tbuckley/cabot-search huggingface dataset:
Age differentially impacts adaptive immune responses induced by adenoviral versus mRNA vaccines against COVID-19
Authors: Beatrice Dallan, Davide Proietto, Martina De Laurentis, Eleonora Gallerani, Mara Martino, Sara Ghisellini, Amedeo Zurlo, Stefano Volpato, Benedetta Govoni, Michela Borghesi, Valentina Albanese, Victor Appay, Stefano Bonnini, Sian Llewellyn-Lacey, Salvatore Pacifico, Laura Grumiro, Martina Brandolini, Simona Semprini, Vittorio Sambri, Kristin Ladell, Helen M. Parry, Paul A. H. Moss, David A. Price, Elena Barbieri, Tatiana Bernardi, Michela Boni, Linda Dall’Olio, Martina De Laurentis, Caterina Fiorini, Michele Fiorini, Maurizio Govoni, Margherita Neri, Fabio Palma, Franco Romagnoni, Antonella Caputo, Riccardo Gavioli, Francesco Nicoli
Journal: Nature Aging (2024)
A feedback loop driven by H3K9 lactylation and HDAC2 in endothelial cells regulates VEGF-induced angiogenesis
Authors: Wei Fan, Shuhao Zeng, Xiaotang Wang, Guoqing Wang, Dan Liao, Ruonan Li, Siyuan He, Wanqian Li, Jiaxing Huang, Xingran Li, Jiangyi Liu, Na Li, Shengping Hou
Journal: Genome biology (2024)

Vascular endothelial growth factor (VEGF) is one of the most powerful proangiogenic factors and plays an important role in multiple diseases. Increased glycolytic rates and lactate accumulation are associated with pathological angiogenesis.
An Injectable Hydrogel Composing Anti‐Inflammatory and Osteogenic Therapy toward Bone Erosions Microenvironment Remodeling in Rheumatoid Arthritis
Authors: Xingzhu Liu, Qin Zhang, Yi Cao, Zahid Hussain, Mingsheng Xu, Yuanshan Liu, Ismat Ullah, Zhongzhong Lu, Akiyoshi Osaka, Jun Lin, Renjun Pei
Journal: Advanced Healthcare Materials (2024)

Healing bone erosions in rheumatoid arthritis (RA) remains greatly challenging via biomaterial strategies. Given the unsuccessful innate bone erosion healing due to an inflammatory disorder, over-activated osteoclasts, and impaired osteoblasts differentiation, RA pathogenesis-guided engineering of an innovative hydrogel platform is needed for remodeling osteoimmune and osteogenic microenvironment of bone erosion healing. Herein, in situ adaptable and injectable interpenetrating polymer network (IPN) hydrogel is developed through an ingenious combination of a bio-orthogonal reaction between hyaluronic acid (HA) and collagen, along with effective electrostatic interactions leveraging bisphosphonate (BP)-functionalized HA macromers (HABP) and nanorod shaped zinc (Zn)-doped biphasic calcium phosphate (ZnBCP). IPN hydrogel exhibits exceptional adaptability to the local shape complexity at bone erosions, and by integrating ZnBCP and HABP, a multi-stage releasing platform is engineered, facilitating controlled cargo delivery for remodeling more anti-inflammatory M2 cells and reducing over-activated osteoclastic activities, thereby reconstructing the bone regeneration microenvironment. Sustainedly co-delivering multiple ions (calcium and phosphate) can display excellent osteogenic properties and be conducive to the bone formation process, by effects of osteogenesis-associated cell differentiation. Overall, the introduced bioactive IPN hydrogel therapy remodels the osteoimmune environment by synergistic pro-inflammation-resolving, osteogenesis, and anti-osteoclastic activities, displaying excellent bone reconstruction in the collagen-induced arthritis rabbit model.
Metabolic blood profile and response to treatment with the pyruvate kinase activator mitapivat in patients with sickle cell disease
Authors: Myrthe J. van Dijk, Titine J. J. Ruiter, Sigrid van der Veen, Minke A. E. Rab, Brigitte A. van Oirschot, Jennifer Bos, Cleo Derichs, Anita W. Rijneveld, Marjon H. Cnossen, Erfan Nur, Bart J. Biemond, Marije Bartels, Roger E. G. Schutgens, Wouter W. van Solinge, Judith J. M. Jans, Eduard J. van Beers, Richard van Wijk
Journal: HemaSphere (2024)

