tbuckley/cabot-search huggingface dataset:
Tryptophan deficiency induced by indoleamine 2,3‐dioxygenase 1 results in glucose transporter 1‐dependent promotion of aerobic glycolysis in pancreatic cancer
Authors: Heng Liang, Jiani Zhan, Yunqiu Chen, Zikang Xing, Zhen Ning Tony He, Yuying Liu, Xuewen Li, Yijia Chen, Zhiyao Li, Chunxiang Kuang, Dan Yang, Qing Yang
Journal: MedComm (2024)

Abstract Indoleamine 2,3‐dioxygenase 1 (IDO1), the key enzyme in the catabolism of the essential amino acid tryptophan (Trp) through kynurenine pathway, induces immune tolerance and is considered as a critical immune checkpoint, but its impacts as a metabolism enzyme on glucose and lipid metabolism are overlooked. We aim to clarify the potential role of IDO1 in aerobic glycolysis in pancreatic cancer (PC). Analysis of database revealed the positive correlation in PC between the expressions of IDO1 and genes encoding important glycolytic enzyme hexokinase 2 (HK2) , pyruvate kinase (PK) , lactate dehydrogenase A (LDHA) and glucose transporter 1 (GLUT1) . It was found that IDO1 could modulate glycolysis and glucose uptake in PC cells, Trp deficiency caused by IDO1 overexpression enhanced glucose uptake by stimulating GLUT1 translocation to the plasma membrane of PC cells. Besides, Trp deficiency caused by IDO1 overexpression suppressed the apoptosis of PC cells via promoting glycolysis, which reveals the presence of IDO1–glycolysis–apoptosis axis in PC. IDO1 inhibitors could inhibit glycolysis, promote apoptosis, and exhibit robust therapeutic efficacy when combined with GLUT1 inhibitor in PC mice. Our study reveals the function of IDO1 in the glucose metabolism of PC and provides new insights into the therapeutic strategy for PC.
Microglial CMPK2 promotes neuroinflammation and brain injury after ischemic stroke
Authors: Xin Guan, Sitong Zhu, Jinqian Song, Kui Liu, Mei Liu, Luyang Xie, Yifang Wang, Jin Wu, Xiaojun Xu, Tao Pang
Journal: Cell Reports Medicine (2024)

Neuroinflammation plays a significant role in ischemic injury, which can be promoted by oxidized mitochondrial DNA (Ox-mtDNA). Cytidine/uridine monophosphate kinase 2 (CMPK2) regulates mtDNA replication, but its role in neuroinflammation and ischemic injury remains unknown. Here, we report that CMPK2 expression is upregulated in monocytes/macrophages and microglia post-stroke in humans and mice, respectively. Microglia/macrophage CMPK2 knockdown using the Cre recombination-dependent adeno-associated virus suppresses the inflammatory responses in the brain, reduces infarcts, and improves neurological outcomes in ischemic CX3CR1Cre/ERT2 mice. Mechanistically, CMPK2 knockdown limits newly synthesized mtDNA and Ox-mtDNA formation and subsequently blocks NLRP3 inflammasome activation in microglia/macrophages. Nordihydroguaiaretic acid (NDGA), as a CMPK2 inhibitor, is discovered to reduce neuroinflammation and ischemic injury in mice and prevent the inflammatory responses in primary human monocytes from ischemic patients. Thus, these findings identify CMPK2 as a promising therapeutic target for ischemic stroke and other brain disorders associated with neuroinflammation.
Control compounds for preclinical drug-induced liver injury assessment: Consensus-driven systematic review by the ProEuroDILI network
Authors: Antonio Segovia-Zafra, Marina Villanueva-Paz, Ana Sofia Serras, Gonzalo Matilla-Cabello, Ana Bodoque-García, Daniel E. Di Zeo-Sánchez, Hao Niu, Ismael Álvarez-Álvarez, Laura Sanz-Villanueva, Sergej Godec, Irina Milisav, Pierre Bagnaninchi, Raúl J. Andrade, M Isabel Lucena, José C. Fernández-Checa, Francisco Javier Cubero, Joana Paiva Miranda, Leonard J. Nelson
Journal: Journal of Hepatology (2024)

