tbuckley/cabot-search huggingface dataset:
Prospects and challenges of tissue-derived extracellular vesicles
Authors: Justin C. Lee, Roslyn M. Ray, Tristan A. Scott
Journal: Molecular Therapy (2024)

Extracellular vesicles (EVs) are considered a vital component of cell-to-cell communication and represent a new frontier in diagnostics and a means to identify pathways for therapeutic intervention. Recently, studies have revealed the importance of tissue-derived EVs (Ti-EVs), which are EVs present in the interstitial spaces between cells, as they better represent the underlying physiology of complex, multicellular tissue microenvironments in biology and disease. EVs are native, lipid bilayer membraned nano-sized particles produced by all cells that are packaged with varied functional biomolecules including proteins, lipids, and nucleic acids. They are implicated in short- and long-range cellular communication and may elicit functional responses in recipient cells. To date, studies have often utilized cultured cells or biological fluids as a source for EVs that do not capture local molecular signatures of the tissue microenvironment. Recent work utilizing Ti-EVs has elucidated novel biomarkers for disease and provided insights into disease mechanisms that may lead to the development of novel therapeutic agents. Still, there are considerable challenges facing current studies. This review explores the vast potential and unique challenges for Ti-EV research and provides considerations for future studies that seek to advance this exciting field.
Invasive metastatic tumor-camouflaged ROS responsive nanosystem for targeting therapeutic brain injury after cardiac arrest
Authors: Yiyang Xia, Chenming Zou, Weichao Kang, Tianhua Xu, Rongjiao Shao, Ping Zeng, Bixi Sun, Jie Chen, Yiming Qi, Zhaozhong Wang, Tiancheng Lin, Haichao Zhu, Yuanyuan Shen, Xintao Wang, Shengrong Guo, Derong Cui
Journal: Biomaterials (2024)

Drug transmission through the blood-brain barrier (BBB) is considered an arduous challenge for brain injury treatment following the return of spontaneous circulation after cardiac arrest (CA-ROSC). Inspired by the propensity of melanoma metastasis to the brain, B16F10 cell membranes are camouflaged on 2-methoxyestradiol (2ME2)-loaded reactive oxygen species (ROS)-triggered "Padlock" nanoparticles that are constructed by phenylboronic acid pinacol esters conjugated D-a-tocopheryl polyethylene glycol succinate (TPGS-PBAP). The biomimetic nanoparticles (BM@TP/2ME2) can be internalized, mainly mediated by the mutual recognition and interaction between CD44v6 expressed on B16F10 cell membranes and hyaluronic acid on cerebral vascular endothelial cells, and they responsively release 2ME2 by the oxidative stress microenvironment. Notably, BM@TP/2ME2 can scavenge excessive ROS to reestablish redox balance, reverse neuroinflammation, and restore autophagic flux in damaged neurons, eventually exerting a remarkable neuroprotective effect after CA-ROSC in vitro and in vivo. This biomimetic drug delivery system is a novel and promising strategy for the treatment of cerebral ischemia-reperfusion injury after CA-ROSC.
Histological improvements following energy restriction and exercise: The role of insulin resistance in resolution of MASH
Authors: Justine M. Mucinski, Amadeo F. Salvador, Mary P. Moore, Talyia M. Fordham, Jennifer M. Anderson, Grace Shryack, Rory P. Cunningham, Guido Lastra, Ayman H. Gaballah, Alberto Diaz-Arias, Jamal A. Ibdah, R. Scott Rector, Elizabeth J. Parks
Journal: Journal of Hepatology (2024)
Starry sky pattern predicts <scp>RAS</scp> pathway activation in <i>NPM1</i>‐mutated acute myeloid leukemia
Authors: Alessandra Venanzi, Valeria Cardinali, Vincenzo Perriello, Francesco Albano, Gaetano Cimino, Giovanni Martino, Andrea Marra, Paolo Sportoletti, Vibeke Andresen, Bjorn T. Gjertsen, Simona Sica, Patrizia Chiusolo, Maria Paola Martelli, Enrico Tiacci, Brunangelo Falini
Journal: American Journal of Hematology (2024)
P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression
Authors: Quanfu Li, Yiyang Liu, Jingxian Wu, Zewen Zhu, Jianjun Fan, Linhui Zhai, Ziruoyu Wang, Guiping Du, Ling Zhang, Junchi Hu, Dengke K. Ma, Jun O. Liu, Hai Huang, Minjia Tan, Yongjun Dang, Wei Jiang
Journal: Leukemia (2024)

