"Programme EXCELES ID Project No. LX22NPO5103"
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Tick-borne encephalitis virus (TBEV) targets the central nervous system (CNS), leading to potentially severe neurological complications. The neurovascular unit plays a fundamental role in the CNS and in the neuroinvasion of TBEV. However, the role of human brain pericytes, a key component of the neurovascular unit, during TBEV infection has not yet been elucidated. In this study, TBEV infection of the primary human brain perivascular pericytes was investigated with highly virulent Hypr strain and mildly virulent Neudoerfl strain. We used Luminex assay to measure cytokines/chemokines and growth factors. Both viral strains showed comparable replication kinetics, peaking at 3 days post infection (dpi). Intracellular viral RNA copies peaked at 6 dpi for Hypr and 3 dpi for Neudoerfl cultures. According to immunofluorescence staining, only small proportion of pericytes were infected (3% for Hypr and 2% for Neudoerfl), and no cytopathic effect was observed in the infected cells. In cell culture supernatants, IL-6 production was detected at 3 dpi, together with slight increases in IL-15 and IL-4, but IP-10, RANTES and MCP-1 were the main chemokines released after TBEV infection. These chemokines play key roles in both immune defense and immunopathology during TBE. This study suggests that pericytes are an important source of these signaling molecules during TBEV infection in the brain.
- MeSH
- chemokin CCL5 * metabolismus MeSH
- chemokin CXCL10 * metabolismus MeSH
- cytokiny metabolismus MeSH
- klíšťová encefalitida * virologie metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- mozek * virologie metabolismus patologie MeSH
- pericyty * virologie metabolismus MeSH
- replikace viru MeSH
- viry klíšťové encefalitidy * fyziologie patogenita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: A proportion of head and neck carcinomas (HNSCCs) are induced by high-risk human papillomaviruses (HPVs) and are associated with better patient outcomes compared to patients with HNSCCs related to tobacco and alcohol abuse. In the microenvironment of solid tumors, including HNSCCs, oxygen levels are often reduced, and a hypoxic state is induced. This can lead to a poor treatment response and a worse patient prognosis. One of the hypoxia-responsive genes is aspartate-β-hydroxylase (ASPH), whose activity promotes the growth, invasiveness, and metastasis of many types of solid tumors. METHODS: In our study, HNSCC samples were analyzed for the expression of ASPH and selected endogenous hypoxia markers by real-time PCR and/or multiplex fluorescence immunohistochemistry. RESULTS: Except for the EPAS1 gene, which had higher mRNA expression in the HPV-negative group of HNSCC (p < 0.05), we found no other differences in the expression of the tested genes that were related to HPV status. On the contrary, a statistically significantly higher number of cells producing ASPH (p < 0.0001), HIF1A (p < 0.0001), GLUT1 (p < 0.0001), and MMP13 (p < 0.05) proteins were detected in the HPV-positive tumor group than in the HPV-negative sample group. All the evaluated markers, except for MMP9/13, were more abundant in the tumor parenchyma than in the tumor stroma. The Cox proportional hazard models showed that increased numbers of cells with GLUT1 and HIF1A protein expression were positive prognostic markers for overall and disease-specific survival in patients independent of HPV tumor status. CONCLUSION: The study examined HNSCC samples and found that elevated ASPH and hypoxia marker proteins, typically associated with poor prognosis, may actually indicate active HPV infection, the strongest prognostic factor in HNSCC patients. In cases where HPV status is uncertain, increased expression of HIF1A and GLUT1 can serve as positive prognostic factors.
- Publikační typ
- časopisecké články MeSH
For most retroviruses, including HIV, association with the plasma membrane (PM) promotes the assembly of immature particles, which occurs simultaneously with budding and maturation. In these viruses, maturation is initiated by oligomerization of polyprotein precursors. In contrast, several retroviruses, such as Mason-Pfizer monkey virus (M-PMV), assemble in the cytoplasm into immature particles that are transported across the PM. Therefore, protease activation and specific cleavage must not occur until the pre-assembled particle interacts with the PM. This interaction is triggered by a bipartite signal consisting of a cluster of basic residues in the matrix (MA) domain of Gag polyprotein and a myristoyl moiety N-terminally attached to MA. Here, we provide evidence that myristoyl exposure from the MA core and its insertion into the PM occurs in M-PMV. By a combination of experimental methods, we show that this results in a structural change at the C-terminus of MA allowing efficient cleavage of MA from the downstream region of Gag. This suggests that, in addition to the known effect of the myristoyl switch of HIV-1 MA on the multimerization state of Gag and particle assembly, the myristoyl switch may have a regulatory role in initiating sequential cleavage of M-PMV Gag in immature particles.
BACKGROUND: Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 positively affect the fecal bacteriome in children with celiac disease autoimmunity after 6 months of supplementation. The aim of the present investigation was to study the effects of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 on the single-cell parasitome, with a primary focus on Blastocystis. METHODS: Stool samples were collected from 78 Swedish children with celiac disease autoimmunity participating in a randomized, double-blind, placebo-controlled clinical trial to either receive a mixture of supplementation with L. plantarum HEAL9 and L. paracasei 8700:2 (n = 38) or placebo (n = 40). A total of 227 stool samples collected at baseline and after 3 and 6 months of intervention, respectively, were retrospectively analyzed for Blastocystis by quantitative real-time PCR and subtyped by massively parallel amplicon sequencing. Other single-cell parasites were detected by untargeted 18S rDNA amplicon sequencing and verified by real-time PCR. The relation between the parasites and the bacteriome community was characterized by using 16S rDNA profiling of the V3-V4 region. RESULTS: Three different single-cell protists were identified, of which the highest prevalence was found for Dientamoeba fragilis (23.1%, 18/78 children), followed by Blastocystis (15.4%, 12/78) and Entamoeba spp. (2.6%, 2/78). The quantity of the protists was stable over time and not affected by probiotic intervention (P = 0.14 for Blastocystis, P = 0.10 for D. fragilis). The positivity of the protists was associated with increased bacteriome diversity (measured by multiple indices, P < 0.03). Bacterial composition was influenced by the presence of the protists: positivity of Blastocystis was inversely associated with Akkermansia (at the levels of the genus as well as its family, order, class and phylum); P < 0.002), Faecalibacterium (P = 0.003) and Romboutsia (P = 0.029); positivity of D. fragilis was inversely associated with families Enterobacteriaceae (P = 0.016) and Coriobacteriaceae (P = 0.022) and genera Flavonifractor (P < 0.001), Faecalibacterium (P = 0.009), Lachnoclostridium (P = 0.029), Ruminococcus (P < 0.001) and Granulicatella (P = 0.018). CONCLUSIONS: The prevalence of single-cell protists is low in children with celiac disease autoimmunity. The colonization was stable regardless of the probiotic intervention and associated with increased diversity of the fecal bacteriome but inversely associated with some beneficial bacteria.
- MeSH
- autoimunita MeSH
- Bacteria MeSH
- Blastocystis * genetika MeSH
- celiakie * MeSH
- dítě MeSH
- dvojitá slepá metoda MeSH
- feces parazitologie MeSH
- Lacticaseibacillus MeSH
- Lactobacillus paracasei * MeSH
- lidé MeSH
- probiotika * terapeutické užití farmakologie MeSH
- retrospektivní studie MeSH
- ribozomální DNA MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
The relative inhibitory activities of diazabicyclooctanes (avibactam, relebactam, zidebactam, nacubactam, durlobactam), boronic acid derivatives (vaborbactam, taniborbactam, xeruborbactam), and penicillin-based sulfone derivative enmetazobactam were evaluated against several intrinsic and acquired class C β-lactamases. By contrast to vaborbactam and enmetazobactam, taniborbactam, xeruborbactam, and all diazabicyclooctanes demonstrated effective activities against most AmpC enzymes. Notably, durlobactam exhibited the most pronounced inhibitory effect. Interstingly, the chromosomal AmpC of Acinetobacter baumannii was the least sensitive enzyme to the newly developed β-lactamase inhibitors.
- MeSH
- Acinetobacter baumannii * účinky léků enzymologie MeSH
- antibakteriální látky * farmakologie chemie MeSH
- azabicyklické sloučeniny * farmakologie chemie MeSH
- bakteriální proteiny * antagonisté a inhibitory metabolismus MeSH
- beta-laktamasy * metabolismus MeSH
- bicyklické sloučeniny heterocyklické farmakologie chemie MeSH
- cyklooktany MeSH
- inhibitory beta-laktamasy * farmakologie chemie MeSH
- kyseliny boronové * farmakologie chemie MeSH
- laktamy MeSH
- mikrobiální testy citlivosti * MeSH
- peniciliny farmakologie chemie MeSH
- piperidiny MeSH
- sulfony farmakologie chemie MeSH
- Publikační typ
- časopisecké články MeSH
The impact of bacterial pneumonia on patients with COVID-19 infection remains unclear. This prospective observational monocentric cohort study aims to determine the incidence of bacterial community- and hospital-acquired pneumonia (CAP and HAP) and its effect on mortality in critically ill COVID-19 patients admitted to the intensive care unit (ICU) at University Hospital Olomouc between 1 November 2020 and 31 December 2022. The secondary objectives of this study include identifying the bacterial etiology of CAP and HAP and exploring the capabilities of diagnostic tools, with a focus on inflammatory biomarkers. Data were collected from the electronic information hospital system, encompassing biomarkers, microbiological findings, and daily visit records, and subsequently evaluated by ICU physicians and clinical microbiologists. Out of 171 patients suffering from critical COVID-19, 46 (27%) had CAP, while 78 (46%) developed HAP. Critically ill COVID-19 patients who experienced bacterial CAP and HAP exhibited higher mortality compared to COVID-19 patients without any bacterial infection, with rates of 38% and 56% versus 11%, respectively. In CAP, the most frequent causative agents were chlamydophila and mycoplasma; Enterobacterales, which were multidrug-resistant in 71% of cases; Gram-negative non-fermenting rods; and Staphylococcus aureus. Notably, no strains of Streptococcus pneumoniae were detected, and only a single strain each of Haemophilus influenzae and Moraxella catarrhalis was isolated. The most frequent etiologic agents causing HAP were Enterobacterales and Gram-negative non-fermenting rods. Based on the presented results, commonly used biochemical markers demonstrated poor predictive and diagnostic accuracy. To confirm the diagnosis of bacterial CAP in our patient cohort, it was necessary to assess the initial values of inflammatory markers (particularly procalcitonin), consider clinical signs indicative of bacterial infection, and/or rely on positive microbiological findings. For HAP diagnostics, it was appropriate to conduct regular detailed clinical examinations (with a focus on evaluating respiratory functions) and closely monitor the dynamics of inflammatory markers (preferably Interleukin-6).
- Publikační typ
- časopisecké články MeSH
