Multiple sclerosis (MS) is a chronic neurodegenerative disease that affects the central nervous system (CNS). Currently, MS treatment is limited to several Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved medications that slow disease progression by immunomodulatory action. Fingolimod and siponimod have similar mechanisms of action, and consequently, their therapeutic effects may be comparable. However, while fingolimod is mainly used for relapsing-remitting MS (RRMS), siponimod, according to EMA label, is recommended for active secondary progressive MS (SPMS). Clinicians and scientists are analysing whether patients can switch from fingolimod to siponimod and identifying the advantages or disadvantages of such a switch from a therapeutic point of view. In this review, we aim to discuss the therapeutic effects of these two drugs and the advantages/disadvantages of switching treatment from fingolimod to siponimod in patients with the most common forms of MS, RRMS and SPMS.

• MeSH
• chronicko-progresivní roztroušená skleróza * farmakoterapie   chemicky indukované   MeSH
• fingolimod hydrochlorid škodlivé účinky   MeSH
• hodnocení rizik MeSH
• imunosupresiva škodlivé účinky   MeSH
• lidé MeSH
• neurodegenerativní nemoci * chemicky indukované   farmakoterapie   MeSH
• recidiva MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fingolimod hydrochlorid MeSH
• imunosupresiva MeSH
• siponimod MeSH Prohlížeč

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with a very poor prognosis, with near-identical incidence and mortality. According to the World Health Organization Globocan Database, the estimated number of new cases worldwide will rise by 70% between 2020 and 2040. There are no effective screening methods available so far, even for high-risk individuals. The prognosis of PDAC, even at its early stages, is still mostly unsatisfactory. Impaired glucose metabolism is present in about 3/4 of PDAC cases. METHODS: Available literature on pancreatic cancer and diabetes mellitus was reviewed using a PubMed database. Data from a national oncology registry (on PDAC) and information from a registry of healthcare providers (on diabetes mellitus and a number of abdominal ultrasound investigations) were obtained. RESULTS: New-onset diabetes mellitus in subjects older than 60 years should be an incentive for a prompt and detailed investigation to exclude PDAC. Type 2 diabetes mellitus, diabetes mellitus associated with chronic non-malignant diseases of the exocrine pancreas, and PDAC-associated type 3c diabetes mellitus are the most frequent types. Proper differentiation of particular types of new-onset diabetes mellitus is a starting point for a population-based program. An algorithm for subsequent steps of the workup was proposed. CONCLUSIONS: The structured, well-differentiated, and elaborately designed approach to the elderly with a new onset of diabetes mellitus could improve the current situation in diagnostics and subsequent poor outcomes of therapy of PDAC.

• Klíčová slova
• age over 60 years, diagnostic algorithm, new-onset diabetes mellitus, pancreatic ductal adenocarcinoma,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Alzheimer's disease is diagnosed via means of daily activity assessment. The EEG recording evaluation is a supporting tool that can assist the practitioner to recognize the illness, especially in the early stages. This paper presents a new approach for detecting Alzheimer's disease and potentially mild cognitive impairment according to the measured EEG records. The proposed method evaluates the amount of novelty in the EEG signal as a feature for EEG record classification. The novelty is measured from the parameters of EEG signal adaptive filtration. A linear neuron with gradient descent adaptation was used as the filter in predictive settings. The extracted feature (novelty measure) is later classified to obtain Alzheimer's disease diagnosis. The proposed approach was cross-validated on a dataset containing EEG records of 59 patients suffering from Alzheimer's disease; seven patients with mild cognitive impairment (MCI) and 102 controls. The results of cross-validation yield 90.73% specificity and 89.51% sensitivity. The proposed method of feature extraction from EEG is completely new and can be used with any classifier for the diagnosis of Alzheimer's disease from EEG records.

• Klíčová slova
• Alzheimer’s disease, EEG, Gradient descent, Linear neural unit, Novelty detection,
• MeSH
• Alzheimerova nemoc * diagnóza   MeSH
• elektroencefalografie MeSH
• kognitivní dysfunkce * diagnóza   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články 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.

• Klíčová slova
• Variola virus, docking, molecular dynamics, smallpox, thymidylate kinase,
• Publikační typ
• časopisecké články MeSH

Gait disorders accompany a number of neurological and musculoskeletal disorders that significantly reduce the quality of life. Motion sensors enable high-quality modelling of gait stereotypes. However, they produce large volumes of data, the evaluation of which is a challenge. In this publication, we compare different data reduction methods and classification of reduced data for use in clinical practice. The best accuracy achieved between a group of healthy individuals and patients with ataxic gait extracted from the records of 43 participants (23 ataxic, 20 healthy), forming 418 segments of straight gait pattern, is 98% by random forest classifier preprocessed by t-distributed stochastic neighbour embedding.

• Klíčová slova
• SARA, ataxia, classification, gait, machine learning,
• MeSH
• ataxie diagnóza   MeSH
• chůze (způsob) MeSH
• kvalita života * MeSH
• lidé MeSH
• neurologické poruchy chůze * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

We designed a concept of 3D-printed attachment with porous glass filter disks-SLIDE (Sweat sampLIng DevicE) for easy sampling of apocrine sweat. By applying advanced mass spectrometry coupled with the liquid chromatography technique, the complex lipid profiles were measured to evaluate the reproducibility and robustness of this novel approach. Moreover, our in-depth statistical evaluation of the data provided an insight into the potential use of apocrine sweat as a novel and diagnostically relevant biofluid for clinical analyses. Data transformation using probabilistic quotient normalization (PQN) significantly improved the analytical characteristics and overcame the 'sample dilution issue' of the sampling. The lipidomic content of apocrine sweat from healthy subjects was described in terms of identification and quantitation. A total of 240 lipids across 15 classes were identified. The lipid concentrations varied from 10-10 to 10-4 mol/L. The most numerous class of lipids were ceramides (n = 61), while the free fatty acids were the most abundant ones (average concentrations of 10-5 mol/L). The main advantages of apocrine sweat microsampling include: (a) the non-invasiveness of the procedure and (b) the unique feature of apocrine sweat, reflecting metabolome and lipidome of the intracellular space and plasmatic membranes. The SLIDE application as a sampling technique of apocrine sweat brings a promising alternative, including various possibilities in modern clinical practice.