Abstract Mitapivat is an investigational, oral, small‐molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red blood cell (RBC) with sufficient amounts of adenosine triphosphate (ATP). In sickle cell disease (SCD), decreased 2,3‐DPG levels increase the oxygen affinity of hemoglobin, thereby preventing deoxygenation and polymerization of sickle hemoglobin. The PK activator mitapivat has been shown to decrease levels of 2,3‐DPG and increase levels of ATP in RBCs in patients with SCD. In this phase 2, investigator‐initiated, open‐label study ( https://www.clinicaltrialsregister.eu/ NL8517; EudraCT 2019‐003438‐18), untargeted metabolomics was used to explore the overall metabolic effects of 8‐week treatment with mitapivat in the dose‐finding period. In total, 1773 unique metabolites were identified in dried blood spots of whole blood from ten patients with SCD and 42 healthy controls (HCs). The metabolic phenotype of patients with SCD revealed alterations in 139/1773 (7.8%) metabolites at baseline when compared to HCs (false discovery rate‐adjusted p &lt; 0.05), including increases of (derivatives of) polyamines, purines, and acyl carnitines. Eight‐week treatment with mitapivat in nine patients with SCD altered 85/1773 (4.8%) of the total metabolites and 18/139 (12.9%) of the previously identified altered metabolites in SCD (unadjusted p &lt; 0.05). Effects were observed on a broad spectrum of metabolites and were not limited to glycolytic intermediates. Our results show the relevance of metabolic profiling in SCD, not only to unravel potential pathophysiological pathways and biomarkers in multisystem diseases but also to determine the effect of treatment.
Phospholipids with two polyunsaturated fatty acyl tails: an important driver of ferroptosis
Authors: Chu Lu, Xiaoxue Zhou, Long Zhang
Journal: MedComm (2024)

