BACKGROUND: Renal cell carcinoma (RCC) is a disease typified by anomalies in cell metabolism. The function of mitochondria, including subunits of mitochondrial respiratory complex II (CII), in particular SDHB, are often affected. Here we investigated the state and function of CII in RCC patients. METHODS: We evaluated tumour tissue as well as the adjacent healthy kidney tissue of 78 patients with RCC of different histotypes, focusing on their mitochondrial function. As clear cell RCC (ccRCC) is by far the most frequent histotype of RCC, we focused on these patients, which were grouped based on the pathological WHO/ISUP grading system to low- and high-grade patients, indicative of prognosis. We also evaluated mitochondrial function in organoids derived from tumour tissue of 7 patients. RESULTS: ccRCC tumours were characterized by mutated von Hippel-Lindau gene and high expression of carbonic anhydrase IX. We found low levels of mitochondrial DNA, protein and function, together with CII function in ccRCC tumour tissue, but not in other RCC types and non-tumour tissues. Mitochondrial content increased in high-grade tumours, while the function of CII remained low. Tumour organoids from ccRCC patients recapitulated molecular characteristics of RCC tissue. CONCLUSIONS: Our findings suggest that the state of CII, epitomized by its assembly and SDHB levels, deteriorates with the progressive severity of ccRCC. These observations hold the potential for stratification of patients with worse prognosis and may guide the exploration of targeted therapeutic interventions.

• MeSH
• antigeny nádorové MeSH
• dospělí MeSH
• karboanhydrasa IX metabolismus   genetika   MeSH
• karcinom z renálních buněk * patologie   metabolismus   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitochondriální DNA genetika   metabolismus   MeSH
• mitochondrie * metabolismus   patologie   genetika   MeSH
• mutace MeSH
• nádorový supresorový protein VHL genetika   metabolismus   MeSH
• nádory ledvin * patologie   metabolismus   genetika   MeSH
• respirační komplex II * metabolismus   genetika   MeSH
• senioři MeSH
• sukcinátdehydrogenasa genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

A novel Gram-stain-negative, strictly aerobic, rod-shaped, light-yellow-pigmented, and chemo-organoheterotrophic bacterium, designated DF-77T, was isolated from dense mats of filamentous algae collected in March 2004 at Okinawa in Japan. The microorganism grew at 0-2.0% NaCl concentrations (w/v), pH 6.0-9.0, and 20-30 °C. The 16S rRNA gene sequence-based phylogenetic tree demonstrated that the strain DF-77T is a novel member of the family Flavobacteriaceae and was greatly related to Flagellimonas nanhaiensis SM1704T with sequence similarity of 95.5%. The main fatty acids were iso-C15:1 G, iso-C15:0, and iso-C17:0 3-OH, and the only isoprenoid quinone was menaquinone-6. The dominant polar lipids were phosphatidylethanolamine, two unidentified aminolipids, an unidentified phosphoaminolipid, and four unidentified lipids. The genome size of strain DF-77T was 3.60 Mbp with a DNA G + C content of 47.5%. The average nucleotide identity (ANI) value between the genomes of strain DF-77T and its closely related species was 69.8-70.7%. The digital DNA - DNA hybridization (dDDH) value of strain DF-77T with the strain of F. nanhaiensis SM1704T was 16.8%. The genome of the strain DF-77T revealed that it encoded several genes involved in bio-macromolecule degradation, indicating a high potential for producing industrially useful enzymes. Consequently, the strain is described as a new species in the genus Flagellimonas, for which the name Flagellimonas algarum sp. nov., is proposed with the type strain DF-77T (= KCTC 72791T = NBRC 114251T).

• MeSH
• DNA bakterií genetika   chemie   MeSH
• Flavobacteriaceae * klasifikace   izolace a purifikace   genetika   MeSH
• fosfolipidy analýza   MeSH
• fylogeneze MeSH
• genom bakteriální MeSH
• hybridizace nukleových kyselin MeSH
• mastné kyseliny analýza   MeSH
• RNA ribozomální 16S genetika   MeSH
• sekvenční analýza DNA MeSH
• techniky typizace bakterií MeSH
• vitamin K 2 analýza   analogy a deriváty   MeSH
• zastoupení bazí MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Japonsko MeSH

Halophilic bacteria are extremophiles that thrive in saline environment. Their ability to withstand such harsh conditions makes them an ideal choice for industrial applications such as lignocellulosic biomass degradation. In this study, a halophilic bacterium with the ability to produce extracellular cellulases and hemicellulases, designated as Nesterenkonia sp. CL21, was isolated from mangrove sediment in Tanjung Piai National Park, Malaysia. Thus far, studies on lignocellulolytic enzymes concerning bacterial species under this genus are limited. To gain a comprehensive understanding of its lignocellulose-degrading potential, the whole genome was sequenced using the Illumina NovaSeq 6000 platform. The genome of strain CL21 was assembled into 25 contigs with 3,744,449 bp and a 69.74% GC content and was predicted to contain 3,348 coding genes. Based on taxonomy analysis, strain CL21 shares 73.8 to 82.0% average nucleotide identity with its neighbouring species, below the 95% threshold, indicating its possible status as a distinct species in Nesterenkonia genus. Through in-depth genomic mining, a total of 81 carbohydrate-active enzymes were encoded. Among these, 24 encoded genes were identified to encompass diverse cellulases (GH3), xylanases (GH10, GH11, GH43, GH51, GH127 and CE4), mannanases (GH38 and GH106) and pectinases (PL1, PL9, and PL11). The production of lignocellulolytic enzymes was tested in the presence of several substrates. This study revealed that strain CL21 can produce a diverse array of enzymes which are active at different time points. By combining experimental data with genomic information, the ability of strain CL21 to produce lignocellulolytic enzymes has been elucidated, with potential applications in biorefinery industry.

• MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• celulasy genetika   metabolismus   MeSH
• fylogeneze * MeSH
• genom bakteriální * MeSH
• genomika * MeSH
• geologické sedimenty mikrobiologie   MeSH
• glykosidhydrolasy * genetika   metabolismus   MeSH
• lignin * metabolismus   MeSH
• RNA ribozomální 16S genetika   MeSH
• sekvenování celého genomu MeSH
• zastoupení bazí MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Neonatal hypoglycaemia is the most common metabolic disorder of various causes, relatively rare being MODY (Maturity Onset Diabetes of the Young). CONTENT: Data search of relevant articles focused on hypoglycaemia in carriers of selected MODY gene mutations published from 2007 to 2022 was performed in databases Medline, PubMed, Cochrane and UptoDate based on key words: 'hyperinsulinemic hypoglycaemia', 'congenital hyperinsulinism', 'MODY', 'HNF4A mutation', 'HNF1A mutation'. SUMMARY: Loss of function of HNF4A and HNF1A genes comprises approximately to 5.9 % of diazoxide responsive hyperinsulinemic hypoglycaemia, which may appear in 15 % HNF4A mutation carriers. A typical finding of HNF4A mutation carriers with neonatal hypoglycaemia was a birth weight above 4000 g or above 97th percentile. OUTLOOK: Although mutations in MODY genes represent a rare cause of neonatal hypoglycaemia, they should be considered in the differential diagnosis, particularly in cases of persistent hypoglycaemia requiring intensive care.

• MeSH
• diabetes mellitus 2. typu * genetika   komplikace   MeSH
• hepatocytární jaderný faktor 1-alfa genetika   MeSH
• hepatocytární jaderný faktor 4 * genetika   MeSH
• hypoglykemie * genetika   etiologie   patologie   MeSH
• lidé MeSH
• mutace * MeSH
• nemoci novorozenců * genetika   MeSH
• novorozenec MeSH
• rodiče MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The parasitic protozoan Entamoeba histolytica secretes extracellular vesicles (EVs), but so far little is known about their function in the interaction with the host immune system. Infection with E. histolytica trophozoites can lead to formation of amebic liver abscesses (ALAs), in which pro-inflammatory immune responses of Ly6Chi monocytes contribute to liver damage. Men exhibit a more severe pathology as the result of higher monocyte recruitment and a stronger immune response. To investigate the role of EVs and pathogenicity in the host immune response, we studied the effect of EVs secreted by low pathogenic EhA1 and highly pathogenic EhB2 amebae on monocytes. Size and quantity of isolated EVs from both clones were similar. However, they differed in their proteome and miRNA cargo, providing insight into factors potentially involved in amebic pathogenicity. In addition, EVs were enriched in proteins with signaling peptides compared with the total protein content of trophozoites. Exposure to EVs from both clones induced monocyte activation and a pro-inflammatory immune response as evidenced by increased surface presentation of the activation marker CD38 and upregulated gene expression of key signaling pathways (including NF-κB, IL-17 and TNF signaling). The release of pro-inflammatory cytokines was increased in EV-stimulated monocytes and more so in male- than in female-derived cells. While EhA1 EV stimulation caused elevated myeloperoxidase (MPO) release by both monocytes and neutrophils, EhB2 EV stimulation did not, indicating the protective role of MPO during amebiasis. Collectively, our results suggest that parasite-released EVs contribute to the male-biased immunopathology mediated by pro-inflammatory monocytes during ALA formation.

• MeSH
• amébový absces jater imunologie   parazitologie   MeSH
• cytokiny metabolismus   MeSH
• entamébóza imunologie   parazitologie   MeSH
• Entamoeba histolytica * imunologie   patogenita   genetika   MeSH
• extracelulární vezikuly * imunologie   metabolismus   MeSH
• lidé MeSH
• monocyty * imunologie   parazitologie   MeSH
• signální transdukce * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

This study elucidated the impacts of coenzyme Q10 (COQ10) supplementation in a high-fat diet (HFD) on growth, lipid metabolism and mitochondrial function in spotted seabass (Lateolabrax maculatus). Totally five diets were formulated: a diet with normal fat content (11 % lipid, NFD), a HFD (17 % lipid) and three additional diets by supplementing 5, 20 or 80 mg/kg of COQ10 to the HFD. After an 8-week culture period, samples were collected and analysed. The results demonstrated that COQ10 inclusion prevented the HFD-induced deterioration of growth performance and feed utilisation. COQ10 alleviated the deposition of saturated fatty acids following HFD intake and promoted the assimilation of n-3 and n-6 PUFA. Moreover, COQ10 administration inhibited the surge in serum transaminase activity and reduced hepatic lipid content following HFD ingestion, which was consistent with the results of oil red O staining. In addition, HFD feeding led to reduced hepatic citrate synthase and succinate dehydrogenase activities and decreased ATP content. Notably, COQ10 administration improved these indices and up-regulated the expression of mitochondrial biogenesis-related genes (pgc-1α, pgc-1β, nrf-1, tfam) and autophagy-related genes (pink1, mul1, atg5). In summary, supplementing 20-80 mg/kg of COQ10 in the HFD promoted growth performance, alleviated hepatic fat accumulation and enhanced liver mitochondrial function in spotted seabass.

• MeSH
• dieta s vysokým obsahem tuků * škodlivé účinky   MeSH
• játra metabolismus   účinky léků   MeSH
• krmivo pro zvířata analýza   MeSH
• metabolismus lipidů účinky léků   MeSH
• mitochondrie * účinky léků   metabolismus   MeSH
• Percoidea * růst a vývoj   metabolismus   MeSH
• potravní doplňky MeSH
• ubichinon * analogy a deriváty   farmakologie   aplikace a dávkování   MeSH
• ztučnělá játra * veterinární   etiologie   farmakoterapie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Colorectal cancer (CRC) ranks as the second most prevalent malignancy globally, highlighting the urgent need for more effective diagnostic and therapeutic strategies, as well as a deeper understanding of its molecular basis. Extensive research has demonstrated that cells actively secrete extracellular vesicles (EVs) to mediate intercellular communication at both proximal and distal sites. In this study, we conducted a comprehensive analysis of the RNA content of small extracellular vesicles (sEVs) secreted into the culture media of five frequently utilised CRC cell lines (RKO, HCT116, HCT15, HT29, and DLD1). RNA sequencing data revealed significant insights into the RNA profiles of these sEVs, identifying nine protein-coding genes and fourteen long non-coding RNA (lncRNA) genes that consistently ranked among the top 30 most abundant across all cell lines. Notably, the genes found in sEVs were highly similar among the cell lines, indicating a conserved molecular signature. Several of these genes have been previously documented in the context of cancer biology, while others represent novel discoveries. These findings provide valuable insights into the molecular cargo of sEVs in CRC, potentially unveiling novel biomarkers and therapeutic targets.

• MeSH
• extracelulární vezikuly * metabolismus   genetika   MeSH
• HCT116 buňky MeSH
• kolorektální nádory * genetika   patologie   metabolismus   MeSH
• lidé MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• regulace genové exprese u nádorů MeSH
• RNA dlouhá nekódující genetika   MeSH
• sekvenční analýza RNA MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Multidisciplinary molecular tumor boards (MTB) are already well established in many comprehensive cancer centers and play an important role in the individual treatment planning for cancer patients. Comprehensive genomic profiling of tumor tissue based on next-generation sequencing is currently performed for diagnostic and mainly predictive testing. If somatic genomic variants are identified, which are suspected to be pathogenic germline variants (PGVs), MTB propose genetic counseling and germline DNA testing. Commonly used comprehensive genomic profiling approaches of tumor tissue do not include a matched germline DNA control. Therefore, the detection of PGVs could be only predicted based on the content of tumor cells (CTC) in selected tumor area (%) and variant allele frequency score (%). For conclusion, the role of a medical geneticist is essential in these cases. The overall prevalence of PGVs in patients with pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) is approximately 10%. In this single-center study, we present 37 patients with PDAC and 48 patients with CRC who were presented at MTB and tested using the large combined DNA/RNA sequencing panel. Content of tumor cells and variant allele frequency scores were evaluated in all tested patients. In case of suspicion of PGV and no previous genetic testing based on the standard guidelines, genetic counseling was recommended regardless of age, sex, and family history. In the PDAC subgroup, five patients were recommended by MTB for genetic counseling based on suspicious genetic findings. Based on a medical geneticist's decision, germline DNA sequencing was performed in four of these cases, and all of them tested positive for PGV in the following genes: ATM, ATM, BRCA1, and BRCA2. In the CRC subgroup, no PGV was confirmed in the two patients genetically tested based on the MTB recommendations. Furthermore, we present data from our center's registry of patients with PDAC and CRC who underwent genetic counseling and germline DNA testing based on the standard screening criteria. Our data confirm that comprehensive genomic profiling of tumor tissue can identify patients with hereditary forms of PDAC, who could remain unidentified by standard screening for hereditary forms of cancer.

• MeSH
• dospělí MeSH
• duktální karcinom slinivky břišní genetika   diagnóza   MeSH
• genetické poradenství MeSH
• genetické testování metody   MeSH
• genomika metody   MeSH
• kolorektální nádory * genetika   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory slinivky břišní * genetika   diagnóza   MeSH
• náhodný nález MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• zárodečné mutace * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Chronic otitis media (COM) is a common middle ear disease in children and young adults. Dysfunction of the Eustachian tube and bacterial infection are the main causes. This pilot study aimed to describe and compare bacteriomes of the middle ear in children and young adults with serious forms of COM, such as cholesteatoma and retraction pocket (RP) of the tympanic membrane, with bacteriomes in healthy middle ears. STUDY DESIGN: Observational study. SETTING: Clinical practice in a tertiary center. From January 1, 2021 to August 31, 2022. Patients aged 0 to 20 years. METHODS: In this case-control study, middle ears were swabbed during surgery on children with cholesteatoma (N = 23) or RP (N = 26) and on children indicated for cochlear implant (N = 15, controls). Genomic DNA extraction was followed by creation of a 16S ribosomal DNA gene library and sequencing on a MiSeq instrument. Samples with relative abundance of at least one bacterial genus >20% were considered positive for the specific genus. RESULTS: Bacterial diversity was generally low in the middle ear samples from patients with COM, with DNA content from 1 or 2 bacteria usually dominating in the sample. A significant difference in positivity for one or more bacterial genera was observed between patients with cholesteatoma or RP (38.8%) versus patients indicated for cochlear implants (6.7%). CONCLUSION: While middle ear bacteriomes in cases of cholesteatoma and RP differed from those of controls, findings in the 2 pathological conditions were similar. These results support the statement that the RP could be a precholesteatoma stage.

• Publikační typ
• časopisecké články MeSH

The opportunistic pathogen Candida parapsilosis is a major causative agent of candidiasis leading to death in immunocompromised individuals. Azoles are the first line of defense in their treatment. The purpose of this study was to characterize eight fluconazole-resistant and sensitive C. parapsilosis hospital isolates through a battery of phenotypic tests that target pathogenicity attributes such as virulence, biofilm formation, stress resistance, and ergosterol content. Whole genome sequencing was carried out to identify mutations in key pathogenicity and resistance genes. Phylogenetic comparison was performed to determine strain relatedness and clonality. Genomic data and phylogenetic analysis revealed that two isolates were C. orthopsilosis and C. metapsilosis misidentified as C. parapsilosis. Whole genome sequencing analysis revealed known and novel mutations in key drug resistance and pathogenicity genes such as ALS6, ALS7, SAPP3, SAP7, SAP9, CDR1, ERG6, ERG11 and UPC2. Phylogenetic analysis revealed a high degree of relatedness and clonality within our C. parapsilosis isolates. Our results showed that resistant isolates exhibited an increase in biofilm content compared to the sensitive isolates. In conclusion, our study is the first of its kind in Lebanon to describe phenotypic and genotypic characteristics of nosocomial C. parapsilosis complex isolates having a remarkable ability to form biofilms.

• MeSH
• antifungální látky * farmakologie   MeSH
• biofilmy * růst a vývoj   MeSH
• Candida parapsilosis * genetika   izolace a purifikace   klasifikace   MeSH
• fenotyp * MeSH
• flukonazol farmakologie   MeSH
• fungální léková rezistence * genetika   MeSH
• fylogeneze * MeSH
• genotyp * MeSH
• infekce spojené se zdravotní péčí mikrobiologie   MeSH
• kandidóza * mikrobiologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti * MeSH
• nemocnice MeSH
• sekvenování celého genomu * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Libanon MeSH