Translation of Epigenetics in Cell-Free DNA Liquid Biopsy Technology and Precision Oncology.

Technological advancements in cell-free DNA (cfDNA) liquid biopsy have triggered exponential growth in numerous clinical applications. While cfDNA-based liquid biopsy has made significant strides in personalizing cancer treatment, the exploration and translation of epigenetics in liquid biopsy to clinical practice is still nascent. This comprehensive review seeks to provide a broad yet in-depth narrative of the present status of epigenetics in cfDNA liquid biopsy and its associated challenges. It highlights the potential of epigenetics in cfDNA liquid biopsy technologies with the hopes of enhancing its clinical translation. The momentum of cfDNA liquid biopsy technologies in recent years has propelled epigenetics to the forefront of molecular biology. We have only begun to reveal the true potential of epigenetics in both our understanding of disease and leveraging epigenetics in the diagnostic and therapeutic domains. Recent clinical applications of epigenetics-based cfDNA liquid biopsy revolve around DNA methylation in screening and early cancer detection, leading to the development of multi-cancer early detection tests and the capability to pinpoint tissues of origin. The clinical application of epigenetics in cfDNA liquid biopsy in minimal residual disease, monitoring, and surveillance are at their initial stages. A notable advancement in fragmentation patterns analysis has created a new avenue for epigenetic biomarkers. However, the widespread application of cfDNA liquid biopsy has many challenges, including biomarker sensitivity, specificity, logistics including infrastructure and personnel, data processing, handling, results interpretation, accessibility, and cost effectiveness. Exploring and translating epigenetics in cfDNA liquid biopsy technology can transform our understanding and perception of cancer prevention and management. cfDNA liquid biopsy has great potential in precision oncology to revolutionize conventional ways of early cancer detection, monitoring residual disease, treatment response, surveillance, and drug development. Adapting the implementation of liquid biopsy workflow to the local policy worldwide and developing point-of-care testing holds great potential to overcome global cancer disparity and improve cancer outcomes.

Anesthesia-Induced Neuronal Apoptosis in the Developing Retina: A Window of Opportunity.

BACKGROUND: Anesthetics cause widespread apoptosis in the developing brain, resulting in neurocognitive abnormalities. However, it is unknown whether anesthesia-induced neurotoxicity occurs in humans because there is currently no modality to assess for neuronal apoptosis in vivo. The retina is unique in that it is the only portion of the central nervous system that can be directly visualized noninvasively. Thus, we aimed to determine whether isoflurane induces apoptosis in the developing retina. METHODS: CD-1 male mouse pups underwent 1-hour exposure to isoflurane (2%) or air. After exposure, activated caspase-3, caspase-9, and caspase-8 were quantified in the retina, cytochrome c release from retinal mitochondria was assessed, and the number and types of cells undergoing apoptosis were identified. Retinal uptake and the ability of fluorescent-labeled annexin V to bind to cells undergoing natural cell death and anesthesia-induced apoptosis in the retina were determined after systemic injection. RESULTS: Isoflurane activated the intrinsic apoptosis pathway in the inner nuclear layer (INL) and activated both the intrinsic and extrinsic pathways in the ganglion cell layer. Immunofluorescence demonstrated that bipolar and amacrine neurons within the INL underwent physiologic cell death in both cohorts and that amacrine cells were the likely targets of isoflurane-induced apoptosis. After injection, fluorescent-labeled annexin V was readily detected in the INL of both air-exposed and isoflurane-exposed mice and colocalized with activated caspase-3-positive cells. CONCLUSIONS: These findings indicate that isoflurane-induced neuronal apoptosis occurs in the developing retina and lays the groundwork for development of a noninvasive imaging technique to detect anesthesia-induced neurotoxicity in infants and children.

Novel Chlamydia trachomatis strains in heterosexual sex partners, Indianapolis, Indiana, USA.

Chlamydia trachomatis causes a high number of sexually transmitted infections worldwide, but reproducible and precise strain typing to link partners is lacking. We evaluated multilocus sequence typing (MLST) for this purpose by detecting sequence types (STs) concordant for the ompA genotype, a single-locus typing standard. We tested samples collected during April 2000-October 2003 from members of established heterosexual partnerships (dyads) in the Indianapolis, Indiana, USA, area who self-reported being coital partners within the previous 30 days. C. trachomatis DNA from 28 dyads was tested by MLST; sequences were aligned and analyzed for ST and phylogenetic relationships. MLST detected 9 C. trachomatis STs, 4 unique to Indianapolis; STs were identical within each dyad. Thirteen unique strains were identified; 9 (32%) dyads harbored novel recombinant strains that phylogenetically clustered with strains comprising the recombinants. The high rate of novel C. trachomatis recombinants identified supports the use of MLST for transmission and strain diversity studies among at-risk populations.