"VT2019-2021"
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A host's immune system can be invaded by mycotoxin deoxynivalenol (DON) poisoning and porcine circovirus type 2 (PCV2) infections, which affect the host's natural immune function. Pro-inflammatory cytokines, IL-1β and IL-6, are important regulators in the process of natural immune response, which participate in inflammatory response and enhance immune-mediated tissue damage. Preliminary studies have shown that DON promotes PCV2 infection by activating the MAPK signaling pathway. Here, we explored whether the mRNA expression of IL-1β and IL-6, induced by the combination of DON and PCV2, would depend on the MAPK signaling pathway. Specific pharmacological antagonists U0126, SP600125 and SB203580, were used to inhibit the activities of ERK, JNK and p38 in the MAPK signaling pathway, respectively. Then, the mRNA expression of IL-1β and IL-6 in PK-15 cells was detected to explore the effect of the MAPK signaling pathway on IL-1β and IL-6 mRNA induced by DON and PCV2. The results showed that PK-15 cells treated with DON or PCV2 induced the mRNA expression of IL-1β and IL-6 in a time- and dose-dependent manner. The combination of DON and PCV2 has an additive effect on inducing the mRNA expression of IL-1β and IL-6. Additionally, both DON and PCV2 could induce the mRNA expression of IL-1β and IL-6 via the ERK and the p38 MAPK signal pathways, while PCV2 could induce it via the JNK signal pathway. Taken together, our results suggest that MAPKs play a contributory role in IL-1β and IL-6 mRNA expression when induced by both DON and PCV2.
- MeSH
- buněčné linie MeSH
- Circovirus * MeSH
- infekce viry čeledi Circoviridae genetika metabolismus MeSH
- interleukin-1beta genetika MeSH
- interleukin-6 genetika MeSH
- MAP kinasový signální systém účinky léků MeSH
- messenger RNA MeSH
- prasata MeSH
- trichotheceny toxicita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The ingestion of contaminated water and food is known to cause food illness. Moreover, on assessing the patients suffering from foodborne disease has revealed the role of microbes in such diseases. Concerning which different methods have been developed for protecting food from microbes, the treatment of food with chemicals has been reported to exhibit an unwanted organoleptic effect while also affecting the nutritional value of food. Owing to these challenges, the demand for natural food preservatives has substantially increased. Therefore, the interest of researchers and food industries has shifted towards fruit polyphenols as potent inhibitors of foodborne bacteria. Recently, numerous fruit polyphenols have been acclaimed for their ability to avert toxin production and biofilm formation. Furthermore, various studies have recommended using fruit polyphenols solely or in combination with chemical disinfectants and food preservatives. Currently, different nanoparticles have been synthesized using fruit polyphenols to curb the growth of pathogenic microbes. Hence, this review intends to summarize the current knowledge about fruit polyphenols as antibacterial agents against foodborne pathogens. Additionally, the application of different fruit extracts in synthesizing functionalized nanoparticles has also been discussed.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- Bacteria účinky léků metabolismus MeSH
- biofilmy účinky léků MeSH
- lidé MeSH
- nanočástice MeSH
- ovoce chemie MeSH
- polyfenoly chemie farmakologie MeSH
- potravinářská mikrobiologie MeSH
- potravinářské konzervační látky chemie farmakologie MeSH
- rostlinné extrakty chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Fruit extracts have natural bioactive molecules that are known to possess significant therapeutic potential. Traditionally, metallic nanoparticles were synthesized via chemical methods, in which the chemical act as the reducing agent. Later, these traditional metallic nanoparticles emerged as the biological risk, which prompted researchers to explore an eco-friendly approach. There are different eco-friendly methods employed for synthesizing these metallic nanoparticles via the usage of microbes and plants, primarily via fruit extract. These explorations have paved the way for using fruit extracts for developing nanoparticles, as they eliminate the usage of reducing and stabilizing agents. Metallic nanoparticles have gained significant attention, and are used for diverse biological applications. The present review discusses the potential activities of phytochemicals, and it intends to summarize the different metallic nanoparticles synthesized using fruit extracts and their associated pharmacological activities like anti-cancerous, antimicrobial, antioxidant and catalytic efficiency.
At present, Alzheimer's disease (AD) and related dementias cannot be cured. Therefore, scientists all over the world are trying to find a new approach to prolong an active life of patients with initial dementia. Both pharmacological and non-pharmacological pathways are investigated to improve the key symptom of the disease, memory loss. In this respect, influencing the neuromodulator acetylcholine via muscarinic receptors, such as cevimeline, might be one of the therapeutic alternatives. The purpose of this study is to explore the potential of cevimeline on the cognitive functions of AD patients. The methodology is based on a systematic literature review of available studies found in Web of Science, PubMed, Springer, and Scopus on the research topic. The findings indicate that cevimeline has shown an improvement in experimentally induced cognitive deficits in animal models. Furthermore, it has demonstrated to positively influence tau pathology and reduce the levels of amyloid-β (Aβ) peptide in the cerebral spinal fluid of Alzheimer's patients. Although this drug has not been approved by the FDA for its use among AD patients and there is a lack of clinical studies confirming and extending this finding, cevimeline might represent a breakthrough in the treatment of AD.
