tbuckley/cabot-search huggingface dataset:
Discovery of indole analogue Tc3 as a potent pyroptosis inducer and identification of its combination strategy against hepatic carcinoma
Authors: Xiao Hu, Xiaomei Tang, Xiaoman Tian, Xing Lv, Yuanyuan Zhang, Yingyue Pang, Weilong Deng, Yali Wang, Changliang Shan, Luqing Shang
Journal: Theranostics (2024)

Rationale: Hepatic carcinoma, one of the most malignant cancers in the world, has limited success with immunotherapy and a poor prognosis in patients.While pyroptosis is considered as a promising immunotherapy strategy for tumors, it still suffers from a lack of effective inducers.Methods: We designed, synthesized and screened an indole analogue, Tc3, featuring a 2, 4-thiazolidinedione substituted indole scaffold.Western blotting, qPCR and immunofluorescence were employed to detect the levels of pyroptosis pathway induced by Tc3.RNA sequencing was used to identify the mechanisms of Tc3 in hepatic carcinoma.To validate anti-tumor effect of Tc3, we used CDXs and PDXs mouse models in vivo.Then, the syngeneic effects of Tc3 with cisplatin and anti-PD-1 antibody were verified via western blotting, immunofluorescence, flow cytometry and ELISA.Results: Treatment with Tc3 notably inhibited the growth of hepatic carcinoma both in vitro and in vivo.Mechanistically, Tc3 inhibited the function of PRDX1 and up-regulated excessive ROS.Then, Tc3 induced gasderminE-mediated pyroptosis by activating the endoplasmic reticulum stress.Tumor cells with high expression of GSDME achieved better responses to Tc3-therapy.Tc3 also improved the efficacy of cisplatin against hepatic carcinoma.Additionally, superior synergistic treatment was observed when Tc3 was combined with anti-PD-1 antibody.Notably, Tc3 activated the tumor immune microenvironment (TIME) and enhanced CD8 + T cell infiltration in hepatic carcinoma.Conclusions: Collectively, we identified Tc3 as a promising and effective compound for treating hepatic carcinoma and established its synergistic therapeutic strategy as a pyroptosis inducer.
Regulation of ezrin tension by S-nitrosylation mediates non-small cell lung cancer invasion and metastasis: Erratum
Authors: Xiaolong Zhang, Guangming Li, Yichen Guo, Ying Song, Linlin Chen, Qinli Ruan, Yifan Wang, Lixia Sun, Yunfeng Hu, Jingwen Zhou, Bin Ren, Jun Guo
Journal: Theranostics (2024)

[This corrects the article DOI: 10.7150/thno.32479.].
Hypoxia-responsive nanoparticles for fluorescence diagnosis and therapy of cancer
Authors: Yubing Zhang, Jiaqi Xing, Juan Jiang, Maoliang Liao, Guojun Pan, Yanfeng Wang
Journal: Theranostics (2024)

Hypoxia, caused by rapid tumor growth and insufficient oxygen supply, is a defining characteristic of numerous solid tumors and exerts a significant influence on tumor growth, metastasis, and invasion.Early diagnosis and effective killing of tumor cells are crucial for cancer treatment.In recent years, the emergence of nanomaterials has overcome the difficulties in the delivery of chemotherapeutic drugs and contrast agents to tumor area.In this review, we summarize the development of hypoxia-responsive nanoparticles for fluorescence imaging and tumor therapy in the last five years, and further discuss their design strategies and applications in bioimaging.In addition, we discuss the therapeutic strategies of hypoxia-responsive prodrugs on different nanoplatforms and the future prospects of hypoxia-responsive nanomedicine in tumor therapy.
Cancer-targeted pro-theranostic bi-metallic organo-coordination nanoparticles
Authors: Hengbo Huang, Lei Fang, Janaka Wansapura, Julie L. Prior, Brad Manion, Baogang Xu, Cody Hongsermeier, Nisha Gamadia, Nicole Blasi, Rui Tang, Christopher Egbulefu, Monica Shokeen, James D. Quirk, Samuel Achilefu
Journal: Theranostics (2024)

