tbuckley/cabot-search huggingface dataset:
Programmable Release of Chemotherapeutics from Ferrocene‐Based Injectable Hydrogels Slows Melanoma Growth
Authors: Rebecca Rothe, Yong Xu, Johanna Wodtke, Florian Brandt, Sebastian Meister, Markus Laube, Pier‐Luigi Lollini, Yixin Zhang, Jens Pietzsch, Sandra Hauser
Journal: Advanced Healthcare Materials (2024)

Abstract Hydrogel‐based injectable drug delivery systems provide temporally and spatially controlled drug release with reduced adverse effects on healthy tissues. Therefore, they represent a promising therapeutic option for unresectable solid tumor entities. In this study, a peptide‐starPEG/hyaluronic acid‐based physical hydrogel is modified with ferrocene to provide a programmable drug release orchestrated by matrix‐drug interaction and local reactive oxygen species (ROS). The injectable ROS‐responsive hydrogel (hiROSponse) exhibits adequate biocompatibility and biodegradability, which are important for clinical applications. HiROSponse is loaded with the two cytostatic drugs (hiROSponse dox/ptx ) doxorubicin (dox) and paclitaxel (ptx). Dox is a hydrophilic compound and its release is mainly controlled by Fickian diffusion, while the hydrophobic interactions between ptx and ferrocene can control its release and thus be regulated by the oxidation of ferrocene to the more hydrophilic state of ferrocenium. In a syngeneic malignant melanoma‐bearing mouse model, hiROSponse dox/ptx slows tumor growth without causing adverse side effects and doubles the relative survival probability. Programmable release is further demonstrated in a tumor model with a low physiological ROS level, where dox release, low dose local irradiation, and the resulting ROS‐triggered ptx release lead to tumor growth inhibition and increased survival.
A Diketopyrrolopyrrole‐Based All‐in‐One Nanoplatform for Self‐Reinforcing Mild Photothermal Therapy Cascade Immunotherapy for Tumors
Authors: Xinsheng Li, Lingyan Liu, Kaini Yang, Zhiqiang Wang, Tao Yuan, Qingyang Sha, Wei Chen, Tao Yi, Jianli Hua
Journal: Advanced Healthcare Materials (2024)

Abstract Mild photothermal therapy (PTT) has attracted attention for effectively avoiding the severe side effects associated with high‐temperature tumor ablation. However, its progress is hindered by the limited availability of high‐performance photothermal agents (PTAs) and the thermoresistance of cancer cells induced by heat shock reactions. Herein, this work proposes a new strategy to expand the library of high‐performance organic small‐molecule PTAs and utilize it to construct a multifunctional nano‐theranostic platform. By incorporating additional acceptors and appropriate π‐bridges, a diketopyrrolopyrrole‐based dye BDB is developed, which exhibits strong absorption and bright fluorescence emission in the near‐infrared (NIR) region. Subsequently, BDB is co‐coated with the heat shock protein (HSP) inhibitor tanespimycin (17‐AAG) using the functional amphiphilic polymers DSPE‐Hyd‐PEG 2000 ‐cRGD to form an all‐in‐one nanoplatform BAG NPs. As a result, BAG NPs can precisely target tumor tissue, guide the treatment process in real‐time through NIR‐II fluorescence/photoacoustic/photothermal imaging, and release 17‐AAG on demand to enhance mild PTT. Additionally, the mild PTT has been demonstrated to induce immunogenic cell death (ICD) and activate a systemic anti‐tumor immune response, thereby suppressing both primary and distant tumors. Overall, this study presents a multifunctional nanoplatform designed for precise mild PTT combined with immunotherapy for effective tumor treatment.
Exosomes from Hypoxia Preconditioned Muscle‐Derived Stem Cells Enhance Cell‐Free Corpus Cavernosa Angiogenesis and Reproductive Function Recovery
Authors: Tianwen Peng, Muyuan Chai, Zhicong Chen, Man Wu, Xiaomin Li, Feixue Han, Shuyan Chen, Chen Liao, Ming Yue, You‐Qiang Song, Hongkai Wu, Long Tian, Geng An
Journal: Advanced Healthcare Materials (2024)

Tissue engineering for penile corpora cavernosa defects requires microvascular system reconstruction.GelMA hydrogels show promise for tissue regeneration. However, using stem cells faces challenges such as immune rejection, limited proliferation and differentiation, and biosafety concerns. Therefore, acellular tissue regeneration may avoid these issues. Exosomes are used from muscle-derived stem cells (MDSCs) to modify 3D-printed hydrogel scaffolds for acellular tissue regeneration. Hypoxia-preconditioned MDSC-derived exosomes are obtained to enhance the therapeutic effect. In contrast to normoxic exosomes (N-Exos), hypoxic exosomes (H-Exos) are found to markedly enhance the proliferation, migration, and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). High-throughput sequencing analysis of miRNAs isolated from both N-Exos and H-Exos revealed a significant upregulation of miR-21-5p in H-Exos following hypoxic preconditioning. Further validation demonstrated that the miR-21-5p/PDCD4 pathway promoted the proliferation of HUVECs. Epigallocatechin gallate (EGCG) is introduced to improve the mechanical properties and biocompatibility of GelMA hydrogels. EGCG-GelMA scaffolds loaded with different types of Exos are transplanted to repair rabbit penile corpora cavernosa defects, observed the blood flow and repair status of the defect site through color Doppler ultrasound and magnetic resonance imaging, and ultimately restored the rabbit penile erection function and successfully bred offspring. Thus, acellular hydrogel scaffolds offer an effective treatment for penile corpora cavernosa defects.
Systemic Administration of Neurotransmitter‐Derived Lipidoids‐PROTACs‐DNA Nanocomplex Promotes Tau Clearance and Cognitive Recovery for Alzheimer's Disease Therapy
Authors: Baofeng Gong, Weicong Zhang, Wei Cong, Yuankai Gu, Wenbo Ji, Tong Yin, Honglei Zhou, Honggang Hu, Jianhua Zhuang, Yi Luo, Yan Liu, Jie Gao, You Yin
Journal: Advanced Healthcare Materials (2024)

Abstract Alzheimer's disease (AD) poses a significant burden on the economy and healthcare systems worldwide. Although the pathophysiology of AD remains debatable, its progression is strongly correlated with the accumulation of tau aggregates. Therefore, tau clearance from brain lesions can be a promising strategy for AD therapy. To achieve this, the present study combined proteolysis‐targeting chimera (PROTAC), a novel protein‐degradation technique that mediates degradation of target proteins via the ubiquitin‐proteasome system, and a neurotransmitter‐derived lipidoid (NT‐lipidoid) nanoparticle delivery system with high blood‐brain barrier‐penetration activity, to generate a novel nanomedicine named NPD. Peptide 1, a cationic tau‐targeting PROTAC is loaded onto the positively charged nanoparticles using DNA‐intercalation technology. The resulting nanomedicine displayed good encapsulation efficiency, serum stability, drug release profile, and blood‐brain barrier‐penetration capability. Furthermore, NPD potently induced tau clearance in both cultured neuronal cells and the brains of AD mice. Moreover, intravenous injection of NPD led to a significant improvement in the cognitive function of the AD mice, without any remarkable abnormalities, thereby supporting its clinical development. Collectively, the novel nanomedicine developed in this study may serve as an innovative strategy for AD therapy, since it effectively and specifically induces tau protein clearance in brain lesions, which in turn enhances cognition.
Neutrophil extracellular traps in cancer
Authors: Yuxi Ma, Jielin Wei, Wenshan He, Jinghua Ren
Journal: MedComm (2024)

Neutrophil extracellular traps (NETs), which consist of chromatin DNA studded with granule proteins, are released by neutrophils in response to both infectious and sterile inflammation. Beyond the canonical role in defense against pathogens, the extrusion of NETs also contributes to the initiation, metastasis, and therapeutic response of malignant diseases. Recently, NETs have been implicated in the development and therapeutic responses of various types of tumors. Although extensive work regarding inflammation in tumors has been reported, a comprehensive summary of how these web-like extracellular structures initiate and propagate tumor progression under the specific microenvironment is lacking. In this review, we demonstrate the initiators and related signaling pathways that trigger NETs formation in cancers. Additionally, this review will outline the current molecular mechanisms and regulatory networks of NETs during dormant cancer cells awakening, circulating tumor cells (CTCs) extravasation, and metastatic recurrence of cancer. This is followed by a perspective on the current and potential clinical potential of NETs as therapeutic targets in the treatment of both local and metastatic disease, including the improvement of the efficacy of existing therapies.
Exosome nanovesicles: biomarkers and new strategies for treatment of human diseases
Authors: Chuan Xu, Chaoyang Jiang, Zhihui Li, Hui Gao, Jing Xian, Wenyan Guo, Dan He, Xingchen Peng, Daijun Zhou, Dong Li
Journal: MedComm (2024)

