tbuckley/cabot-search huggingface dataset:
Update on Recommendations for Cancer Screening and Surveillance in Children with Genomic Instability Disorders
Authors: Yoshiko Nakano, Roland P. Kuiper, Kim E. Nichols, Christopher C. Porter, Harry Lesmana, Julia Meade, Christian P. Kratz, Lucy A. Godley, Luke D. Maese, Maria Isabel Achatz, Payal P. Khincha, Sharon A. Savage, Andrea S. Doria, Mary-Louise C. Greer, Vivian Y. Chang, Lisa L. Wang, Sharon E. Plon, Michael F. Walsh
Journal: Clinical Cancer Research (2024)

Abstract Genomic instability disorders are characterized by DNA or chromosomal instability resulting in various clinical manifestations including developmental anomalies, immunodeficiency, and increased risk to develop cancers beginning in childhood. Many of these genomic instability disorders also present with exquisite sensitivity to anticancer treatments such as ionizing radiation and chemotherapy, which may further increase the risk of second cancers. In July 2023, the American Association of Cancer Research held the second Childhood Cancer Predisposition Workshop where multidisciplinary international experts discussed, reviewed, and updated recommendations for children with cancer predisposition syndromes. This article will discuss childhood cancer risks and surveillance recommendations for the group of genomic instability disorders with predominantly recessive inheritance, including the DNA repair disorders ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi anemia, Xeroderma Pigmentosum, Bloom syndrome, and Rothmund-Thomson syndrome, as well as the telomere biology disorders and mosaic variegated aneuploidy. Recognition of children with genomic instability disorders is important in order to make the proper diagnosis, enable genetic counseling, and inform cancer screening, cancer risk reduction, and choice of anti-cancer therapy.
Establishment of an <scp>ELISA</scp>‐based in vitro test system to quantify the major honey bee venom allergen Api m 10 in crude bee venoms and therapy allergen products
Authors: Alisa Landgraf, Sascha Hein, Kathrin Elisabeth Paulus‐Tremel, Michelle Beatrice Wolff, Meike Arend, Ann‐Christine Junker, Daniel Strecker, Sascha Döring, Elke Völker, Thomas Holzhauser, Sandra Schmidt, Susanne Kaul, Stefan Schülke, Vera Mahler
Journal: Allergy (2024)
Role of ACSL4 in modulating farnesoid X receptor expression and M2 macrophage polarization in HBV‐induced hepatocellular carcinoma
Authors: Wenbiao Chen, Huixuan Xu, Liliangzi Guo, Fengping Zheng, Jun Yao, Lisheng Wang
Journal: MedComm (2024)

Abstract The intricate relationship between bile acid (BA) metabolism, M2 macrophage polarization, and hepatitis B virus‐hepatocellular carcinoma (HBV‐HCC) necessitates a thorough investigation of ACSL4's (acyl‐CoA synthetase long‐chain family member 4) role. This study combines advanced bioinformatics and experimental methods to elucidate ACSL4's significance in HBV‐HCC development. Using bioinformatics, we identified differentially expressed genes in HBV‐HCC. STRING and gene set enrichment analysis analyses were employed to pinpoint critical genes and pathways. Immunoinfiltration analysis, along with in vitro and in vivo experiments, assessed M2 macrophage polarization and related factors. ACSL4 emerged as a pivotal gene influencing HBV‐HCC. In HBV‐HCC liver tissues, ACSL4 exhibited upregulation, along with increased levels of M2 macrophage markers and BA. Silencing ACSL4 led to heightened farnesoid X receptor (FXR) expression, reduced BA levels, and hindered M2 macrophage polarization, thereby improving HBV‐HCC conditions. This study underscores ACSL4's significant role in HBV‐HCC progression. ACSL4 modulates BA‐mediated M2 macrophage polarization and FXR expression, shedding light on potential therapeutic targets and novel insights into HBV‐HCC pathogenesis.
Interleukin‐12 sustained release system promotes hematopoietic recovery after radiation injury
Authors: Chuanchuan Lin, Yang Xiang, Yangyang Zhang, Zhenxing Yang, Nanxi Chen, Weiwei Zhang, Lanyue Hu, Jianxin Chen, Ya Luo, Xueying Wang, Yanni Xiao, Qing Zhang, Xi Ran, Li Chen, Jigang Dai, Zhongjun Li, Qian Ran
Journal: MedComm (2024)

