The alternative splicing of PML precursor mRNA gives rise to various PML isoforms, yet their expression profile in breast cancer cells remains uncharted. We discovered that PML1 is the most abundant isoform in all breast cancer subtypes, and its expression is associated with unfavorable prognosis in estrogen receptor-positive (ER+) breast cancers. PML depletion reduces cell proliferation, invasion, and stemness, while heterologous PML1 expression augments these processes and fuels tumor growth and resistance to fulvestrant, an FDA-approved drug for ER+ breast cancer, in a mouse model. Moreover, PML1, rather than the well-known tumor suppressor isoform PML4, rescues the proliferation of PML knockdown cells. ChIP-seq analysis reveals significant overlap between PML-, ER-, and Myc-bound promoters, suggesting their coordinated regulation of target gene expression, including genes involved in breast cancer stem cells (BCSCs), such as JAG1, KLF4, YAP1, SNAI1, and MYC. Loss of PML reduces BCSC-related gene expression, and exogenous PML1 expression elevates their expression. Consistently, PML1 restores the association of PML with these promoters in PML-depleted cells. We identified a novel association between PML1 and WDR5, a key component of H3K4 methyltransferase (HMTs) complexes that catalyze H3K4me1 and H3K4me3. ChIP-seq analyses showed that the loss of PML1 reduces H3K4me3 in numerous loci, including BCSC-associated gene promoters. Additionally, PML1, not PML4, re-establishes the H3K4me3 mark on these promoters in PML-depleted cells. Significantly, PML1 is essential for recruiting WDR5, MLL1, and MLL2 to these gene promoters. Inactivating WDR5 by knockdown or inhibitors phenocopies the effects of PML1 loss, reducing BCSC-related gene expression and tumorsphere formation and enhancing fulvestrant’s anticancer activity. Our findings challenge the conventional understanding of PML as a tumor suppressor, redefine its role as a promoter of tumor growth in breast cancer, and offer new insights into the unique roles of PML isoforms in breast cancer.

A scoping review was performed of trauma-informed psychological interventions to treat anxiety, depression, and posttraumatic stress symptoms in youth in response to natural/biologic disasters. The specific aims were to identify psychosocial interventions used in response to natural/biologic disasters, report the interventions’ effectiveness, describe limitations, and provide treatment recommendations and future directions. Of the 45 studies extracted, 28 were on natural disasters and 17 on biologic disasters with the majority related to the COVID-19 pandemic. The most commonly implemented interventions were Cognitive Behavioral Therapy (CBT), Trauma-Focused Cognitive Behavioral Therapy (TF-CBT), and eye movement desensitization and reprocessing (EMDR). The UCLA Posttraumatic Stress Disorder Reaction Index (UCLA PTSD-RI) and the Strengths and Difficulties Questionnaire (SDQ) were the most frequently used measures. Methodological rigor was varied, with 60% randomized, controlled trials. Overall, there was a significant decrease in posttraumatic stress symptoms, distress, anxiety, and depression regardless of whether the participant received CBT, TF-CBT, or EMDR. Generally, there was not a significant decrease in anxiety and depression with yoga, cognitive fear-reduction, emotion-based drawing, and community health education. Recommendations for future directions include larger-scale studies with group and on-line interventions that include younger children with moderation analyses by gender and race/ethnicity.

Walnuts (Juglans regia L.) have shown promising effects in terms of ameliorating inflammatory bowel disease (IBD), attributed to their abundant bioactive compounds. This review comprehensively illustrates the key mechanisms underlying the therapeutic potential of walnuts in IBD management, including the modulation of intestinal mucosa permeability, the regulation of inflammatory pathways (such as NF-kB, COX/COX2, MAPCK/MAPK, and iNOS/NOS), relieving oxidative stress, and the modulation of gut microbiota. Furthermore, we highlight walnut-derived anti-inflammatory compounds, such as polyunsaturated fatty acids (PUFA; e.g., ω-3 PUFA), tocopherols, phytosterols, sphingolipids, phospholipids, phenolic compounds, flavonoids, and tannins. We also discuss unique anti-inflammatory compounds such as peptides and polysaccharides, including their extraction and preparation methods. Our review provides a theoretical foundation for dietary walnut supplementation in IBD management and provides guidance for academia and industry. In future, research should focus on the targeted isolation and purification of walnut-derived anti-inflammatory compounds or optimizing extraction methods to enhance their yields, thereby helping the food industry to develop dietary supplements or walnut-derived functional foods tailored for IBD patients.

This is the first study to use the Common-Sense Model of Self-Regulation theory for oral health interventions in pediatric practices. The objective of this qualitative study was to assess adoption and implementation of theory-based multilevel oral health interventions, by clinicians (pediatricians and nurse practitioners) participating in a cluster randomized clinical trial, to create an oral health toolkit for widespread dissemination into pediatric practices. Semistructured interviews were conducted at the conclusion of the cluster randomized clinical trial with 21 clinicians from 9 practices participating in the intervention arm. Clinicians in this arm received Common-Sense Model of Self-Regulation theory–based education and resources to deliver oral health interventions to parents/caregivers and document in electronic medical record. Semistructured interview questions were based on the Diffusion of Innovations Theory, assessing adoption and implementation. The interviews were coded using NVivo (QRS International) software. Main themes were identified using a thematic analysis approach. Five themes identified from the interviews included strengths of theory-based oral health training for clinicians, oral health resources to improve quality of care, considerations for efficient future implementation, financial considerations, and parent benefits and challenges. Clinicians found that the theory-based training and resources increased knowledge and confidence when addressing oral health with parents and required only ≤2 minutes in their workflow with no financial consequences. Clinicians reported an increase in oral health awareness among parents but suggested an overall need for more pediatric dentists. The Common-Sense Model of Self-Regulation theory–based education and resources were well received by clinicians and perceived to be beneficial without adverse impact on workflow or practice finances. An online toolkit is planned because these oral health interventions can be successfully implemented and delivered in medical settings.