https://hdl.handle.net/20.500.14178/904 2026-04-14T11:39:52Z 2026-04-14T11:39:52Z Ryšavá, Markéta Stredanska, Katarina Schwarzerova, Jana Jakubickova, Marketa Cejkova, Darina Aytan-Aktug, Derya Otani, Saria Dolejská, Monika Palkovičová, Jana https://hdl.handle.net/20.500.14178/3735 2026-04-14T01:00:20Z 2026-01-01T00:00:00Z

Dynamic changes in the plasmidome and resistome in the gastrointestinal tract of chickens Ryšavá, Markéta; Stredanska, Katarina; Schwarzerova, Jana; Jakubickova, Marketa; Cejkova, Darina; Aytan-Aktug, Derya; Otani, Saria; Dolejská, Monika; Palkovičová, Jana The expansion of intensive poultry farming has led to a substantial increase in antibiotic use, which, in turn, has promoted the accumulation of antibiotic resistance genes (ARGs). The chicken gut serves as a reservoir for these genes and provides favorable conditions for their horizontal transfer via mobile genetic elements, such as plasmids. Through this process, commensal bacteria can transfer ARGs to pathogens, facilitating their spread and increasing the risk of transmission to humans. In this study, long-read sequencing was used to characterize the plasmidome and resistome in 12 fecal samples from 3 houses of a commercial broiler chicken farm. All chickens received enrofloxacin in the first days of life, with one house additionally treated with sulfamethoxazole/trimethoprim combination. For comparison, metagenomic analysis using short-read sequencing was performed on the same samples. This study revealed the presence of various ARGs associated with resistance to 25 antibiotic classes. A strong genetic association between MOBP-type plasmids and fluoroquinolone resistance was observed within broiler chicken farms. Temporal trends indicated progressive mobilization of these ARGs, suggesting an increasing potential for horizontal gene transfer. While fluoroquinolone resistance expanded over time, diaminopyrimidine resistance remained stable despite the antibiotic treatment. Most ARGs were carried on small plasmids, and complete plasmid reconstructions ranged from 2.6 to 47.6 kb. Our findings demonstrate that plasmidome sequencing enables high-resolution detection of resistance-associated plasmids that may be overlooked by conventional metagenomic approaches. The observed patterns are consistent with an association between fluoroquinolone use in poultry farms and the presence of plasmid-mediated resistance genes with potential for horizontal dissemination.

2026-01-01T00:00:00Z Gil-Korilis, Adrián Ergui-Arbizu, Jorge Hanák, Petr Danešová, Natálie Tomášová, Kristýna Valíčková, Anna Horák, Josef Gentiluomo, Manuel Levý, Miroslav Křivonosková, Soňa Král, Jan Jungwirth, Jiří Vodičková, Ľudmila Vymetálková, Veronika Azqueta, Amaya Campa, Daniele Vodička, Pavel Vodenková, Soňa https://hdl.handle.net/20.500.14178/3733 2026-04-14T01:00:14Z 2026-01-01T00:00:00Z

Unraveling the telomere-mitochondrial axis in colorectal cancer: Results from a prospectively followed cohort Gil-Korilis, Adrián; Ergui-Arbizu, Jorge; Hanák, Petr; Danešová, Natálie; Tomášová, Kristýna; Valíčková, Anna; Horák, Josef; Gentiluomo, Manuel; Levý, Miroslav; Křivonosková, Soňa; Král, Jan; Jungwirth, Jiří; Vodičková, Ľudmila; Vymetálková, Veronika; Azqueta, Amaya; Campa, Daniele; Vodička, Pavel; Vodenková, Soňa Background Telomere shortening and mitochondrial dysfunction are well-known independent contributors to many diseases, but emerging evidence suggests a reciprocal relationship between the two processes. The role of the so-called telomere-mitochondrial axis in colorectal cancer (CRC) remains largely unknown. Methods This prospective cohort study screened CRC patients who underwent surgery, from whom peripheral blood, intestinal mucosa, and tumor samples were collected. Colonoscopically confirmed cancer- and adenoma-free healthy individuals were screened as controls, from whom peripheral blood and intestinal mucosa samples were obtained. Relative mitochondrial DNA copy number (mtDNA-CN) and relative telomere length (RTL) were measured in all samples by real-time quantitative polymerase chain reaction and were further compared and correlated considering clinical data. Relative mtDNA-CN was quantified using both TaqMan probes and SYBR Green to compare both methods. Finally, multivariable analyses were conducted to investigate the association between both biomarkers and the risk of tumor recurrence and mortality. Results A total of 166 CRC patients and 61 healthy individuals were included in the study. In TNM stage I patients, relative mtDNA-CN and RTL were negatively correlated with each other in intestinal mucosa (ρ = -0.77, p < 0.0001), tumor tissue (ρ = -0.41, p = 0.032), and the tumor-to-intestinal mucosa ratio (ρ = -0.39, p = 0.046). However, these associations disappeared with increasing TNM stage, suggesting a dysregulation of the telomere-mitochondrial axis in advanced disease. Higher relative mtDNA-CN in blood was associated with a lower risk of disease recurrence even after adjusting for multiple covariates (HR = 0.43, 95% CI 0.20-0.97, p = 0.041), highlighting its potential use as a prognostic tool. The quantification of mtDNA-CN performed by both methods -TaqMan probes and SYBR Green- was shown to be positively correlated (p < 0.01). Relative mtDNA-CN and RTL were found to be tissue-dependent in both CRC patients and healthy controls. Conclusions This study provides a novel contribution to the understanding of the almost unexplored telomere-mitochondrial axis in CRC, highlighting its potential role in disease progression and prognosis.