Aberrations in the Hedgehog (Hh) signaling pathway are significantly prevailed in various cancers, including B-cell lymphoma. A critical facet of Hh signal transduction involves the dynamic regulation of the suppressor of fused homolog (SUFU)-glioma-associated oncogene homolog (GLI) complex within the kinesin family member 7 (KIF7)-supported ciliary tip compartment. However, the specific post-translational modifications of SUFU-GLI complex within this context have remained largely unexplored. Our study reveals a novel regulatory mechanism involving prolyl 4-hydroxylase 2 (P4HA2), which forms a complex with KIF7 and is essential for signal transduction of Hh pathway. We demonstrate that, upon Hh pathway activation, P4HA2 relocates alongside KIF7 to the ciliary tip. Here, it hydroxylates SUFU to inhibit its function, thus amplifying the Hh signaling. Moreover, the absence of P4HA2 significantly impedes B lymphoma progression. This effect can be attributed to the suppression of Hh signaling in stromal fibroblasts, resulting in decreased growth factors essential for malignant proliferation of B lymphoma cells. Our findings highlight the role of P4HA2-mediated hydroxylation in modulating Hh signaling and propose a novel stromal-targeted therapeutic strategy for B-cell lymphoma.
Semaglutide and Cardiovascular Outcomes by Baseline HbA1c and Change in HbA1c in People With Overweight or Obesity but Without Diabetes in SELECT
Authors: Ildiko Lingvay, John Deanfield, Steven E. Kahn, Peter E. Weeke, Hermann Toplak, Benjamin M. Scirica, Lars Rydén, Naveen Rathor, Jorge Plutzky, Cristobal Morales, A. Michael Lincoff, Michael Lehrke, Ole Kleist Jeppesen, Grzegorz Gajos, Helen M. Colhoun, Bertrand Cariou, Donna Ryan
Journal: Diabetes Care (2024)

To evaluate the cardiovascular effects of semaglutide by baseline glycated hemoglobin (HbA1c) and change in HbA1c in a prespecified analysis of Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT).
Effect of Semaglutide on Regression and Progression of Glycemia in People With Overweight or Obesity but Without Diabetes in the SELECT Trial
Authors: Steven E. Kahn, John E. Deanfield, Ole Kleist Jeppesen, Scott S. Emerson, Trine Welløv Boesgaard, Helen M. Colhoun, Robert F. Kushner, Ildiko Lingvay, Bartolome Burguera, Grzegorz Gajos, Deborah Bade Horn, Irene M. Hramiak, Ania M. Jastreboff, Alexander Kokkinos, Michael Maeng, Ana Laura S.A. Matos, Francisco J. Tinahones, A. Michael Lincoff, Donna H. Ryan
Journal: Diabetes Care (2024)

To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes.
Photodynamic therapy for cancer: mechanisms, photosensitizers, nanocarriers, and clinical studies
Authors: Wanchen Zhao, Liqing Wang, Meihong Zhang, Zhiqi Liu, Chuanbin Wu, Xin Pan, Zhengwei Huang, Chao Lu, Guilan Quan
Journal: MedComm (2024)

Photodynamic therapy (PDT) is a temporally and spatially precisely controllable, noninvasive, and potentially highly efficient method of phototherapy. The three components of PDT primarily include photosensitizers, oxygen, and light. PDT employs specific wavelengths of light to active photosensitizers at the tumor site, generating reactive oxygen species that are fatal to tumor cells. Nevertheless, traditional photosensitizers have disadvantages such as poor water solubility, severe oxygen-dependency, and low targetability, and the light is difficult to penetrate the deep tumor tissue, which remains the toughest task in the application of PDT in the clinic. Here, we systematically summarize the development and the molecular mechanisms of photosensitizers, and the challenges of PDT in tumor management, highlighting the advantages of nanocarriers-based PDT against cancer. The development of third generation photosensitizers has opened up new horizons in PDT, and the cooperation between nanocarriers and PDT has attained satisfactory achievements. Finally, the clinical studies of PDT are discussed. Overall, we present an overview and our perspective of PDT in the field of tumor management, and we believe this work will provide a new insight into tumor-based PDT.
The Final Frontier in Diabetes Care: Implementing Research in Real-World Practice
Authors: Jennifer B. Green, Matthew J. Crowley, Sathish Thirunavukkarasu, Nisa M. Maruthur, Brian Oldenburg
Journal: Diabetes Care (2024)