We highlight the latest work of Qiu et al. on the core mechanism of ferroptosis induced by rare phospholipids with two polyunsaturated fatty acyl tails (PL-PUFA2s), which has been published in Cell. It has long been acknowledged that PLs containing one PUFA tail (PL-PUFA1s) serve as substrates for phospholipid peroxidation during the process of ferroptosis, owing to their susceptibility to oxidation and prevalence in vivo. However, the authors note that PL-PUFA2s, rather than PL-PUFA1s, represent critical lipid classes involved in the pro-ferroptosis process. Exogenous phosphatidylcholine-PUFA2s accumulate in mitochondria and combine with Complex I within the electron transport chain, thereby potentially resulting in an elevation of mitochondrial reactive oxygen species levels. Then, these mitochondrial peroxides prompt the substantial accumulation of peroxides within the endoplasmic reticulum, ultimately culminating in ferroptosis. These findings shed light on the potential molecular mechanisms underlying the induction of ferroptosis by dietary PL-PUFA2s and offer novel insights for both the evaluation of cellular iron death sensitivity and the treatment of cancer. This article will provide a more comprehensive elucidation of the paper and facilitate an enhanced understanding of the underlying mechanisms for readers.
Platinum Nanoparticles‐Enhanced Ferritin–Mn<sup>2+</sup> Interaction for Magnetic Resonance Contrast Enhancement and Efficient Tumor Photothermal Therapy (Adv. Healthcare Mater. 16/2024)
Authors: Shuangqing Liu, Liya Tian, Mengyao Mu, Ziyan Liu, Mengzhen Dong, Yufang Gong, Hui Liu, Ximing Wang, Qingwei Meng, Haidong Zhang, Xiao Sun
Journal: Advanced Healthcare Materials (2024)
A Triple‐Responsive Polymeric Prodrug Nanoplatform with Extracellular ROS Consumption and Intracellular H<sub>2</sub>O<sub>2</sub> Self‐Generation for Imaging‐Guided Tumor Chemo‐Ferroptosis‐Immunotherapy (Adv. Healthcare Mater. 16/2024)
Authors: Yongjuan Li, Yongjian Cao, Kunru Ma, Rong Ma, Mengzhe Zhang, Yichen Guo, Haiwei Song, Nannan Sun, Zhenzhong Zhang, Weijing Yang
Journal: Advanced Healthcare Materials (2024)
Microfluidic Chip‐Assisted Upconversion Luminescence Biosensing Platform for Point‐of‐Care Virus Diagnostics (Adv. Healthcare Mater. 16/2024)
Authors: Yuan Liu, Xinyue Lao, Man‐Chung Wong, Menglin Song, Huang Lai, Pui Wang, Yingjin Ma, Lihua Li, Mo Yang, Honglin Chen, Jianhua Hao
Journal: Advanced Healthcare Materials (2024)
Anti‐Wound Dehiscence and Antibacterial Dressing with Highly Efficient Self‐Healing Feature for Guided Bone Regeneration Wound Closure (Adv. Healthcare Mater. 16/2024)
Authors: Shenghao Xue, Ning Tang, Cheng Zhou, Shuobo Fang, Hossam Haick, Jiao Sun, Xueying Wu
Journal: Advanced Healthcare Materials (2024)
Hierarchical Dendritic Photonic Crystal Beads for Efficient Isolation and Proteomic Analysis of Multiple Cell Types (Adv. Healthcare Mater. 16/2024)
Authors: Wenya Chang, Yu Li, Yuhan Cai, Shu Wang, Xiaorong Song, Jie Sun, Dawei Deng, Zhongze Gu, Zhuoying Xie
Journal: Advanced Healthcare Materials (2024)
Cyclometalated iridium(III) complex based on isoquinoline alkaloid synergistically elicits the ICD response and IDO inhibition via autophagy-dependent ferroptosis
Authors: Yuan Lu, Shan-Shan Wang, Meng-Ya Li, Rong Liu, Meng-Fan Zhu, Liang-Mei Yang, Feng-Yang Wang, Ke-Bin Huang, Hong Liang
Journal: Acta Pharmaceutica Sinica B (2024)

The development of anticancer drugs to treat triple-negative breast cancer (TNBC) is an ongoing challenge. Immunogenic cell death (ICD) has garnered considerable interest worldwide as a promising synergistic modality for cancer chemoimmunotherapy. However, only few drugs or treatment modalities can trigger an ICD response and none of them exert a considerable clinical effect against TNBC. Therefore, new agents with potentially effective chemoimmunotherapeutic response are required. In this study, five new cyclometalated Ir(III) complexes containing isoquinoline alkaloid CˆN ligands were designed and synthesized. Among them, Ir-1 exhibited the highest in vitro cytotoxicity. Mechanistically, Ir-1 could trigger autophagy-dependent ferroptosis and a subsequent ferroptosis-dependent ICD response as well as indoleamine 2,3-dioxygenase (IDO) inhibition via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in MDA-MB-231 cells. When immunocompetent BALB/c mice were vaccinated with Ir-1-treated dying TNBC cells, antitumor CD8+ T-cell response and Foxp3+ T-cell depletion were induced, resulting in long-lasting antitumor immunity in TNBC cells. Moreover, combination therapy with Ir-1 and anti-PD1 could substantially augment in vivo therapeutic effects. Based on these results, Ir-1 is a promising candidate for chemoimmunotherapy against TNBC and its effects are mediated synergistically via ICD induction and IDO blockage.
Routine venoarterial extracorporeal membrane oxygenation for acute myocardial infarction-related cardiogenic shock: what we know and don’t know
Authors: Holger Thiele, Jan Belohlavek, Christian Hassager
Journal: Intensive Care Medicine (2024)

