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Cervical cancer remains the fourth most common cancer among women globally, disproportionately impacting low- and middle-income countries despite the existence of HPV vaccines. While DNA methylation has been studied extensively as a biomarker, other epigenetic mechanisms remain underexplored. This scoping review aims to report such underexplored epigenetic biomarkers linked to cervical cancer, shifting the focus beyond global nuclear DNA methylation. Literature searches were performed using Google Scholar via Publish or Perish software including studies published until January 2025. Our review focused on mitochondrial DNA, non-coding RNA, histone modifications, and repetitive elements. Mitochondrial DNA methylation has been proposed as a cervical cancer biomarker, although supporting evidence is limited. Histone modifications are more consistently reported to be involved both in cervical cancer onset and aggressiveness. Similarly, aberrant expression of lncRNAs, circRNAs, miRNAs, and piRNAs has been associated with poor prognosis. Finally, hypomethylation in repetitive elements such as LINE-1 and Alu is often observed in cervical cancer, contributing to genomic instability and tumorigenesis. Highlighting these alternative epigenetic mechanisms, our review emphasizes the importance of expanding biomarker discovery beyond the traditional nuclear DNA methylation. Understanding these mechanisms may improve early detection and personalized disease management strategies for cervical cancer.

Biocatalysts exerting activity against ester bonds have a broad range of applications in modern biotechnology. Here, we have identified a new esterolytic enzyme by screening a metagenomic sample collected from a hot spring in Kamchatka, Russia. Biochemical characterization of the new esterase, termed EstDZ2, revealed that it is highly active against medium chain fatty acid esters at temperatures between 25 and 60 °C and at pH values 7–8. The new enzyme is moderately thermostable with a half-life of more than six hours at 60 °C, but exhibits exquisite stability against high concentrations of organic solvents. Phylogenetic analysis indicated that EstDZ2 is likely an Acetothermia enzyme that belongs to a new family of bacterial esterases, for which we propose the index XV. One distinctive feature of this new family, is the presence of a conserved GHSAG catalytic motif. Multiple sequence alignment, coupled with computational modelling of the three-dimensional structure of EstDZ2, revealed that the enzyme lacks the largest part of the “cap” domain, whose extended structure is characteristic for the closely related Family IV esterases. Thus, EstDZ2 appears to be distinct from known related esterolytic enzymes, both in terms of sequence characteristics, as well as in terms of three-dimensional structure.

With the ultimate goal of identifying robust cellulases for industrial biocatalytic conversions, we have isolated and characterized a new thermostable and very halotolerant GH5 cellulase. This new enzyme, termed CelDZ1, was identified by bioinformatic analysis from the genome of a polysaccharide-enrichment culture isolate, initiated from material collected from an Icelandic hot spring. Biochemical characterization of CelDZ1 revealed that it is a glycoside hydrolase with optimal activity at 70°C and pH 5.0 that exhibits good thermostability, high halotolerance at near-saturating salt concentrations, and resistance towards metal ions and other denaturing agents. X-ray crystallography of the new enzyme showed that CelDZ1 is the first reported cellulase structure that lacks the defined sugar-binding 2 subsite and revealed structural features which provide potential explanations of its biochemical characteristics.

Background Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test. Methods A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K ( n  = 76) or EPIC 850K ( n  = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05. Results At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2 , and APBB1IP . Conclusions Using prospective time-to-event data, we detected associations between CADM1 -, DAPK1 -, PAX1 -, and RARB -related CpGs and cervical disease progression, and we identified novel progression-associated CpGs. Impact Methylation levels at novel CpG sites may help identify individuals with ≤CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines.

Increasing evidence suggests vaginal dysbiosis is associated with persistent high-risk human papillomavirus (hrHPV) infection and cervical intraepithelial neoplasia (CIN) development. In this pilot longitudinal study, we investigate the potential of vaginal microbiome biomarkers to predict CIN3 development in hrHPV-positive (hrHPV+) women of reproductive age and assess loop electrosurgical excision procedure (LEEP) outcomes. Fifty-nine non-menopausal women 20–53 years old, with normal cytology, were selected from the ARTISTIC trial and followed up twice over six years. Vaginal microbiome was analysed by 16S rRNA sequencing. HrHPV+ women with CIN3 showed a significant overrepresentation of Sneathia amnii , Megasphaera genomosp., Peptostreptococcus anaerobius and Achromobacter spanius ( p  < 0.05). Successfully LEEP-treated hrHPV-negative women exhibited increased Lactobacillus species, especially Lactobacillus gasseri . Additionally, Lactobacillus helveticus , suntoryeus and vaginalis showed a potential protective role against CIN3 development. These unique microbial biomarkers associated with CIN3 development and recovery following LEEP treatment bring new insights into the vaginal microbiome’s role on disease progression. Examination of vaginal microbiome’s role in predicting CIN3 in high-risk HPV positive women. Sneathia amnii links to CIN3 incidence, while Lactobacillus , especially L. gasseri , is associated with successful treatment and potential protection.

Geological storage of CO2 is a fast-developing technology that can mitigate rising carbon emissions. However, there are environmental concerns with the long-term storage and implications of a leak from a carbon capture storage (CCS) site. Traditional monitoring lacks clear protocols and relies heavily on physical methods. Here, we discuss the potential of biotechnology, focusing on microbes with a natural ability to utilize and assimilate CO2 through different metabolic pathways. We propose the use of natural microbial communities for CCS monitoring and CO2 utilization, and, with examples, demonstrate how synthetic biology may maximize CO2 uptake within and above storage sites. An integrated physical and biological approach, combined with metagenomics data and biotechnological advances, will enhance CO2 sequestration and prevent large-scale leakages. Microorganisms have the ability to respond quickly to environmental changes and to bind CO2, potentially removing it from the surrounding environment. High-throughput sequencing can be used to identify the microbial metagenomic fingerprint, which can be used to develop simplified, efficient genetic methods to monitor CCS sites. CCS monitoring would be most effective with a multidisciplinary monitoring program, combining geology, biogeochemistry, physics, microbiology, molecular biology, and genomics. The advances in our knowledge in prokaryotic genomics, metabolic pathways, microbial communities, and the potential to engineer CO2 binding properties in microbes provide opportunities for transforming CCS sites into bioreactors for value-added chemicals.

Background/Objectives: Several independent studies have associated prostate cancer (PCa) with specific groups of bacteria, most of them reporting the presence of anaerobic or microaerophilic species such as Cutibacterium acnes (C. acnes). Such findings suggest a prostate cancer-related bacterial dysbiosis, in a manner similar to the association between Helicobacter pylori infection and gastric cancer. In an earlier exploratory study looking for such dysbiosis events, using a culturomics approach, we discovered that the presence of obligate anaerobes (OAs) along with C. acnes was associated with increased prostate-specific antigen (PSA) levels in 39 participants. Methods: Building on this, in this study, we analyzed 89 post-rectal examination urine samples, from men with prostate cancer attending the PROVENT trial, using 16S rDNA sequencing. Our investigation focused on the impact of six previously identified OA genera (Finegoldia, Fusobacterium, Prevotella, Peptoniphilus_A, Peptostreptococcus, and Veillonella_A) on PSA levels. However, an additional data-driven approach was followed to uncover more taxa linked to increased PSA. Results: Our analysis revealed a statistically significant association between Peptostreptococcus and elevated PSA levels. Additionally, there were potential interactions between Prevotella and Fusobacterium. Interestingly, we also found that an aerobe, Ochrobactrum_A,was significantly linked to higher PSA levels. Conclusions: These findings suggest that OA-related dysbiosis may contribute to elevated PSA levels through prostate cell damage even before prostate cancer develops, possibly playing a role in chronic inflammation and the hypervascular changes seen in precancerous lesions. Future clinical trials with larger cohorts are needed to further evaluate the role of OA in prostate cancer development and progression.

Background Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test. Methods A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05. Results At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP. Conclusions Using prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs. Impact Methylation levels at novel CpG sites may help identify individuals with [less than or equal to]CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines. Keywords: Cervical cancer, Cancer surveillance and screening, DNA methylation, Epigenomics, Epigenetics, Cancer risk, Pre-neoplasia

The rapid evolution of all sequencing technologies, described by the term Next Generation Sequencing (NGS), have revolutionized metagenomic analysis. They constitute a combination of high-throughput analytical protocols, coupled to delicate measuring techniques, in order to potentially discover, properly assemble and map allelic sequences to the correct genomes, achieving particularly high yields for only a fraction of the cost of traditional processes (i.e., Sanger). From a bioinformatic perspective, this boils down to many GB of data being generated from each single sequencing experiment, rendering the management or even the storage, critical bottlenecks with respect to the overall analytical endeavor. The enormous complexity is even more aggravated by the versatility of the processing steps available, represented by the numerous bioinformatic tools that are essential, for each analytical task, in order to fully unveil the genetic content of a metagenomic dataset. These disparate tasks range from simple, nonetheless non-trivial, quality control of raw data to exceptionally complex protein annotation procedures, requesting a high level of expertise for their proper application or the neat implementation of the whole workflow. Furthermore, a bioinformatic analysis of such scale, requires grand computational resources, imposing as the sole realistic solution, the utilization of cloud computing infrastructures. In this review article we discuss different, integrative, bioinformatic solutions available, which address the aforementioned issues, by performing a critical assessment of the available automated pipelines for data management, quality control, and annotation of metagenomic data, embracing various, major sequencing technologies and applications.