tbuckley/cabot-search huggingface dataset:
Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice
Authors: Sara Zumerle, Miles Sarill, Miriam Saponaro, Manuel Colucci, Liliana Contu, Edoardo Lazzarini, Roberta Sartori, Camilla Pezzini, Anna Rinaldi, Anna Scanu, Jacopo Sgrignani, Patrizia Locatelli, Marianna Sabbadin, Aurora Valdata, Daniela Brina, Isabella Giacomini, Beatrice Rizzo, Alessandra Pierantoni, Saman Sharifi, Silvia Bressan, Claudia Altomare, Yulia Goshovska, Chiara Giraudo, Roberto Luisetto, Luca Iaccarino, Cristina Torcasio, Simone Mosole, Emiliano Pasquini, Andrea Rinaldi, Laura Pellegrini, Gregorio Peron, Matteo Fassan, Stefano Masiero, Andrea Maria Giori, Stefano Dall’Acqua, Johan Auwerx, Pietro Cippà, Andrea Cavalli, Marco Bolis, Marco Sandri, Lucio Barile, Monica Montopoli, Andrea Alimonti
Journal: Nature Aging (2024)

Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence and thus improve healthspan. Here, we show that daily oral administration of a standardized extract of Salvia haenkei (Haenkenium (HK)) extended lifespan and healthspan of naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis and senescence markers across several tissues, as well as increased muscle strength and fur thickness compared with age-matched controls. We also found that HK treatment reduced acutely induced senescence by the chemotherapeutic agent doxorubicin, using p16
Mapping spatially resolved transcriptomes in human and mouse pulmonary fibrosis
Authors: Lovisa Franzén, Martina Olsson Lindvall, Michael Hühn, Victoria Ptasinski, Laura Setyo, Benjamin P. Keith, Astrid Collin, Steven Oag, Thomas Volckaert, Annika Borde, Joakim Lundeberg, Julia Lindgren, Graham Belfield, Sonya Jackson, Anna Ollerstam, Marianna Stamou, Patrik L. Ståhl, Jorrit J. Hornberg
Journal: Nature Genetics (2024)

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis and limited treatment options. Efforts to identify effective treatments are thwarted by limited understanding of IPF pathogenesis and poor translatability of available preclinical models. Here we generated spatially resolved transcriptome maps of human IPF (n = 4) and bleomycin-induced mouse pulmonary fibrosis (n = 6) to address these limitations. We uncovered distinct fibrotic niches in the IPF lung, characterized by aberrant alveolar epithelial cells in a microenvironment dominated by transforming growth factor beta signaling alongside predicted regulators, such as TP53 and APOE. We also identified a clear divergence between the arrested alveolar regeneration in the IPF fibrotic niches and the active tissue repair in the acutely fibrotic mouse lung. Our study offers in-depth insights into the IPF transcriptional landscape and proposes alveolar regeneration as a promising therapeutic strategy for IPF.
Systemic Deletion of ARRDC4 Improves Cardiac Reserve and Exercise Capacity in Diabetes
Authors: Yoshinobu Nakayama, Satoru Kobayashi, Aliya Masihuddin, Syed Amir Abdali, A.M. Pramodh Bandara Seneviratne, Sachiyo Ishii, Jun Iida, Qiangrong Liang, Jun Yoshioka
Journal: Circulation Research (2024)

Exercise intolerance is an independent predictor of poor prognosis in diabetes. The underlying mechanism of the association between hyperglycemia and exercise intolerance remains undefined. We recently demonstrated that the interaction between ARRDC4 (arrestin domain-containing protein 4) and GLUT1 (glucose transporter 1) regulates cardiac metabolism.
A new Korean nomenclature for steatotic liver disease: Nonalcoholic Fatty Liver Disease (NAFLD) Nomenclature Revision Consensus Task Force on behalf of the Korean Association for the Study of the Liver (KASL)
Authors: Byoung Kuk Jang, Dae Won Jun, Sang Gyune Kim, Seung Up Kim, Won Kim, Sung Won Lee, Ju Hyun Shim, Su Jong Yu
Journal: Clinical and Molecular Hepatology (2024)

A new Korean nomenclature for steatotic liver disease: Nonalcoholic Fatty Liver Disease (NAFLD) Nomenclature Revision Consensus Task Force on behalf of the Korean Association for the Study of the Liver (KASL)
Current status and perspective on molecular targets and therapeutic intervention strategy in hepatic ischemia-reperfusion injury
Authors: Jia Liu, Ranyi Luo, Yinhao Zhang, Xiaojiaoyang Li
Journal: Clinical and Molecular Hepatology (2024)

Hepatic ischemia‒reperfusion injury (HIRI) is a common and inevitable complication of hepatic trauma, liver resection, or liver transplantation. It contributes to postoperative organ failure or tissue rejection, eventually affecting patient prognosis and overall survival. The pathological mechanism of HIRI is highly complex and has not yet been fully elucidated. The proposed underlying mechanisms include mitochondrial damage, oxidative stress imbalance, abnormal cell death, immune cell hyperactivation, intracellular inflammatory disorders and other complex events. In addition to serious clinical limitations, available antagonistic drugs and specific treatment regimens are still lacking. Therefore, there is an urgent need to not only clarify the exact etiology of HIRI but also reveal the possible reactions and bottlenecks of existing drugs, helping to reduce morbidity and shorten hospitalizations. We analyzed the possible underlying mechanism of HIRI, discussed various outcomes among different animal models and explored neglected potential therapeutic strategies for HIRI treatment. By thoroughly reviewing and analyzing the literature on HIRI, we gained a comprehensive understanding of the current research status in related fields and identified valuable references for future clinical and scientific investigations.
Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study)
Authors: Iván Márquez-Rodas, Ana Álvarez, Ana Arance, Izaskun Valduvieco, Miguel-Ángel Berciano-Guerrero, Raquel Delgado, Ainara Soria, Fernándo Lopez Campos, Pedro Sánchez, Jose Luis Romero, Juan Martin-Liberal, Anna Lucas, Roberto Díaz-Beveridge, Antonio-José Conde-Moreno, Maria del Carmen Álamo de la Gala, Almudena García-Castaño, Pedro José Prada, María González Cao, Enrique Puertas, Joana Vidal, Palmira Foro, Carlos Aguado de la Rosa, Juan Antonio Corona, Pablo Cerezuela-Fuentes, Paco López, Pablo Luna, Neus Aymar, Teresa Puértolas, Pilar Sanagustín, Alfonso Berrocal
Journal: Neuro-Oncology (2024)

Abstract Background Encorafenib plus binimetinib (EB) is a standard-of-care treatment for advanced BRAFV600-mutant melanoma. We assessed the efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response. Methods E-BRAIN/GEM1802 was a prospective, multicenter, single-arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved a partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression. Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%. Results The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After 2 months, icRR was 70.8% (95% CI: 55.9–83.1); 10.4% complete response. Median intracranial progression-free survival (PFS) and OS were 8.5 (95% CI: 6.4–11.8) and 15.9 (95% CI: 10.7–21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grades 3–4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%). Conclusions Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high-grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response.
CREB3 suppresses hepatocellular carcinoma progression by depressing AKT signaling through competitively binding with insulin receptor and transcriptionally activating RNA‐binding motif protein 38
Authors: Yi He, Shenqi Han, Han Li, Yu Wu, Wenlong Jia, Zeyu Chen, Yonglong Pan, Ning Cai, Jingyuan Wen, Ganxun Li, Junnan Liang, Jianping Zhao, Qiumeng Liu, Huifang Liang, Zeyang Ding, Zhao Huang, Bixiang Zhang
Journal: MedComm (2024)

Abstract cAMP responsive element binding protein 3 (CREB3), belonging to bZIP family, was reported to play multiple roles in various cancers, but its role in hepatocellular carcinoma (HCC) is still unclear. cAMP responsive element binding protein 3 like 3 (CREB3L3), another member of bZIP family, was thought to be transcription factor (TF) to regulate hepatic metabolism. Nevertheless, except for being TFs, other function of bZIP family were poorly understood. In this study, we found CREB3 inhibited growth and metastasis of HCC in vitro and in vivo. RNA sequencing indicated CREB3 regulated AKT signaling to influence HCC progression. Mass spectrometry analysis revealed CREB3 interacted with insulin receptor (INSR). Mechanistically, CREB3 suppressed AKT phosphorylation by inhibiting the interaction of INSR with insulin receptor substrate 1 (IRS1). In our study, CREB3 was firstly proved to affect activation of substrates by interacting with tyrosine kinase receptor. Besides, CREB3 could act as a TF to transactivate RNA‐binding motif protein 38 (RBM38) expression, leading to suppressed AKT phosphorylation. Rescue experiments further confirmed the independence between the two functional manners. In conclusion, CREB3 acted as a tumor suppressor in HCC, which inhibited AKT phosphorylation through independently interfering interaction of INSR with IRS1, and transcriptionally activating RBM38.
Intravital imaging of cardiac tissue utilizing tissue-stabilized heart window chamber in live animal model
Authors: Soyeon Ahn, Jung-yeon Yoon, Pilhan Kim
Journal:  (2024)

Abstract Aims To develop and validate an optimized intravital heart microimaging protocol using a suction-based tissue motion-stabilizing cardiac imaging window to facilitate real-time observation of dynamic cellular behaviours within cardiac tissue in live mouse models. Methods and results Intravital heart imaging was conducted using dual-mode confocal and two-photon microscopy. Mice were anesthetized, intubated, and maintained at a stable body temperature during the procedure. LysM-eGFP transgenic mice were utilized to visualize immune cell dynamics with vascular labelling by intravenous injection of anti-CD31 antibody and DiD-labelled red blood cells (RBCs). A heart imaging window chamber with a vacuum-based tissue motion stabilizer with 890–920 mbar was applied following a chest incision to expose the cardiac tissue. The suction-based heart imaging window chamber system and artificial intelligence-based motion compensation function significantly reduced motion artefacts and facilitated real-time in vivo cell analysis of immune cell and RBC trafficking, revealing a mean neutrophil movement velocity of 1.66 mm/s, which was slower compared to the RBC flow velocity of 9.22 mm/s. Intravital two-photon microscopic heart imaging enabled label-free second harmonic generation imaging of cardiac muscle structures with 820–840 nm excitation wavelength, revealing detailed biodistributions and structural variations in sarcomeres and fibrillar organization in the heart. Conclusion The optimized intravital heart imaging protocol successfully demonstrates its capability to provide high-resolution, real-time visualization of dynamic cellular activities within live cardiac tissue.
Expression of Concern: Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Antitumor T-cell Immunity
Authors: Aayoung Hong, Marco Piva, Sixue Liu, Willy Hugo, Shirley H. Lomeli, Vincent Zoete, Christopher E. Randolph, Zhentao Yang, Yan Wang, Jordan J. Lee, Skylar J. Lo, Lu Sun, Agustin Vega-Crespo, Alejandro J. Garcia, David B. Shackelford, Steven M. Dubinett, Philip O. Scumpia, Stephanie D. Byrum, Alan J. Tackett, Timothy R. Donahue, Olivier Michielin, Sheri L. Holmen, Antoni Ribas, Gatien Moriceau, Roger S. Lo
Journal: Cancer Discovery (2024)
Expression of Concern: Exploiting Drug Addiction Mechanisms to Select against MAPKi-Resistant Melanoma
Authors: Aayoung Hong, Gatien Moriceau, Lu Sun, Shirley Lomeli, Marco Piva, Robert Damoiseaux, Sheri L. Holmen, Norman E. Sharpless, Willy Hugo, Roger S. Lo
Journal: Cancer Discovery (2024)
Precision Targeting of the Gut Microbiome for Cancer Immunotherapy
Authors: Pasquale Lombardi, David J. Pinato
Journal: Cancer Discovery (2024)

Transforming gut microbial status from a prognostic trait to a therapeutic target is a key goal to understand and reverse resistance to anticancer immunotherapy. Glitza and colleagues propose selective manipulation of the gut microbiome with SER401 following antibiotic preconditioning and highlight multiple challenges in delivering microbiome manipulation to the clinic. See related article by Glitza et al., p. 1161 (8).
Expression of Concern: Reduced miR-128 in Breast Tumor–Initiating Cells Induces Chemotherapeutic Resistance via Bmi-1 and ABCC5
Authors: Yinghua Zhu, Fengyan Yu, Yu Jiao, Juan Feng, Wei Tang, Herui Yao, Chang Gong, Jianing Chen, Fengxi Su, Yan Zhang, Erwei Song
Journal: Clinical Cancer Research (2024)
Editor’s Note: <i>Ex Vivo</i> Testing of Patient-Derived Xenografts Mirrors the Clinical Outcome of Patients with Pancreatic Ductal Adenocarcinoma
Authors: David Roife, Bingbing Dai, Ya’an Kang, Mayrim V. Rios Perez, Michael Pratt, Xinqun Li, Jason B. Fleming
Journal: Clinical Cancer Research (2024)
Targeted Bias: The Next Swing at IL2 Therapy
Authors: Kayla R. Kulhanek, Anusha Kalbasi
Journal: Cancer Discovery (2024)

Despite its long history of toxicity and limited efficacy, IL2 has re-entered the clinic as a companion to the recently FDA-approved tumor infiltrating lymphocyte therapy. In back-to-back articles, Moynihan and Kaptein introduce a new fusion protein that delivers a biased IL2 mutein to CD8 T cells. See related article by Moynihan et al., p. 1206 (6). See related article by Kaptein et al., p. 1226 (7).
Pan-RAF:MEK Molecular Glues Take Center Stage
Authors: Matthew J. Hangauer, Jorge Silvio Gutkind, Fleur M. Ferguson
Journal: Cancer Discovery (2024)

In this issue, Ryan and colleagues describe the preclinical development of a pan-RAF:MEK molecular glue with superior efficacy, brain penetrance, and tolerability in xenograft models of Ras/Raf/MAPK pathway-driven tumors. See related article by Ryan et al., p. 1190 (1).
Highlighted research articles
Journal: Blood Cancer Discovery (2024)

In This Issue| July 01 2024 Highlighted research articles Author & Article Information Online ISSN: 2643-3249 Print ISSN: 2643-3230 ©2024 American Association for Cancer Research2024American Association for Cancer Research Blood Cancer Discov (2024) 5 (4): 228. https://doi.org/10.1158/2643-3230.BCD-5-4-ITI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record July 1 2024 Citation Highlighted research articles. Blood Cancer Discov 1 July 2024; 5 (4): 228. https://doi.org/10.1158/2643-3230.BCD-5-4-ITI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Data on long-term responses are critical to understanding the curative potential of CAR-T–cell therapy (CART). In several lymphoma types, these data are still scarce, as the first CART trials have been conducted only recently. Mo and colleagues present a follow-up of two patients treated with anti-CD20 CART, one mantle cell (MCL) and one follicular lymphoma (FL), who sustained clinical responses for over 7 years, among the longest known to date for these disease subtypes. The responses are more remarkable because they occur alongside residual disease and in the absence of sustained CAR-T activity, as inferred by the lack of B-cell aplasia. Immunological assays of T-cell repertoire and humoral and cellular immune responses against autologous tumor suggest that endogenous anti-lymphoma immunity developed following CAR-T–cell infusions. Secondary T-cell responses to antigens released from target cells killed by the initial immune response, termed "epitope spreading," is fundamental to successful immune defense against pathogens.... You do not currently have access to this content.
A Nationwide Target Trial Emulation Assessing the Risk of Antidepressant-Induced Mania Among Patients With Bipolar Depression
Authors: Christopher Rohde, Søren Dinesen Østergaard, Oskar Hougaard Jefsen
Journal: American Journal of Psychiatry (2024)

Antidepressants are commonly used to treat bipolar depression but may increase the risk of mania. The evidence from randomized controlled trials, however, is limited by short treatment durations, providing little evidence for the long-term risk of antidepressant-induced mania. The authors performed a target trial emulation to compare the risk of mania among individuals with bipolar depression treated or not treated with antidepressants over a 1-year period.
Interplay between gut microbiome, host genetic and epigenetic modifications in MASLD and MASLD-related hepatocellular carcinoma
Authors: Suki Ha, Vincent Wai-Sun Wong, Xiang Zhang, Jun Yu
Journal: Gut (2024)

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a wide spectrum of liver injuries, ranging from hepatic steatosis, metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis to MASLD-associated hepatocellular carcinoma (MASLD-HCC). Recent studies have highlighted the bidirectional impacts between host genetics/epigenetics and the gut microbial community. Host genetics influence the composition of gut microbiome, while the gut microbiota and their derived metabolites can induce host epigenetic modifications to affect the development of MASLD. The exploration of the intricate relationship between the gut microbiome and the genetic/epigenetic makeup of the host is anticipated to yield promising avenues for therapeutic interventions targeting MASLD and its associated conditions. In this review, we summarise the effects of gut microbiome, host genetics and epigenetic alterations in MASLD and MASLD-HCC. We further discuss research findings demonstrating the bidirectional impacts between gut microbiome and host genetics/epigenetics, emphasising the significance of this interconnection in MASLD prevention and treatment.
Acoustic-holography-patterned primary hepatocytes possess liver functions
Authors: Changcan Li, Gang Xu, Yinhan Wang, Laixin Huang, Feiyan Cai, Long Meng, Bao Jin, Zhuoran Jiang, Hang Sun, Haitao Zhao, Xin Lu, Xingting Sang, Pengyu Huang, Fei Li, Huayu Yang, Yilei Mao, Hairong Zheng
Journal: Biomaterials (2024)

Acoustic holography (AH), a promising approach for cell patterning, emerges as a powerful tool for constructing novel invitro 3D models that mimic organs and cancers features. However, understanding changes in cell function post-AH remains limited. Furthermore, replicating complex physiological and pathological processes solely with cell lines proves challenging. Here, we employed acoustical holographic lattice to assemble primary hepatocytes directly isolated from mice into a cell cluster matrix to construct a liver-shaped tissue sample. For the first time, we evaluated the liver functions of AH-patterned primary hepatocytes. The patterned model exhibited large numbers of self-assembled spheroids and superior multifarious core hepatocyte functions compared to cells in 2D and traditional 3D culture models. AH offers a robust protocol for long-term in vitro culture of primary cells, underscoring its potential for future applications in disease pathogenesis research, drug testing, and organ replacement therapy.
Stabilization of EREG via STT3B-mediated N-glycosylation is critical for PDL1 upregulation and immune evasion in head and neck squamous cell carcinoma
Authors: Shengming Xu, Haifeng Wang, Yu Zhu, Yong Han, Liu Liu, Xiangkai Zhang, Jingzhou Hu, Wuchang Zhang, Shengzhong Duan, Jiong Deng, Zhiyuan Zhang, Shuli Liu
Journal: International Journal of Oral Science (2024)

Dysregulated Epiregulin (EREG) can activate epidermal growth factor receptor (EGFR) and promote tumor progression in head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underlying EREG dysregulation remain largely unknown. Here, we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues. Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway. Of note, we found that N-glycosylation of EREG was essential for its stability, membrane location, biological function, and upregulation of its downstream target PDL1 in HNSCC. EREG was glycosylated at N47 via STT3B glycosyltransferases, whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG. Consistently, knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells. Moreover, treatment of HNSCC cells with NGI-1, an inhibitor of STT3B, blocked STT3B-mediated glycosylation of EREG, leading to its degradation and suppression of PDL1. Finally, combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo. Taken together, STT3B-mediated N-glycosylation is essential for stabilization of EREG, which mediates PDL1 upregulation and immune evasion in HNSCC.
Optimizing the Value of β-Lactam Antibiotics Through Extended Infusion
Authors: Miranda So
Journal: JAMA Network Open (2024)

Sara M. Karaba, MD, PhD, MHS; Sara E. Cosgrove, MD, MS; Jae Hyoung Lee, MD, MPH; Suiyini Fiawoo, MD, MPH; Emily L. Heil, PharmD, MS; Katelyn S. Quartuccio, PharmD, BCIDP, BCPS; Katherine C. Shihadeh, PharmD; Pranita D. Tamma, MD, MHS
Machine Learning for AI Breeding in Plants
Authors: Qian Cheng, Xiangfeng Wang
Journal: Genomics Proteomics & Bioinformatics (2024)

What makes artificial intelligence (AI) smart is machine learning (ML), a "field of study that gives computers the ability to learn without being explicitly programmed", as defined by ML pioneer Arthur Samuel in 1959.ML deduces data patterns without relying on prior assumptions as statistics does, greatly reducing the human effort required to understand the data.ML comprises a large family of algorithms, many of which support big data analytics [1].With the rapid advances in multi-omics technologies, plant breeding has entered the "genome, germplasm, genes, genomic breeding, and gene editing (5G)" generation [2], in which biological knowledge and omics data are integrated to expedite trait improvement.ML holds great promise for 5G breeding, with many reports of ML applications for omics-driven gene discovery, genotype-to-phenotype (G2P) prediction, genomic selection (GS), and plant phenomics.However, there remains a gap between basic research and breeding practices in plants [3].Given multi-omics, genotypic, phenomic, and environmental datasets have become highly dimensional and heterogeneous, novel ML algorithms are expected.Hereby, we propose ways to overcome major challenges in the application of cutting-edge ML models to plant research, with the ultimate goal of making plant breeding smart and easy.