Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.

• MeSH
• COVID-19 * imunologie   prevence a kontrola   MeSH
• dospělí MeSH
• glykoprotein S, koronavirus imunologie   MeSH
• humorální imunita MeSH
• lidé středního věku MeSH
• lidé MeSH
• neutralizující protilátky * krev   imunologie   MeSH
• příjemce transplantátu * MeSH
• protilátky virové * krev   imunologie   MeSH
• SARS-CoV-2 * imunologie   MeSH
• sekundární imunizace MeSH
• senioři MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• vakcína BNT162 imunologie   aplikace a dávkování   MeSH
• vakcíny proti COVID-19 imunologie   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Alergie na pyly břízovitých stromů je narůstajícím problémem průmyslových zemí. Onemocnění se vyvíjí u predisponovaných osob v důsledku inhalace pylových zrn břízy a dalších příbuzných stromů. Klinické projevy alergie na pyl jarních stromů (sezónní alergická rhinokonjunktivitis, sezónní alergické astma bronchiale a sekundární pylově potravinový syndrom) mají signifikantně negativní vliv na kvalitu života pacientů. Tento přehledový článek pojednává o taxonomii stromů, zkřížené reaktivitě mezi nimi a mezi relevantními potravinami, epidemiologii, vlivu klimatických změn a v neposlední řadě o možnostech léčby včetně alergenové imunoterapie.

Tree pollen allergy presents an increasing problem in industrialized countries. This disease develops in sensitised people after inhalation of pollen grains of birch and other related trees. Clinical symptoms of tree pollen allergy (seasonal allergic rhinoconjunctivitis, seasonal asthma bronchiale and secondary pollen food syndrome) have significant negative impact on the quality of life in these patients. The purpose of this review is to touch the taxonomy of the trees, describe cross-reactivity of relevant allergens, prevalence, the influence of climatic changes and to stress the importance of allergen immunotherapy as a disease modifying treatment.

• Klíčová slova
• zkřížená reaktivita, pylově potravinový syndrom,
• MeSH
• bříza škodlivé účinky   MeSH
• břízovité škodlivé účinky   MeSH
• desenzibilizace imunologická MeSH
• lidé MeSH
• sezónní alergická rýma * patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: The potential cross-protective effect of measles, mumps, and rubella (MMR) vaccination against coronavirus disease 2019 (COVID-19) is debated. Although immunological studies suggest cross-reactivity between MMR-induced immunity and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), epidemiological evidence remains inconclusive. This study examined the association between an additional MMR dose and both COVID-19 clinical and serological outcomes in an adult cohort with verified pre-pandemic measles immunity. METHODS: In 2019, prior to the COVID-19 pandemic, 3027 healthcare workers from a Czech university hospital underwent measles serology testing. Seronegative individuals were offered a single additional MMR dose. Between 2020 and 2021, 261 individuals from the original sample subsequently contracted COVID-19 and underwent post-infection SARS-CoV-2 immunoglobulin G (IgG) serology testing, having remained unvaccinated against COVID-19 until that time. RESULTS: Among 212 women and 49 men (mean age: 42.7 years), 150 were measles-seropositive (without additional vaccination) and 111 were measles-seronegative but received an additional MMR dose. Following COVID-19, 216 participants (82.8 %) exhibited SARS-CoV-2 IgG seropositivity. No significant relationship was observed between measles immunity or MMR vaccine administration and COVID-19 clinical characteristics. However, individuals who received an additional MMR dose were significantly more likely to develop SARS-CoV-2 IgG seropositivity (88.3 % vs. 78.7 %; p = 0.042). Regression analysis confirmed additional MMR vaccination as an independent predictor of post-COVID-19 seropositivity (odds ratio 1.81, 95 % confidence interval 1.17-2.81, p = 0.008), irrespective of the interval between MMR vaccination and COVID-19 symptom onset. No correlation was found between pre-pandemic measles antibody titers and SARS-CoV-2 antibody levels (r = 0.09, p = 0.246). CONCLUSION: While no protective effect of adult MMR vaccination on COVID-19 clinical outcomes was observed, a significant immunological interaction was identified. These findings align with the concept of trained immunity and warrant further investigation.