Despite extensive evidence related to the prevention and management of type 2 diabetes (T2D) and its complications, most people at risk for and people who have diabetes do not receive recommended guideline-based care. Clinical implementation of proven care strategies is of the utmost importance because without this, even the most impressive research findings will remain of purely academic interest. In this review, we discuss the promise and challenges of implementing effective approaches to diabetes prevention and care in the real-world setting. We describe successful implementation projects in three critical areas of diabetes care—diabetes prevention, glycemic control, and prevention of diabetes-related complications—which provide a basis for further clinical translation and an impetus to improve the prevention and control of T2D in the community. Advancing the clinical translation of evidence-based care must include recognition of and assessment of existing gaps in care, identification of barriers to the delivery of optimal care, and a locally appropriate plan to address and overcome these barriers. Care models that promote team-based approaches, rather than reliance on patient-provider interactions, will enhance the delivery of contemporary comprehensive diabetes care.
Biodegradable Cascade‐Amplified Nanotheranostics for Photoacoustic‐Guided Synergistic PTT/CDT/Starvation Antitumor in the NIR‐II Window
Authors: Weiwei Kang, Yuhang Wang, Lei Xin, Lin Chen, Keqi Zhao, Lujie Yu, Xiaorui Song, Ziliang Zheng, Rong Dai, Weiwei Zhang, Ruiping Zhang
Journal: Advanced Healthcare Materials (2024)

The development of nanoassemblies, activated by the tumor microenvironment, capable of generating photothermal therapy (PTT) and amplifying the "ROS (·OH) storm," is essential for precise and effective synergistic tumor treatment. Herein, an innovative cascade-amplified nanotheranostics based on biodegradable Pd-BSA-GOx nanocomposite for NIR-II photoacoustic imaging (PAI) guides self-enhanced NIR-II PTT/chemodynamic therapy (CDT)/starvation synergistic therapy. The Pd-BSA-GOx demonstrates the ability to selectively convert overexpressed H
Targeting polymorphonuclear myeloid‐derived suppressor cells in the immunosuppressive tumor microenvironment for cancer immunotherapy
Authors: Shiqi Li, Xinghua Long
Journal: MedComm (2024)

Tumor-driven immune suppression is a critical mechanism by which cancer cells evade the host immune system, leading to tumor growth and metastasis. The tumor immune microenvironment contains a large population of immune-suppressing myeloid cells, which play a key role in tumor development and drug resistance to existing immunotherapy. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are important components of the immunosuppressive microenvironment. Uncovering the molecular mechanisms of PMN-MDSCs and finding specific targets for PMN-MDSCs to regulate tumor immune microenvironment is the focus and challenge of current immunotherapy. In a recent issue of Nature, Wang and colleagues revealed that CD300ld on PMN-MDSCs is required for tumor-driven immune suppression(1), this provided a new target for cancer immunotherapy, The study identified CD300ld as a novel, highly conserved tumor immunosuppressive receptor. CD300ld is highly expressed specifically on PMN-MDSCs and is a key receptor in regulating the recruitment and immunosuppressant function of PMN-MDSCs. Targeting CD300ld can reshape the tumor immune microenvironment by inhibiting the recruitment and function of PMN-MDSCs, resulting in broad-spectrum anti-tumor effects. CD300ld target shows good safety, conservation, anti-tumor effectiveness, and synergism with the Programmed death-1 target, which is expected to become a new ideal target for tumor immunotherapy.
Integrin αM promotes macrophage alternative M2 polarization in hyperuricemia‐related chronic kidney disease
Authors: Jing Liu, Fan Guo, Xiaoting Chen, Ping Fu, Liang Ma
Journal: MedComm (2024)

Hyperuricemia is an essential risk factor in chronic kidney disease (CKD), while urate-lowering therapy to prevent or delay CKD is controversial. Alternatively activated macrophages in response to local microenvironment play diverse roles in kidney diseases. Here, we aim to investigate whether and how macrophage integrin αM (ITGAM) contributes to hyperuricemia-related CKD. In vivo, we explored dynamic characteristics of renal tissue in hyperuricemia-related CKD mice. By incorporating transcriptomics and phosphoproteomics data, we analyzed gene expression profile, hub genes and potential pathways. In vitro, we validated bioinformatic findings under different conditions with interventions corresponding to core nodes. We found that hyperuricemia-related CKD was characterized by elevated serum uric acid levels, impaired renal function, activation of macrophage alternative (M2) polarization, and kidney fibrosis. Integrated bioinformatic analyses revealed
The Interplay between Mechanoregulation and ROS in Heart Physiology, Disease, and Regeneration
Authors: Arturo Elias‐Llumbet, Rokshana Sharmin, Kirstine Berg‐Sorensen, Romana Schirhagl, Aldona Mzyk
Journal: Advanced Healthcare Materials (2024)

