tbuckley/cabot-search huggingface dataset:
2025 update on clinical trials in immune thrombocytopenia
Authors: Hanny Al‐Samkari
Journal: American Journal of Hematology (2024)

Although the development and regulatory approval of the thrombopoietin receptor agonists revolutionized aspects of the immune thrombocytopenia (ITP) treatment landscape over the past two decades, there remain many areas of high unmet need. Therefore, a number of investigational and repurposed agents are currently undergoing clinical development in ITP. In a departure from historical trials, which largely focused on the indefinite treatment of persistent or chronic ITP, ongoing trials run the gamut of disease phases, and include novel agents being evaluated in early phases of the disease to attempt to modify the disease course. Many agents in development target disease pathophysiologic mechanisms not previously targeted by agents in current use, including platelet autoantibody recycling, B-cell maturation and differentiation, long-lived plasma cells, and the complement system, among others. These agents represent promising treatment options for patients with otherwise refractory disease or who are intolerant of currently available therapies. Additionally, with our increasing understanding of the diverse immune mechanisms at play in ITP, the expansion of the therapeutic armamentarium to include agents targeting diverse pathophysiologic mechanisms may allow a more personalized therapeutic selection in the future. This manuscript provides an up-to-date, in-depth overview of recently completed and ongoing clinical trials in ITP.
Targeting p97–Npl4 interaction inhibits tumor Treg cell development to enhance tumor immunity
Authors: Pingping Nie, Zhifa Cao, Ruixian Yu, Chao Dong, Weihong Zhang, Yan Meng, Hui Zhang, Yu Pan, Zhenzhu Tong, Xiaoya Jiang, Shilong Wang, Mengwen Zhu, Yi Han, Wenjia Wang, Yiming Zhang, Lijie Tan, Chuanchuan Li, Yuanzhi Xu, Liwei An, Bin Li, Shi Jiao, Zhaocai Zhou
Journal: Nature Immunology (2024)
Exosome-like nanoparticles derived from fruits, vegetables, and herbs: innovative strategies of therapeutic and drug delivery
Authors: Bo Zhao, Hangjuan Lin, Xinchi Jiang, Wanshu Li, Yuli Gao, Minghui Li, Yanan Yu, Ninggang Chen, Jianqing Gao
Journal: Theranostics (2024)

Over the past ten years, significant advancements have been made in exploring plant-derived exosome-like nanoparticles (PELNs) for disease therapeutics and drug delivery. PELNs, as inherent nanoscale particles comprised of proteins, lipids, nucleic acids, and secondary metabolites, exhibit the capacity for cellular uptake by human cells. This intercellular interaction transcends biological boundaries, effectively influencing biological functions in animals. PELNs have outstanding biocompatibility, low immunogenicity, enhanced safety, and environmentally friendly sustainability. This article summarized the preparation methods and characteristics of PELNs. It provided a systematic review of the varied roles of PELNs derived from fruits, vegetables, and herbs in disease therapeutics and drug delivery. The challenges in their production and application were discussed, and future prospects in this rapidly evolving field were explored.
Microfluidic chips in female reproduction: a systematic review of status, advances, and challenges
Authors: Tong Wu, Jinfeng Yan, Kebing Nie, Ying Chen, Yangyang Wu, Shixuan Wang, Jinjin Zhang
Journal: Theranostics (2024)

The female reproductive system is essential to women's health, human reproduction and societal well-being.However, the clinical translation of traditional research models is restricted due to the uncertain effects and low efficiency.Emerging evidence shows that microfluidic chips provide valuable platforms for studying the female reproductive system, while no paper has ever comprehensively discussed the topic.Here, a total of 161 studies out of 14,669 records are identified in PubMed, Scopus, Web of Science, ScienceDirect and IEEE Xplore databases.Among these, 61 studies focus on oocytes, which further involves culture, cell surgeries (oocyte separation, rotation, enucleation, and denudation), evaluation and cryopreservation.Forty studies investigate embryo manipulation via microfluidic chips, covering in vitro fertilization, cryopreservation and functional evaluation.Forty-six studies reconstitute both the physiological and pathological statuses of in vivo organs, mostly involved in placenta and fetal membrane research.Fourteen studies perform drug screening and toxicity testing.In this review, we summarize the current application of microfluidic chips in studying the female reproductive system, the advancements in materials and methods, and discuss the future challenges.The present evidence suggests that microfluidic chips-assisted reproductive system reconstruction is promising and more studies are urgently needed.
Transcranial blood-brain barrier opening in Alzheimer's disease patients using a portable focused ultrasound system with real-time 2-D cavitation mapping
Authors: Sua Bae, Keyu Liu, Antonios N. Pouliopoulos, Robin Ji, Sergio Jiménez-Gambín, Omid Yousefian, Alina R. Kline-Schoder, Alec J. Batts, Fotios N. Tsitsos, Danae Kokossis, Akiva Mintz, Lawrence S. Honig, Elisa E. Konofagou
Journal: Theranostics (2024)