Rationale: Cancer remains a leading cause of mortality, with aggressive, treatment-resistant tumors posing significant challenges.Current combination therapies and imaging approaches often fail due to disparate pharmacokinetics and difficulties correlating drug delivery with therapeutic response.Methods: In this study, we developed radionuclide-activatable theranostic nanoparticles (NPs) comprising folate receptor-targeted bimetallic organo-nanoparticles (Gd-Ti-FA-TA NPs).Polyvalent tannic acid was used to coordinate titanium (Ti), a reactive oxygen species (ROS)-generating catalyst, gadolinium (Gd), a magnetic resonance imaging (MRI) contrast agent, and cypate, a near-infrared fluorescent dye. Results:The NPs exhibited higher magnetic field-dependent relaxivities (r1 = 20.8mM⁻¹s⁻¹, r2 = 72.1 mM⁻¹s⁻¹) than Gd-DTPA (r1 = 4.8 mM⁻¹s⁻¹, r2 = 4.9 mM⁻¹s⁻¹) on a 3 T MRI scanner.Tannic acid coordination reduced the Ti band gap from 3.3 eV in TiO₂ NPs to 2.0 eV, tripling ROS generation under UV light exposure.In breast cancer models (4T1 and PyMT-Bo1), Cerenkov radiating radiopharmaceuticals activated Gd-Ti-FA-TA NPs in vitro and in vivo, generating cytotoxic ROS to inhibit tumor cell viability and prevent tumor progression.In vivo, the NPs selectively accumulated in 4T1 tumors and enhanced both T1 and T2 MRI contrast, highlighting a strategy to locally activate cytotoxic ROS generation with radiopharmaceuticals for cancer treatment, utilizing cross-modality PET/MRI and optical imaging for shallow and deep tissue visualization. Conclusion:The integrated nanoplatform allows direct imaging of drug delivery, providing guidance for the optimal timeline to activate therapeutic effects of pro-theranostic NPs via external triggers such as radionuclide-stimulated dynamic treatment.
RPS23RG1 inhibits SORT1-mediated lysosomal degradation of MDGA2 to protect against autism
Authors: Yuanhui Huo, Dongdong Zhao, Xiang Zhu, Naizhen Zheng, Dingting Yang, Jian Meng, Yiqing Chen, Yun-wu Zhang
Journal: Theranostics (2024)

Rationale: Mutations in the synaptic protein MAM domain containing glycosylphosphatidylinositol anchor 2 (MDGA2) have been associated with autism spectrum disorder (ASD).Therefore, elucidating the regulatory mechanisms of MDGA2 can help develop effective treatments for ASD.Methods: Liquid chromatography-tandem mass spectrometry was carried out to identify proteins interacting with the extracellular domain of RPS23RG1 and with MDGA2, followed by co-immunoprecipitation assays to confirm protein-protein interactions.RPS23RG1 and SORT1 levels were downregulated by siRNAs to study their effects on MDGA2 degradation, with additional applications of immunoblotting and immunostaining assays.Lysosome isolation was performed to determine the lysosomal degradation of MDGA2 further.Rps23rg1 knockout mice and Mdga2 +/-mice were subjected to various behavioral tests to study their ASD-like phenotypes.AAVs expressing MDGA2 were delivered in Rps23rg1 knockout mice, and RPS23RG1-derived peptide was delivered in Mdga2 +/- mice to study their rescuing effects.Results: We found that both RPS23RG1 and SORT1 interacted with MDGA2.MDGA2 was primarily degraded through the SORT1-mediated lysosomal degradation pathway.RPS23RG1 competed with SORT1 for MDGA2 binding to inhibit MDGA2 degradation.Furthermore, we showed that Rps23rg1 knockout mice exhibited decreased MDGA2 levels and ASD-like behaviors, whereas restoration of MDGA2 levels attenuated social defects in Rps23rg1 KO mice.Moreover, we identified a crucial region of RPS23RG1 for MDGA2 interaction and found that a peptide derived from this region not only bound MDGA2 and promoted MDGA2 levels, but also rescued social defects in Mdga2 +/-mice.Conclusion: Our findings highlight a crucial role of RPS23RG1 in antagonizing SORT1-mediated lysosomal degradation of MDGA2 and suggest a potential for targeting the RPS23RG1-MDGA2 axis to treat ASD with MDGA2 deficiency.
Octopod PtCu Nanoframe for Dual-Modal Imaging-Guided Synergistic Photothermal Radiotherapy: Erratum
Authors: Jinghua Li, Xiangyang Zu, Gaofeng Liang, KeKe Zhang, Yuliang Liu, Ke Li, Zhong Luo, Kaiyong Cai
Journal: Theranostics (2024)