- MeSH
- agonisté muskarinových receptorů farmakologie MeSH
- chinuklidiny farmakologie MeSH
- kognitivní poruchy farmakoterapie MeSH
- léčivé přípravky aplikace a dávkování MeSH
- lidé MeSH
- neurodegenerativní nemoci farmakoterapie MeSH
- neurofarmakologie * MeSH
- thiofeny farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Poisoning with organophosphorus compounds used as pesticides or misused as chemical weapons remains a serious threat to human health and life. Their toxic effects result from irreversible blockade of the enzymes acetylcholinesterase and butyrylcholinesterase, which causes overstimulation of the cholinergic system and often leads to serious injury or death. Treatment of organophosphorus poisoning involves, among other strategies, the administration of oxime compounds. Oximes reactivate cholinesterases by breaking the covalent bond between the serine residue from the enzyme active site and the phosphorus atom of the organophosphorus compound. Although the general mechanism of reactivation has been known for years, the exact molecular aspects determining the efficiency and selectivity of individual oximes are still not clear. This hinders the development of new active compounds. In our research, using relatively simple and widely available molecular docking methods, we investigated the reactivation of acetyl- and butyrylcholinesterase blocked by sarin and tabun. For the selected oximes, their binding modes at each step of the reactivation process were identified. Amino acids essential for effective reactivation and those responsible for the selectivity of individual oximes against inhibited acetyl- and butyrylcholinesterase were identified. This research broadens the knowledge about cholinesterase reactivation and demonstrates the usefulness of molecular docking in the study of this process. The presented observations and methods can be used in the future to support the search for new effective reactivators.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- aktivace enzymů MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory farmakologie MeSH
- fosfor chemie MeSH
- katalytická doména MeSH
- konformace proteinů MeSH
- kvantová teorie MeSH
- lidé MeSH
- ligandy MeSH
- molekulární modely MeSH
- myši MeSH
- organofosfáty chemie MeSH
- oximy chemie MeSH
- proteosyntéza MeSH
- reaktivátory cholinesterasy farmakologie MeSH
- sarin chemie MeSH
- shluková analýza MeSH
- simulace molekulového dockingu * MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
New psychoactive substances are being used as drugs and appear to be quite popular nowadays. Thanks to their specific properties, these drugs create inimitable experiences for intoxicated people. Synthetic cathinones are the most common compounds in these new drugs. Among them, α-pyrrolidopentadione (α-PVP), or "Flakka" (street name), is one of the most famous cathinone-designed drugs. Similar to other synthetic cathinone drugs, α-PVP can effectively inhibit norepinephrine and dopamine transmitters. The adverse reactions of α-PVP mainly include mania, tachycardia, and hallucinations. An increasing number of people are being admitted to emergency wards due to the consequences of their use. This work mainly summarizes the history, synthesis, pharmacology, toxicology, structure-activity relationship, metabolism, clinical process and health risks, poisoning and death, forensic toxicology, and legal status of α-PVP. We hope this review will help bring more attention to the exploration of this substance in order to raise awareness of its negative impacts on humans.
- MeSH
- alkaloidy otrava MeSH
- lidé MeSH
- pentanony otrava MeSH
- poruchy spojené s užíváním psychoaktivních látek etiologie patologie MeSH
- psychotropní léky otrava MeSH
- pyrrolidiny otrava MeSH
- stimulanty centrálního nervového systému otrava MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zakázané drogy otrava MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
In this paper, the potential antidote efficacy of commercially available formulations of various feed additives such as Minazel-Plus®, Mycosorb®, and Mycofix® was considered by recording their incidence on general health, body weight, and food and water intake, as well as through histopathology and semiquantitative analysis of gastric alterations in Wistar rats treated with the T-2 toxin in a single-dose regimen of 1.67 mg/kg p.o. (1 LD50) for 4 weeks. As an organic adsorbent, Mycosorb® successfully antagonized acute lethal incidence of the T-2 toxin (protective index (PI) = 2.25; p < 0.05 vs. T-2 toxin), and had adverse effects on body weight gain as well as food and water intake during the research (p < 0.001). However, the protective efficacy of the other two food additives was significantly lower (p < 0.05). Treatment with Mycosorb® significantly reduced the severity of gastric damage, which was not the case when the other two adsorbents were used. Our results suggest that Mycosorb® is a much better adsorbent for preventing the adverse impact of the T-2 toxin as well as its toxic metabolites compared with Minazel-plus® or Mycofix-plus®, and it almost completely suppresses its acute toxic effects and cytotoxic potential on the gastric epithelial, glandular, and vascular endothelial cells.