Cardiovascular diseases are currently the most common cause of death in developed countries. Due to lifestyle and environmental factors, this problem is only expected to increase in the future. Reactive oxygen species (ROS) are a key player in the onset of cardiovascular diseases but also have important functions in healthy cardiac tissue. Here, the interplay between ROS generation and cardiac mechanical forces is shown, and the state of the art and a perspective on future directions are discussed. To this end, an overview of what is currently known regarding ROS and mechanosignaling at a subcellular level is first given. There the role of ROS in mechanosignaling as well as the interplay between both factors in specific organelles is emphasized. The consequences at a larger scale across the population of heart cells are then discussed. Subsequently, the roles of ROS in embryogenesis, pathogenesis, and aging are further discussed, exemplifying some aspects of mechanoregulation. Finally, different models that are currently in use are discussed to study the topics above.
Pivotal role of the endoplasmic reticulum stress-related XBP1s/miR-22/SIRT1 axis in acute myeloid leukemia apoptosis and response to chemotherapy
Authors: Céline Philippe, Manon Jaud, Kelly Féral, Alexandre Gay, Loïc Van Den Berghe, Manon Farce, Marina Bousquet, Stéphane Pyronnet, Laurent Mazzolini, Kevin Rouault-Pierre, Christian Touriol
Journal: Leukemia (2024)

Malignant growth relies on rapid protein synthesis frequently leading to endoplasmic reticulum (ER) overload and accumulation of unfolded or misfolded protein in this cellular compartment. In the ER, protein homeostasis is finely regulated by a mechanism called the unfolded protein response (UPR), involving the activation of signalization pathways mediated by three transmembrane proteins, namely PERK, IRE1 and ATF6. IRE1 endoribonuclease activation leads in particular to the splicing of the cytosolic mRNA encoding the key UPR-specific transcription factor XBP1s. Our study shows that sustained activation of XBP1s expression in acute myeloid leukemia (AML) cells induces apoptosis in vitro and in vivo, whereas a moderate XBP1s expression sensitizes cells to chemotherapeutic treatments. ChIP-seq experiments identified specific XBP1s target genes including the MIR22HG lncRNA, the precursor transcript of microRNA-22-3p. miR-22-3p upregulation by XBP1s or forced expression of miR-22 significantly decreases cell's viability and sensitizes leukemic cells to chemotherapy. We found that miR-22-3p intracellular effects result at least partially from the targeting of the mRNA encoding the deacetylase sirtuin-1 (SIRT1), a well-established pro-survival factor. Therefore, this novel XBP1s/miR-22/SIRT1 axis identified could play a pivotal role in the proliferation and chemotherapeutic response of leukemic cells.
Hyperglycemic Crises in Adults With Diabetes: A Consensus Report
Authors: Guillermo E. Umpierrez, Georgia M. Davis, Nuha A. ElSayed, Gian Paolo Fadini, Rodolfo J. Galindo, Irl B. Hirsch, David C. Klonoff, Rozalina G. McCoy, Shivani Misra, Robert A. Gabbay, Raveendhara R. Bannuru, Ketan K. Dhatariya
Journal: Diabetes Care (2024)