[This corrects the article DOI: 10.7150/thno.22557.].
Piezo1 specific deletion in macrophage protects the progression of liver fibrosis in mice: Erratum
Authors: Shangfei Luo, Xiaoduo Zhao, Jintao Jiang, Bo Deng, Silin Liu, Honglin Xu, Qiaorui Tan, Yu'an Chen, Ziyan Zhang, Xianmei Pan, Rentao Wan, Xiaoting Chen, Youfen Yao, Jing Li
Journal: Theranostics (2024)

[This corrects the article DOI: 10.7150/thno.86103.].
Transferrin-binding domain inserted-adenovirus hexon engineering enables systemic immune evasion and intratumoral T-cell activation
Authors: Dae Hoon Lee, Youngtae Kwon, Ki Hwan Um, Jung Ki Yoo, Wootae Ha, Ki-Su Kim, Jintak Cha, Ha-Eun Cho, Kyung Sun Park, Min Jeong Kye, Jin Woo Choi
Journal: Theranostics (2024)

Rationale: Adenovirus-based therapies have encountered significant challenges due to host immunity, particularly from pre-existing antibodies.Many trials have struggled to evade antibody response; however, the efficiency of these efforts was limited by the diversity of antibody Fv-region recognizing multiple amino acid sequences.Methods: In this study, we developed an antibody-evading adenovirus vector by encoding a plasma-rich protein transferrin-binding domain.The coding sequence was employed from Neisseria Meningitides and inserted in the experimentally-optimized site within the adenovirus capsid protein.Result: This engineered antibody-evading oncolytic adenovirus overcame the reduction in productivity and infectivity typically caused by the insertion of a foreign domain.We observed decreased immune recognition and compromised formation of anti-adenovirus antibodies.Furthermore, the anti-tumor efficacy was demonstrated both in vitro and in vivo, with increased recruitment of CD8 + T cells.Conclusion: This novel antibody-evading strategy effectively evades neutralizing antibodies and innate immunity while boosting cytotoxic immunity by recruiting CD8 + T cells at the tumor site.Additionally, this strategy holds potential for application in other gene therapies and adenovirus vectors.
Tumor cell-derived lactic acid inhibits the interaction between PD-L1 protein and PD-L1 antibody in the PD-1/PD-L1 blockade therapy-resistant tumor
Authors: Wonkyung Oh, Alyssa Min Jung Kim, Deepika Dhawan, Deborah W Knapp, Seung-Oe Lim
Journal: Molecular Therapy (2024)
IVIM-Morph: Motion-compensated quantitative Intra-voxel Incoherent Motion (IVIM) analysis for functional fetal lung maturity assessment from diffusion-weighted MRI data
Authors: Noga Kertes, Yael Zaffrani-Reznikov, Onur Afacan, Sila Kurugol, Simon K. Warfield, Moti Freiman
Journal: Medical Image Analysis (2024)
Two Hits of EDCs Three Generations Apart: Evaluating Multigenerational Anxiety-Like Behavioral Phenotypes in Male Rats Exposed to Aroclor 1221 and Vinclozolin
Authors: Emily N. Hilz, Ross Gillette, Lindsay M. Thompson, David Crews, Andrea C. Gore
Journal: Environmental Health Perspectives (2024)