Exosomes are nanoscale vesicles of cellular origin. One of the main characteristics of exosomes is their ability to carry a wide range of biomolecules from their parental cells, which are important mediators of intercellular communication and play an important role in physiological and pathological processes. Exosomes have the advantages of biocompatibility, low immunogenicity, and wide biodistribution. As researchers' understanding of exosomes has increased, various strategies have been proposed for their use in diagnosing and treating diseases. Here, we provide an overview of the biogenesis and composition of exosomes, describe the relationship between exosomes and disease progression, and focus on the use of exosomes as biomarkers for early screening, disease monitoring, and guiding therapy in refractory diseases such as tumors and neurodegenerative diseases. We also summarize the current applications of exosomes, especially engineered exosomes, for efficient drug delivery, targeted therapies, gene therapies, and immune vaccines. Finally, the current challenges and potential research directions for the clinical application of exosomes are also discussed. In conclusion, exosomes, as an emerging molecule that can be used in the diagnosis and treatment of diseases, combined with multidisciplinary innovative solutions, will play an important role in clinical applications.
Detection of minimal hepatic encephalopathy in patients with cirrhosis based on the Stroop‐CN model (NCRCID‐CHESS 2106): a prospective multicenter study
Authors: Xiaoyan Li, Shanghao Liu, Ying Guo, Hongmei Zu, Huiling Xiang, Shaoqi Yang, Xiaoning Zhang, Fanping Meng, Yangzhen Bianba, Jie Li, Fei Liu, Chuang Lei, Jiaojian Lv, Qiao‐hua Yang, Wei Fu, Wei Ye, Jiafang Chen, Yanjing Gao, Caiyun Wu, Ningning Wang, Qi Zheng, Fang Wang, Jiali Yu, Jing Wang, Xiaoting Yang, Xiangmei Wang, Yayuan Liu, Xuelan Zhao, Chenxi Wu, Wei Gou, Jasmohan S. Bajaj, Fu‐Sheng Wang, Junliang Fu, Xiaolong Qi
Journal: MedComm (2024)

Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop-CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop-CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child-Pugh grades and the Model for End-stage Liver Disease and Sodium (MELD-Na) scores in the test and validation cohort. The EuroQol 5-D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop-CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.
Single‐cell atlas of peripheral blood by CyTOF revealed peripheral blood immune cells metabolic alterations and neutrophil changes in intracranial aneurysm rupture
Authors: Xiaolong Ya, Chenglong Liu, Long Ma, Peicong Ge, Xiaoxue Xu, Zhiyao Zheng, Siqi Mou, Rong Wang, Qian Zhang, Xun Ye, Dong Zhang, Yan Zhang, Wenjing Wang, Hao Li, Jizong Zhao
Journal: MedComm (2024)

Previous studies have found that the peripheral immune environment is closely related to the occurrence and development of intracranial aneurysms. However, it remains unclear how the metabolism of peripheral blood mononuclear cells (PBMCs) and the composition of polymorphonuclear leukocytes (PMNs) changes in the process of intracranial aneurysm rupture. This study utilized cytometry by time of flight technology to conduct single-cell profiling analysis of PBMCs and PMNs from 72 patients with IAs. By comparing the expression differences of key metabolic enzymes in PBMCs between patients with ruptured intracranial aneurysms (RIAs) and unruptured intracranial aneurysms, we found that most PBMCs subsets from RIA group showed upregulation of rate-limiting enzymes related to the glycolytic pathway. By comparing the composition of PMNs, it was found that the proinflammatory CD101+HLA DR+ subsets were increased in the RIA group, accompanied by a decrease in the anti-inflammatory polymorphonuclear myeloid-derived suppressor cells. In conclusion, this study showed the changes in the peripheral immune profile of RIAs, which is helpful for our understanding of the mechanisms underlying peripheral changes and provides a direction for future related research.
Loss of Y Chromosome and Cardiovascular Events in Chronic Kidney Disease
Authors: Michael Weyrich, Sebastian Cremer, Martin Gerster, Tamim Sarakpi, Tina Rasper, Stephen Zewinger, Sammy R. Patyna, David M. Leistner, Gunnar H. Heine, Christoph Wanner, Winfried März, Danilo Fliser, Stefanie Dimmeler, Andreas M. Zeiher, Thimoteus Speer
Journal: Circulation (2024)