The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), Joint British Diabetes Societies for Inpatient Care (JBDS), American Association of Clinical Endocrinology (AACE), and Diabetes Technology Society (DTS) convened a panel of internists and diabetologists to update the ADA consensus statement on hyperglycemic crises in adults with diabetes, published in 2001 and last updated in 2009. The objective of this consensus report is to provide up-to-date knowledge about the epidemiology, pathophysiology, clinical presentation, and recommendations for the diagnosis, treatment, and prevention of diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) in adults. A systematic examination of publications since 2009 informed new recommendations. The target audience is the full spectrum of diabetes health care professionals and individuals with diabetes.
Reversible opening of the blood-labyrinth barrier by low-pressure pulsed ultrasound and microbubbles for the treatment of inner ear diseases
Authors: Yuanwei He, Ziyu Chen, Qinglang Liu, Zhiyang Li, Dingsheng Wen, Hong Zhang, Ming Zhang, Di Jiang, Huaan Li, Lu Wen, Gang Chen
Journal: Journal of Controlled Release (2024)
Enhanced diabetic wound healing with injectable hydrogel containing self-assembling nanozymes
Authors: Sicheng Jiang, Dingqi Xie, Zehui Hu, Honghai Song, Pan Tang, Yang Jin, Jiechao Xia, Yinwen Ji, Ying Xiao, Shuai Chen, Qinrui Fu, Jiayong Dai
Journal: Journal of Controlled Release (2024)
Immunogenicity-masking delivery of uricase against hyperuricemia and gout
Authors: Zhenglan Ban, Madi Sun, Huihong Ji, Quanxin Ning, Chuanxu Cheng, Tongfei Shi, Minghao He, Xuenian Chen, Huanfen Lu, Xuan He, Chenyang Guo, Yan He, Dan Shao, Yi He
Journal: Journal of Controlled Release (2024)
Dissolving microarray patches loaded with a rotigotine nanosuspension: A potential alternative to Neupro® patch
Authors: Yaocun Li, Jiawen Wang, Lalitkumar K Vora, Akmal Hidayat Bin Sabri, Mary B McGuckin, Alejandro J Paredes, Ryan F Donnelly
Journal: Journal of Controlled Release (2024)

Parkinson's disease (PD), affecting about ten million people globally, presents a significant health challenge. Rotigotine (RTG), a dopamine agonist, is currently administered as a transdermal patch (Neupro®) for PD treatment, but the daily application can be burdensome and cause skin irritation. This study introduces a combinatorial approach of dissolving microarray patch (MAP) and nanosuspension (NS) for the transdermal delivery of RTG, offering an alternative to Neupro®. The RTG-NS was formulated using a miniaturized media milling method, resulting in a nano-formulation with a mean particle size of 274.09 ± 7.43 nm, a PDI of 0.17 ± 0.04 and a zeta potential of -15.24 ± 2.86 mV. The in vitro dissolution study revealed an enhanced dissolution rate of the RTG-NS in comparison to the coarse RTG powder, under sink condition. The RTG-NS MAPs, containing a drug layer and a 'drug-free' supporting baseplate, have a drug content of 3.06 ± 0.15 mg/0.5 cm
Circulating receptor activator of nuclear factor kappa-B ligand (RANKL) levels predict response to immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC)
Authors: Michele Iuliani, Sonia Simonetti, Leonardo Cristofani, Silvia Cavaliere, Alessio Cortellini, Marco Russano, Bruno Vincenzi, Giuseppe Tonini, Daniele Santini, Francesco Pantano
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Receptor activator of nuclear factor kappa-B ligand (RANKL) can directly promote tumor growth and indirectly support tumor immune evasion by altering the tumor microenvironment and immune cell responses. This study aimed to assess the prognostic significance of soluble RANKL in patients with advanced non-small cell lung cancer (NSCLC) receiving programmed cell death 1 (PD1)/programmed death-ligand 1 (PDL1) checkpoint inhibitor therapy. Methods Plasma RANKL levels were measured in 100 patients with advanced NSCLC without bone metastases undergoing monotherapy with PD1/PDL1 checkpoint inhibitors. To establish the optimal cut-off value, we used the Cutoff Finder package in R. Survival curves for four distinct patient groups, according to their RANKL and PDL1 levels (high or low), were generated using the Kaplan-Meier method and compared with the log-rank test. The Cox regression model calculated HRs and 95% CIs for overall survival (OS) and progression-free survival (PFS). Results The optimal RANKL cut-off was established at 280.4 pg/mL, categorizing patients into groups with high or low RANKL levels. A significant association was observed between increased RANKL concentrations and decreased survival rates at 24 months, only within the subgroup expressing high levels of PDL1 (p=0.002). Additionally, low RANKL levels in conjunction with elevated PDL1 expression correlated with improved PFS (median 22 months, 95% CI 6.70 to 50 vs median 4 months, 95% CI 3.0 to 7.30, p=0.009) and OS (median 26 months, 95% CI 20 to not reached vs median 7 months, 95% CI 6 to 13, p=0.003), indicating RANKL’s potential as an indicator of adverse prognosis in these patients. Multivariate analysis identified RANKL as an independent negative prognostic factor for both PFS and OS, regardless of other clinicopathological features. Conclusion These results highlight the prognostic and predictive value of RANKL specifically in patients with high PDL1 expression.