Acute myocardial infarction-related cardiogenic shock (AMI-CS) carries a dismal prognosis.Short-term mortality is in the range of 40-50% [1].Until recently, only treatment of the culprit lesion by percutaneous coronary intervention (PCI) reduced mortality within randomized controlled trials (RCT) [1].High expectations have been placed on venoarterial extracorporeal membrane oxygenation (VA-ECMO) and its use has risen by up to 40 times in the last decade despite a lack of relevant evidence from RCTs [2].The concept is to provide temporary partial or complete circulatory and also respiratory support during the critical first days as a bridge-to-recovery, bridge-todecision, bridge-to-durable left ventricular assist device (LVAD), or bridge-to-transplantation.
Transformation of peptides to small molecules in medicinal chemistry: Challenges and opportunities
Authors: Zeyu Han, Zekai Shen, Jiayue Pei, Qidong You, Qiuyue Zhang, Lei Wang
Journal: Acta Pharmaceutica Sinica B (2024)

Peptides are native binders involved in numerous physiological life procedures, such as cellular signaling, and serve as ready-made regulators of biochemical processes. Meanwhile, small molecules compose many drugs owing to their outstanding advantages of physiochemical properties and synthetic convenience. A novel field of research is converting peptides into small molecules, providing a convenient portable solution for drug design or peptidomic research. Endowing properties of peptides onto small molecules can evolutionarily combine the advantages of both moieties and improve the biological druggability of molecules. Herein, we present eight representative recent cases in this conversion and elaborate on the transformation process of each case. We discuss the innovative technological methods and research approaches involved, and analyze the applicability conditions of the approaches and methods in each case, guiding further modifications of peptides to small molecules. Finally, based on the aforementioned cases, we summarize a general procedure for peptide-to-small molecule modifications, listing the technological methods available for each transformation step and providing our insights on the applicable scenarios for these methods. This review aims to present the progress of peptide-to-small molecule modifications and propose our thoughts and perspectives for future research in this field.
Extracellular Vesicle‐Inspired Therapeutic Strategies for the COVID‐19
Authors: Ziwei Hu, Wei Wang, Ying Lin, Hui Guo, Yiwen Chen, Junjie Wang, Feng Yu, Lang Rao, Zhijin Fan
Journal: Advanced Healthcare Materials (2024)

Emerging infectious diseases like coronavirus pneumonia (COVID-19) present significant challenges to global health, extensively affecting both human society and the economy. Extracellular vesicles (EVs) have demonstrated remarkable potential as crucial biomedical tools for COVID-19 diagnosis and treatment. However, due to limitations in the performance and titer of natural vesicles, their clinical use remains limited. Nonetheless, EV-inspired strategies are gaining increasing attention. Notably, biomimetic vesicles, inspired by EVs, possess specific receptors that can act as "Trojan horses," preventing the virus from infecting host cells. Genetic engineering can enhance these vesicles by enabling them to carry more receptors, significantly increasing their specificity for absorbing the novel coronavirus. Additionally, biomimetic vesicles inherit numerous cytokine receptors from parent cells, allowing them to effectively mitigate the "cytokine storm" by adsorbing pro-inflammatory cytokines. Overall, this EV-inspired strategy offers new avenues for the treatment of emerging infectious diseases. Herein, this review systematically summarizes the current applications of EV-inspired strategies in the diagnosis and treatment of COVID-19. The current status and challenges associated with the clinical implementation of EV-inspired strategies are also discussed. The goal of this review is to provide new insights into the design of EV-inspired strategies and expand their application in combating emerging infectious diseases.
UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL
Authors: Renyu Zhang, Can Li, Shuai Zhang, Lingmin Kong, Zekun Liu, Yixiao Guo, Ying Sun, Cong Zhang, Yule Yong, Jianjun Lv, Meng Lu, Man Liu, Dong Wu, Tianjiao Zhang, Haijiao Yang, Ding Wei, Zhinan Chen, Huijie Bian
Journal: Clinical and Molecular Hepatology (2024)

Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking.
LYMPHOSCORE (Lymphoscintigraphy Scoring Reliability) Reliability of a New Qualitative and Semiquantitative Lymphoscintigraphy Scoring System for Primary Lymphedema
Authors: Sophie Guillemard, Lionel Moulis, Diana Ilonca, Sandrine Mestre, Emmanuel Deshayes, Isabelle Quéré, Salma Adham
Journal: Clinical Nuclear Medicine (2024)

Primary lymphedema (PLE) is a rare chronic disorder. Extremity lymphoscintigraphy offers access for dynamic and functional information on peripheral lymphatics and lymph nodes. We aimed to assess intraobserver and interobserver reliability of a new lymphoscintigraphy quantitative and qualitative scoring system in a homogeneous population of adult patients followed for PLE of the lower limb(s). This is a monocentric retrospective study. Clinical files of patients who underwent a lymphoscintigraphy were reviewed for inclusion. Lymphoscintigraphies were interpreted twice by 2 observers with a washout period. To assess intraobserver and interobserver reliability for both lower limbs, Cohen κ and Gwet's AC1 reliability coefficients were calculated with 95% confidence interval and P value of the zero-reliability comparison test. To interpret reliability coefficients, we used the orders of magnitude reported by Landis and Koch. One hundred forty-four patients (288 limbs) with PLE were included. For intraobserver reliability, agreement range was 0.87-1 with an almost perfect agreement in all staging items of the score for both limbs with the lower limit of the 95% confidence interval ≥80%. Interobserver reliability was overall strong or almost perfect, ranging from 0.67 to 0.97. This new scoring system demonstrated excellent intraobserver reliability and a very good interobserver reliability. Lymphoscintigraphy, when performed in a referral center and interpreted by trained nuclear medicine physicians, is a reliable means of investigation in patients with PLE of the lower limbs. This reproducibility advocates for further use of lymphoscintigraphy in multicentric cohorts of PLE patients.
Increased 68Ga-FAPI-04 Uptake in Meningioma
Authors: Hasan Önner, Halil Özer, Burak Gezer
Journal: Clinical Nuclear Medicine (2024)

A 65-year-old woman with long-standing symptoms of COVID-19 participated in our clinical study on the role of 68 Ga-FAPI-04 PET/CT in pulmonary fibrosis. Neither sequela parenchymal changes nor 68 Ga-FAPI-04 uptake was observed in the lungs. However, focal 68 Ga-FAPI-04 uptake was localized in a smoothly circumscribed mass observed in the right frontal region. A meningioma diagnosis was made based on the radiological findings.
Poly (adenosine diphosphate‐ribose) polymerase inhibitors in the treatment of triple‐negative breast cancer with homologous repair deficiency
Authors: Peng Yuan, Nan Ma, Binghe Xu
Journal: Medicinal Research Reviews (2024)

Breast cancer (BC) is a highly heterogeneous disease, and the presence of germline breast cancer gene mutation (gBRCAm) is associated with a poor prognosis. Triple-negative breast cancer (TNBC) is a BC subtype, characterized by the absence of hormone and growth factor receptor expression, making therapeutic decisions difficult. Defects in the DNA damage response pathway due to mutation in breast cancer genes (BRCA 1/2) lead to homologous recombination deficiency (HRD). However, in HRD conditions, poly (adenosine diphosphate-ribose) polymerase (PARP) proteins repair DNA damage and lead to tumor cell survival. Biological understanding of HRD leads to the development of PARP inhibitors (PARPi), which trap PARP proteins and cause genomic instability and tumor cell lysis. HRD assessment can be an important biomarker in identifying gBRCAm patients with BC who could benefit from PARPi therapy. HRD can be identified by homologous recombination repair (HRR) gene-based assays, genomic-scarring assays and mutational signatures, transcription and protein expression profiles, and functional assays. However, gold standard methodologies that are robust and reliable to assess HRD are not available currently. Hence, there is a pressing need to develop accurate biomarkers identifying HRD tumors to guide targeted therapies such as PARPi in patients with BC. HRD assessment has shown fruitful outcomes in chemotherapy studies and preliminary evidence on PARPi intervention as monotherapy and combination therapy in HRD-stratified patients. Furthermore, ongoing trials are exploring the potential of PARPi in BC and clinically complex TNBC settings, where HRD testing is used as an adjunct to stratify patients based on BRCA mutations.
False-Positive Bone Lesion With Different PET/CT Tracers
Authors: Aurélie Moreau, Valentin Pretet, David Kryza
Journal: Clinical Nuclear Medicine (2024)

Collateral circulation is often secondary to a regional thrombosis. This phenomenon can lead to the detection of misleading bone lesions on imaging and is a well-known source of false-positives. Here, we present 2 different tracers PET/CT images, 18 F-FDG and 18 F-choline, with collateral circulation but without obvious thrombosis. Both cases displayed bone uptake, which mimicked metastasis. However, clinical follow-up ruled out metastasis and revealed false-positive bone lesions related to collateral circulation, even in the lack of acute or chronic underlying thrombotic processes.
18F-FDG PET/CT Unveils Coexistent Myelomatous Hepatosplenic and Thyroid Cartilage Involvement
Authors: Ahmed Saad Abdlkadir, Nidal Almasri, Enrique Estrada, Murat Fani Bozkurt, Akram Al-Ibraheem
Journal: Clinical Nuclear Medicine (2024)

Extramedullary myelomatous disease is an aggressive condition where clonal plasma cells proliferate outside the bone marrow, allowing independent survival. This state is generally associated with negative outcomes. A 65-year-old woman presented with progressive bilateral hypochondrial pain, was initially misattributed to an inflammatory etiology, and was consequently managed with corticosteroid therapy. A bone marrow biopsy was offered after further deterioration confirming plasma cell myeloma. Afterward, 18 F-FDG PET/CT revealed medullary and extramedullary hepatosplenic and thyroid cartilage involvement, concluding an overall picture of an atypical and extensive extramedullary myelomatous disease.
<scp>MEK1</scp>/2‐ and <scp>ERK1</scp>/2‐Mediated Lung Endothelial Injury and Altered Hemostasis Promote Diffuse Alveolar Hemorrhage in Murine Lupus
Authors: Haoyang Zhuang, Shuhong Han, Neil S. Harris, Westley H. Reeves
Journal: Arthritis & Rheumatology (2024)

About 3% of patients with lupus develop severe diffuse alveolar hemorrhage (DAH) with pulmonary vasculitis. C57BL/6 (B6) mice with pristane-induced lupus also develop DAH, but BALB/c mice are resistant. DAH is independent of Toll-like receptor signaling and other inflammatory pathways. This study examined the role of the MEK1/2 pathway (MEK1/2-ERK1/2, JNK, p38).
How risky is a second allogeneic stem cell transplantation?
Authors: Olaf Penack, Mouad Abouqateb, Christophe Peczynski, William Boreland, Nicolaus Kröger, Robert Zeiser, Fabio Ciceri, Thomas Schroeder, Peter Dreger, Jakob Passweg, Johannes Schetelig, Matthias Stelljes, Igor Wolfgang Blau, Georg-Nikolaus Franke, Katarina Riesner, Hélène Schoemans, Ivan Moiseev, Zinaida Peric
Journal: Leukemia (2024)

There is no consensus on second allogeneic stem cell transplantation (alloSCT) indications in patients with hematologic malignancies relapsing after a first alloSCT. In historic publications, a very high non-relapse mortality (NRM) has been described, arguing against performing a second alloSCT. We analysed the outcome of 3356 second alloSCTs performed 2011-21 following a hematologic malignancy relapse. Outcomes at two years after second alloSCT were: NRM 22%, relapse incidence 50%, overall survival 38%, and progression-free survival 28%. Key risk factors for increased NRM were: older age, low performance score, high disease-risk-index, early relapse after the first alloSCT, unrelated/haploidentical donor, and GVHD before second alloSCT. Any type of GVHD after first alloSCT was also important risk factor for acute GVHD and chronic GVHD after second alloSCT. There was a preferential use of a different donor (80%) at second alloSCT from first alloSCT. However, in multivariate analysis, the use of the same alloSCT donor for second alloSCT vs. a different donor was not associated with any of the survival or GVHD endpoints. We show considerably improved outcome as compared to historic reports. These current data support a wider use of second alloSCT and provide risk factors for NRM that need to be considered.