The Perelman School of Medicine, commonly known as Penn Med, is the medical school of the University of Pennsylvania. It is located in the University City section of Philadelphia. Founded in 1765, the Perelman School of Medicine is the oldest medical school in the United States and is one of the seven Ivy League medical schools. Penn Med is consistently one of the top recipients of NIH research awards and is currently ranked third for research among American medical schools by U.S. News & World Report.
p53-dependent apoptosis is a major determinant of its tumor suppressor activity and can be triggered by hypoxia. No p53 target is known to be induced by p53 or to mediate p53-dependent apoptosis during hypoxia. We report that p53 can directly upregulate expression of Bnip3L, a cell death inducer. During hypoxia, Bnip3L is highly induced in wild-type p53-expressing cells, in part due to increased recruitment of p53 and CBP to Bnip3L. Apoptosis is reduced in hypoxia-exposed cells with functional p53 following Bnip3L knockdown. In vivo, Bnip3L knockdown promotes tumorigenicity of wild-type versus mutant p53-expressing tumors. Thus, Bnip3L, capable of attenuating tumorigenicity, mediates p53-dependent apoptosis under hypoxia, which provides a novel understanding of p53 in tumor suppression.
Since 2021, the American Cancer Society has published its biennial report on the status of cancer disparities in the United States. In this 2025 report, the authors provide updated data on disparities in cancer occurrence and outcomes by sex, race, ethnicity, socioeconomic status (SES [educational attainment as a proxy]), and geographic location (including urbanicity of county of residence and congressional district), along with contributors to these disparities, including major cancer risk factors, screening, and select social determinants of health (SDOH) and health‐related social needs. The authors found substantial disparities across the cancer continuum, including risk factors, incidence, stage at diagnosis, receipt of care, survival, and mortality for many cancers and in evaluated SDOH by race and ethnicity, educational attainment, and geographic location. During 2019 through 2023, Black and American Indian/Alaska Native populations had the highest cancer mortality rates, both overall and for the leading causes of cancer death. Cancer mortality rates were also consistently higher among adults with lower SES. However, differences in cancer mortality were substantially larger by education than by race, indicating that SES plays a major role in driving racial disparities in cancer mortality. Overall cancer mortality rates were higher in Black adults than in White adults with the same education level by 7%–28% among males and by 2%–43% among females. Within each race, however, overall cancer mortality rates were higher in adults with ≤12 years of education than in those with ≥16 years of education by 143%–192% among males and by 71%–140% among females. Mortality from all cancers combined was 21% higher in nonmetropolitan than in large metropolitan counties, with the greatest differences for lung (45%) and cervical (36%) cancers and the smallest for prostate, female breast, and pancreatic cancers (7%–8%). By congressional district, the highest cancer mortality rates both overall and for lung, colorectal, and breast cancers were largely found in the South and East North‐Central division of the Midwest; however, for prostate cancer, there was no distinct geographic pattern. Sociodemographic groups that had higher cancer mortality generally had higher exposure to risk factors, lower health insurance coverage, and limited access to cancer prevention, early detection, and treatment compared with groups that had lower cancer mortality, largely reflecting fundamental disparities in SDOH. Mitigating cancer disparities in the United States requires intersectoral stakeholder engagement, targeted funding, effective policies at the federal, state, and local levels, and broad implementation of evidence‐based interventions, such as expanding health insurance coverage, including through strengthening Marketplaces and protecting and expanding access to Medicaid.
Human genetic studies have repeatedly associated ADAMTS7 with atherosclerotic cardiovascular disease. Subsequent investigations in mice demonstrated that ADAMTS7 is proatherogenic and induced in response to vascular injury. However, the cell-specific mechanisms governing ADAMTS7 proatherogenicity remain unclear. To determine which vascular cell types express ADAMTS7, we interrogated single-cell RNA-seq of human carotid atherosclerosis and found ADAMTS7 expression in smooth muscle cells (SMCs), endothelial cells (ECs), and fibroblasts. We subsequently created SMC- and EC-specific Adamts7 conditional KO and transgenic mice. Conditional KO of Adamts7 in either cell type did not reduce atherosclerosis, whereas transgenic induction in either cell type increased atherosclerosis. In SMC transgenic mice, this increase coincides with an expansion of lipid-laden SMC foam cells and a decrease in fibrous cap formation. RNA-seq of Adamts7-overexpressing SMCs revealed an upregulation of lipid genes typically assigned to macrophages. Mechanistically, ADAMTS7 increases SMC oxidized LDL uptake through CD36, whose expression is upregulated by PU.1. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) and motif analysis revealed increased chromatin accessibility at AP-1-enriched regions, consistent with AP-1-dependent remodeling of PU.1-regulated lipid-handling loci. In summary, ADAMTS7 promotes atherosclerosis by driving SMC foam cell formation through an AP-1/PU.1/CD36 regulatory axis.
Biofluid proteomics can enhance our understanding of the neurodegenerative mechanisms underlying Alzheimer’s disease and related dementias (ADRDs). Oligodendrocyte myelin glycoprotein (OMG) is a brain-specific protein implicated in myelination, but its potential mechanistic, biomarker, and therapeutic roles in ADRDs requires further elucidation. After detecting an inverse association between its abundance in peripheral circulation and cortical amyloid deposition in two community-based cohorts, the current study characterized OMG’s role in ADRDs with high-throughput proteomics from sixteen independent cohorts. Data included a variety of cross-sectional and longitudinal community-based and clinical cohorts from North America, Europe, and Asia, and incorporated complementary biofluids, biospecimens, and proteomic platforms. Statistical analyses were conducted separately in each cohort. We detected lower plasma OMG in individuals with cortical amyloid deposition, compromised brain structure, dementia, and multiple sclerosis, as well as in individuals who developed dementia over 7- to 20-year follow-up periods. OMG’s CSF and brain proteomic signatures reflected broader neuroprotective mechanisms, especially axonal structural integrity, and two-sample Mendelian randomization causally implicated OMG as protective against multiple neurodegenerative diseases. Our findings implicate OMG as a mechanistic determinant of neurodegenerative resiliency among older adults, which is reliably captured by its abundance in peripheral circulation
This cross-sectional study assessed patterns in gestational diabetes rates across 6 primary racial and ethnic groups as well as individual Asian and Hispanic ethnicities in the US from 2016 to 2024.