Increasing evidence supports an association of endocrine-disrupting chemical (EDC) exposures with adverse biological effects in humans and wildlife. Recent studies reveal that health consequences of environmental exposures may persist or emerge across generations. This creates a dual conundrum: that we are exposed to contemporary environmental chemicals overlaid upon the inheritance of our ancestors' exposure profiles. Even when legacy EDCs are phased out, they may remain relevant due to persistence in the environment together with intergenerational inheritance of their adverse biological effects. Thus, we all possess a body burden of legacy contaminants, and we are also increasingly exposed to new generations of EDCs.
Two Hits of EDCs Three Generations Apart: Evaluating Multigenerational Anxiety-Like Behavioral Phenotypes in Female Rats Exposed to Aroclor 1221 and Vinclozolin
Authors: Emily N. Hilz, Ross Gillette, Lindsay M. Thompson, Lexi Ton, Timothy Pham, M. Nicole Kunkel, David Crews, Andrea C. Gore
Journal: Environmental Health Perspectives (2024)

Endocrine-disrupting chemicals (EDCs) are exogenous chemical compounds that interfere with the normal function of the endocrine system and are linked to direct and inherited adverse effects in both humans and wildlife. Legacy EDCs such as polychlorinated biphenyls (PCBs) are no longer used yet remain detectable in biological specimens around the world; concurrently, we are exposed to newer EDCs like the fungicide vinclozolin (VIN). This combination of individuals' direct environmental chemical exposures and any heritable changes caused by their ancestors' chemical exposures leads to a layered pattern of both direct and ancestrally inherited exposures that might have cumulative effects over generations.
Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression
Authors: Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason
Journal: American Journal of Psychiatry (2025)

Unlike classical antidepressants, psychedelics such as psilocybin have been shown to induce a rapid antidepressant response. In the wake of this development, interest has emerged in ultra-fast, short-acting psychedelics such as 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and N,N-dimethyltryptamine (DMT) with the expectation that these can produce rapid antidepressant effects following an intense but brief psychedelic intervention. The current paper reviews the clinical pharmacology of 5-MeO-DMT and DMT and their potential benefits and challenges in the treatment of depression. Both compounds display affinities for a variety of monoamine receptors and transporters, but mostly so for serotonergic (5HT) receptors, including 5HT
Single-Dose Psilocybin for Depression With Severe Treatment Resistance: An Open-Label Trial
Authors: Scott T. Aaronson, Andrew van der Vaart, Tammy Miller, Jeffrey LaPratt, Kimberly Swartz, Audrey Shoultz, Margo Lauterbach, Trisha Suppes, Harold A. Sackeim
Journal: American Journal of Psychiatry (2025)

Depression varies along a difficulty-to-treat spectrum. Patients whose illness fails to respond to at least five treatments may be considered to have severely treatment-resistant depression (TRD). The objective of this study was to document the safety and efficacy of psilocybin in patients with severe TRD.
Research and Implementation of Psychedelic-Assisted Therapy in the Veterans Health Administration
Authors: Aaron S. Wolfgang, Vetisha L. McClair, Paula P. Schnurr, Paul E. Holtzheimer, Josh D. Woolley, Christopher S. Stauffer, R. Cameron Wolf, Leith J. States, David M. Benedek, Vincent F. Capaldi, John Bradley, Matthew A. Fuller, Miriam J. Smyth, Eric D. A. Hermes, Wendy Tenhula, Ilse R. Wiechers
Journal: American Journal of Psychiatry (2025)
Psychedelics for the Treatment of Psychiatric Disorders: Interpreting and Translating Available Evidence and Guidance for Future Research
Authors: Roger S. McIntyre, Angela T. H. Kwan, Rodrigo B. Mansur, Albino J. Oliveira-Maia, Kayla M. Teopiz, Vladimir Maletic, Trisha Suppes, Stephen M. Stahl, Joshua D. Rosenblat
Journal: American Journal of Psychiatry (2025)

During the past decade, there has been extraordinary public, media, and medical research interest in psychedelics as promising therapeutics for difficult-to-treat psychiatric disorders. Short-term controlled trial data suggest that certain psychedelics are effective and safe in the treatment of major depressive disorder, treatment-resistant depression, and posttraumatic stress disorder. Preliminary evidence also supports efficacy in other psychiatric disorders (e.g., tobacco and alcohol use disorders). Notwithstanding the interest and promise of psychedelics, concerns have arisen with respect to the interpretability and translatability of study results. For example, aspects related to short- and long-term safety, abuse liability, and the essentiality of the psychedelic "trip" and psychological support are, inter alia, insufficiently characterized with psychedelic agents. The overarching aims in this overview are 1) to review methodological aspects that affect inferences and interpretation of extant psychedelic studies in psychiatric disorders, and 2) to provide guidance for future research and development of psychedelic treatment in psychiatry, critical to study interpretation and clinical implementation.
Primum Non Nocere: The Onus to Characterize the Potential Harms of Psychedelic Treatment
Authors: Sharmin Ghaznavi, Jeremy N. Ruskin, Stephen J. Haggerty, Franklin King, Jerrold F. Rosenbaum
Journal: American Journal of Psychiatry (2025)

The last few years have seen exponential growth in interest, investment, advocacy, and research into psychedelics as therapeutics. This reflects an optimism about the potential promise of psychedelics as therapeutics. As with all therapeutic interventions, research is needed not only into their benefits but also potential risks. Indeed, when substances with therapeutic potential are scrutinized over time, especially in broad populations with psychiatric and medical comorbidities typically excluded from clinical trials, and applied in less well-regulated or controlled settings, a greater understanding of the cautions emerges. Here, we review the literature on the known and potential harms, including enduring perceptual disturbances; triggering or enhancing the risk for onset of mania or psychosis; overuse, misuse, and dependence; challenging experiences or "bad trips"; risks associated with increased neuroplastic potential; and acute and cumulative cardiovascular effects. Each of these issues is addressed in this review, along with the call for continued research, including recommendations for further research and monitoring.
Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial
Authors: Broc A. Pagni, Richard J. Zeifman, Sarah E. Mennenga, Brennan M. Carrithers, Noam Goldway, Snehal Bhatt, Kelley C. O’Donnell, Stephen Ross, Michael P. Bogenschutz
Journal: American Journal of Psychiatry (2025)

Evidence suggests that psilocybin-assisted therapy (PAT) leads to durable shifts in personality structure. However, such changes have yet to be characterized in disorders of addiction. In this secondary analysis from a randomized controlled trial, the authors examined the effect of PAT on personality dimensions in patients with alcohol use disorder (AUD), hypothesizing that PAT would attenuate personality abnormalities in AUD and that reductions in trait impulsiveness would be associated with lower drinking.
<scp>BLOC1S1</scp> Control of Vacuolar Organelle Fidelity Modulates Murine <scp>T<sub>H</sub>2</scp> Cell Immunity and Allergy Susceptibility
Authors: Rahul Sharma, Kaiyuan Wu, Kim Han, Anna Chiara Russo, Pradeep K. Dagur, Christian A. Combs, Xianglan Yao, Stewart J. Levine, Michael N. Sack
Journal: Allergy (2024)

The levels of biogenesis of lysosome organelles complex 1 subunit 1 (BLOC1S1) control mitochondrial and endolysosome organelle homeostasis and function. Reduced fidelity of these vacuolar organelles is increasingly being recognized as important in instigating cell-autonomous immune cell activation. We reasoned that exploring the role of BLOC1S1 in CD4
Spatial proteomics reveals sirtuin 1 to be a determinant of T-cell infiltration in human melanoma
Authors: Jan-Malte Placke, Jenny Bottek, Renata Váraljai, Batool Shannan, Sarah Scharfenberg, Christoph Krisp, Philippa Spangenberg, Camille Soun, Devon Siemes, Lars Borgards, Franziska Hoffmann, Fang Zhao, Anette Paschen, Hartmut Schlueter, Ferdinand von Eggeling, Iris Helfrich, Florian Rambow, Selma Ugurel, Alpaslan Tasdogan, Dirk Schadendorf, Daniel R Engel, Alexander Roesch
Journal: British Journal of Dermatology (2024)

Abstract Background The tumour microenvironment significantly influences the clinical response of patients to therapeutic immune checkpoint inhibition (ICI), but a comprehensive understanding of the underlying immune-regulatory proteome is still lacking. Objectives To decipher targetable biologic processes that determine tumour-infiltrating lymphocytes (TiLs) as a cellular equivalent of clinical response to ICI. Methods We mapped the spatial distribution of proteins in TiL-enriched vs. TiL-low compartments in melanoma by combining microscopy, matrix-assisted laser desorption mass spectrometry imaging and liquid chromatography–mass spectrometry, as well as computational data mining. Pharmacological modulation of sirtuin 1 (SIRT1) activity in syngeneic mouse models was used to evaluate the efficacy of pharmacological SIRT1 activation in two syngeneic melanoma mouse models, one known to be α-programmed cell death protein 1 (PD-1) sensitive and the other α-PD-1 resistant. Results Spatial proteomics and gene ontology-based enrichment analysis identified &amp;gt; 145 proteins enriched in CD8high tumour compartments, including negative regulators of mammalian target of rapamycin signalling such as SIRT1. Multiplexed immunohistochemistry confirmed that SIRT1 protein was expressed more in CD8high than in CD8low compartments. Further analysis of bulk and single-cell RNA sequencing data from melanoma tissue samples suggested the expression of SIRT1 by different lymphocyte subpopulations (CD8+ T cells, CD4+ T cells and B cells). Furthermore, we showed in vivo that pharmacological SIRT1 activation increased the immunological effect of α-PD-1 ICI against melanoma cells in mice, which was accompanied by an increase in T-cell infiltration and T-cell-related cytokines, including interferon (IFN)-γ, CCL4, CXCL9, CXCL10 and tumour necrosis factor-α. In silico analysis of large transcriptional data cohorts showed that SIRT1 was positively associated with the proinflammatory T-cell chemokines CXCL9, CXCL10 and IFN-γ, and prolonged overall survival of patients with melanoma. Conclusions Our study deciphers the proteomics landscape in human melanoma, providing important information on the tumour microenvironment and identifying SIRT1 as having important prognostic and therapeutic implications.
Deubiquitinase MYSM1 drives myocardial ischemia/reperfusion injury by stabilizing STAT1 in cardiomyocytes
Authors: Xiaowen Shi, Jianjiang Xu, Lei Liu, Shenggang Zhao, Yuanyuan Qian, Zimin Fang, Liming Lin, Xia Zhao, Shangcai Xie, Fengjie Shi, Jibo Han
Journal: Theranostics (2024)

Rationale: Myocardial ischemia/reperfusion (I/R) injury leads to irreversible cardiomyocyte death and aggravates myocardial infarction. Deubiquitinating enzymes (DUBs) are essential for maintaining substrate protein stability and functionality, playing significant roles in cardiac pathophysiology. In this study, we aimed to clarify the regulatory role of a DUB, Myb-like, SWIRM, and MPN domains 1 protein (MYSM1), in myocardial I/R injury and explore the molecular mechanism behind. Methods and Results: Firstly, it was found that the expression of MYSM1 positively correlates with myocardial I/R injury. Genetic knockdown of MYSM1 significantly conferred protection against I/R injury in hearts. Correspondingly, AAV9-mediated cardiomyocyte-specific knockdown of MYSM1 had a therapeutic effect on myocardial I/R injury. Through a comprehensive proteome-wide quantitative analysis, we identified signal transducer and activator of transcription 1 (STAT1) as the direct substrate of MYSM1. Mechanistically, MYSM1 mediated the K63-linked deubiquitination and stabilization of STAT1 at position K379 via its MPN metalloprotease domain. Additionally, MYSM1 initiates the expression of necroptosis-related genes by promoting the transcription factor function of STAT1. Conclusion: This study illustrated a MYSM1-STAT1 axis in regulating myocardial I/R injury and identified MYSM1 as a pharmacological target for myocardial I/R injury.