2026-01-01T00:00:00Z Hemminki, Kari Jussi Zitrický, František Sundquist, Kristina Sundquist, Jan Försti, Asta Hemminki, Akseli Hemminki, Oto https://hdl.handle.net/20.500.14178/3725 2026-04-01T01:00:13Z 2026-01-01T00:00:00Z

Familial risks in prostate cancer between brothers and half-brothers as clues to germline genetic and environmental causes Hemminki, Kari Jussi; Zitrický, František; Sundquist, Kristina; Sundquist, Jan; Försti, Asta; Hemminki, Akseli; Hemminki, Oto Swedish family and cancer data constitute the largest source on familial cancer in the world. We analyze here familial risks in prostate cancer (PC) with focus on multiple affected brothers and comparation of full-brothers to maternal and paternal half-brothers. Age-specific incidence and standardized incidence ratios (SIRs) were calculated for PC in brothers. Curves for relative risk (RR) by diagnostic age were plotted for risk distributions. A total of 115,066 PCs were diagnosed in 1.2 million men. Familial SIR for full brothers was 2.23, for maternal half-brothers it was 1.92 and paternal half-brothers was 1.34. Considering SIRs with least possible detection bias (7+ years after first brother's diagnosis) the above SIRs were 2.06, 1.66 and 1.41. SIRs in full brothers increased stepwise by the number of affected brothers reaching 21.33 when 6 brothers were affected. Age-RR curves for two affected brothers declined evenly from RR 2.8 at age 45 to below 2.0 at age 80. When four or more brothers were affected, a discrete high-risk peak (RR 4 to 7) was detected between ages 60 and 69. Data on full-brothers and half-brothers indicate that familial risk in PC is largely genetic which is also supported by discrete RR peaks in high-risk families at ages matching preferential penetrance age for known predisposition genes of PC. Familial risk increased already when two brothers were affected calling for clinical vigilance concerning family history. Family history should deserve a place as an inclusion criterium in schemes for PC screening.

2026-01-01T00:00:00Z Hemminki, Kari Jussi Zitrický, František Sundquist, Kristina Sundquist, Jan Försti, Asta Hemminki, Akseli Hemminki, Otto https://hdl.handle.net/20.500.14178/3723 2026-04-01T01:00:25Z 2026-01-01T00:00:00Z

Familial Risks in 317 000 Patients With Prostate Cancer in Relation to Metastases and Survival-Guiding Diagnostics Hemminki, Kari Jussi; Zitrický, František; Sundquist, Kristina; Sundquist, Jan; Försti, Asta; Hemminki, Akseli; Hemminki, Otto BackgroundSwedish nationwide family and cancer data offer the largest global resource for study of familial cancer. We focus here on familial risks in prostate cancer (PC) with questions on risk in individuals from families of multiple affected members and association of familial risk with metastatic disease and survival.MethodsFamilial relative risk of PC was estimated using standardized incidence ratios (SIRs) for second-generation men with a father or brother affected with PC, considering distinct groups by number and type of affected relatives.ResultsFamilial SIRs ranged from 2.22 (2 brothers with PC) to 11.5 (≥5 brothers with PC). The proportions of affected men increased from about 15% (2-case families) to 50% (≥5-case families). Age-incidence curves showed successively higher rates for men from multi-case families. Older patients with PC had the highest proportion of metastases at diagnosis, but in each age group, familial patients presented with a lower proportion of metastases compared with nonfamilial cases. Among brothers, the proportion of metastasis was higher in brothers first diagnosed compared with brothers with subsequent diagnosis. Survival in familial cases was better compared with nonfamilial cases among patients without metastases. Among such patients, brothers diagnosed first survived worse than subsequent brothers.Conclusions and clinical implicationsThe largest family study yet conducted on PC was based on 34 468 familial cases. Risk varied greatly by family constellations, emphasizing the need for a detailed family history at diagnosis as basis for clinical decision-making and genetic counseling. The reported high risks should encourage implementation of familial risk into schemes for PC screening.Patient summaryPatients with prostate cancer often have a relative who has prostate cancer. When PC is diagnosed, it is important that the patient reports a reliable history of relatives earlier diagnosed with PC. It may influence his treatment.

2026-01-01T00:00:00Z