Associations of epigenetic age acceleration at birth and age 12 years with adolescent cardiometabolic risk: the HOME study.

Background: Cardiometabolic risk factors among youth are rising. Epigenetic age acceleration, a biomarker for aging and disease-risk, has been associated with adiposity in children, but its association with other cardiometabolic risk markers remains understudied. We employed data from the Health Outcomes and Measures of the Environment (HOME) study, a prospective pregnancy and birth cohort in the greater Cincinnati metropolitan area, to examine whether accelerated epigenetic age at birth as well as accelerated epigenetic age and faster pace of biological aging at age 12 years were associated with higher cardiometabolic risk in adolescents.

Multimodal assessment of high-risk human papillomavirus in sinonasal squamous cell carcinoma.

High-risk human papillomavirus (hrHPV) is an emerging risk factor for sinonasal squamous cell carcinoma (SNSCC). The goal of this study was to assess the prevalence of hrHPV and subtype distribution in SNSCC and correlation with patient and clinical characteristics. This retrospective cohort study included 43 cases diagnosed with incident primary SNSCC at the University of Cincinnati Medical Center from 2010 to 2015.

Proton Treatment Suppresses Exosome Production in Head and Neck Squamous Cell Carcinoma.

Proton therapy (PT) is emerging as an effective and less toxic alternative to conventional X-ray-based photon therapy (XRT) for patients with advanced head and neck squamous cell carcinomas (HNSCCs) owing to its clustered dose deposition dosimetric characteristics. For optimal efficacy, cancer therapies, including PT, must elicit a robust anti-tumor response by effector and cytotoxic immune cells in the tumor microenvironment (TME). While tumor-derived exosomes contribute to immune cell suppression in the TME, information on the effects of PT on exosomes and anti-tumor immune responses in HNSCC is not known.

Rapid purification and multiparametric characterization of circulating small extracellular vesicles utilizing a label-free lab-on-a-chip device.

Nano-scale extracellular vesicles are lipid-bilayer delimited particles that are naturally secreted by all cells and have emerged as valuable biomarkers for a wide range of diseases. Efficient isolation of small extracellular vesicles while maintaining yield and purity is crucial to harvest their potential in diagnostic, prognostic, and therapeutic applications. Most conventional methods of isolation suffer from significant shortcomings, including low purity or yield, long duration, need for large sample volumes, specialized equipment, trained personnel, and high costs.

Lifetime Postnatal Exposure to Perfluoroalkyl Substance Mixture and DNA Methylation at Twelve Years of Age.

Per- and polyfluoroalkyl substance (PFAS) exposure has been linked to DNA methylation changes in neonates and adults. We previously reported that prenatal PFAS exposure may have a durable impact on DNA methylation from birth to adolescence. However, few studies have examined the association of postnatal PFAS exposure with alterations in DNA methylation.

Prenatal SARS-CoV-2 infection alters postpartum human milk-derived extracellular vesicles.

Human milk-derived extracellular vesicles (HMEVs) are crucial functional components in breast milk, contributing to infant health and development. Maternal conditions could affect HMEV cargos; however, the impact of SARS-CoV-2 infection on HMEVs remains unknown. This study evaluated the influence of SARS-CoV-2 infection during pregnancy on postpartum HMEV molecules.

Stable methylation loci are associated with systolic blood pressure in a Croatian island population.

The objective was to identify stable and dynamic DNA methylation loci associated with cardiometabolic traits among an adult population from the Croatian island of Hvar. An epigenome-wide association study was conducted using peripheral blood longitudinally collected at two time points 10 years apart via Infinium MethylationEPIC beadarray (n = 112). Stable and dynamic loci were identified using linear mixed models.

Small extravesicular microRNA in head and neck squamous cell carcinoma and its potential as a liquid biopsy for early detection.

Background: The objective was to assess secretion of small extracellular vesicular microRNA (exo-miRNA) in head and neck squamous cell carcinoma (HNSCC) according to human papillomavirus (HPV) status, and determine the translational potential as a liquid biopsy for early detection.

Methods: This study employed a combination of cell culture and case-control study design using archival pretreatment serum. Small extracellular vesicles (sEV) were isolated from conditioned culture media and human serum samples via differential ultracentrifugation.

MicroRNA expression within neuronal-derived small extracellular vesicles in frontotemporal degeneration.

MicroRNAs (miRNAs) are small non-coding RNA that are powerful regulators of gene expression and can affect the expression of hundreds of genes. miRNAs can be packed in small extracellular vesicles (SEV) and released into the extracellular space by neurons and microglia to act locally as well as pass through the blood-brain barrier and act systemically. We sought to understand the differences in neuronal SEV miRNA expression between frontotemporal dementia (FTD), Alzheimer's disease (AD), and healthy aging.

Human Papillomavirus and Survival of Sinonasal Squamous Cell Carcinoma Patients: A Systematic Review and Meta-Analysis.

Human papillomavirus (HPV) is detectable in a subset of sinonasal squamous cell carcinoma (SNSCC), but the impact on patient outcomes is presently unclear due to a modest number of studies with limited statistical power. Therefore, we conducted a systematic review and meta-analysis to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on overall (OS) or disease-free survival (DFS) for SNSCC by HPV status.

Comparability of the small RNA secretome across human biofluids concomitantly collected from healthy adults.

Small extracellular vesicles (sEV) are nano-sized (40-150 nm), membrane-encapsulated vesicles that are released by essentially all cells into the extracellular space and function as intercellular signaling vectors through the horizontal transfer of biologic molecules, including microRNA (miRNA) and other small non-coding RNA (ncRNA), that can alter the phenotype of recipient cells. sEV are present in essentially all extracellular biofluids, including serum, urine and saliva, and offer a new avenue for discovery and development of novel biomarkers of various disease states and exposures. The objective of this study was to systematically interrogate similarities and differences between sEV ncRNA derived from saliva, serum and urine, as well as cell-free small ncRNA (cf-ncRNA) from serum.

Rapid and label-free isolation of small extracellular vesicles from biofluids utilizing a novel insulator based dielectrophoretic device.

Exosomes are nano-scale membrane-encapsulated vesicles produced by the majority of cells and have emerged as a rich source of biomarkers for a wide variety of diseases. Although many approaches have been developed for exosome isolation from biofluids, most of them have substantial shortcomings including long processing time, inefficiency, high cost, lack of specificity and/or surface marker-dependency. To address these issues, here we report a novel insulator-based dielectrophoretic (iDEP) device predicated on an array of borosilicate micropipettes to rapidly isolate exosomes from conditioned cell culture media and biofluids, such as plasma, serum, and saliva.

Comprehensive mapping of the methylation landscape of 16 CpG-dense regions in oral and pharyngeal squamous cell carcinoma.

The goal of this study was to comprehensively interrogate and map DNA methylation across 16 CpG-dense regions previously associated with oral and pharyngeal squamous cell carcinoma (OPSCC). Targeted multiplex bisulfite amplicon sequencing was performed on four OPSCC cell lines and primary non-neoplastic oral epithelial cells. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed for a subset of associated genes.

Balancing yield, purity and practicality: a modified differential ultracentrifugation protocol for efficient isolation of small extracellular vesicles from human serum.

Ultracentrifugation remains the gold standard for isolation of small extracellular vesicles (sEV), particularly for cancer applications. The objective of this study was to determine if a widely used ultracentrifugation protocol for isolation of serum sEV could be modified to reduce the number of ultracentrifugation cycles and increase efficiency, while maintaining equal or better sample purity and yield. Serum was obtained from two healthy subjects.

Differential expression and prognostic value of long non-coding RNA in HPV-negative head and neck squamous cell carcinoma.

Background: Long non-coding RNA (lncRNA) has emerged as a new avenue of interest due to its various biological functions in cancer. Abnormal expression of lncRNA has been reported in other malignancies but has been understudied in head and neck squamous cell carcinoma (HNSCC).

Methods: The lncRNA expression was interrogated via quantitative real-time polymerase chain reaction (qRT-PCR) array for 19 human papillomavirus (HPV)-negative HNSCC tumor-normal pairs.

Comprehensive microRNA-sequencing of exosomes derived from head and neck carcinoma cells reveals common secretion profiles and potential utility as salivary biomarkers.

Exosomes are nano-scale, membrane encapsulated vesicles that are released by cells into the extracellular space and function as intercellular signaling vectors through horizontal transfer of biologic molecules, including microRNA (miRNA). There is evidence that cancer-derived exosomes enable the tumor to manipulate its microenvironment, thus contributing to the capacity of the tumor for immune evasion, growth, invasion, and metastatic spread. The objective of this study was to characterize differential secretion of exosomal miRNA by head and neck squamous cell carcinoma (HNSCC) and identify a set of candidate biomarkers that could be detected in non-invasive saliva samples.

Immune Response to HPV16 E6 and E7 Proteins and Patient Outcomes in Head and Neck Cancer.

Importance: Pathology-based measures of human papillomavirus (HPV) status are routinely obtained in the care of head and neck cancer and are clearly associated with patient outcome for cancers of the oropharynx. However, it is unclear if HPV status is of high value for cancers of the larynx and oral cavity. In addition, it is possible to assess HPV infection using serology-based methods; however, the suitability of this pathology-independent measure for predicting patient outcome in head and neck cancer is unknown.

CpG island methylation profile in non-invasive oral rinse samples is predictive of oral and pharyngeal carcinoma.

Background: There are currently no screening tests in routine use for oral and pharyngeal cancer beyond visual inspection and palpation, which are provided on an opportunistic basis, indicating a need for development of novel methods for early detection, particularly in high-risk populations. We sought to address this need through comprehensive interrogation of CpG island methylation in oral rinse samples.

Methods: We used the Infinium HumanMethylation450 BeadArray to interrogate DNA methylation in oral rinse samples collected from 154 patients with incident oral or pharyngeal carcinoma prior to treatment and 72 cancer-free control subjects.

Human papillomavirus serology and tobacco smoking in a community control group.

Background: HPV infection is an established risk factor for oropharyngeal cancer, and it has been proposed that cigarette smoking may potentiate HPV infection in the oral epithelium. We sought to test the hypothesis that cigarette smoking increases HPV infection in an HPV16 serology study of cancer-free individuals.

Methods: Subjects were participants in a risk factor study for head and neck cancer, and were required to have no prior history of either HNSCC or any other cancer.

Obesity and head and neck cancer risk and survival by human papillomavirus serology.

Purpose: Previous studies examining the association of body mass index (BMI) with risk of and survival from head and neck squamous cell carcinoma (HNSCC) have been inconsistent, although an inverse association has been noted for obesity and risk of HNSCC in several studies. Previous studies have not examined whether these associations differ by human papillomavirus (HPV) status.

Methods: We utilized the resources of a population-based case-control study of HNSCC from the greater Boston area (959 cases and 1,208 controls were eligible for this analysis).