Abstract The continuous production of mature blood cell lineages is maintained by hematopoietic stem cells but they are highly susceptible to damage by ionizing radiation (IR) that induces death. Thus, devising therapeutic strategies that can mitigate hematopoietic toxicity caused by IR would benefit acute radiation syndrome (ARS) victims and patients receiving radiotherapy. Herein, we describe the preparation of an injectable hydrogel formulation based on Arg‐Gly‐Asp‐alginate (RGD‐Alg) and Laponite using a simple mixing method that ensured a slow and sustained release of interleukin‐12 (IL‐12) (RGD‐Alg/Laponite@IL‐12). The local administration of RGD‐Alg/Laponite@IL‐12 increased survival rates and promoted the hematopoietic recovery of mice who had received sublethal‐dose irradiation. Local intra‐bone marrow (intra‐BM) injection of RGD‐Alg/Laponite@IL‐12 hydrogel effectively stimulated IL12 receptor‐phosphoinositide 3‐kinase/protein kinase B (IL‐12R‐PI3K/AKT) signaling axis, which promoted proliferation and hematopoietic growth factors secretion of BM mesenchymal stem/stromal cells. This signaling axis facilitates the repair of the hematopoietic microenvironment and plays a pivotal role in hematopoietic reconstitution. In conclusion, we describe a biomaterial‐sustained release of IL‐12 for the treatment of irradiated hematopoietic injury and provide a new therapeutic strategy for hematopoietic ARS.
O-GlcNAcylation regulation of RIPK1-dependent apoptosis dictates sensitivity to sunitinib in renal cell carcinoma
Authors: Xiangbo Zeng, Zhiliang Chen, Yuanchao Zhu, Lei Liu, Zhiyong Zhang, Yongyuan Xiao, Qiong Wang, Shiyu Pang, Fengjin Zhao, Bihong Xu, Mengxin Leng, Xiaocen Liu, Chenxi Hu, Siying Zeng, Fei Li, Wenlian Xie, Wanlong Tan, Zaosong Zheng
Journal: Drug Resistance Updates (2024)
Enhanced Nitric Oxide Delivery Through Self‐Assembling Nanoparticles for Eradicating Gram‐Negative Bacteria
Authors: Xiangfeng Lai, Lei Yu, Xiangyi Huang, Wil Gardner, Sarah E. Bamford, Paul J. Pigram, Shuhong Wang, Anton P. Le Brun, Benjamin W. Muir, Jiangning Song, Yajun Wang, Hsien‐Yi Hsu, Philip Wai Hong Chan, Hsin‐Hui Shen
Journal: Advanced Healthcare Materials (2024)

Abstract In the current battle against antibiotic resistance, the resilience of Gram‐negative bacteria against traditional antibiotics is due not only to their protective outer membranes but also to mechanisms like efflux pumps and enzymatic degradation of drugs, underscores the urgent need for innovative antimicrobial tactics. Herein, this study presents an innovative method involving the synthesis of three furoxan derivatives engineered to self‐assemble into nitric oxide (NO) donor nanoparticles (FuNPs). These FuNPs, notably supplied together with polymyxin B (PMB), achieve markedly enhanced bactericidal efficacy against a wide spectrum of bacterial phenotypes at considerably lower NO concentrations (0.1–2.8 µg mL −1 ), which is at least ten times lower than the reported data for NO donors (≥200 µg mL −1 ). The bactericidal mechanism is elucidated using confocal, scanning, and transmission electron microscopy techniques. Neutron reflectometry confirms that FuNPs initiate membrane disruption by specifically engaging with the polysaccharides on bacterial surfaces, causing structural perturbations. Subsequently, PMB binds to lipid A on the outer membrane, enhancing permeability and resulting in a synergistic bactericidal action with FuNPs. This pioneering strategy underscores the utility of self‐assembly in NO delivery as a groundbreaking paradigm to circumvent traditional antibiotic resistance barriers, marking a significant leap forward in the development of next‐generation antimicrobial agents.
Dye‐Based Fluorescent Organic Nanoparticles, New Promising Tools for Optogenetics
Authors: Jérémy Lesas, Thomas C.M. Bienvenu, Eleonore Kurek, Jean‐Baptiste Verlhac, Zoé Grivet, Maude Têtu, Delphine Girard, Frédéric Lanore, Mireille Blanchard‐Desce, Cyril Herry, Jonathan Daniel, Cyril Dejean
Journal: Advanced Healthcare Materials (2024)

Abstract Dye‐based fluorescent organic nanoparticles are a specific class of nanoparticles obtained by nanoprecipitation in water of pure dyes only. While the photophysical and colloidal properties of the nanoparticles strongly depend on the nature of the aggregated dyes, their excellent brightness in the visible and in the near infrared make these nanoparticles a unique and versatile platform for in vivo application. This article examines the promising utilization of these nanoparticles for in vivo optogenetics applications. Their photophysical properties as well as their biocompatibility and their capacity to activate Chrimson opsin in vivo through the fluorescence reabsorption process are demonstrated. Additionally, an illustrative example of employing these nanoparticles in fear reduction in mice through closed‐loop stimulation is presented. Through an optogenetic methodology, the nanoparticles demonstrate an ability to selectively manipulate neurons implicated in the fear response and diminish the latter. Dye‐based fluorescent organic nanoparticles represent a promising and innovative strategy for optogenetic applications, holding substantial potential in the domain of translational neuroscience. This work paves the way for novel therapeutic modalities for neurological and neuropsychiatric disorders.
An Environmentally Stable, Biocompatible, and Multilayered Wound Dressing Film with Reversible and Strong Adhesion
Authors: Baohong Chen, Bingzhi He, Alexander M. Tucker, Ian Biluck, Thomas H. Leung, Thomas P. Schaer, Shu Yang
Journal: Advanced Healthcare Materials (2024)

Abstract Reversible adhesives for wound care improve patient experiences by permitting reuse and minimizing further tissue injury. Existing reversible bandages are vulnerable to water and can undergo unwanted deformation during removal and readdressing procedures. Here, a biocompatible, multilayered, reversible wound dressing film that conforms to skin and is waterproof is designed. The inner layer is capable of instant adhesion to various substrates upon activation of the dynamic boronic ester bonds by water; intermediate hydrogel layer and outer silicone backing layer can enhance the dressing's elasticity and load distribution for adhesion, and the silicone outer layer protects the dressing from exposure to water. The adhesive layer is found to be biocompatible with mouse skin. Skin injuries on the mouse skin heal more rapidly with the film compared to no dressing controls. Evaluations of the film on skin of freshly euthanized minipigs corroborate the findings in the mouse model. The film remains attached to skins without delamination despite subjecting to various degrees of deformation. Exposure to water softens the film to allow removal from the skin without pulling any hair off. The multilayered design considers soft mechanics in each layer and will offer new insights to improve wound dressing performance and patient comfort.
Estimating GFR in Kidney Transplant Recipients: Considerations for Selecting Equations
Authors: Krishna A Agarwal, Ogechi M Adingwupu, Hocine Tighiouart, Shiyuan Miao, Marc Froissart, Michael Mauer, Wei Yang, Vicente Torres, Martin de Borst, Goran Klintmalm, Emilio D Poggio, Peter Rossing, Ruben Velez, Anders Grubb, Andrew D Rule, Kamran Shaffi, Ashtar Chami, Andrew S Levey, Lesley A Inker
Journal: Kidney International (2024)
A first-in-human phase 1 study of BXQ-350, a first-in-class sphingolipid metabolism regulator, in patients with advanced/recurrent solid tumors or high-grade gliomas
Authors: Olivier Rixe, John L. Villano, Robert Wesolowski, Anne M. Noonan, Vinay K. Puduvalli, Trisha M. Wise-Draper, Richard Curry, Emrullah Yilmaz, Charlie Cruze, Besim Ogretmen, Gilles Tapolsky, Ray Takigiku
Journal: Clinical Cancer Research (2024)

Abstract Purpose: BXQ-350, a nanovesicle formulation of saposin C, is an allosteric sphingolipid metabolism regulator that increases proapoptotic ceramide and decreases oncogenic sphingosine-1-phosphate levels. We conducted a first-in-human phase I study of BXQ-350. Patients and Methods: Adults (≥18 years old) with advanced/recurrent, treatment-refractory solid tumors or high-grade gliomas received BXQ-350 intravenously in five dose cohorts (0.7–2.4 mg/kg) in a 3+3 dose escalation and expansion design. The primary endpoints during dose escalation were dose-limiting toxicities and maximum tolerated dose; the primary objective in expansion parts was assessment of antitumor activity (RECIST v1.1/Response Assessment in Neuro-Oncology criteria). Results: Eighty-six patients were enrolled. Dose-limiting toxicities were not observed during dose escalation (n = 18), and a maximum tolerated dose was not identified. An additional 68 patients received the 2.4 mg/kg dose. Nine patients (10%) discontinued due to adverse events. The most common treatment-related adverse events were nausea (24%) and fatigue (23%). Eight patients had a progression-free survival of ≥6 months. Two of these achieved a partial response, and six had stable disease, among whom three had a reduction in ≥1 target lesion. Of those with progression-free survival of ≥6 months, seven remained on study for &amp;gt;12 months, five for &amp;gt;24 months, and after 7 years, two remained on study without disease progression. Conclusions: BXQ-350 was well-tolerated as monotherapy at doses up to 2.4 mg/kg. It provided some lasting clinical benefit in patients with recurrent solid malignancies across several tumor types, consistent with a decreased systemic sphingosine-1-phosphate/ceramide metabolic rheostat. BXQ-350 warrants further clinical investigation alone and combined with standard of care for advanced solid tumors.
TAK1 Promotes an Immunosuppressive Tumor Microenvironment through Cancer-Associated Fibroblast Phenotypic Conversion in Pancreatic Ductal Adenocarcinoma
Authors: Nan Sheng, Koji Shindo, Kenoki Ohuchida, Tomohiko Shinkawa, Bo Zhang, Haimin Feng, Takeo Yamamoto, Taiki Moriyama, Naoki Ikenaga, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura
Journal: Clinical Cancer Research (2024)

Abstract Purpose: We aim to clarify the precise function of Transformed growth factor-beta 1 activated kinase-1 (TAK1) in cancer-associated fibroblasts (CAFs) within human pancreatic ductal adenocarcinoma (PDAC) by investigating its role in cytokine-mediated signaling pathways. Experimental Design: The expression of TAK1 in pancreatic cancer was confirmed by TCGA data and human pancreatic cancer specimens. CAFs from freshly resected PDAC specimens were cultured and used in a three-dimensional model for direct and indirect co-culture with PDAC tumors to investigate TAK1 function. Additionally, organoids from KPC (LSL-K-RasLSLG12D/+; LSL-p53R172H/+; Pdx1-Cre) mice were mixed with CAFs and injected subcutaneously into C57BL/6 mice to explore in vivo functional interactions of TAK1. Results: TCGA data revealed significant upregulation of TAK1 in PDAC, associating with a positive correlation with the T-cell exhaustion signature. Knockdown of TAK1 in CAFs decreased the iCAF signature and increased the myCAF signature both in vitro and in vivo. The absence of TAK1 hindered CAF proliferation, blocked several inflammatory factors via multiple pathways associated with immunosuppression, and hindered EMT, outgrowth in vitro in spheroid co-cultures with PDAC cells. Additionally, TAK1 inhibitor restrained tumor growth, increased CD4+ and CD8+ T cell abundance, and reduced immunosuppressive cells present in vivo. Conclusions: Blocking the TAK1+CAF phenotype leads to the conversion of protumorigenic CAFs to antitumorigenic CAFs. This highlights TAK1 as a potential therapeutic target, particularly in CAFs, and represents a novel avenue for combined immunotherapy in PDAC.
The oral ferroportin inhibitor vamifeport prevents liver iron overload in a mouse model of hemochromatosis
Authors: Naja Nyffenegger, Anna Flace, Ahmet Varol, Patrick Altermatt, Cédric Doucerain, Hanna Sundstrom, Franz Dürrenberger, Vania Manolova
Journal: HemaSphere (2024)

