Search

Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type in the world and is associated with an overall poor prognosis. The protein methyltransferase SET and MYND domain-containing 3 (SMYD3), which trimethylates H3K4, activates gene transcription and enhances several oncogenic pathways, including epithelial-mesenchymal transition and cell cycle related pathways, in various cancer types. It was also recently shown that SMYD3 is overexpressed in HPV-negative HNSCC, and represses the expression of type I IFN response genes, contributing to resistance to anti-PD-1 checkpoint blockade in this disease. In this study, we show that SMYD3 depletion using siRNA interference or CRISPR decreases cellular proliferation and clonal capacity, induces cell cycle arrest and decreases the invasive potential of HPV-negative HNSCC cell lines. Accordingly, xenografts of SMYD3 knockout tumors derived from a human HPV-negative HNSCC cell line grew significantly slower compared to control tumors in mice. Genome-wide mapping for SMYD3 and H3K4me3 in HPV-negative HNSCC cells using cleavage under targets and release using nuclease (CUT&RUN) assays identified direct downstream gene targets regulated by SMYD3, including cell cycle- and EMT-promoting genes. This study provides insights into the epigenetic role of SMYD3 as an oncogene in HPV-negative HNSCC and supports SMYD3 as a rational therapeutic target in HPV-negative HNSCC., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

SET and MYND-domain containing protein 3 (SMYD3) mediates epigenetic repression of type I IFN response genes in human papillomavirus (HPV)-negative HNSCC cells, and Smyd3 depletion using anti-sense oligonucleotides (ASOs) increases the sensitivity of syngeneic mouse oral carcinoma (MOC1) models to anti-PD-1 therapy. In this study, we utilized single-cell RNA-seq of MOC1 tumors treated with Smyd3 ASOs and found enrichment of type I IFN response pathways in cancer cells, a shift of CD8 + T-cells toward an activated/memory phenotype, and a shift of neutrophils toward an anti-tumorigenic phenotype. Mechanisms of resistance to the Smyd3 ASO and anti-PD-1 combination were derived from cancer cells, macrophages, and CD8 + T-cells, including neutrophil enrichment through the upregulation of Cxcl2 , repression of Cxcl9, and defective antigen presentation. This study sheds light on the immunomodulatory functions of Smyd3 in vivo and provides insight into actionable mechanisms of resistance to improve the efficacy of Smyd3 ASOs and anti-PD-1 combination., Competing Interests: Xiaolin Luo was an employee of Ionis Pharmaceuticals Inc during this study. The other authors declare no competing interests.

Objective: This study aimed to assess if Nigella sativa oil (NSO), a health supplement containing thymoquinone as a major component, can act as a protective agent in salivary gland stem cells following radiotherapy (RT) damage., Methods: Forty, 10-week-old, male C3H/HeJ mice were randomized to four experimental groups: sham RT + H 2 O gavage (control) ( N  = 4); 15 Gy RT + H 2 O gavage ( N  = 12); sham RT + NSO gavage ( N  = 12); and 15 Gy RT + NSO gavage ( N  = 12). Weight changes, saliva production, and salivary gland histopathologic staining were recorded for each group over the course of the experiment., Results: All mice in the sham RT + H 2 O gavage and sham RT + NSO gavage groups demonstrated 100% 60-day survival. RT + H 2 O compared to RT + NSO gavaged mice were significantly underweight by an average of 6.4 g ( p  < .001). Salivary output showed significant decline in RT + H 2 O gavaged mice at days 3 and 16, whereas salivary output in RT + NSO during these same time periods was comparable to the control. At day 60, all mice that survived recovered salivary function regardless of their treatment arm. Salivary specimens from the RT + NSO gavage group demonstrated early signs of recovery of Kr 5+ salivary gland stem cells in both submandibular and sublingual glands at day 16 with complete recovery by day 60, marked by strong histopathologic staining, whereas the RT + H 2 O gavage group did not recover as effectively., Conclusion: NSO may help preserve salivary function in mice treated with RT and may mitigate xerostomia by accelerating the recovery of salivary gland stem cells., Level of Evidence: Not applicable., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: Nocturnal enuresis (NE) is a frequent diagnosis in pediatric and adolescent populations with an estimated prevalence of around 15% at the age of 6 years. NE can have a substantial impact on multiple health domains. Bedwetting alarms, which typically consist of a sensor and moisture-activated alarm, are a common treatment., Objective: This study aimed to determine areas of satisfaction versus dissatisfaction reported by the parents and caregivers of children using current bedwetting alarms., Methods: Using the search term "bedwetting alarms" on the Amazon marketplace, products with >300 reviews were included. For each product, the 5 reviews ranked the "most helpful" for each star category were selected for analysis. Meaning extraction method was applied to identify major themes and subthemes. A percent skew was calculated by summing the total number of mentions of each subtheme,+1 for a positive mention, 0 for a neutral mention, and -1 for a negative mention, and dividing this total by the number of reviews in which that particular subtheme was observed. Subanalyses were performed for age and gender., Results: Of 136 products identified, 10 were evaluated based on the selection criteria. The main themes identified across products were long-term concerns, marketing, alarm systems, and device mechanics and features. The subthemes identified as future targets for innovation included alarm accuracy, volume variability, durability, user-friendliness, and adaptability to girls. In general, durability, alarm accuracy, and comfort were the most negatively skewed subthemes (with a negative skew of -23.6%, -20.0%, and -12.4% respectively), which are indicative of potential areas for improvement. Effectiveness was the only substantially positively skewed subtheme (16.8%). Alarm sound and device features were positively skewed for older children, whereas ease of use had a negative skew for younger children. Girls and their caretakers reported negative experiences with devices that featured cords, arm bands, and sensor pads., Conclusions: This analysis provides an innovation roadmap for future device design to improve patient and caregiver satisfaction and compliance with bedwetting alarms. Our results highlight the need for additional options in alarm sound features, as children of different ages have divergent preferences in this domain. Additionally, girls and their parents and caretakers provided more negative overall reviews regarding the range of current device features compared to boys, indicating a potential focus area for future development. The percent skew showed that subthemes were often more negatively skewed toward girls, with the ease of use being -10.7% skewed for boys versus -20.5% for girls, and comfort being -7.1% skewed for boys versus -29.4% for girls. Put together, this review highlights multiple device features that are targets for innovation to ensure translational efficacy regardless of age, gender, or specific family needs., (©Astha Sahoo, Savannah Leah Starr, Vadim Osadchiy, Sophia Desai, Neha Iyer, Marie Luff, Grace E Sollender, Renea Sturm. Originally published in the Interactive Journal of Medical Research (https://www.i-jmr.org/), 06.07.2023.)

Head and neck cancer is the sixth most common cancer in the world, with more than 300,000 deaths attributed to the disease annually. Aggressive surgical resection often with adjuvant chemoradiation is the cornerstone of treatment. However, the necessary chemoradiation treatment can result in collateral damage to adjacent vital structures causing a profound impact on quality of life. Here, we present a novel polymer of poly(lactic-co-glycolic) acid and polyvinyl alcohol that can serve as a versatile multidrug delivery platform as well as for detection on cross-sectional imaging while functioning as a fiduciary marker for postoperative radiotherapy and radiotherapeutic dosing. In a mouse xenograft model, the dual-layered polymer composed of calcium carbonate/thymoquinone was used for both polymer localization and narrow-field infusion of a natural therapeutic compound. A similar approach can be applied in the treatment of head and neck cancer patients, where immunotherapy and traditional chemotherapy can be delivered simultaneously with independent release kinetics., (© 2022. The Author(s).)

Flagellate green algae have developed a visual system, the eyespot apparatus, which allows the cell to phototax. To further understand the molecular organization of the eyespot apparatus and the phototactic movement that is controlled by light and the circadian clock, a detailed understanding of all components of the eyespot apparatus is needed. We developed a procedure to purify the eyespot apparatus from the green model alga Chlamydomonas reinhardtii. Its proteomic analysis resulted in the identification of 202 different proteins with at least two different peptides (984 in total). These data provide new insights into structural components of the eyespot apparatus, photoreceptors, retina(l)-related proteins, members of putative signaling pathways for phototaxis and chemotaxis, and metabolic pathways within an algal visual system. In addition, we have performed a functional analysis of one of the identified putative components of the phototactic signaling pathway, casein kinase 1 (CK1). CK1 is also present in the flagella and thus is a promising candidate for controlling behavioral responses to light. We demonstrate that silencing CK1 by RNA interference reduces its level in both flagella and eyespot. In addition, we show that silencing of CK1 results in severe disturbances in hatching, flagellum formation, and circadian control of phototaxis.

Predictions of plant and animal species distributions are important for conservation and for the assessment of large-scale ecosystem change. Land cover data are becoming more widely available for use in land management and conservation. We use a logistic regression modelling approach to investigate the utility of these data for modelling. The relationship between the distribution of 137 British ground beetles species and land cover was investigated using data from 1,687 10 km national grid squares. Land cover data were simplified using ordination and the axes used as predictors in logistic regression with presence absence data for individual beetle species as response variables. Significant regression models were generated for all species with first and second axis scores. The amounts of variation explained by models were generally low, but predictions derived from models generally matched the known distributions of the species in Britain. Species with coastal preferences were poorly modelled and predicted to occur throughout lowland Britain whilst a number of species occurring in southern Britain were predicted to occur into Scotland. A validation exercise comparing model predictions with new data from a survey of 59 10 km(2) produced mixed results with the distribution of grassland species being better predicted than riverine species. Jack-knifing was used to assess the robustness of models for four species which differed in their apparent responses to the land cover variables. Methods for improving the predictive power of these models and their potential for use in assessing the impact of global climate change are discussed.

Body weight and traits associated with production of wool were measured over a 2-year period between 1985 and 1987 in south-western New South Wales in a flock of Merino wethers experimentally infected with footrot. The disease was allowed to spread freely amongst 150 of the flock but kept at very low prevalence in the remaining 50 by preventive footbathing during transmission periods. Severe, underrunning footrot had a significant adverse effect on body weight, for each year of the trial. Body weight was most severely reduced at times of the year when footrot was spreading among animals and lesions were severe. The mean body weight of the infected group at the end of the 2 years of observation was 7.3 kg (11.6%) below that of the control group. Footrot also depressed wool growth, with the mean clean fleece weight of the infected group being 0.4 kg (8%) lighter than that of the controls at each of the 2 annual shearings. There were no consistent differences between the groups for the other wool characteristics measured.

During studies of flies that visit farm animals in north-east England, samples of Muscidae were obtained on a regular basis from grazing animals (mainly cattle) and from Manitoba traps. Female flies were examined to determine their wing length, degree of wing damage, whether or not they had mated, whether their crop or gut contained blood, the stage they had reached in ovarian development and the number of eggs present. This information was used to assess the timing of mating, the stage at which blood meals were taken and the potential fecundity of the more numerous species, especially Hydrotaea irritans (Fallén) and Morellia simplex (Loew). A relationship between the size of the individual and the number of eggs it carried was found in several species.