• Klíčová slova
• apocrine sweat, lipidomics, mass spectrometry, microsampling, profiling,
• MeSH
• lidé MeSH
• lipidomika metody   MeSH
• lipidy analýza   MeSH
• metabolomika metody   MeSH
• odběr biologického vzorku * MeSH
• pot chemie   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lipidy MeSH

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.

• Klíčová slova
• IL-1β, IL-6, MAPK, PCV2, deoxynivalenol,
• 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
• Názvy látek
• deoxynivalenol MeSH Prohlížeč
• interleukin-1beta MeSH
• interleukin-6 MeSH
• messenger RNA MeSH
• trichotheceny MeSH

Since December 2019, SARS-CoV-2 (COVID-19) has been a worldwide pandemic with enormous consequences for human health and the world economy. Remdesivir is the only drug in the world that has been approved for the treating of COVID-19. This drug, as well as vaccination, still has uncertain effectiveness. Drug repurposing could be a promising strategy how to find an appropriate molecule: rapamycin could be one of them. The authors performed a systematic literature review of available studies on the research describing rapamycin in association with COVID-19 infection. Only peer-reviewed English-written articles from the world's acknowledged databases Web of Science, PubMed, Springer and Scopus were involved. Five articles were eventually included in the final analysis. The findings indicate that rapamycin seems to be a suitable candidate for drug repurposing. In addition, it may represent a better candidate for COVID-19 therapy than commonly tested antivirals. It is also likely that its efficiency will not be reduced by the high rate of viral RNA mutation.

• Klíčová slova
• COVID-19, SARS-CoV-19, mTOR inhibitor, rapamycin, sirolimus,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Mushroom poisoning has always been a threat to human health. There are a large number of reports about ingestion of poisonous mushrooms every year around the world. It attracts the attention of researchers, especially in the aspects of toxin composition, toxic mechanism and toxin application in poisonous mushroom. Inocybe is a large genus of mushrooms and contains toxic substances including muscarine, psilocybin, psilocin, aeruginascin, lectins and baeocystin. In order to prevent and remedy mushroom poisoning, it is significant to clarify the toxic effects and mechanisms of these bioactive substances. In this review article, we summarize the chemistry, most known toxic effects and mechanisms of major toxic substances in Inocybe mushrooms, especially muscarine, psilocybin and psilocin. Their available toxicity data (different species, different administration routes) published formerly are also summarized. In addition, the treatment and medical application of these toxic substances in Inocybe mushrooms are also discussed. We hope that this review will help understanding of the chemistry and toxicology of Inocybe mushrooms as well as the potential clinical application of its bioactive substances to benefit human beings.

• Klíčová slova
• Inocybe mushroom, muscarine, psilocin, psilocybin, toxicology,
• MeSH
• Agaricales chemie   metabolismus   fyziologie   MeSH
• lektiny chemie   farmakologie   MeSH
• lidé MeSH
• muskarin chemie   otrava   toxicita   MeSH
• organofosforové sloučeniny chemie   toxicita   MeSH
• otrava houbami etiologie   terapie   MeSH
• psilocybin analogy a deriváty   chemie   otrava   toxicita   MeSH
• tryptaminy chemie   toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• lektiny MeSH
• muskarin MeSH
• N, N, N-trimethyl-4-phosphoryloxytryptamine MeSH Prohlížeč
• organofosforové sloučeniny MeSH
• psilocin MeSH Prohlížeč
• psilocybin MeSH
• tryptaminy MeSH

Ethnomedicinal plants have a significant role in the lives of people of rural and tribal areas. Thousands of medicinal plant species are used to treat various diseases, including jaundice, and are considered an important therapeutic resource to minimize these diseases. Jaundice (icterus) is a chronic disease that occurs when the amount of bilirubin in the blood increases. This review describes different ethnomedicinal plants used for curing jaundice by tribal and rural people of Himachal Pradesh. The study reveals 87 ethnomedicinal plant species belonging to 51 different families, which are used for treating jaundice in Himachal Pradesh. These plants are arranged in a systematic way, which includes a description of their common name, botanical name, along with its family, plant parts used, region, and mode of use in tabulated form. Some of the plant extracts have already been explored for their phytochemical and pharmacological significance and proved their potential in the preparation of new medicines or drugs against the treatment of jaundice. This review is an attempt to highlight the indigenous knowledge of medicinal plants, which are specifically used for the treatment of jaundice. The data mentioned in the present review is compiled from various sources like existing literature, books, Google Scholar, and Scopus publications. Among all the observed plant species, most used medicinal plants for the treatment of jaundice include Justicia adhatoda, Emblica officinalis, Ricinus communis, Saccharum officinarum, Terminalia chebula, Berberis aristata, Cuscuta reflexa, and Tinospora cordifolia. Plants that are mostly utilized for the treatment of jaundice need to be scientifically validated by pharmacological analysis and should be subsequently used for the preparation of new drugs, which may prove far more beneficial than the existing one.

• Klíčová slova
• bilirubin, ethnomedicinal plants, hepatoprotective, jaundice, phytoconstituents,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH