The honeybee (Apis mellifera) is a key pollinator critical to global agriculture, facing threats from various stressors, including the ectoparasitic Varroa mite (Varroa destructor). Previous studies have identified shared bacteria between Varroa mites and honeybees, yet it remains unclear if these bacteria assemble similarly in both species. This study builds on existing knowledge by investigating co-occurrence patterns in the microbiomes of both Varroa mites and honeybees, shedding light on potential interactions. Leveraging 16S rRNA datasets, we conducted co-occurrence network analyses, explored Core Association Networks (CAN) and assess network robustness. Comparative network analyses revealed structural differences between honeybee and mite microbiomes, along with shared core features and microbial motifs. The mite network exhibited lower robustness, suggesting less resistance to taxa extension compared to honeybees. Furthermore, analyses of predicted functional profiling and taxa contribution revealed that common central pathways in the metabolic networks have different taxa contributing to Varroa mites and honeybee microbiomes. The results show that while both microbial systems exhibit functional redundancy, in which different taxa contribute to the functional stability and resilience of the ecosystem, there is evidence for niche specialization resulting in unique contributions to specific pathways in each part of this host-parasite system. The specificity of taxa contribution to key pathways offers targeted approaches to Varroa microbiome management and preserving honeybee microbiome. Our findings provide valuable insights into microbial interactions, aiding farmers and beekeepers in maintaining healthy and resilient bee colonies amid increasing Varroa mite infestations.

• MeSH
• Bacteria * klasifikace   genetika   izolace a purifikace   MeSH
• mikrobiota * MeSH
• RNA ribozomální 16S genetika   MeSH
• Varroidae * mikrobiologie   MeSH
• včely mikrobiologie   parazitologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Roboticky asistovaná radikální prostatektomie je standardní metodou léčby lokalizovaného karcinomu prostaty. Přesto zůstávají pozdní funkční komplikace jako stresová inkontinence moči, erektilní dysfunkce a striktury hrdla močového měchýře zásadními faktory ovlivňujícími kvalitu života pacientů. Tento článek se zabývá možnostmi prevence těchto komplikací prostřednictvím optimalizace chirurgických technik a individualizované rehabilitační péče. Důraz je kladen na šetrné operační postupy, zachování klíčových anatomických struktur a důslednou pooperační péči a fyzioterapii. Výsledky studií ukazují, že kombinace těchto přístupů může významně přispět ke zlepšení pooperačních výsledků a urychlit návrat pacientů k běžnému životu. Komplexní přístup zahrnující precizní chirurgické metody, systematickou rehabilitaci a edukaci pacientů je nezbytný pro minimalizaci nežádoucích účinků a maximalizaci kvality života po operaci.

Robot-assisted radical prostatectomy is the standard treatment for localized prostate cancer. However, late functional complications such as stress urinary incontinence, erectile dysfunction, and bladder neck strictures continue to be critical factors affecting patients' quality of life. This article explores strategies to prevent these complications through optimized surgical techniques and individualized rehabilitation care. Emphasis is placed on minimally invasive surgical approaches, preservation of key anatomical structures, and comprehensive postoperative management, including physiotherapy, pharmacological support, and technical aids. Studies indicate that combining these approaches can significantly improve postoperative outcomes and accelerate patients' return to daily life. A comprehensive approach integrating precise surgical methods, systematic rehabilitation, and patient education is essential to minimizing adverse effects and maximizing quality of life after surgery.

• MeSH
• erektilní dysfunkce etiologie   prevence a kontrola   MeSH
• lidé MeSH
• pooperační komplikace prevence a kontrola   MeSH
• prostatektomie * metody   škodlivé účinky   MeSH
• roboticky asistované výkony MeSH
• stresová inkontinence moči etiologie   prevence a kontrola   MeSH
• striktura uretry etiologie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• přehledy MeSH

Zachování funkčního hrtanu a dosažení dlouhodobé remise je základním postulátem léčby pacientů s maligními nádory hrtanu, a to i pokročilých stadií. Rozvíjeny jsou proto nechirurgické protokoly léčby a hrtan zachovávající chirurgické postupy. Totální laryngektomie je historicky základní výkon laryngeální chirurgie, jehož význam s rozvojem výše uvedených postupů klesá. Přesto jsou stále skupiny nemocných, kteří mohou profitovat z jejího provedení. Rozhodující jsou lokální i celkové charakteristiky tumoru a pacienta. Velikost tumoru, destrukce a nefunkčnost struktur hrtanu, infiltrace štítné chrupavky včetně zevního perichondria případně extralaryngeální propagace jsou faktory, kdy je předpokládaný efekt nechirurgické léčby nedostatečný nebo by vedl k zachování nefunkčního hrtanu. K výkonu také indikujeme pacienty, u nichž pro kontraindikace nemůžeme využít orgán šetřicí protokoly nebo je vysoké riziko komplikací této léčby. Totální laryngektomie má stále své místo v rámci záchranné chirurgie a u specifických malignit, u nichž není efektivní nechirurgická léčba (nejčastěji sarkomy). V této práci je představen náš pohled na indikaci totální laryngektomie v současnosti, který vychází z doporučených postupů a zkušeností s multidisciplinárním klinickým rozhodováním.

Preserving a functional larynx and achieving long-term control is the basic postulate of treating patients with malignant tumors of the larynx, even in advanced stages. Therefore, non-surgical treatment protocols and larynx-preserving surgical procedures are preferred. Total laryngectomy is historically the basic procedure of laryngeal surgery still with the best survival outcomes in advanced laryngeal cancer, but with significantly lower quality of life following surgery. Nevertheless, there are still groups of patients who can benefit from this implementation. Local and overall characteristics are important for the recommendation of treatment. Tumor size, destruction and dysfunction of laryngeal structures, infiltration of the thyroid cartilage including the external perichondrium, or extralaryngeal extent are local factors when the expected effect of non-surgical treatment is insufficient or would only lead to the preservation of a non-functional larynx. We also recommend patients in whom organ-saving protocols are not suitable due to contraindications or there is a high risk of complications. Total laryngectomy still has its place as part of salvage surgery in failure of non-surgical treatment and for specific malignancies for which a non-surgical approach is not effective (most often sarcomas). We present our current view on the indications of total laryngectomy, which is based on international recommendations and our experience with multidisciplinary clinical decision-making.

• MeSH
• laryngektomie * dějiny   metody   statistika a číselné údaje   MeSH
• larynx umělý MeSH
• larynx chirurgie   patologie   MeSH
• léčba šetřící orgány metody   MeSH
• lidé MeSH
• nádory hrtanu chirurgie   diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Across the tree of life, DNA damage response (DDR) proteins play a pivotal, yet dichotomous role in organismal development and evolution. Here, we present a comprehensive analysis of 432 DDR proteins encoded by 68 genomes, including that of Nucleospora cyclopteri, an intranuclear microsporidia sequenced in this study. We compared the DDR proteins encoded by these genomes to those of humans to uncover the DNA repair-ome across phylogenetically distant eukaryotes. We also performed further analyses to understand if organismal complexity and lifestyle play a role in the evolution of DDR protein length and conserved domain architecture. We observed that the genomes of extreme parasites such as Paramicrocytos, Giardia, Spironucleus, and certain microsporidian lineages encode the smallest eukaryotic repertoire of DDR proteins and that pathways involved in modulation of nucleotide pools and nucleotide excision repair are the most preserved DDR pathways in the eukaryotic genomes analysed here. We found that DDR and DNA repair proteins are consistently longer than housekeeping and metabolic proteins. This is likely due to the higher number of physical protein-protein interactions which DDR proteins are involved. We find that although DNA repair proteins are generally longer than housekeeping proteins, their functional domains occupy a relatively smaller footprint. Notably, this pattern holds true across diverse organisms and shows no dependence on either lifestyle or mitochondrial status. Finally, we observed that unicellular organisms harbour proteins that are tenfold longer than their human homologues, with the extra amino acids forming interdomain regions with a clearly novel albeit undetermined function.

• MeSH
• Eukaryota * genetika   MeSH
• fylogeneze MeSH
• lidé MeSH
• Microsporidia genetika   MeSH
• molekulární evoluce * MeSH
• oprava DNA * MeSH
• poškození DNA * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Ultraviolet (UV) radiation is a significant environmental stressor that affects the growth, physiology, and biochemical integrity of various organisms. This study investigates the potential protective effects of a zinc-cysteine (Zn-Cys) complex against UV-C radiation, with a focus on its impact on selected microalgae (Coccomyxa peltigerae and Parachlorella kessleri) and maize (Zea mays L.). We demonstrate that exposure of the Zn-Cys complex to UV-C (254 nm) results in the formation of fluorescent photoproducts, which exhibit UV-protective properties. The study reveals that Zn-Cys significantly mitigates UV-induced stress. In both microalgae species, the Zn-Cys complex enhanced growth even under UV exposure, with the 20% concentration showing the most robust protective effects. Further hyperspectral imaging confirmed the protective mechanism of Zn-Cys by monitoring changes in light reflectance in Parachlorella kessleri, indicating reduced photosynthetic efficiency and structural alterations induced by UV exposure, while Zn-Cys significantly mitigated these effects. In addition, in maize plants (Zea mays L.), Zn-Cys treatment preserved chlorophyll content and reduced polyphenol accumulation, indicating reduced oxidative stress. These findings highlight the potential of the Zn-Cys complex as a sustainable and cost-effective strategy for UV protection in both terrestrial and extraterrestrial agriculture, advancing our understanding of plant adaptation to extreme environments.

• MeSH
• Chlorophyta účinky záření   účinky léků   MeSH
• cystein * chemie   farmakologie   MeSH
• fotosyntéza účinky léků   účinky záření   MeSH
• komplexní sloučeniny * chemie   farmakologie   MeSH
• kukuřice setá účinky záření   účinky léků   metabolismus   MeSH
• mikrořasy účinky záření   účinky léků   MeSH
• ultrafialové záření * MeSH
• zinek * chemie   farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH

Dlouhodobé podávání betablokátorů pacientům po infarktu myokardu (IM) se zachovalou ejekční frakcí levé komory (EFLK) zůstává kontroverzní. Zatímco benefit betablokátorů je prokázán u pacientů se sníženou EFLK, pro nemocné s EFLK > 40 % chybí jednoznačná data z randomizovaných klinických studií. Dvě nedávno publikované studie (REDUCE-AMI a ABYSS) přinesly rozdílné výsledky ohledně bezpečnosti vysazení betablokátorů. REDUCE-AMI neprokázala přínos dlouhodobého podávání betablokátorů na mortalitu nebo nový IM, zatímco ABYSS ukázala vyšší riziko KV hospitalizací po vysazení, zejména u hypertoniků. Výsledky metaanalýz zůstávají rozporuplné. Fixní kombinace betablokátorů s jinými léky může zlepšit adherenci a kardiovaskulární prognózu, zejména u hypertenzních pacientů. Odpověď na otázku trvalé indikace betablokátorů by měly přinést tři probíhající studie (BETAMI, DANBLOCK, REBOOT).

The long-term use of beta-blockers in patients after myocardial infarction (MI) with preserved left ventricular ejection fraction (LVEF) remains controversial. While benefits of beta-blockers are well established in patients with reduced LVEF, there is a lack of randomized clinical trial data for patients with LVEF > 40 %. Two recent studies (REDUCE-AMI and ABYSS) yielded conflicting results regarding the safety of beta-blocker discontinuation. REDUCE-AMI showed no mortality or reinfarction benefit from long-term beta-blocker therapy, while ABYSS indicated increased cardiovascular hospitalizations, especially in hypertensive patients. Results of meta-analyses remain inconclusive. Fixed-dose combinations of beta-blockers with other cardiovascular medications may improve adherence and long-term outcomes, particularly in hypertensive patients. Ongoing randomized trials (BETAMI, DANBLOCK, REBOOT) may provide definitive answers.

• Klíčová slova
• kardiovaskulární riziko,
• MeSH
• beta blokátory * farmakologie   terapeutické užití   MeSH
• diastolické srdeční selhání * farmakoterapie   MeSH
• infarkt myokardu farmakoterapie   MeSH
• kardiovaskulární nemoci etiologie   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• přerušení léčby MeSH
• Check Tag
• lidé MeSH

Antagonists with a long residence time at the receptors are desired for the possibility of reducing daily doses and side effects. KH-5 (1-{2-[4-(hexyloxy)benzoyloxy]ethyl}-1-methyl-1,2,3,6-tetrahydropyridin-1-ium iodide) is the long-acting M1-preferring bitopic muscarinic antagonist with a half-life at muscarinic receptors of up to five hours. The binding of 2-hexyloxy and 3-hexyloxy analogues of KH-5 was simulated in silico, compounds were synthesized and their binding and antagonistic properties were measured experimentally in CHO cells expressing individual subtypes of muscarinic acetylcholine receptors. The overall binding affinities of the new compounds were similar to their respective parent compounds. Shifting the hexyloxy chain to ortho and meta positions led to a decrease in potency at the M1 receptor but an increase in potency at the M2 receptor and abolition of long-term antagonism. Preservation of the para position of the hexyloxy chain is essential for the further development of M1-preferring antagonists. Modifications of the basic centre may be the way to improve the geometry of antagonists towards long residence times to obtain the desired long-acting muscarinic antagonists in the future. The additional challenge for further development is the low metabolic stability of compounds.

• MeSH
• antagonisté muskarinových receptorů * farmakologie   MeSH
• CHO buňky MeSH
• Cricetulus * MeSH
• pyridiny farmakologie   chemie   MeSH
• receptor muskarinový M1 metabolismus   antagonisté a inhibitory   MeSH
• receptory muskarinové metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Telomeres, essential for maintaining genomic stability, are typically preserved through the action of telomerase, a ribonucleoprotein complex that synthesizes telomeric DNA. One of its two core components, telomerase RNA (TR), serves as the template for this synthesis, and its evolution across different species is both complex and diverse. This review discusses recent advancements in understanding TR evolution, with a focus on plants (Viridiplantae). Utilizing novel bioinformatic tools and accumulating genomic and transcriptomic data, combined with corresponding experimental validation, researchers have begun to unravel the intricate pathways of TR evolution and telomere maintenance mechanisms. Contrary to previous beliefs, a monophyletic origin of TR has been demonstrated first in land plants and subsequently across the broader phylogenetic megagroup Diaphoretickes. Conversely, the discovery of plant-type TRs in insects challenges assumptions about the monophyletic origin of TRs in animals, suggesting evolutionary innovations coinciding with arthropod divergence. The review also highlights key challenges in TR identification and provides examples of how these have been addressed. Overall, this work underscores the importance of expanding beyond model organisms to comprehend the full complexity of telomerase evolution, with potential applications in agriculture and biotechnology.

• MeSH
• fylogeneze MeSH
• molekulární evoluce * MeSH
• RNA * genetika   metabolismus   MeSH
• rostliny genetika   MeSH
• telomerasa * genetika   metabolismus   MeSH
• telomery * metabolismus   genetika   MeSH
• Viridiplantae genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PURPOSE: Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to the HGSOC microenvironment stand out as promising combinatorial partners for ICIs in this oncological indication. EXPERIMENTAL DESIGN: We harnessed a variety of transcriptomic, spatial, and functional assays to characterize the differential impact of neoadjuvant paclitaxel-carboplatin on the immunological configuration of paired primary and metastatic HGSOC biopsies as compared to neoadjuvant chemotherapy (NACT)-naïve HGSOC samples from five independent patient cohorts. RESULTS: We found NACT-driven endoplasmic reticulum stress and calreticulin exposure in metastatic HGSOC lesions culminates with the establishment of a dense immune infiltrate including follicular T cells (TFH cells), a prerequisite for mature tertiary lymphoid structure (TLS) formation. In this context, TLS maturation was associated with an increased intratumoral density of ICI-sensitive TCF1+PD1+ CD8+ T cells over their ICI-insensitive TIM-3+PD1+ counterparts. Consistent with this notion, chemotherapy coupled with a PD1-targeting ICI provided a significant survival benefit over either therapeutic approach in syngeneic models of HGSOC bearing high (but not low) tumor mutational burden. CONCLUSIONS: Altogether, our findings suggest that NACT promotes TLS formation and maturation in HGSOC lesions, de facto preserving an intratumoral ICI-sensitive T-cell phenotype. These observations emphasize the role of rational design, especially relative to the administration schedule, for clinical trials testing chemotherapy plus ICIs in patients with HGSOC. See related commentary by Bravo Melgar and Laoui, p. 10.

• MeSH
• CD8-pozitivní T-lymfocyty * imunologie   účinky léků   MeSH
• ektopické lymfoidní struktury * imunologie   patologie   MeSH
• hepatocytární jaderný faktor 1-alfa * genetika   metabolismus   MeSH
• inhibitory kontrolních bodů * terapeutické užití   farmakologie   MeSH
• karboplatina aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• nádorové mikroprostředí * imunologie   účinky léků   MeSH
• nádory vaječníků * farmakoterapie   imunologie   patologie   MeSH
• neoadjuvantní terapie metody   MeSH
• paclitaxel aplikace a dávkování   terapeutické užití   farmakologie   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   farmakologie   MeSH
• serózní cystadenokarcinom farmakoterapie   patologie   imunologie   MeSH
• stres endoplazmatického retikula účinky léků   imunologie   MeSH
• tumor infiltrující lymfocyty imunologie   účinky léků   metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH