tbuckley/cabot-search huggingface dataset:
<i>Rpl13a</i> snoRNAs <i>U34</i> and <i>U35a</i> : New Targets for Sickle Cell Disease Complications
Authors: Waseem Chauhan, Sudharshan Setra Janardhana Shetty, Shirin Ferdowsi, Sweta Kafle, Rahima Zennadi
Journal: Circulation Research (2025)

BACKGROUND: In sickle cell disease (SCD), erythrocyte reactive oxygen species (ROS) production and oxidative stress play a critical role in vaso-occlusion, a hallmark of SCD. Small noncoding nucleolar RNAs (snoRNAs) of the Rpl13a locus have been described as regulators of ROS levels. However, whether Rpl13a snoRNAs are present in sickle red blood cells (RBCs) and regulate ROS levels and whether they contribute to SCD pathophysiology remain unknown. METHODS: To determine whether sickle RBC ROS levels are associated with Rpl13a snoRNA levels and identify the mechanism by which they regulate ROS and snoRNAs’ effects on SCD hemodynamics, we used human RBCs, Rpl13a snoRNA knockout sickle mice, K562 U32a , U33 , U34 , U35a , and the control U25 knockout mutants generated by CRISPR-Cas9–targeted genome editing, and genetic targeting with antisense oligonucleotides. RESULTS: Excessive ROS production in sickle RBCs of patients with SCD is associated with high Rpl13a snoRNAs U32a , U33 , U34 , and U35a levels. U32a , U34 , and U35a regulate ROS and hydrogen peroxide levels in sickle erythroid populations by modulating peroxidase activity. This was due to U32a - and U34 -guided 2’-O-methylation on Prdx2 (peroxiredoxin 2) messenger RNA, a modification conveyed by fibrillarin during erythropoiesis, subsequently reducing Prdx2 expression and activity. The snoRNA U35a impaired Prdx2 expression/activity but independently of Prdx2 messenger RNA 2’-O-methylation. Excess sickle RBC ROS increased in turn Rpl13a snoRNAs levels. In vivo targeting combinations of U34 + U35a and U32a + U34 + U35a in sickle mice with antisense oligonucleotide blunted RBC ROS generation, improved erythropoiesis and anemia, alleviated leukocytosis and endothelial damage, diminished cell adhesion in inflamed vessels and vaso-occlusion, restored blood flow, and reduced animal mortality. CONCLUSIONS: Rpl13a snoRNAs U34 and U35a specifically increase ROS levels, which, in turn, regulate snoRNA expression, in sickle erythroid cells, modulating Prdx2 expression/activity, subsequently impairing hemodynamics. Targeted U34+ U35a with antisense oligonucleotide may represent a novel and safe therapy to ameliorate erythropoiesis and downstream events in SCD.
SM22α-Lineage Perivascular Stromal Cells Contribute to Abdominal Aortic Aneurysm
Authors: Xiaoxi Pan, Run Zhang, Bingling Lu, Siyuan Chen, Hongjin Chen, Mengyao Li, Le Qin, Zhiyun Song, Yi Yang, Zhe Wang, Fuhua Yan, Aijun Sun, Fang Wu, Lichi Zhang, Jiguang Wang, Tomasz J. Guzik, Pingjin Gao
Journal: Circulation Research (2025)

BACKGROUND: Perivascular adipose tissue (PVAT) is a key regulator of vascular dysfunction. Impairment of PVAT phenotypic plasticity with aging may play a role in vascular pathology including abdominal aortic aneurysms (AAAs). Yet, the mechanisms underlying PVAT plasticity in aneurysm pathogenesis remain elusive. METHODS: Single-cell RNA sequencing was performed on perivascular stromal cells from young (2- to 3-month-old) and aged (18- to 20-month-old) mice. The expression of PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α) was measured in PVAT of aged mice and human aneurysm samples. Loss- and gain-of-function approaches were used to investigate the role of SM22α-lineage perivascular stromal cell–derived PGC-1α in aneurysm development. Molecular mechanisms were explored through transcriptome and functional studies in young and aged mice, SM22α Cre ; Rosa26 RFP/+ ; PGC1α f/f and SM22α Cre ; Rosa26 RFP/+ mice with Ang II (angiotensin II)–induced and deoxycorticosterone acetate/salt-induced AAA models. RESULTS: SM22α + cells accumulated in PVAT of Ang II–treated aged mice and patients with aortic aneurysms. Single-cell RNA sequencing analysis revealed that aging disrupted the differentiation potential of SM22α-lineage perivascular stromal cells and led to reduced PGC-1α levels. PGC1α downregulation in PVAT was observed in both mouse AAA models and human aneurysm lesions. In mice with SM22α-driven PGC-1α deletion, Ang II–induced AAA formation was accompanied by perivascular stromal cell-to-myofibroblast differentiation. In vitro PGC1α knockdown suppressed nuclear YAP (Yes-associated protein) signaling, reducing adipocyte differentiation, while increasing MMP2 (matrix metalloproteinase 2)-secreting myofibroblasts. Furthermore, PGC-1α overexpression in aged mice or administration of the YAP signaling inhibitor verteporfin in SM22α Cre ; Rosa26 RFP/+ ; PGC1α f/f mice restored PVAT function and conferred protection against aneurysm formation. Last, we used the radiomics analysis to noninvasively evaluate PVAT in the context of AAA severity in humans. CONCLUSIONS: PGC-1α deficiency in SM22α-lineage stromal cells disrupts the balance between adipogenic and myofibrogenic differentiation through regulating YAP signaling, ultimately promoting aneurysm development. Radiomics assessment may present a promising noninvasive approach for PVAT evaluation in aneurysms, offering valuable potential for clinical research.
Palliative and End-of-Life Care During Critical Cardiovascular Illness: A Scientific Statement From the American Heart Association
Authors: Erin A. Bohula, Michael J. Landzberg, Venu Menon, Carlos L. Alviar, Gregory W. Barsness, Daniela R. Crousillat, Nelia Jain, Robert Page, Rachel Wells, Abdulla A. Damluji
Journal: Circulation (2025)

Cardiac intensive care units are witnessing a demographic shift, characterized by patients with increasingly complex or end-stage cardiovascular disease with a greater burden of concomitant comorbid noncardiovascular disease. Despite technical advances in care that may be offered, many critically ill cardiovascular patients will nevertheless experience significant morbidity and mortality during the acute decompensation, including physical and psychological suffering. Palliative care, with its specialized focus on alleviating suffering, aligns treatments with patient and caregiver values and improves overall care planning. Integrating palliative care into cardiovascular disease management extends the therapeutic approach beyond life-sustaining measures to encompass life-enhancing goals, addressing the physical, emotional, psychosocial, and spiritual needs of critically ill patients. This American Heart Association scientific statement aims to explore the definitions and conceptual framework of palliative care and to suggest strategies to integrate palliative care principles into the management of patients with critical cardiovascular illness.
Zn‐Based Multi‐Active Framework Nanoparticles TSA‐CAN‐Zn Inhibit Skin Glycation via Dual Blockade of HMGB1/RAGE and AGEs/RAGE Pathways
Authors: Cheng Yao, Heqi Wang, Jingxia Han, Kai Yang, Tingting Lin, Jing Jin, Caibin Zhu, Huijuan Liu
Journal: Advanced Healthcare Materials (2025)

Abstract Receptor for advanced glycation end products (RAGE) plays an important role in skin glycation damage. High‐mobility group 1B protein (HMGB1) and advanced glycation end products (AGEs) are key RAGE ligands. Simultaneous inhibition of HMGB1/RAGE and AGEs/RAGE pathways maybe an effective strategy to alleviate glycation induced skin damage. In this work, Theasinensin A (TSA) is identified as the active molecule inhibiting HMGB1‐RAGE interaction through molecular docking. To simultaneously suppress HMGB1/RAGE and AGEs/RAGE pathways, Zn‐based multi‐active framework nanoparticles TSA‐CAN‐Zn are designed, which contain TSA and the active molecule L‐carnosine (CAN) that inhibits AGEs production. In vitro studies demonstrated that TSA‐CAN‐Zn have radical scavenging activity and AGEs formation inhibition activity. TSA‐CAN‐Zn can not only inhibit ROS accumulation, cell apoptosis, and inflammatory factors production induced by glycation in HaCaT cells but also enhanced the lysosomal degradation of AGEs. TSA‐CAN‐Zn also mitigated the damage caused by glycation in mouse skin glycation model. Single‐cell RNA sequencing results revealed the impact of TSA‐CAN‐Zn on different cell types of skin tissue, especially the basal cells of the epidermal layer and inflammation‐related macrophages. And pathway analysis revealed that TSA‐CAN‐Zn mainly influences the downstream pathways of RAGE. Collectively, TSA‐CAN‐Zn is a promising therapeutic candidate for ameliorating glycation‐induced skin damage.
Microneedle‐Enabled Breakthroughs in Nucleic Acid Therapeutics
Authors: Pengfei Wu, Tian Zhang, Deyao Zhao, Yingqiu Xie, Dong Huang, Zhihong Li, Yuanyu Huang
Journal: Advanced Healthcare Materials (2025)

Abstract Nucleic acid therapy demonstrates great potential in cancer treatment, infectious disease prevention, and vaccine development due to its advantages, such as rapid production, long‐lasting effects, and high target specificity. Although nucleic acid therapy is considered ideal for the development of novel therapeutic strategies, its clinical application still faces numerous challenges, including the lack of efficient delivery systems, insufficient drug formulation stability, and the limitations imposed by the skin barrier on drug dosage delivery. Microneedles, as an innovative transdermal drug delivery technology, can penetrate the stratum corneum and directly access the skin's microcirculation, enabling the efficient delivery of genes and drugs. This technology offers several advantages, such as ease of operation, minimally invasive and painless application, and high safety. Combining microneedle technology with nucleic acid therapy fully leverages the strengths of both approaches, significantly enhancing therapeutic efficacy and bioavailability while maximizing treatment potential. This review explores the application prospects and advantages of combining microneedle delivery systems with nucleic acid therapy.
Editor’s Note: Blockade of Deubiquitylating Enzyme USP1 Inhibits DNA Repair and Triggers Apoptosis in Multiple Myeloma Cells
Authors: Deepika Sharma Das, Abhishek Das, Arghya Ray, Yan Song, Mehmet Kemal Samur, Nikhil C. Munshi, Dharminder Chauhan, Kenneth C. Anderson
Journal: Clinical Cancer Research (2025)
Retraction: Prostaglandin E2 Enhances Pancreatic Cancer Invasiveness through an Ets-1-Dependent Induction of Matrix Metalloproteinase-2
Authors: Hiromichi Ito, Mark Duxbury, Eric Benoit, Thomas E. Clancy, Michael J. Zinner, Stanley W. Ashley, Edward E. Whang
Journal: Cancer Research (2025)
Targeting the Enhanced Sensitivity of Radiotherapy in Cancer: Mechanisms, Applications, and Challenges
Authors: Yuanyuan Zhao, Fangqin Tan, Jiajia Zhao, Shuchang Zhou, Yao Luo, Chen Gong
Journal: MedComm (2025)

Cancer is a major public health, societal, and economic challenge worldwide. According to Global Cancer Statistics 2022, it is estimated that by 2050, there will be 35 million new cancer cases globally. Although patient survival rates have improved through various therapeutic approaches, including surgery, chemotherapy, and radiotherapy, treatment efficacy remains limited once tumor metastasis occurs. Among various cancer treatment strategies, radiotherapy plays a crucial role. Along with surgery and chemotherapy, radiotherapy is a cost-effective single-modality treatment, accounting for approximately 5% of total cancer care costs. The use of radiosensitizing agents such as histone deacetylase inhibitors, 2-deoxy-d-glucose, enterolactone, and squalene epoxidase can enhance radiotherapy effectiveness. Recent radiosensitization methods involve physical stimuli and chemical radiosensitizers. However, improving their efficacy, durability, and overcoming radioresistance remain significant challenges. This review first introduces current applications of radiotherapy in cancer treatment, the molecular mechanisms underlying its anticancer effects, and its side effects. Second, it discusses the main types of radiosensitizers, their latest applications, and recent challenges in cancer treatment. Finally, it emphasizes on clinical trials of radiosensitizing agents and explores potential biomarkers for radiotherapy response in cancer. Multifunctional nanoparticles have shown greater clinical applicability than single-functional nanoparticles. Future research will focus on enhancing the drug-carrying capacity of nanomaterials to further improve radiotherapy outcomes.
PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C‐Myc Feedback Loop
Authors: Fan Yang, Ping Song, Zhaofeng Xiao, Renyi Su, Xin Fang, Yichao Wu, Xiao Xu, Kai Wang
Journal: MedComm (2025)

The oncogenic role and underlying mechanism of PRMT5 in pancreatic ductal adenocarcinoma (PAAD) remained to be elucidated. In this study, we aimed to investigate the oncogenic role, underlying molecular mechanisms, and potential therapeutic value of PRMT5 in PAAD. PRMT5 was significantly upregulated in pancreatic cancer than adjacent nontumor pancreas, which was positively correlated with poor prognosis. Genetic and pharmacological inhibition of PRMT5 suppressed PAAD proliferation in vitro and in vivo, exhibiting promising therapeutic effect in vivo. Mechanistically, PRMT5 directly bound to the promoter region of c-Myc and activated its transcription. Transcriptionally activated c-Myc in turn inhibited proteasome-mediated degradation of PRMT5 and enhanced its protein stability, resulting in increased PRMT5 expression. The maintained PRMT5 further enhanced the transcription of c-Myc. In conclusion, PRMT5 forms a positive feedback loop with c-Myc to promote the proliferation of pancreatic cancer. Targeting this oncogenic communication may represent a novel and potential therapeutic approach for pancreatic cancer.
Minimal Residual Disease Detection: Implications for Clinical Diagnosis and Cancer Patient Treatment
Authors: Meiling Song, Wenjing Pan, Xinjie Yu, Jie Ren, Congli Tang, Zhu Chen, Zhe Wang, Yan Deng, Nongyue He, Hongna Liu, Song Li
Journal: MedComm (2025)

Minimal residual disease (MRD) serves as a pivotal biomarker for the clinical diagnosis and subsequent treatment of cancer patients. In hematological malignancies, MRD pose an increasingly serious threat to the health of Chinese people. Accurate MRD detection is essential for assessing relapse risk and optimizing therapeutic strategies, yet current methods such as flow cytometry, polymerase chain reaction (PCR), and next-generation sequencing (NGS) each have distinct limitations, and significant gaps remain in achieving optimal sensitivity and specificity of these technologies. This review provides a comprehensive analysis of MRD detection methods, high-lighting their clinical implications, including their roles in treatment decision-making, risk stratification, and patient outcomes. It discusses the strengths and weaknesses of existing techniques and explores emerging technologies that promise enhanced diagnostic precision. Key advancements such as integrating NGS with other methodologies and novel approaches like liquid biopsy and PCR are examined. The review underscores the academic and practical value of early and accurate MRD detection, emphasizing its impact on improving patient management and treatment outcomes. By addressing the limitations of current technologies and exploring future directions, this review aims to advance the field and support personalized medicine approaches to cancer treatment.
Combining STING Agonists with PARP Inhibitors Mounts an NK-Dependent Defense against Therapy-Resistant Breast Cancer
Authors: Zahra Gohari, Lora Stojanovic, Feyruz V. Rassool
Journal: Cancer Research (2025)

Breast cancers with BRCA1 or BRCA2 mutations are defective in repair of DNA double-strand breaks by homologous recombination, resulting in compensatory error-prone repair that causes genomic instability. Poly(ADP-ribose) polymerase inhibitors (PARPi) are FDA-approved to treat homologous recombination–defective cancers, inducing therapy responses by synthetic lethality. PARPis increase micronuclei formation and cytosolic double-stranded DNA accumulation, activating stimulator of interferon genes (STING). Activation of STING can mediate anticancer innate immune responses by increasing T-cell infiltration into the tumor microenvironment. However, PARPi responses are not durable, and therapy resistance ensues with limited therapeutic options available for these patients. Using PARPi-sensitive and -resistant patient-derived xenografts and mouse-derived allografts, Pedretti and colleagues show in this issue of Cancer Research that the PARPi olaparib in combination with the next-generation STING agonist diABZI can overcome PARPi resistance in a manner dependent on NK cell function in the tumor microenvironment. Their study highlights a novel component of the STING-dependent innate immune response repertoire required for fighting PARPi-resistant cancer. Potent and specific next-generation STING agonists are being tested in the clinic in solid and liquid tumors, indicating a resurgence of these drugs after a long period of modest clinical activity, with a special focus on combination therapy strategies to fight therapy-resistant cancer. See related article by Pedretti et al., p. 1888
Editor’s Note: A Novel Role for Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6 as a Determinant of Gemcitabine Chemoresistance in Pancreatic Adenocarcinoma Cells
Authors: Mark S. Duxbury, Hiromichi Ito, Eric Benoit, Talat Waseem, Stanley W. Ashley, Edward E. Whang
Journal: Cancer Research (2025)
FADD Functions as an Oncogene in Chr11q13.3-Amplified Head and Neck Squamous Cell Carcinoma
Authors: Yang Zheng, Yinan Chen, Xiaoyan Meng, Li Zhang, Yanni Ma, Rong Zhou, Shuiting Fu, Heng Chen, Xinyang Xuanyuan, Ruixin Jiang, Pengcong Hou, Xiaomeng Song, Yanqiu Wang, Jingjing Sun, Wuchang Zhang, Jiang Li, Zhonglong Liu, Zhiyuan Zhang, Hanlin Zeng, Yue He
Journal: Cancer Research (2025)

Abstract Chromosomal 11q13.3 amplification is the most common gene copy-number variation event in head and neck squamous cell carcinoma (HNSCC) that corresponds with poor prognosis. Although cyclin D1, a G1/S phase cell-cycle regulatory protein at this locus, is considered as a key driver of malignant progression, further exploration is needed to develop more effective targets for cases with this amplification. Using CRISPR-based gene knockout screening of genes located in chr11q13.3, we found that loss of the gene encoding the Fas-associated death domain (FADD) protein, a well-recognized adapter to caspase-8 that induces cell apoptosis, significantly reduced cancer cell proliferation. FADD expression was elevated in chr11q13.3-amplified tumors and correlated with poor prognosis. RNA sequencing, mass spectrometry, and proteomics analyses revealed a direct relationship between FADD and the DNA helicase MCM5 in the S phase. FADD and cyclin D1 acted at different stages of the cell cycle to synergistically induce proliferation, and caspase-8 deficiency was required for the oncogenic activity of FADD. In a patient-derived xenograft model with chr11q13.3 amplification, combined administration of the DNA helicase complex inhibitor and CDK4/6 inhibitor effectively curtailed tumor growth. Overall, this study identified a nonclassic oncogenic role for FADD in mediating tumor progression in HNSCC and provided a feasible treatment option for patients with chr11q13.3 amplification. Significance: FADD promotes progression of tumors with chr11q13.3 amplification by binding to the DNA helicase complex, which can be targeted in combination with cyclin D1 as a viable therapeutic strategy for HNSCC patients.
Editor’s Note: RNA Interference Demonstrates a Novel Role for Integrin-Linked Kinase as a Determinant of Pancreatic Adenocarcinoma Cell Gemcitabine Chemoresistance
Authors: Mark S. Duxbury, Hiromichi Ito, Eric Benoit, Talat Waseem, Stanley W. Ashley, Edward E. Whang
Journal: Clinical Cancer Research (2025)
Advancing Policy and Practice in Alcohol-Associated Liver Disease and Alcohol-Attributable Cancer: Correspondence to the editorial on “Rising Burden of Alcohol-Associated Liver Disease and Cancers: Insights into Sex Disparities and Policy Implications”
Authors: Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Amit G Singal, Ju Dong Yang
Journal: Clinical and Molecular Hepatology (2025)
Dissecting small cell carcinoma of the esophagus ecosystem by single-cell transcriptomic analysis
Authors: Hao-Xiang Wu, Yu-Kun Chen, Ying-Nan Wang, Jia-Ying Chen, Shu-Jing Xiang, Ying Jin, Zi-Xian Wang, Chun-Yu Huang, Lu-Ping Yang, Ye He, Wen-Long Guan, Long Bai, Yan-Xing Chen, Min Wang, Chao-Ye Wang, Run-Jie Huang, Yue Huang, Jin-Ling Zhang, Zhi-Da Lv, Si-Qi Yang, Rui-Hua Xu, Qi Zhao, Feng Wang
Journal: Molecular Cancer (2025)
Repurposing glucose-lowering drugs for cancer therapy
Authors: Michaela Luconi, Giulia Cantini, Clara Crescioli
Journal: Trends in cancer (2025)

The acknowledged relationship between metabolism and cancer retains important potential as a novel target in therapy. Reallocating glucose-lowering drugs (GLDs) in cancer treatment offers valuable perspectives for the ability of these molecules to regulate metabolism at cellular and systemic level. This comprehensive review addresses the therapeutic potential of the main antidiabetic classes of glucose-lowering drugs with emerging anticancer effects, such as metformin, rosiglitazone, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium/glucose cotransporter-2 inhibitors. The multifaceted actions of these drugs are explored, from in vitro evidence to clinical evidence as monotherapy or as a sparing agent with chemotherapy and immunotherapy. For each molecule, unconventional mechanisms, benefits, and limitations are dissected and possible concerns addressed, supporting evidence for the potential use of the drug in cancer.