• MeSH
• COVID-19 * imunologie   prevence a kontrola   epidemiologie   MeSH
• dospělí MeSH
• imunoglobulin G krev   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• příušnice prevence a kontrola   MeSH
• protilátky virové krev   imunologie   MeSH
• retrospektivní studie MeSH
• SARS-CoV-2 imunologie   MeSH
• sekundární imunizace * MeSH
• spalničky prevence a kontrola   imunologie   MeSH
• vakcína proti spalničkám, příušnicím a zarděnkám * imunologie   aplikace a dávkování   MeSH
• zarděnky prevence a kontrola   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Berberine (BBR), a small molecule protoberberine isoquinoline alkaloid, is easy to cross the blood-brain barrier and is a potential drug for neurodegenerative diseases. Here, we explored the role and molecular mechanism of BBR in Alzheimer's disease (AD) progression. Weighted gene co-expression network analysis (WGCNA) was conducted to determine AD pathology-associated gene modules and differentially expressed genes (DEGs) were also identified. GO and KEGG analyses were performed for gene function and signaling pathway annotation. Cell counting kit-8 (CCK8) assay was applied to analyze cell viability. Immunofluorescence (IF) staining assay was conducted to measure the levels of polarization markers. The production of inflammatory cytokines was analyzed by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) were detected using a ROS detection kit and a MMP Detection Kit (JC-1), respectively. AD pathology-associated DEGs were applied for GO function annotation and KEGG enrichment analysis, and the results uncovered that AD pathology was related to immune and inflammation. Lipopolysaccharide (LPS) exposure induced the M1 phenotype of microglia, and BBR suppressed LPS-induced M1 polarization and induced microglia toward M2 polarization. Through co-culture of microglia and neuronal cells, we found that BBR exerted a neuro-protective role by attenuating the injury of LPS-induced HMC3 on SH-SY5Y cells. Mechanically, BBR switched the M1/M2 phenotypes of microglia by activating PI3K-AKT signaling. In summary, BBR protected neuronal cells from activated microglia-mediated neuro-inflammation by switching the M1/M2 polarization in LPS-induced microglia via activating PI3K-AKT signaling. Key words Alzheimer's Disease, Berberine, Microglia polarization, Neuroinflammation, PI3K-AKT signaling.

• MeSH
• Alzheimerova nemoc * metabolismus   farmakoterapie   patologie   MeSH
• berberin * farmakologie   terapeutické užití   MeSH
• fosfatidylinositol-3-kinasy * metabolismus   MeSH
• lidé MeSH
• mikroglie * účinky léků   metabolismus   MeSH
• myši MeSH
• neuroprotektivní látky * farmakologie   MeSH
• polarita buněk účinky léků   MeSH
• protoonkogenní proteiny c-akt * metabolismus   MeSH
• signální transdukce * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Tick-borne encephalitis virus (TBEV) is an emerging pathogen that initially causes flu-like symptoms and can progress to central nervous system (CNS) infections. Tick-borne encephalitis (TBE) is an endemic disease in southern coastal counties with regular human cases, while the causative agent, TBEV, is prevalent in ticks in most of the coastal regions of Norway. This study was aimed to understand TBEV infection status across Norway including both TBE endemic and non-endemic areas. For this, we analyzed a total of 1940 residual serum samples from 19 counties of Norway (as of 2016). The samples were initially screened by ELISA, followed by virus neutralization tests for TBEV confirmation. We found a similar TBEV seroprevalence of 1.7% in TBE endemic and 1.6% in non-endemic areas. Since TBE cases are only reported from endemic regions, our findings suggest a potential subclinical or asymptomatic infection and underdiagnosis in non-endemic areas. Notably, only 43% of the ELISA-positive samples were confirmed by virus neutralization tests indicating that not all ELISA positives are true TBEV infections. Additionally, 137 samples of patients presenting with symptoms of CNS infections from a non-endemic area were included. Of these samples, 11 ELISA-positive samples were analyzed for cross-reactivity among flaviviruses. Cross-reactivity was detected with Dengue virus, West Nile Virus, and non-specific reactions. This underscores the importance of using multiple diagnostic tests to confirm TBEV infections. None of the patients with CNS infection was found to be TBE positive, and in the whole cohort, we found a low TBEV seroprevalence of 0.7%.

• MeSH
• dítě MeSH
• dospělí MeSH
• ELISA MeSH
• klíšťová encefalitida * krev   diagnóza   epidemiologie   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• neutralizační testy MeSH
• předškolní dítě MeSH
• protilátky virové * krev   MeSH
• retrospektivní studie MeSH
• senzitivita a specificita MeSH
• séroepidemiologické studie MeSH
• viry klíšťové encefalitidy MeSH
• zkřížené reakce MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Norsko MeSH

Copper radioisotopes can be used for imaging as well as for therapy and, thus, can form ideal theranostic pairs. The Cu(II) complexes of cross-bridged cyclam (cb-cyclam) derivatives are considered to be highly stable in vivo. However, the complexes are mostly formed under harsh conditions not compatible with sensitive biomolecules. Here, a new class of cb-cyclam derivatives, cross-bridged bis(phosphinate)cyclams ("cb-BPC"), were investigated. Ligands with one or two methylene-bis(phosphinate) -CH2-PO2H-CH2-PO2H(R) (R = H, OH, substituted alkyl) pendant arms were synthesized. Bifunctionalization on the distant phosphorus atom was carried out by employing P-nitrobenzyl (R = CH2-Ph-4-NO2) precursors and/or, for cb-BPC with two bis(phosphinate) pendant arms, by reactions of silyl-phosphites obtained by silylation of their P(O)-H fragments. The reactive bifunctional groups include amine, carboxylate, azide, isothiocyanate, maleimide and/or tetrazine, and also their orthogonally reactive combination in a single molecule of chelator. The cb-BPCs with one bis(phosphinate) arm were not efficiently radiolabelled with 64Cu. The cb-BPCs with two pendant arms were radiolabelled even at room temperature and with only a small excess of chelator, leading to a high specific activity. Radiolabelling was fully comparable with that of analogous bis(phosphinate) derivatives of cyclam and identical radiolabelling of cyclam and cb-cyclam derivatives was observed for the first time. The cb-BPCs with two bis(phosphinate) pendant arms represent a new class of rigid chelators for copper radioisotopes that are easily synthetically modifiable, highly hydrophilic and radiolabelled under mild conditions.

• Publikační typ
• časopisecké články MeSH

Brucellosis is a zoonosis caused by Brucella, which poses a great threat to human health and animal husbandry. Pathogen surveillance is an important measure to prevent brucellosis, but the traditional method is time-consuming and not suitable for field applications. In this study, a recombinase polymerase amplification-SYBR Green I (RPAS) assay was developed for the rapid and visualized detection of Brucella in the field by targeting BCSP31 gene, a conserved marker. The method was highly specific without any cross-reactivity with other common bacteria and its detection limit was 2.14 × 104 CFU/mL or g of Brucella at 40 °C for 20 min. It obviates the need for costly instrumentation and exhibits robustness towards background interference in serum, meat, and milk samples. In summary, the RPAS assay is a rapid, visually intuitive, and user-friendly detection that is highly suitable for use in resource-limited settings. Its simplicity and ease of use enable swift on-site detection of Brucella, thereby facilitating timely implementation of preventive measures.

• MeSH
• Brucella * genetika   izolace a purifikace   MeSH
• brucelóza * diagnóza   mikrobiologie   MeSH
• DNA bakterií genetika   MeSH
• lidé MeSH
• limita detekce MeSH
• mléko mikrobiologie   MeSH
• rekombinasy * metabolismus   genetika   MeSH
• senzitivita a specificita MeSH
• skot MeSH
• techniky amplifikace nukleových kyselin * metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The infection of Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the main causes of economic losses in sericulture. Thus, it is essential to establish rapid and effective method for BmNPV detection. In the present study, we have developed a recombinase-aided amplification (RAA) to amplify the BmNPV genomic DNA at 37 °C within 30 min, and achieved a rapid detection method by coupling with a lateral flow dipstick (LFD). The RAA-LFD method had a satisfactory detection limit of 6 copies/μL of recombinant plasmid pMD19-T-IE1, and BmNPV infection of silkworm can be detected 12 h post-infection. This method was highly specific for BmNPV, and without cross-reactivity to other silkworm pathogens. In contrast to conventional polymerase chain reaction (PCR), the RAA-LFD assay showed higher sensitivity, cost-saving, and especially is apt to on-site detection of BmNPV infection in the sericulture production.