Abstract Hemochromatosis is an inherited iron overload condition caused by mutations that reduce the levels of the iron‐regulatory hormone hepcidin or its binding to ferroportin. The hepcidin–ferroportin axis is pivotal to iron homeostasis, providing opportunities for therapeutic intervention in iron overload disorders like hemochromatosis. The aim of this study was to evaluate the efficacy of the oral ferroportin inhibitor vamifeport in the Hfe C282Y mouse model, which carries the most common mutation found in patients with hemochromatosis. A single oral dose of vamifeport lowered serum iron levels in Hfe C282Y mice, with delayed onset and shorter duration than observed in wild‐type mice. Vamifeport induced transient hypoferremia by inhibiting ferroportin and resulted in a feedback regulation of liver Hamp in wild‐type mice, which was absent in Hfe C282Y mice, reflecting the dysregulated systemic iron sensing in this hemochromatosis model. Chronic dosing with vamifeport led to sustained serum and liver iron reductions in Hfe C282Y mice, as well as markedly reducing liver Hamp expression in Hfe C282Y mice, suggesting distinct regulation of liver Hamp expression following acute or continuous iron restriction via vamifeport. At the tested dose, vamifeport retained its activity when combined with phlebotomy and did not significantly interfere with liver iron removal by phlebotomy in Hfe C282Y mice. These data demonstrate that chronic vamifeport treatment significantly reduces serum iron levels and prevents liver iron loading in the Hfe C282Y mouse model of hemochromatosis, thus providing preclinical proof of concept for the efficacy of vamifeport in hemochromatosis with or without phlebotomy.
The Epstein-Barr virus nuclear antigen 1 variant associated with nasopharyngeal carcinoma defines the sequence criteria for serologic risk prediction
Authors: Benjamin E. Warner, Japan Patel, Renwei Wang, Jennifer Adams-Haduch, Yu-Tang Gao, Woon-Puay Koh, Ka Wo Wong, Alan K.S. Chiang, Jian-Min Yuan, Kathy H. Y. Shair
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Antibodies to select Epstein–Barr virus proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against Epstein–Barr virus nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years before diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay. Experimental Design: Mammalian-expressed constructs were developed to represent EBNA1 variants 487V and 487A, which can differ by ≥15 amino acids in the N- and C-termini. Denatured lysates were evaluated by a refined IgA and IgG immunoblot assay in a case-control study using prediagnostic NPC sera from two independent cohorts in Singapore and Shanghai, the People’s Republic of China. Results: At 95% sensitivity, 487V yielded a 94.9% specificity compared with 86.1% for 487A. EBNA1 deleted for the conserved glycine–alanine repeats (GAr) reduced false positives by 22.8%. NPC sera reacted more strongly to the C-terminus than healthy controls, but the C-terminal construct (a.a. 390–641) showed lower specificity (84.8%) than the EBNA1 GAr–deleted construct (92.4%) at 95% sensitivity. Conclusions: Although EBNA1 IgA was present in healthy sera, most epitopes localized to the immunodominant GAr. We conclude that a refined EBNA1 antigen deleted for the GAr, but with residues consistently detected in Southeast Asian NPC tumors, is optimized for risk prediction with an extended sojourn time of 7.5 years. Furthermore, distinct EBNA1 serologic profiles enhanced the utility of the EBNA1 IgA assay for risk stratification. This illustrates the importance of serologically relevant EBNA1 sequences for NPC risk prediction and early detection.
Fecal microbiota transplantation derived from mild cognitive impairment individuals impairs cerebral glucose uptake and cognitive function in wild-type mice: <i>Bacteroidetes</i> and TXNIP-GLUT signaling pathway
Authors: Tao Wang, Ling Hao, Kexin Yang, Wenjing Feng, Zhiting Guo, Miao Liu, Rong Xiao
Journal: Gut Microbes (2024)

