obvious, many pieces of information remain missing, for example with regard to the mechanisms of UGTs regulation.

Coronavirus disease COVID-19 is highly infectious disease caused by SARS-CoV-2 virus as a novel coronavirus led to pandemic. Due to fast transmission COVID-19 has become a global problem. The virus is spread by aerosol from infected people and persists in the air for a long period. SARS-CoV-2 affects the lungs, but it can also affect digestiv or cardiovascular systems, can attact the brain, damage vessels and can lead to neurological manifestation. COVID-19 has several clinical symptoms and can lead to multiorgan dysfunction and death. On the other hand, in some infected persons COVID-19 can take place asymptomatic. Due to the risk of rapid spread of COVID-19, the early prediction of the onset of the epidemic is important. The Water Based Epidemiology (WBE) is an effective tool for monitoring the number of infections and can serve as a tool to monitoring various human activity including health status of population in given area. One of the advantage of WBE in last pandemic is their capability to reveal the outbreaks at an early stage, including presymptomatic or asymptomatic transmission of SARS-CoV-2. The use of WBE is based on the principle of viral shedding in stool samples and on the detection of SARS-CoV-2 viral mRNA by PCR method in wastewater samples. On the other hand, some non-specific markers from COVID-19 infected persons can also be used in WBE. Viral infections are associated with inflammation. Neopterin, a pteridine derivative, is produced in the metabolism after some stimulus. Neopterin was found in urine and other body fluids, as blood serum, cerebral spinal fluid in COVID-19 infected persons in high levels. Through urinary excretion, neopterin was detected in wastewater samples. The other markers, as toxin-like peptides, similar or identical to toxic components of venoms from animals, such as conotoxins, phospholipases, phosphodiesterases, zinc metal proteinases, and bradykinins, were identified in blood plasma, urine and faecal samples from COVID-19 patients. These markers, including neopterin, can be potencially useful in WBE as markers of rapid prediction of the onset of the epidemic. The early detection of the presence of SARS-CoV-2 within communities can also give healthcare authorities time to prepare for potential outbreaks and time to prepare measures to protect population.

Oxime reactivators are causal antidotes commonly used against organophosphate (OP) poisoning. Although OPs are utilized in agriculture as pesticides, they can be misused by terroristic groups as nerve agents (NA). These compounds are fast acting inhibitors of human acetylcholinesterase (AChE) causing cholinergic crisis ultimately leading to death by respiratory failure. Treatment of OP intoxication consists of immediate administration of symptomatic drugs, namely, atropine and diazepam and antidotes in form of oxime reactivators of AChE. Undoubtedly commercially used reactivators are the best countermeasure for OP intoxications so far, however they have several downsides. First of all, there is no broad-spectrum reactivator effective against all NAs, secondly they cannot reactivate “aged” form of AChE and lastly they poorly cross the blood-brain barrier (BBB) due to low lipophilicity (1). For instance, widely used reactivator 2-PAM crosses the BBB approximately from only 10% (2). However, most of the techniques used for measuring the concentration of reactivator crossing BBB are relying on HPLC combined with MS or UV detector. BODIPY probe could be great alternative as it is a strongly fluorescing probe standardly used for imaging techniques in vitro (3). The aim of this work is in vitro evaluation and analysis of physicochemical properties of BODIPY labeled oxime reactivators of AChE.

Neurotoxicity is commonly associated not only with neurodegenerative damage but also with organophosphate intoxication. Neuronal death may be associated with acute and life-threatening symptoms and subsequent long-term secondary disorders. This study focuses on the development and validation of a cellular model of mature human neurons. A model was obtained by differentiating the neuroblastoma cell line SH-SY5Y. In vitro cell model is suitable for studying neurotoxicity and its potential countermeasures. The protocol involved stimulation of the cell line with retinoic acid and brain-derived neurotrophic factor for 9-12 days. Observation of morphological signs of neurons (characteristic synaptic connections), using lighting microscopy and a detection of specific neuronal markers (tau protein, microtubulle-associated protein (MAP), synaptophysin (SYN), post-synaptic density protein (PSD-95)) using fluorescence microscopy was used for validating this model. Another experiment was focused on the quantification of acetylcholinesterase in differentiated and undifferentiated cells. As a result, it has been shown that the level of enzyme in the differentiated cells is significantly higher than in the original undifferentiated cells. Another planned use of the model is in vitro testing of the neurotoxic effects of organophosphates and screening of potential prophylactics or drugs for the treatment of neurodegenerative injuries.

The aim of this project is heterologous expression of chosen carbonyl-reducing enzymes from Haemonchus contortus, a gastrointestinal nematode of small ruminants. Carbonyl-reducing enzymes (such as SDR and AKR) catalyze the first phase of xenobiotics biotransformation and thus participate in drug metabolism. Increased elimination leads to  decreased toxicity and reduced efficacy of drugs in Barber´s pole worm. One of the proven mechanisms of  deactivation of anthelmintics (e.g., flubendazole) is the reduction of the carbonyl group by these enzymes.
In addition, the previous metabolism analysis has demonstrated a higher ability of resistant strain of H. contortus to reduce flubendazole more effectively than the sensitive strain. The genome of H. contortus contains approximately 70 SDR genes and 24 AKR genes; however, information about expression and function is  not yet known. Furthermore, previous quantitative analysis of gene expression in H. contortus, have shown that the most highly expressed genes were SDR1, SDR3, SDR12 and SDR18. Also, expression of SDR12 was significantly higher in all life stages of the resistant strain.
These genes have been selected for heterologous expression, including cloning and expression in two systems: in E. coli typical expression system for soluble enzymes, and in eucaryotic cell lines, an  expression system enabling a higher level of posttranslational modifications. Expression of selected SDR or AKR, in a suitable system will allow us to characterize them, determine their enzyme activity, even test new potential inhibitors in the future.

Helenalin (HEL) is a sesquiterpene lactone used as an antiphlogistic in European and Chinese folk medicine. Its characteristic anti-inflammatory activity is mediated by direct alkylation of Cys38 within the DNA binding domain of NF-κB subunit p65/RelA. In addition, HEL is a broad-spectrum active compound, featuring an antitumor, antibacterial, and antiprotozoal activity. Recently, a new interest in the biological and pharmacological activities of HEL or its synthetic analogs has been observed (1). HEL has been found to undergo oxidative as well as reductive biotransformation in human liver. In addition, HEL acted as a mechanism-based inhibitor of human cytochrome P450 enzymes (2). Yet, information concerning its potential hepatotoxicity in human is limited. To address this issue, the hepatotoxic effect of HEL was studied in differentiated HepaRG cells that represent a human hepatocytes-like model. Firstly, the cytotoxic effect of HEL was determined using neutral red uptake (NRU) and MTT assay. After 72-hour incubation, the half-maximal inhibitory concentration (IC₅₀) of HEL was 13 µM and 11 µM using NRU and MTT assay, respectively. Secondly, the pro-oxidant activity of HEL was assessed using oxidant-sensitive probe. HEL was found to increase the formation of reactive oxygen species in a time- and concentration-dependent manner. Thirdly, a comprehensive proteomic analysis using isobaric labeling was performed to study the changes in hepatic proteome upon HEL treatment.

Despite widespread use of metal nanoparticles (NPs) in diagnostic and therapeutic applications for neurodegenerative disorders, there is a lack of reliable neurotoxicological studies on the exact molecular mechanisms of NPs action on neuronal cells (1). The aim of the present study was to evaluate neurotoxic potential of silver NPs (AgNPs) of different sizes (10, 100 nm) in rat pheochromocytoma cells PC12. The cells were cultured in the presence of AgNPs (0.1–10 µg/ml) for different time periods (3–72 h) depending on the used analysis. Cell viability was assessed by detection of mitochondrial activity based on the MTT reduction and membrane integrity measuring LDH release. Intracellular ROS levels were measured using fluorescent probe DCF-DA. Levels of IL-6 in the culture media were measured by ELISA kit. Differentiation of PC12 cell was induced by recombinant human β-NGF (100 ng/ml), average length of neurites was evaluated based on microscopic images on days 1, 3, 5 of treatment (2). The exposure of PC12 cells to AgNPs induced concentration- and time-dependent inhibition of cell viability and increase of LDH release. The value IC₅₀ ranged from 40 to 4 µg/ml depending on NP size and time of exposure. AgNPs (10 µg/ml) elevated ROS levels at all times monitored. Treatment of cells with AgNPs had no effect on IL-6 levels. Inhibition of neurite outgrowth induced by rhNGF in PC12 cells was observed after AgNPs treatment. In-depth evaluation of the neurotoxicity of NPs is crucial for designing safer nanosystems.

Antimicrobial drugs are chemical substances (of natural or synthetic origin) that suppress the growth of (or destroy) microorganisms (e. g. antibiotics act primarily against bacteria). Copper complexes ([Cu₂(pmdien)₂(H₂O)₂(μ-fu)](ClO₄)₂ – complex No. 5; [Cu₂(pmdien)₂(H₂O)₂(μ-dtdp)](ClO₄)₂ – complex No. 6), on which this study is focused, show antibacterial activity (1). As with every promising compound, these copper complexes were tested for their potential to inhibit activities of liver microsomal cytochromes P450 (CYP) in vitro. Porcine liver microsomes served as a model system. In the first step, possible effect of these copper complexes on enzyme activity of CYP2D (bufuralol 1´ hydroxylation) was determined. Copper complexes decreased enzyme activity of CYP2D to 1 % (IC_{50 complex No. 5} = 3.4 μmol.l^-1), 4 % (IC5_{0 complex No. 6} = 24.9 μmol.l^-1), respectively, at 50 μmol.l^-1 concentration of individual complexes in the reaction mixture. The Dixon plots and Lineweaver–Burk plots indicate most probably a partially noncompetitive inhibition in both cases. Verification of this interaction was confirmed with human liver microsomal CYP2D6. Enzyme activity of human CYP2D6 was affected too (decrease to 0 % of activity in both cases at 50 μmol.l^-1 concentration of individual complexes in the reaction mixture). IC_{50 complex No. 5} = 12.4 μmol.l^-1 and IC_{50 complex No. 6} = 6.3 μmol.l^-1 for human CYP2D6 were determined. Potential adverse drug interactions could occur in patients taking e. g. antidepressants (amitriptyline, paroxetine) or analgesics (codeine, tramadol) which are known to be metabolized by the CYP2D6 enzyme (2). However, determination of interaction of this copper complexes with another important liver microsomal drug metabolizing CYP should be studied in further experiments in vitro.

Inflammatory bowel disease (IBD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). This article reviews the epidemiology, pathophysiology, risk factors and treatment implications of ASCVD in IBD patients. A number of processes are involved in the increased risk of ASCVD, including inflammation, endothelial dysfunction, hypercoagulability, platelet abnormalities, dyslipidaemia, gut microbiome abnormalities and the use of corticosteroids. While the precise pathophysiology remains complex, the management of inflammation and cardiovascular risk factors is essential to reduce the risk of atherosclerosis in IBD patients. Collaboration between gastroenterologists and preventive cardiologists is emphasised for risk factor management and promotion of disease remission.

It was with interest and pleasure that I read the contribution of Petronilho & Figueroa-Villaret in the MMSL reviewing the literature on agents for defense against chemical warfare [Petronilho & Figueroa-Villaret, 2015]. The authors briefly touch on the history of organophosphates emphasizing the pioneering contribution of Jean Louis Lassaigne, the synthesis of triethyl- phosphate (TEP) and finally the achievements of Philippe de Clermont who codeveloped the first organophosphate (OP) acetylcholinesterase inhibitor, tetraethyl pyrophosphate (TEEP). They continue by pointing out that Wilson and Ginsburg managed to reactivate OP-inhibited acetylcholinesterase using pralidoxime (2 -PAM), which reactivates the enzyme much faster than hydroxylamine. I believe that the scientists involved in organophosphorus cholinesterase inhibitor & reactivator development deserve more attention and that the colleagues' contribution contains a number of ambiguities deserving additional...

The majority of nanomaterials have unique properties that make them helpful in a variety of biotechnology applications. The study assesses the phytochemical, antioxidant (using a DPPH radical scavenging assay) and antimicrobial activities and identifies minimum inhibitor concentrations of Citrus sinensis (orange), Citrus Limonum (lemon), and Citrus reticulata (tangerine) extracts and their silver nanoparticles. Fourier Transform Infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) was used to analyze the produced AgNPs. The synthesized AgNPs have a size of less than 100 nm according to SEM examination. Their DPPH radical scavenging activity and reducing power increased in a dose-dependent way that was more than that of their aqueous and alcoholic extracts. In comparison to Staphylococcus aureus and Candida albicans, silver nanoparticles were found to be more efficient towards Escherichia coli. Their activities were increased with increasing dosage. Whereas, no inhibition zones were conducted with the examined plain citrus peel extracts. This finding revealed that the biomolecules that cover nanoparticles can increase metal nanoparticles' biological activity and the organic AgNPs green alcoholic and aqueous extracts from orange, lemon, and tangerine peels could be used as a potential source of new antioxidant and antimicrobial agents.

Essential oils can be used in a variety of ways to treat microorganisms that have evolved antibiotic resistance. The research assessed the antimicrobial and antioxidant activities of essential oil obtained from Citrus Limonum, Citrus reticulate, and Citrus sinensis fresh peels using the hydro-distillation method. Their chemical compositions were analyzed by Gas Chromatography-Mass Spectrometer. Citrus oils had antimicrobial and antioxidant properties and their activity was increased with increasing concentrations. Oils had a significant antimicrobial effect on tested bacteria except on P. aeruginosa only C. Limonum had significant (p≤0.05) inhibitory effects at both 100 and 200 mg/ml. There was no significant (p>0.05) difference in the inhibition zone of tested oils against A. baumannii and ciprofloxacin at 25 mg/ml, which was the same as against E. coli at 200 mg/ml. The oil inhibitory effect on K. pneumoniae, P. mirabilis, and S. aureus was less than that obtained from ciprofloxacin at concentrations used.  At 100 mg/mL, C. reticulate oil had a 23 mm inhibitory zone, while C. sinensis oil had a 23 mm inhibitory zone at 200 mg/mL, which was the same as the inhibitory area of ciprofloxacin against S. marcescens. Oils had convergent antifungal activity against Candida albicans that increased with increasing concentrations. The extracts competed favorably with voriconazole being used as a positive control. Citrus oils had convergent scavenging activities at the concentrations used. The studies confirmed the medicinal and industrial use of citrus essential oils as a therapeutic and antioxidant agent.

Introduction: Sufficient continuous preparation is needed to ensure that citizens are able to respond adequately in the event of emergencies. This preparation is a continuous process of education in the Czech Republic that is part of primary school educational programmes.Objective: To determine the knowledge of 6^th and 9^th grade primary school students in the field of protection of people in emergencies.Methodology: A questionnaire survey was conducted among a group of 1,943 respondents at 19 primary schools in the Olomouc and Moravian-Silesian regions in 2018 to 2019.Results: The results showed that students in 6^th, 7^th and 8^th grades have the same level of knowledge, and that the knowledge of students in the 9^th grade is at a higher level. An average level of knowledge was found in 42.98% of students, 29.64% of students have below-average knowledge, and 27.38% of students have above-average knowledge.Conclusion: The results indicate that the sub-objectives set out in the Framework Education Programme for Basic Education have not been fully met. The authors propose teaching the topic of Protection of People in Emergencies from the 6^th to 8^th grade cross-sectionally in individual subjects, and adding it as a separate subject in the 9^th grade.

The profession of paramedic has become an integral part of the health care delivery system in the Czech Republic. It is a profession belonging to the group of regulated professions, with clearly defined rules for education and practice itself.This study attempted to map how the competences and professional training methods of RNs differ in the Czech Republic, Poland, Germany and Slovakia, which are the closest states to the Czech Republic and also have a similar approach to the pre-hospital care system. There is a real assumption that the principles of training paramedics and their competence will not differ significantly within these EU states. The study was carried out as a research, overview. A content analysis of the current legislation was carried out, regarding the education and work content of paramedics in the environment of the Czech Republic, Germany, Poland and Slovakia.As part of the comparison of these states, it was found that the education and the system of activity of a paramedic differ in details, given by national legislative specifics. Especially in the areas of ZZ competences, it was found that paramedic is the most limited in the conditions of the Czech Republic. However, these limits should not have a major impact on the quality of care provided within the prehospital care, due to the dense network of RZP stations and the low arrival times of crews with doctors.

In 2025, we commemorated the 50^th anniversary of the ratification of the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction (Biological Weapons Convention, BWC). By 2025, 189 countries had signed the treaty, including the four original signatory states. However, research on microorganisms or their products – toxins – that can be misused for military or terrorist purposes is still being carried out in military facilities in many countries. For this reason, constant attention should be paid to the issues related to the individual Articles of the convention. This article, taking advantage of this anniversary, seeks to provide a precise definition of biological weapons, a brief historical overview of the use of biological agents in armed conflict, and a brief description of the efforts to prohibit the use of microorganisms or their products as weapons of mass destruction, especially against human targets. In its concluding remarks, given the overlap between biomedical and military research on the use of biological agents. The text addresses the still not completely resolved issue of the misuse of biological agents, referring to the long and layered history of their use for nefarious purposes, contributes to distinguish between defensive and offensive biological research, and draws attention to the complexity of issues related to the biological security of world´s states.

Objectives: Due to a variety of factors, individuals with diabetes are more likely to develop anemia. Chronic kidney disease, a frequent consequence of diabetes, is one of the key contributing factors. Diabetic neuropathy is another reason that can result in gastrointestinal bleeding and iron malabsorption. Healthcare providers must be aware of the connection between diabetes and anemia in order to closely monitor and treat both disorders and lessen their detrimental effects on general health and quality of life. This review sought to explore the underlying factors that lead to anemia in diabetic individuals, as well as the most prevalent kinds of anemia and suggested management approaches.Methods: PubMed, Cochrane Library and Google scholar were searched to find all relevant articles published in English until October 2023, using the specified search phrases, and we then brought up and analyzed all of the papers that matched the requirements.Results and conclusion: Collectively, managing anemia in diabetes patients is a difficult issue that calls for a multimodal approach. Early detection and effective therapy of anemia in diabetic patients depend on routine monitoring of the blood levels of hemoglobin, glycemic control, blood pressure, foot health, renal and retinal functions, neuropathy, and other comorbidities.

A simple colorimetric biosensor, which uses the modified Ellman's reaction, enables selective analysis of nerve agents based on a different ability of bispyridinium oximes to reactivate enzyme-inhibitor complexes in the phase before dealkylation. The analysis was made based on spectral data of reflectance of the surface of a cotton cloth reaction zone of biosensor with immobilized and stabilized enzyme after inhibition and subsequent reactivation. The evaluation of measured data was made based on a method of artificial neuronal networks. The individual inhibitors from the groups of three nerve agents were identified: sarin, soman, tabun, cyclosarin, agent VX and its Russian analogue, R-33.