• MeSH
• bourec * virologie   MeSH
• DNA virů genetika   MeSH
• limita detekce MeSH
• nukleopolyhedroviry * genetika   izolace a purifikace   MeSH
• rekombinasy * metabolismus   genetika   MeSH
• senzitivita a specificita MeSH
• techniky amplifikace nukleových kyselin * metody   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH

Protein cross-linking has assumed an irreplaceable role in structural proteomics. Recently, significant efforts have been made to develop novel mass spectrometry (MS)-cleavable reagents. At present, only water-insoluble MS-cleavable cross-linkers are commercially available. However, to comprehensively analyse the various chemical and structural motifs making up proteins, it is necessary to target different protein sites with varying degrees of hydrophilicity. Here we introduce the new MS-cleavable cross-linker disulfodisuccinimidyl dibutyric urea (DSSBU), which we have developed in-house for this purpose. DSSBU contains an N-hydroxysulfosuccinimide (sulfo-NHS) reactive group, so it can serve as a water-soluble counterpart to the widely used cross-linker disuccinimidyl dibutyric urea (DSBU). To investigate the applicability of DSSBU, we compared the efficacy of four similar cross-linkers: bis[sulfosuccinimidyl] suberate (BS3), disuccinimidyl suberate (DSS), DSBU and DSSBU with bovine serum albumin. In addition, we compared the efficacy of DSBU and DSSBU with human haemoglobin. Our results demonstrate that the sulfo-NHS group ensures the superior water solubility of DSSBU and thus negates the need for organic solvents such as dimethyl sulfoxide while preserving the effectivity of urea-based MS-cleavable crosslinkers such as DSBU. Additionally, it makes it possible to target polar regions in proteins. The data gathered are available via ProteomeXchange under identifier PXD055284. SIGNIFICANCE: We have synthesized the novel protein cross-linker DSSBU, which combines sulfo-NHS ester chemistry with a mass spectrometry-cleavable urea group. This makes DSSBU a water-soluble, MS-cleavable cross-linker that reacts with amino groups. To our knowledge, it is the first cross-linker which combines all three of these characteristics. We have tested the performance of our novel cross-linker on bovine serum albumin, a model widely used by the cross-linking mass spectrometry community, and on human haemoglobin. We have comprehensively assessed the performance of DSSBU and compared its efficacy with that of three other cross-linkers in current use (BS3, DSS and DSBU). We conclude that our novel cross-linker surpasses its MS-non-cleavable analogue BS3 in performance and that its water solubility eliminates the need for organic solvents while its hydrophilicity allows for the targetting of polar regions in proteins. Therefore, it will likely become a significant addition to the portfolio of N-hydroxysuccinimide ester cross-linkers.

• MeSH
• hmotnostní spektrometrie metody   MeSH
• lidé MeSH
• močovina chemie   MeSH
• proteomika metody   MeSH
• reagencia zkříženě vázaná * chemie   MeSH
• sérový albumin hovězí chemie   MeSH
• skot MeSH
• sukcinimidy * chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

6-Nitrobenzo[b]thiophene 1,1-dioxide (Stattic) is a potent signal transducer and activator of the transcription 3 (STAT3) inhibitor developed originally for anticancer therapy. However, Stattic harbors several STAT3 inhibition-independent biological effects. To improve the properties of Stattic, we prepared a series of analogues derived from 6-aminobenzo[b]thiophene 1,1-dioxide, a compound directly obtained from the reduction of Stattic, that includes a methoxybenzylamino derivative (K2071) with optimized physicochemical characteristics, including the ability to cross the blood-brain barrier. Besides inhibiting the interleukin-6-stimulated activity of STAT3 mediated by tyrosine 705 phosphorylation, K2071 also showed cytotoxicity against a set of human glioblastoma-derived cell lines. In contrast to the core compound, a part of K2071 cytotoxicity reflected a STAT3 inhibition-independent block of mitotic progression in the prophase, affecting mitotic spindle formation, indicating that K2071 also acts as a mitotic poison. Compared to Stattic, K2071 was significantly less thiol-reactive. In addition, K2071 affected cell migration, suppressed cell proliferation in tumor spheroids, exerted cytotoxicity for glioblastoma temozolomide-induced senescent cells, and inhibited the secretion of the proinflammatory cytokine monocyte chemoattractant protein 1 (MCP-1) in senescent cells. Importantly, K2071 was well tolerated in mice, lacking manifestations of acute toxicity. The structure-activity relationship analysis of the K2071 molecule revealed the necessity of the para-substituted methoxyphenyl motif for antimitotic but not overall cytotoxic activity of its derivatives. Altogether, these results indicate that compound K2071 is a novel Stattic-derived STAT3 inhibitor and a mitotic poison with anticancer and senotherapeutic properties that is effective on glioblastoma cells and may be further developed as an agent for glioblastoma therapy.

• Publikační typ
• časopisecké články MeSH