Idiosyncratic drug-induced liver injury (DILI) is a complex and unpredictable event caused by drugs, and herbal or dietary supplements. Early identification of human hepatotoxicity at preclinical stages remains a major challenge, in which the selection of validated in vitro systems and test drugs has a significant impact. In this systematic review, we analyzed the compounds used in hepatotoxicity assays and established a list of DILI-positive and -negative control drugs for validation of in vitro models of DILI, supported by literature and clinical evidence and endorsed by an expert committee from the COST Action ProEuroDILI Network (CA17112).
Association between periungual changes and myositis-specific autoantibodies in patients with idiopathic inflammatory myopathies: A retrospective cohort study
Authors: Ikuko Ueda-Hayakawa, Aya Maekawa, Kyoko Tonomura, Emi Kaneda, Yuriko Yamazaki, Noriko Arase, Manabu Fujimoto
Journal: Journal of the American Academy of Dermatology (2024)
Chandipura Viral Glycoprotein (CNV-G) Promotes Gectosome Generation and Enables Delivery of Intracellular Therapeutics
Authors: Xiaojuan Zhang, Quanbin Xu, Zeyu Liu, Jayson B. Ball, Brandon Black, Saheli Ganguly, Michael E. Harland, Samuel Blackman, Stephanie Bryant, Kristi Anseth, Linda Watkins, Xuedong Liu
Journal: Molecular Therapy (2024)
IL-4Rα signaling promotes barrier-altering oncostatin M and IL-6 production in aspirin-exacerbated respiratory disease
Authors: Chongjia C. Chen, Kathleen M. Buchheit, Pui Y. Lee, Kailey E. Brodeur, Aaqib Sohail, Laura Cho, Carolyn H. Baloh, Barbara Balestrieri, Tahereh Derakhshan, Chunli Feng, Joshua A. Boyce, Daniel F. Dwyer, Tanya M. Laidlaw
Journal: Journal of Allergy and Clinical Immunology (2024)
Mitochondrial retinopathies and optic neuropathies: the impact of retinal imaging on modern understanding of pathogenesis, diagnosis, and management
Authors: Enrico Borrelli, Francesco Bandello, Camiel J.F. Boon, Valerio Carelli, Guy Lenaers, Michele Reibaldi, Srinivas R. Sadda, Alfredo A. Sadun, David Sarraf, Patrick Yu-Wai-Man, Piero Barboni
Journal: Progress in Retinal and Eye Research (2024)
The role of botanical triterpenoids and steroids in bile acid metabolism, transport, and signaling: Pharmacological and toxicological implications
Authors: Zichen Luo, Wei Zhou, Tong Xie, Weichen Xu, Chen Shi, Zihan Xiao, Yu Si, Yan Ma, Qingling Ren, Liuqing Di, Jinjun Shan
Journal: Acta Pharmaceutica Sinica B (2024)

Bile acids (BAs) are synthesized and released by the host liver from cholesterol and are delivered to the intestine, where they undergo further metabolism by gut microbes and circulate between the liver and intestines through various transporters. They serve to emulsify dietary lipids and act as signaling molecules, regulating the host's metabolism and immune homeostasis through specific receptors. Therefore, disruptions in BA metabolism, transport, and signaling are closely associated with cholestasis, metabolic disorders, autoimmune diseases, and others. Botanical triterpenoids and steroids share structural similarities with BAs, and they have been found to modulate BA metabolism, transport, and signaling, potentially exerting pharmacological or toxicological effects. Here, we have updated the research progress on BA, with a particular emphasis on new-found microbial BAs. Additionally, the latest advancements in targeting BA metabolism and signaling for disease treatment are highlighted. Subsequently, the roles of botanical triterpenoids in BA metabolism, transport, and signaling are examined, analyzing their potential pharmacological, toxicological, or drug interaction effects through these mechanisms. Finally, a research paradigm is proposed that utilizes the gut microbiota as a link to interpret the role of these important natural products in BA signaling.
Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application
Authors: Xianglei Fu, Yanbin Shi, Zili Gu, Hengchang Zang, Lian Li, Qingjie Wang, Yongjun Wang, Xiaogang Zhao, Hang Wu, Shengnan Qiu, Yankun Zhang, Jiamin Zhou, Xiangqin Chen, Hua Shen, Guimei Lin
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Despite standard treatment for non-small cell lung cancer (NSCLC) being surgical resection, cancer recurrence and complications, such as induction of malignant pleural effusion (MPE) and significant postoperative pain, usually result in treatment failure. In this study, an alginate-based hybrid hydrogel (SOG) is developed that can be injected into the resection surface of the lungs during surgery. Briefly, endoplasmic reticulum-modified liposomes (MSLs) pre-loaded with the signal transducer and activator of transcription 3 (STAT3) small interfering RNA and lidocaine hydrochloride are encapsulated in SOG. Once applied, MSLs strongly downregulated STAT3 expression in the tumor microenvironment, resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype. Meanwhile, the release of lidocaine hydrochloride was beneficial for pain relief and natural killer cell activation. Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life, including reduced MPE volume and pain relief in orthotopic NSCLC mouse models, even with a single administration. MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC, and may alter the treatment paradigms for other cancers.
MITO END-3: efficacy of avelumab immunotherapy according to molecular profiling in first-line endometrial cancer therapy
Authors: S. Pignata, D. Califano, D. Lorusso, L. Arenare, M. Bartoletti, U. De Giorgi, C. Andreetta, C. Pisano, G. Scambia, D. Lombardi, A. Farolfi, S. Cinieri, A. Passarelli, V. Salutari, C. De Angelis, C. Mignogna, D. Priolo, E.D. Capoluongo, S. Tamberi, G.L. Scaglione, V. Arcangeli, R. De Cecio, G. Scognamiglio, F. Greco, A. Spina, M. Turinetto, D. Russo, V. Carbone, C. Casartelli, C. Schettino, F. Perrone
Journal: Annals of Oncology (2024)
The role of interleukin-6 in anemia associated with hidradenitis suppurativa
Authors: Kayla Babbush Graber, Mondana H. Ghias, Tyler M. Andriano, Justine V. Cohen, Tian R. Zhu, H. Dean Hosgood, Morayma Reyes Gil, Steven R. Cohen
Journal: Journal of the American Academy of Dermatology (2024)
Triple three-dimensional MS/MS spectrum facilitates quantitative ginsenosides-targeted sub-metabolome characterization in notoginseng
Authors: Ke Zhang, Jinru Jia, Ting Li, Wenjing Liu, Pengfei Tu, Jian-Bo Wan, Jun Li, Yuelin Song
Journal: Acta Pharmaceutica Sinica B (2024)

Although serving as the workhorse, MS/MS cannot fully satisfy the analytical requirements of quantitative sub-metabolome characterization. Because more information intrinsically correlates to more structural and concentration clues, here, efforts were devoted to comprehensively tracing and deciphering MS/MS behaviors through constructing triple three-dimensional (3×3D)-MS/MS spectrum. Ginsenosides-targeted metabolomics of notoginseng, one of the most famous edible medicinal plants, was employed as a proof-of-concept. Serial authentic ginsenosides were deployed to build the correlations between 3×3D-MS/MS spectra and structure/concentration features. Through assaying ginsenosides with progressive concentrations using QTOF-MS to configure 1
Intravital Imaging of the Human Cornea Reveals the Differential Effects of Season on Innate and Adaptive Immune Cell Morphodynamics
Authors: Mengliang Wu, Xinyuan Zhang, Senuri Karunaratne, Ji-hyun Lee, Edwin R. Lampugnani, Kevin J. Selva, Amy W. Chung, Scott N. Mueller, Holly R. Chinnery, Laura E. Downie
Journal: Ophthalmology (2024)
A tribute to Dr Robert Baran: The grandfather of European onychology
Authors: Mark Holzberg, Boni Elewski, Carlton Ralph Daniel, Nathaniel J. Jellinek, Shari R. Lipner, Bianca Maria Piraccini, Phoebe Rich, Dimitris Rigopoulos, Beth S. Ruben, Adam I. Rubin, Avner Shemer, Antonella Tosti, Martin Zaiac, Bertrand Richert
Journal: Journal of the American Academy of Dermatology (2024)
Advancement in modulation of brain extracellular space and unlocking its potential for intervention of neurological diseases
Authors: Yu Yong, Yicong Cai, Jiawei Lin, Lin Ma, HongBin Han, Fenfang Li
Journal: Med-X (2024)

Abstract Cells in the brain are surrounded by extracellular space (ECS), which forms porous nets and interconnected routes for molecule transportation. Our view of brain ECS has changed from a largely static compartment to dynamic and diverse structures that actively regulate neural activity and brain states. Emerging evidence supports that dysregulation of brain ECS contributes to the pathogenesis and development of many neurological disorders, highlighting the importance of therapeutic modulation of brain ECS function. Here, we aim to provide an overview of the regulation and dysfunction of ECS in healthy and pathological brains, as well as advanced tools to investigate properties of brain ECS. This review emphasizes modulation methods to manipulate ECS with implications to restore their function in brain diseases. Graphical Abstract
Temporal Trends in Body Composition and Metabolic Markers Prior to Diagnosis of Pancreatic Ductal Adenocarcinoma
Authors: Derk C F Klatte, Alexander Weston, Yaohua Ma, Hanna Sledge, Aman Bali, Candice Bolan, Megan Engels, Jeanin E van Hooft, Monique E van Leerdam, Ahmed Ouni, Michael B Wallace, Yan Bi
Journal: Clinical Gastroenterology and Hepatology (2024)
Glycodiversification of gentamicins through in vivo glycosyltransferase swapping enabled the creation of novel hybrid aminoglycoside antibiotics with potent activity and low ototoxicity
Authors: Xinyun Jian, Cheng Wang, Shijuan Wu, Guo Sun, Chuan Huang, Chengbing Qiu, Yuanzheng Liu, Peter F. Leadlay, Dong Liu, Zixin Deng, Fuling Zhou, Yuhui Sun
Journal: Acta Pharmaceutica Sinica B (2024)

Aminoglycosides (AGs) are a class of antibiotics with a broad spectrum of activity. However, their use is limited by safety concerns associated with nephrotoxicity and ototoxicity, as well as drug resistance. To address these issues, semi-synthetic approaches for modifying natural AGs have generated new generations of AGs, however, with limited types of modification due to significant challenges in synthesis. This study explores a novel approach that harness the bacterial biosynthetic machinery of gentamicins and kanamycins to create hybrid AGs. This was achieved by glycodiversification of gentamicins
Stratification of Barrett’s esophagus surveillance based on p53 immunohistochemistry: a cost-effectiveness analysis by an international collaborative group
Authors: Shyam Menon, Richard Norman, Prasad G. Iyer, Krish Ragunath
Journal: Endoscopy (2024)

Surveillance of nondysplastic Barrett's esophagus (NDBE) is recommended to identify progression to dysplasia; however, the most cost-effective strategy remains unclear. Mutation of
The nasal basal cell population shifts toward a diseased phenotype with impaired barrier formation capacity in allergic rhinitis
Authors: Emma Ruysseveldt, Brecht Steelant, Tine Wils, Jonathan Cremer, Dominique M.A. Bullens, Peter W. Hellings, Katleen Martens
Journal: Journal of Allergy and Clinical Immunology (2024)

Capsule summary: Nasal basal cells are characterized by a diseased phenotype in allergic rhinitis, and in vitro assays demonstrated that this is correlated with impaired barrier formation capacity, highlighting them as an interesting potential therapeutic target.
Polatuzumab vedotin, venetoclax, and an <scp>anti‐CD20</scp> monoclonal antibody in relapsed/refractory B‐cell <scp>non‐Hodgkin</scp> lymphoma
Authors: Sam Yuen, Tycel J. Phillips, Rajat Bannerji, Paula Marlton, Giuseppe Gritti, John F. Seymour, Anna Johnston, Christopher Arthur, Anna Dodero, Sunil Sharma, Jamie Hirata, Lisa Musick, Christopher R. Flowers
Journal: American Journal of Hematology (2024)

The Phase 2 portion of this study evaluated safety and efficacy of polatuzumab vedotin 1.8 mg/kg and venetoclax 800 mg, plus fixed-dose obinutuzumab 1000 mg or rituximab 375 mg/m
A comprehensive approach to evaluate genetic abnormalities in multiple myeloma using optical genome mapping
Authors: Ying S. Zou, Melanie Klausner, Jen Ghabrial, Victoria Stinnett, Patty Long, Laura Morsberger, Jaclyn B. Murry, Katie Beierl, Christopher D. Gocke, Rena R. Xian, Kevin H. Toomer, Jing Christine Ye, Robert Z. Orlowski, Carol Ann Huff, Syed Abbas Ali, Philip H. Imus, Christian B. Gocke, Guilin Tang
Journal: Blood Cancer Journal (2024)
Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in a Dairy Farm Worker
Authors: Timothy M Uyeki, Scott Milton, Cherissa Abdul Hamid, Cynthia Reinoso Webb, Steven M Presley, Varun Shetty, Susan N Rollo, Diana L Martinez, Saroj Rai, Emilio R Gonzales, Krista L Kniss, Yunho Jang, Julia C Frederick, Juan A De La Cruz, Jimma Liddell, Han Di, Marie K Kirby, John R Barnes, C Todd Davis
Journal: New England Journal of Medicine (2024)
Toxic household exposures in children
Authors: Kate King, Rachel Smith, Graham Johnson
Journal: BMJ (2024)

### What you need to know Poisoning is a leading cause of unintentional injury in children worldwide accounting for 11% of all unintentional injuries in children under 15 years old.1 Fatal poisoning rates are four times higher in low and middle income countries compared with high income countries.1 Across Europe, agents most commonly ingested include medications and household products.2 In the UK, poisoning is the third most common cause of injury related admission to hospital, equating to around 4000-5000 admissions per year (box 1).1011 Most children ingesting poisonous substances do not require hospital admission, and many can be managed at home or in the community.11 However, these decisions require adequate clinical assessment and access to appropriate information on the chemicals involved. This article offers an approach to assessing a child with suspected exposure to toxic household chemicals for those working in community settings. Box 1 ### Rise in poisoning from household exposures during the covid-19 pandemic In the UK, there was a steady and significant fall in the incidence of poisoning episodes from 2000 to the start of the covid-19 pandemic with a 23% reduction in admissions of preschool children between 2000 and 2011.3 The drop probably resulted from better accident prevention information and legislative changes, such as child resistant containers, that engineered much of the risk away.12 Covid-19 produced a dramatic reversal of this decline. Reports from France, Italy, and the US suggested up to a 20% increase in calls to national poisons centres, many attributed to misuse of cleaning products used to counteract the virus.456 Sales of bleaches, hand sanitisers, and … RETURN TO TEXT
Oral Drug as Effective as Topical Cream for Male Pattern Baldness
Authors: Emily Harris
Journal: JAMA (2024)

Oral minoxidil works as well as topical minoxidil 5% for treating people with androgenetic alopecia, also known as male pattern baldness, a double-blind, randomized study found. The results are based on data from 68 men in Brazil aged 18 to 55 years.
Prevalence of ichthyoses in Denmark: a nationwide registry-based study
Authors: David Thein, Julia-Tatjana Maul, Peter Schmid-Grendelmeier, Jacob P Thyssen, Alexander Egeberg
Journal: British Journal of Dermatology (2024)

The results demonstrate a prevalence of 1.6 per 10 000 for all types of ichthyoses, based on large Danish national patient registries, including all patients with relevant diagnoses alive on 31 December 2021. A study of this size and depth has not been completed before but may still underestimate the prevalence and potential burden of the diseases.
Combining toll-like receptor agonists with immune checkpoint blockade affects antitumor vaccine efficacy
Authors: Donghwan Jeon, Ethan Hill, Jena E Moseman, Douglas G McNeel
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background T cell checkpoint receptors are expressed when T cells are activated, and modulation of the expression or signaling of these receptors can alter the function of T cells and their antitumor efficacy. We previously found that T cells activated with cognate antigen had increases in the expression of PD-1, and this was attenuated in the presence of multiple toll-like receptor (TLR) agonists, notably TLR3 plus TLR9. In the current report, we sought to investigate whether combining TLR agonists with immune checkpoint blockade can further augment vaccine-mediated T cell antitumor immunity in murine tumor models. Methods TLR agonists (TLR3 plus TLR9) and immune checkpoint inhibitors (antibodies targeting PD-1, CTLA-4, LAG-3, TIM-3 or VISTA) were combined and delivered with vaccines or vaccine-activated CD8+T cells to E.G7-OVA or MyC-CaP tumor-bearing mice. Tumors were assessed for growth and then collected and analyzed by flow cytometry. Results Immunization of E.G7-OVA tumor-bearing mice with SIINFEKL peptide vaccine, coadministered with TLR agonists and αCTLA-4, demonstrated greater antitumor efficacy than immunization with TLR agonists or αCTLA-4 alone. Conversely, the antitumor efficacy was abrogated when vaccine and TLR agonists were combined with αPD-1. TLR agonists suppressed PD-1 expression on regulatory T cells (Tregs) and activated this population. Depletion of Tregs in tumor-bearing mice led to greater antitumor efficacy of this combination therapy, even in the presence of αPD-1. Combining vaccination with TLR agonists and αCTLA-4 or αLAG-3 showed greater antitumor than with combinations with αTIM-3 or αVISTA. Conclusion The combination of TLR agonists and αCTLA-4 or αLAG-3 can further improve the efficacy of a cancer vaccine, an effect not observed using αPD-1 due to activation of Tregs when αPD-1 was combined with TLR3 and TLR9 agonists. These data suggest that optimal combinations of TLR agonists and immune checkpoint blockade may improve the efficacy of human anticancer vaccines.