Gut microbiome dysbiosis has been widely implicated in cognitive impairment, but the identity of the specific bacterial taxa and mechanisms are not fully elucidated. Brain glucose hypometabolism coincides with the cognitive decline. This study explored the link among cognition, gut microbiota and glucose uptake based on the fecal microbiota transplantation from mild cognitive impairment individuals (MCI-FMT) and investigated whether similar mechanisms were involved in 27-hydroxycholesterol (27-OHC)-induced cognitive decline. Our results showed that the MCI-FMT mice exhibited learning and memory decline and morphological lesions in the brain and colon tissues. There were reduced
Localized light-triggered release macrophage cytopharmaceuticals containing O-nitrobenzyl group for enhanced solid tumor cell-chemotherapy
Authors: Jinhu Liu, Han Yang, Xiao Sang, Tong Gao, Zipeng Zhang, Shunli Fu, Huizhen Yang, Lili Chang, Xiaoqing Liu, Shuang Liang, Shijun Yuan, Suyun Wei, Yuxin Yang, Xiaoxin Yan, Xinke Zhang, Weiwei Mu, Yongjun Liu, Na Zhang
Journal: Acta Pharmaceutica Sinica B (2024)

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive
Enhancing intracellular cholesterol efflux in chondrocytes alleviates osteoarthritis progression
Authors: Gyuseok Lee, Jiye Yang, Su‐Jin Kim, Thanh‐Tam Tran, Sun Young Lee, Ka Hyon Park, Seung‐Hee Kwon, Ki‐Ho Chung, Jeong‐Tae Koh, Yun Hyun Huh, Jong‐Keun Seon, Hyun Ah Kim, Jang‐Soo Chun, Je‐Hwang Ryu
Journal: Arthritis & Rheumatology (2024)

Objectives Osteoarthritis (OA) is the most common degenerative disease worldwide with no practical means of prevention and limited treatment options. Recently, our group unveiled a novel mechanism contributing to OA pathogenesis in association with abnormal cholesterol metabolism in chondrocytes. In this study, we aimed to establish a clinical link between lipid profiles and OA in humans, assess the effectiveness of cholesterol‐lowering drugs in suppressing OA development in mice, and uncover the cholesterol‐lowering mechanisms that effectively impede OA progression. Methods Five clinically approved cholesterol‐lowering drugs (fenofibrate, atorvastatin, ezetimibe, niacin, and lomitapide) were injected into the knee joints or administered with diet to DMM‐induced OA mice fed a 2% high‐cholesterol diet. Gene expression linked to cholesterol metabolism were determined using microarray analysis. Furthermore, the in vivo functions of these genes were explored through intra‐articular injection of either its inhibitor or adenovirus. Results Logistic regression analysis confirmed a close relationship between the diagnostic criteria of hyperlipidemia based on serum lipid levels and OA incidence. Among the cholesterol‐lowering drugs examined, fenofibrate exerted the most significant protective effect against cartilage destruction, which was attributed to elevated levels of high‐density lipoprotein cholesterol that is crucial for cholesterol efflux. Notably, cholesterol efflux was suppressed during OA progression via downregulation of apolipoprotein A1 binding protein (AIBP) expression. Overexpression of AIBP effectively inhibits OA progression. Conclusions Our results suggest that restoration of cholesterol homeostasis to a normal state through administration of fenofibrate or AIBP overexpression, both of which induce cholesterol efflux, offers an effective therapeutic option for OA.