- MeSH
- adsorpce MeSH
- antidota chemie farmakologie MeSH
- časové faktory MeSH
- cévní endotel účinky léků patologie MeSH
- jodofory farmakologie MeSH
- LD50 MeSH
- molekulární struktura MeSH
- otrava farmakoterapie patologie MeSH
- potkani Wistar MeSH
- potravinářské přísady chemie farmakologie MeSH
- T-2 toxin otrava MeSH
- vztahy mezi strukturou a aktivitou MeSH
- žaludeční sliznice účinky léků patologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Ageing is an enigmatic and progressive biological process which undermines the normal functions of living organisms with time. Ageing has been conspicuously linked to dietary habits, whereby dietary restrictions and antioxidants play a substantial role in slowing the ageing process. Oxygen is an essential molecule that sustains human life on earth and is involved in the synthesis of reactive oxygen species (ROS) that pose certain health complications. The ROS are believed to be a significant factor in the progression of ageing. A robust lifestyle and healthy food, containing dietary antioxidants, are essential for improving the overall livelihood and decelerating the ageing process. Dietary antioxidants such as adaptogens, anthocyanins, vitamins A/D/C/E and isoflavones slow the ageing phenomena by reducing ROS production in the cells, thereby improving the life span of living organisms. This review highlights the manifestations of ageing, theories associated with ageing and the importance of diet management in ageing. It also discusses the available functional foods as well as nutraceuticals with anti-ageing potential.
- MeSH
- antioxidancia aplikace a dávkování MeSH
- dlouhověkost MeSH
- funkční potraviny MeSH
- jedlé rostliny * MeSH
- lidé MeSH
- oxidační stres MeSH
- potravní doplňky * MeSH
- reaktivní formy kyslíku analýza MeSH
- stárnutí fyziologie MeSH
- zdravá strava metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Continuing the work developed by our research group, in the present manuscript, we performed a theoretical study of 10 new structures derived from the antivirals cidofovir and ribavirin, as inhibitor prototypes for the enzyme thymidylate kinase from Variola virus (VarTMPK). The proposed structures were subjected to docking calculations, molecular dynamics simulations, and free energy calculations, using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method, inside the active sites of VarTMPK and human TMPK (HssTMPK). The docking and molecular dynamic studies pointed to structures 2, 3, 4, 6, and 9 as more selective towards VarTMPK. In addition, the free energy data calculated through the MM-PBSA method, corroborated these results. This suggests that these compounds are potential selective inhibitors of VarTMPK and, thus, can be considered as template molecules to be synthesized and experimentally evaluated against smallpox.
- Publikační typ
- časopisecké články MeSH
Alzheimer's disease (AD) is a multifactorial neurodegenerative condition of the central nervous system (CNS) that is currently treated by cholinesterase inhibitors and the N-methyl-d-aspartate receptor antagonist, memantine. Emerging evidence strongly supports the relevance of targeting butyrylcholinesterase (BuChE) in the more advanced stages of AD. Within this study, we have generated a pilot series of compounds (1-20) structurally inspired from belladine-type Amaryllidaceae alkaloids, namely carltonine A and B, and evaluated their acetylcholinesterase (AChE) and BuChE inhibition properties. Some of the compounds exhibited intriguing inhibition activity for human BuChE (hBuChE), with a preference for BuChE over AChE. Seven compounds were found to possess a hBuChE inhibition profile, with IC50 values below 1 μM. The most potent one, compound 6, showed nanomolar range activity with an IC50 value of 72 nM and an excellent selectivity pattern over AChE, reaching a selectivity index of almost 1400. Compound 6 was further studied by enzyme kinetics, along with in-silico techniques, to reveal the mode of inhibition. The prediction of CNS availability estimates that all the compounds in this survey can pass through the blood-brain barrier (BBB), as disclosed by the BBB score.
- MeSH
- acetylcholinesterasa chemie MeSH
- alkaloidy amarylkovitých chemie MeSH
- butyrylcholinesterasa chemie MeSH
- cholinesterasové inhibitory chemie farmakologie MeSH
- lidé MeSH
- nádorové buňky kultivované MeSH
- neuroblastom farmakoterapie patologie MeSH
- počítačová simulace MeSH
- proliferace buněk MeSH
- simulace molekulového dockingu * MeSH
- tyramin analogy a deriváty chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
