MicroRNAs (miRNAs) have emerged as important regulators of gene expression in various biological processes, including cancer. miR-182-5p has gained attention for its potential implications in gynecologic cancers, including breast, ovarian, endometrial, and cervical cancers. miR-182-5p dysregulation has been associated with multiple facets of tumor biology in gynecologic cancers, including tumor initiation, progression, metastasis, and therapeutic response. Studies have highlighted its involvement in key signaling pathways and cellular processes that contribute to cancer development and progression. In addition, miR-182-5p has shown potential as a diagnostic and prognostic biomarker, with studies demonstrating its correlation with clinicopathological features and patient outcomes. Furthermore, the therapeutic potential of miR-182-5p is being explored in gynecologic cancers. Strategies such as miRNA mimics or inhibitors targeting miR-182-5p have shown promise in preclinical and early clinical studies. These approaches aim to modulate miR-182-5p expression, restoring normal cellular functions and potentially enhancing treatment responses. Understanding the biologic and clinical implications of miR-182-5p in gynecologic cancers is crucial for the development of targeted therapeutic strategies and personalized medicine approaches. Further investigations are needed to unravel the specific target genes and pathways regulated by miR-182-5p. It is important to consider the emerging biologic and clinical implications of miR-182-5p in gynecologic cancers.
PURPOSE: TACE induces variable systemic effects by producing factors that promote inflammation, oncogenesis, and angiogenesis. Here we compare concentrations of microRNAs (miR-21, miR-210 and miR-34a) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) patients undergoing TACE with degradable (DSM) and nondegradable (DEB) particles and potential use of these biomarker changes for prediction of patient outcomes. MATERIALS AND METHODS: Overall, 52 patients with HCC treated with DSM TACE (24 patients) and DEB TACE (28 patients) were included in this prospective study. Concentrations of studied biomarkers were measured from blood plasma preprocedurally, immediately (< 90 min) postprocedurally, and 24-h after TACE. Levels were compared between DSM and DEB TACE and correlated with treatment response six and 12 months after the first TACE. RESULTS: Both DSM and DEB TACE elevated plasma levels of miR-21, miR-34a, and miR-210 at 24 h post-procedure compared to baseline levels (FC 1.25-4.0). MiR-34a elevation immediately after TACE was significantly associated with nonprogressive disease compared to those with progressive disease at both six months (FCa: p = 0.014) and 12 months (FCa: p = 0.029) post-TACE. No significant biomarker changes were found between the embolization particle groups. However, VEGF levels showed a decrease only in the DSM TACE group (FC24: p = < 0.001). CONCLUSION: Embolization particle type did not significantly impact miRNA or VEGF changes post-TACE. However, miR-34a elevation immediately after the procedure predicts better patient outcome and may prove useful as a biomarkers for the monitoring of clinical outcomes. LEVEL OF EVIDENCE: Level 3 Prospective cohort study.
- MeSH
- biologické markery krev MeSH
- chemoembolizace * metody MeSH
- hepatocelulární karcinom * terapie krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- nádorové biomarkery * krev MeSH
- nádory jater * terapie genetika krev MeSH
- prospektivní studie MeSH
- senioři MeSH
- vaskulární endoteliální růstový faktor A * krev MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Cell cycle progression and leukemia development are tightly regulated processes in which even a small imbalance in the expression of cell cycle regulatory molecules and microRNAs (miRNAs) can lead to an increased risk of cancer/leukemia development. Here, we focus on the study of a ubiquitous, multifunctional, and oncogenic miRNA-hsa-miR-155-5p (miR-155, MIR155HG), which is overexpressed in malignancies including chronic lymphocytic leukemia (CLL). Nonetheless, the precise mechanism of how miR-155 regulates the cell cycle in leukemic cells remains the subject of extensive research. METHODS: We edited the CLL cell line MEC-1 by CRISPR/Cas9 to introduce a short deletion within the MIR155HG gene. To describe changes at the transcriptome and miRNome level in miR-155-deficient cells, we performed mRNA-seq/miRNA-seq and validated changes by qRT-PCR. Flow cytometry was used to measure cell cycle kinetics. A WST-1 assay, hemocytometer, and Annexin V/PI staining assessed cell viability and proliferation. RESULTS: The limited but phenotypically robust miR-155 modification impaired cell proliferation, cell cycle, and cell ploidy. This was accompanied by overexpression of the negative cell cycle regulator p21/CDKN1A and Cyclin D1 (CCND1). We confirmed the overexpression of canonical miR-155 targets such as PU.1, FOS, SHIP-1, TP53INP1 and revealed new potential targets (FCRL5, ISG15, and MX1). CONCLUSIONS: We demonstrate that miR-155 deficiency impairs cell proliferation, cell cycle, transcriptome, and miRNome via deregulation of the MIR155HG/TP53INP1/CDKN1A/CCND1 axis. Our CLL model is valuable for further studies to manipulate miRNA levels to revert highly aggressive leukemic cells to nearly benign or non-leukemic types.
- MeSH
- chronická lymfatická leukemie * genetika patologie MeSH
- cyklin D1 genetika metabolismus MeSH
- inhibitor p21 cyklin-dependentní kinasy * genetika metabolismus MeSH
- kontrolní body buněčného cyklu * genetika MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- proliferace buněk genetika MeSH
- proteiny teplotního šoku MeSH
- regulace genové exprese u leukemie MeSH
- transportní proteiny genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Necrotizing enterocolitis (NEC) is one of the most devastating intestinal diseases observed in preterm in the first days of life. Researchers have recently focused on potential predictive biomarkers for early and concomitant diagnoses. Thus, we inquired about the linkage of intestinal dysbiosis, one of the most important factors in NEC development to the gut microbiota. In this study, the systematic differences in the bacterial composition between neonates affected by NEC and healthy newborns were highlighted by metagenomic analysis. The next-generation sequencing of the V3-V4 variable region of the 16S rRNA gene and gene-specific qPCR analyzed the untargeted gut microbiota. Total bacteria, total and fecal coliform loads in stool samples with NEC were higher than control. OTU-level relative abundances of NEC infant was characterized by Firmicutes and Bacteroidetes at phylum levels. At the genus level, NEC stool was identified by the lack of Klebsiella and the presence of Roseburia, Blautia, and Parasutterella. Finally, Clostridium fessum was the predominant species of Clostridium genus in disease and healthy specimens at the species level, whereas Clostridium jeddahitimonense was at NEC diagnosis. Despite a strong relationship between pathophysiology and characterization of gut microbiota at a clinical diagnosis of NEC, our results emphasize the broad difficulty in identifying potential biomarkers.
- MeSH
- Bacteria * klasifikace genetika izolace a purifikace MeSH
- DNA bakterií genetika MeSH
- dysbióza mikrobiologie MeSH
- feces * mikrobiologie MeSH
- lidé MeSH
- metagenomika MeSH
- nekrotizující enterokolitida * mikrobiologie MeSH
- novorozenec nedonošený MeSH
- novorozenec MeSH
- RNA ribozomální 16S * genetika MeSH
- střevní mikroflóra * MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Fructobacillus, a Gram-positive, non-spore-forming, facultative anaerobic bacterium, belongs to the fructophilic lactic acid bacteria (FLAB) group. The group's name originates from fructose, the favored carbon source for its members. Fructobacillus spp. are noteworthy for their distinctive traits, captivating the interest of scientists. However, there have been relatively few publications regarding the isolation and potential utilization of these microorganisms in the industry. In recent years, F. tropaeoli has garnered interest for its promising role in the food and pharmaceutical sectors, although the availability of isolates is rather limited. A more comprehensive understanding of Fructobacillus is imperative to evaluate their functionality in the industry, given their unique and exceptional properties. Our in vitro study on Fructobacillus tropaeoli KKP 3032 confirmed its fructophilic nature and high osmotolerance. This strain thrives in a 30% sugar concentration, shows resistance to low pH and bile salts, and exhibits robust autoaggregation. Additionally, it displays significant antimicrobial activity against foodborne pathogens. Evaluating its probiotic potential, it aligns with EFSA recommendations in antibiotic resistance, except for kanamycin, to which it is resistant. Further research is necessary, but preliminary analyses confirm the high probiotic potential of F. tropaeoli KKP 3032 and its ability to thrive in the presence of high concentrations of fructose. The results indicate that the isolate F. tropaeoli KKP 3032 could potentially be used in the future as a fructophilic probiotic, protective culture, and/or active ingredient in fructose-rich food.
- MeSH
- antibakteriální látky farmakologie MeSH
- fruktosa metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- ovocné a zeleninové šťávy * mikrobiologie MeSH
- pomerančovník čínský mikrobiologie chemie MeSH
- potravinářská mikrobiologie MeSH
- probiotika * izolace a purifikace MeSH
- RNA ribozomální 16S genetika MeSH
- žlučové kyseliny a soli metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
Acute kidney injury (AKI) due to gentamicin nephrotoxicity is a significant concern in clinical medicine, particularly in patients receiving prolonged or high-dose gentamicin therapy. Gentamicin is an aminoglycoside antibiotic frequently used in the treatment of a range of bacterial infections. However, its use is associated with nephrotoxicity which can manifest as AKI. Due to this, it is crucial to diagnose promptly and manage treatment effectively. Ongoing studies are therefore focusing on non-protein-coding RNAs as potential biomarkers for AKI. Numerous microRNAs (miRNAs) have been implicated in gentamicin-induced nephrotoxicity and AKI. They participate in pathways associated with inflammation, cell death, and oxidative stress and each of these factors play critical roles in the development of gentamicin-induced kidney injury. Research studies have demonstrated changes in the expression levels of these miRNAs in response to gentamicin exposure both in vitro and in in vivo models, as well as in human clinical trials involving patients receiving gentamicin therapy. The dysregulation of these miRNAs correlates with the severity of kidney injury and may serve as sensitive biomarkers for early detection and monitoring of AKI induced by gentamicin.
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
In advanced prostate cancer (PC), in particular after acquisition of resistance to androgen receptor (AR) signaling inhibitors (ARSI), upregulation of AR splice variants compromises endocrine therapy efficiency. Androgen receptor splice variant-7 (ARV7) is clinically the most relevant and has a distinct 3' untranslated region (3'UTR) compared to the AR full-length variant, suggesting a unique post-transcriptional regulation. Here, we set out to evaluate the applicability of the ARV7 3'UTR as a therapy target. A common single nucleotide polymorphism, rs5918762, was found to affect the splicing rate and thus the expression of ARV7 in cellular models and patient specimens. Serine/arginine-rich splicing factor 9 (SRSF9) was found to bind to and increase the inclusion of the cryptic exon 3 of ARV7 during the splicing process in the alternative C allele of rs5918762. The dual specificity protein kinase CLK2 interferes with the activity of SRSF9 by regulating its expression. Inhibition of the Cdc2-like kinase (CLK) family by the small molecules cirtuvivint or lorecivivint results in the decreased expression of ARV7. Both inhibitors show potent anti-proliferative effects in enzalutamide-treated or -naive PC models. Thus, targeting aberrant alternative splicing at the 3'UTR of ARV7 by disturbing the CLK2/SRSF9 axis might be a valuable therapeutic approach in late stage, ARSI-resistant PC.
- MeSH
- 3' nepřekládaná oblast genetika MeSH
- alternativní sestřih genetika účinky léků MeSH
- androgenní receptory * metabolismus genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prostaty * genetika metabolismus patologie farmakoterapie MeSH
- protein - isoformy genetika metabolismus MeSH
- protein-serin-threoninkinasy genetika metabolismus antagonisté a inhibitory MeSH
- regulace genové exprese u nádorů * účinky léků MeSH
- serin-arginin sestřihové faktory * metabolismus genetika MeSH
- sestřih RNA genetika MeSH
- tyrosinkinasy * genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Clear-cell renal cell carcinoma (ccRCC) is a common urological malignancy with an increasing incidence. The development of molecular biomarkers that can predict the response to treatment and guide personalized therapy selection would substantially improve patient outcomes. Dysregulation of non-coding RNA (ncRNA) has been shown to have a role in the pathogenesis of ccRCC. Thus, an increasing number of studies are being carried out with a focus on the identification of ncRNA biomarkers in ccRCC tissue samples and the connection of these markers with patients' prognosis, pathological stage and grade (including metastatic potential), and therapy outcome. RNA sequencing analysis led to the identification of several ncRNA biomarkers that are dysregulated in ccRCC and might have a role in ccRCC development. These ncRNAs have the potential to be prognostic and predictive biomarkers for ccRCC, with prospective applications in personalized treatment selection. Research on ncRNA biomarkers in ccRCC is advancing, but clinical implementation remains preliminary owing to challenges in validation, standardization and reproducibility. Comprehensive studies and integration of ncRNAs into clinical trials are essential to accelerate the clinical use of these biomarkers.
- MeSH
- karcinom z renálních buněk * genetika diagnóza MeSH
- lidé MeSH
- nádorové biomarkery * genetika MeSH
- nádory ledvin * genetika diagnóza MeSH
- nekódující RNA * genetika MeSH
- prognóza MeSH
- regulace genové exprese u nádorů MeSH
- stanovení celkové genové exprese MeSH
- transkriptom * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
In this study, lactic acid bacteria (LAB) isolation from fermented foods and molecular identification using magnetic bead technology were performed. And then exopolysaccharide (EPS) production possibility was tested in agar medium, and the positive ones were selected for the next step. The bacteria that could produce higher carbohydrate level were grown in MRS medium fortified with whey and pumpkin waste. In our study, 19 different LAB species were identified from fermented products collected from different places in Hatay (Türkiye) province. In molecular identification, universal primer pairs, p806R/p8FPL, and PEU7/DG74 were used for PCR amplification. After that, PCR products purified using paramagnetic bead technology were sequenced by the Sanger sequencing method. The dominant species, 23.8% of the isolates, were identified as Lactiplantibacillus plantarum. As a technological property of LAB, exopolysaccharide production capability of forty-two LAB isolate was tested in agar medium, and after eleven isolates were selected as positive. Two LAB (Latilactobacillus curvatus SHA2-3B and Loigolactobacillus coryniformis SHA6-3B) had higher EPS production capability when they were grown in MRS broth fortified with pumpkin waste and whey. The highest EPS content (1750 mg/L glucose equivalent) was determined in Loigolactobacillus coryniformis SHA6-3B grown in MRS broth fortified with 10% pumpkin waste. Besides the produced EPS samples were validated with FTIR and SEM methods.
- MeSH
- bakteriální polysacharidy * biosyntéza metabolismus MeSH
- Cucurbita mikrobiologie MeSH
- fermentace MeSH
- fermentované potraviny * mikrobiologie MeSH
- fylogeneze MeSH
- kultivační média chemie MeSH
- Lactobacillales * izolace a purifikace klasifikace genetika metabolismus MeSH
- odpadní produkty * analýza MeSH
- potravinářská mikrobiologie * MeSH
- RNA ribozomální 16S genetika MeSH
- syrovátka MeSH
- Publikační typ
- časopisecké články MeSH