Chronic kidney disease represents one of the strongest risk factors for cardiovascular diseases, and particularly for heart failure. Despite improved pharmaceutical treatments, mortality remains high. Recently, experimental studies demonstrated that mosaic loss of Y chromosome (LOY) associates with cardiac fibrosis in male mice. Since diffuse cardiac fibrosis is the common denominator for progression of all forms of heart failure, we determined the association of LOY on mortality and cardiovascular disease outcomes in patients with chronic kidney disease.
Novel Long Noncoding RNA <i>HEAT4</i> Affects Monocyte Subtypes, Reducing Inflammation and Promoting Vascular Healing
Authors: Jasmin M. Kneuer, Ignacy A. Grajek, Melanie Winkler, Stephan Erbe, Tim Meinecke, Ronald Weiss, Tania Garfias-Veitl, Bilal N. Sheikh, Ann-Christine König, Maximilian N. Möbius-Winkler, Alexander Kogel, Karl-Patrik Kresoja, Sebastian Rosch, Karoline E. Kokot, Vanina Filipova, Susanne Gaul, Holger Thiele, Philipp Lurz, Stephan von Haehling, Thimoteus Speer, Ulrich Laufs, Jes-Niels Boeckel
Journal: Circulation (2024)

Activation of the immune system contributes to cardiovascular diseases. The role of human-specific long noncoding RNAs in cardioimmunology is poorly understood.
Comprehensive and deep evaluation of structural variation detection pipelines with third-generation sequencing data
Authors: Zhi Liu, Zhi Xie, Miaoxin Li
Journal: Genome biology (2024)

Structural variation (SV) detection methods using third-generation sequencing data are widely employed, yet accurately detecting SVs remains challenging. Different methods often yield inconsistent results for certain SV types, complicating tool selection and revealing biases in detection.
Metabolic Reprogramming Is an Initial Step in Pancreatic Carcinogenesis That Can Be Targeted to Inhibit Acinar-to-Ductal Metaplasia
Authors: Thorsten Neuß, Min-Chun Chen, Nils Wirges, Sinem Usluer, Rupert Oellinger, Svenja Lier, Michael Dudek, Tobias Madl, Martin Jastroch, Katja Steiger, Werner Schmitz, Henrik Einwächter, Roland M. Schmid
Journal: Cancer Research (2024)

Abstract Metabolic reprogramming is a hallmark of cancer and is crucial for cancer progression, making it an attractive therapeutic target. Understanding the role of metabolic reprogramming in cancer initiation could help identify prevention strategies. To address this, we investigated metabolism during acinar-to-ductal metaplasia (ADM), the first step of pancreatic carcinogenesis. Glycolytic markers were elevated in ADM lesions compared with normal tissue from human samples. Comprehensive metabolic assessment in three mouse models with pancreas-specific activation of KRAS, PI3K, or MEK1 using Seahorse measurements, nuclear magnetic resonance metabolome analysis, mass spectrometry, isotope tracing, and RNA sequencing analysis revealed a switch from oxidative phosphorylation to glycolysis in ADM. Blocking the metabolic switch attenuated ADM formation. Furthermore, mitochondrial metabolism was required for de novo synthesis of serine and glutathione (GSH) but not for ATP production. MYC mediated the increase in GSH intermediates in ADM, and inhibition of GSH synthesis suppressed ADM development. This study thus identifies metabolic changes and vulnerabilities in the early stages of pancreatic carcinogenesis. Significance: Metabolic reprogramming from oxidative phosphorylation to glycolysis mediated by MYC plays a crucial role in the development of pancreatic cancer, revealing a mechanism driving tumorigenesis and potential therapeutic targets. See related commentary by Storz, p. 2225
Is There a Mathematician on Board?
Authors: Elana J. Fertig
Journal: Cancer Research (2024)

Abstract As convergence science is emerging as a theme in cancer research, scientists from diverse backgrounds, including mathematics, are increasingly entering our research community. The captain of a Southwest Airlines flight recently paged in jest for a mathematician to help support fuel calculations that would enable a flight to arrive safely at the American Association for Cancer Research (AACR) Annual Meeting, epitomizing the need for well-trained mathematicians to address pressing problems. Here, we summarize the roles mathematicians can play in cancer research and the support needed to facilitate their entry into the cancer research field. The inclusion of scientific diversity across quantitative and engineering disciplines is critical for advancing the understanding and treatment of cancer.
Earliest Metabolic Changes Associated with the Initiation of Pancreatic Cancer
Authors: Peter Storz
Journal: Cancer Research (2024)

Pancreatic cancer is usually detected at a late stage, when tumors have already metastasized; therefore, it has a poor prognosis with a 5-year survival rate of 11% to 12%. A key to targeting this high mortality is to develop methods for detecting the disease at a stage in which it is still local to the pancreas. However, this needs a better understanding of the events that govern pancreatic cancer oncogenesis. In this issue of Cancer Research, Neuß and colleagues report metabolic changes associated with acinar-to-ductal metaplasia (ADM), an initiating event that leads to the formation of precursor lesions for pancreatic ductal adenocarcinoma (PDAC). Their findings reveal a switch to aerobic glycolysis, increased c-MYC signaling, and increased serine metabolism as driving factors for the ADM process. These findings are important as they demonstrate that metabolic changes that drive the proliferation and metastasis of full-blown PDAC begin in the earliest lesions. The data not only provide insights into how PDAC develops but also a potential explanation for previously described findings, such as circulating lesion cells can be detected even when no carcinoma in situ is present. In summary, this article is highly relevant for furthering our understanding of how metabolic reprogramming drives the earliest events leading to PDAC development and could lay the groundwork for developing methods for early detection or intervention. See related article by Neuß et al., p. 2297
Evolution and Functional Differentiation of the C-terminal Motifs of FtsZs during Plant Evolution
Authors: Jinjie An, Lulu Wang, Conghao Hong, Hongbo Gao
Journal: Molecular Biology and Evolution (2024)

Abstract Filamentous temperature-sensitive Z (FtsZ) is a tubulin-like GTPase that is highly conserved in bacteria and plants. It polymerizes into a ring at the division site of bacteria and chloroplasts and serves as the scaffold protein of the division complex. While a single FtsZ is present in bacteria and cyanobacteria, there are two subfamilies, FtsZ1 and FtsZ2 in the green lineage, and FtsZA and FtsZB in red algae. In Arabidopsis thaliana, the C-terminal motifs of AtFtsZ1 (Z1C) and AtFtsZ2-1 (Z2C) display distinct functions in the regulation of chloroplast division. Z1C exhibits weak membrane-binding activity, whereas Z2C engages in the interaction with the membrane protein AtARC6. Here, we provide evidence revealing the distinct traits of the C-terminal motifs of FtsZ1 and FtsZ2 throughout the plant evolutionary process. In a range of plant species, the C-terminal motifs of FtsZ1 exhibit diverse membrane-binding properties critical for regulating chloroplast division. In chlorophytes, the C-terminal motifs of FtsZ1 and FtsZ2 exhibit both membrane-binding and protein interaction functions, which are similar to those of cyanobacterial FtsZ and red algal FtsZA. During the transition from algae to land plants, the functions of the C-terminal motifs of FtsZ1 and FtsZ2 exhibit differentiation. FtsZ1 lost the function of interacting with ARC6 in land plants, and the membrane-binding activity of FtsZ2 was lost in ferns. Our findings reveal the functional differentiation of the C-terminal motifs of FtsZs during plant evolution, which is critical for chloroplast division.
Utility of gingival crevicular fluid components for periodontal diagnosis
Authors: Nurcan Buduneli, Başak Bıyıkoğlu, Denis F. Kinane
Journal: Periodontology 2000 (2024)

Periodontal diseases are highly prevalent chronic diseases, and severe periodontitis creates functional and esthetic problems and decreases self-esteem for a large percentage of the older population worldwide. In many cases of periodontitis, there is no distinct tell-tale pain that motivates a patient to seek treatment, rather the signs become clinically detectable late, and typically when the disease has progressed to a problematic level for the life of the dentition. Early periodontal screening and diagnostics tools will provide early recognition of periodontal diseases and facilitate timely management of the disease to reduce tooth loss. To this goal, gingival crevicular fluid is easily sampled, can be repeatedly and non-invasively collected, and can be tested for potential biomarkers. Moreover, the site specificity of periodontal diseases enhances the usefulness of gingival crevicular fluid sampled from specific sites as a biofluid for diagnosis and longitudinal monitoring of periodontal diseases. The present review aimed to provide up-to-date information on potential diagnostic biomarkers with utility that can be assayed from gingival crevicular fluid samples, focusing on what is new and useful and providing only general historic background textually and in a tabulated format.