: Focused ultrasound (FUS) in combination with microbubbles has recently shown great promise in facilitating blood-brain barrier (BBB) opening for drug delivery and immunotherapy in Alzheimer's disease (AD). However, it is currently limited to systems integrated within the MRI suites or requiring post-surgical implants, thus restricting its widespread clinical adoption. In this pilot study, we investigate the clinical safety and feasibility of a portable, non-invasive neuronavigation-guided FUS (NgFUS) system with integrated real-time 2-D microbubble cavitation mapping.
Impact of <i>TP53</i> loss-of-function alterations on the response to PSMA radioligand therapy in metastatic castration-resistant prostate cancer patients
Authors: Peter H.J. Slootbeek, María Victoria Luna-Velez, Bastiaan M. Privé, Maarten J. van der Doelen, Iris S.H. Kloots, Samhita Pamidimarri Naga, Hilde E. Onstenk, James Nagarajah, Harm Westdorp, Inge M. van Oort, Leonie I. Kroeze, Jack. A. Schalken, Haiko J. Bloemendal, Niven Mehra
Journal: Theranostics (2024)

Rationale: PSMA-targeting radioligand therapy (PSMA-RLT) has shown promise in metastatic castration-resistant prostate cancer (mCRPC), particularly in PSMA-avid tumours.However, predicting response remains challenging.Preclinical data suggests aberrant p53-signalling as a predictor of poor response. Methods:The patient population of this pre-planned retrospective cohort study consists of 96 patients with mCRPC who underwent treatment with PSMA-RLT and were molecularly profiled by whole-genome sequencing and or targeted next-generation sequencing.Response to PSMA-RLT was assessed per molecular subtype, including TP53-mutational status.Results: Patients with TP53 loss-of-function alterations had a shorter median progression-free survival (3.7 versus 6.2 months, P<0.001), a lower median PSA change (-55% vs. -75%, P=0.012) and shorter overall survival from initiation of PMSA-RLT (7.6 vs. 13.9 months, P=0.003) compared to TP53-wildtype patients.Pathogenic alterations in AR, MYC, BRCA1, or BRCA2 as well as in genes linked to the PI3K or MAPK pathways or genes involved in homologous recombination repair, were not associated with response.Only lactate dehydrogenase was, alongside TP53-status, significantly associated with response.Transcriptome analysis of 21 patients, identified six p53 signalling genes whose low expression was associated to a shorter progression-free survival (P<0.05).Conclusion: TP53 loss-of-function may serve as a prognostic factor for PSMA-RLT outcomes in patients with mCRPC.
Reconstituting gut microbiota-colonocyte interactions reverses diet-induced cognitive deficits: The beneficial of <i>eucommiae cortex</i> polysaccharides
Authors: Mengli Wang, Penghao Sun, Xuejun Chai, Yong-Xin Liu, Luqi Li, Wei Zheng, Shulin Chen, Xiaoyan Zhu, Shanting Zhao
Journal: Theranostics (2024)

Consumption of a high-fat diet (HFD) has been implicated in cognitive deficits and gastrointestinal dysfunction in humans, with the gut microbiota emerging as a pivotal mediator of these diet-associated pathologies. The introduction of plant-based polysaccharides into the diet as a therapeutic strategy to alleviate such conditions is gaining attention. Nevertheless, the mechanistic paradigm by which polysaccharides modulate the gut microbiota remains largely undefined. This study investigated the mechanisms of action of
Preventive and therapeutic effects of a super-multivalent sialylated filamentous bacteriophage against the influenza virus
Authors: Jinhyo Chung, Sehoon Kim, Jiyoon Jeong, Doyeon Kim, Anna Jo, Hwa Young Kim, Jaehyeon Hwang, Dae-Hyuk Kweon, So Young Yoo, Woo-Jae Chung
Journal: Biomaterials (2024)
In-depth cross-validation of human and mouse CD4-specific minibodies for noninvasive PET imaging of CD4<sup>+</sup> cells and response prediction to cancer immunotherapy
Authors: Stefania Pezzana, Simone Blaess, Jule Kortendieck, Nicole Hemmer, Bredi Tako, Claudia Pietura, Lara Ruoff, Simon Riel, Martin Schaller, Irene Gonzalez-Menendez, Leticia Quintanilla-Martinez, Alessandro Mascioni, Argin Aivazian, Ian Wilson, Andreas Maurer, Bernd J. Pichler, Manfred Kneilling, Dominik Sonanini
Journal: Theranostics (2024)

Increasing evidence emphasizes the pivotal role of CD4 + T cells in orchestrating cancer immunity.Noninvasive in vivo imaging of the temporal dynamics of CD4 + T cells and their distribution patterns might provide novel insights into their effector and regulator cell functions during cancer immunotherapy (CIT).Methods: We conducted a comparative analysis of 89 Zr-labeled anti-mouse (m) and anti-human (h) CD4-targeting minibodies (Mbs) for in vivo positron emission tomography (PET)/magnetic resonance imaging (MRI) of CD4 + T cells in human xenografts, syngeneic tumor-bearing wild-type (WT), and human CD4 + knock-in (hCD4-KI) mouse models.Results: Both 89 Zr-CD4-Mbs yielded high radiolabeling efficiencies of >90%, immunoreactivities of >70%, and specific in vitro binding to their target antigens.The specificity of in vivo targeting of 89 Zr-hCD4-Mb was confirmed by PET/MRI, revealing ~4-fold greater 89 Zr-hCD4-Mb uptake in subcutaneous hCD4 + hematopoietic peripheral blood acute lymphoblastic leukemia tumors (HPB-ALL) than in solid hCD4 -diffuse histiocytic lymphomas (DHL) and 89 Zr-mCD4-Mb uptake in hCD4 + HPB-ALL tumors.In a comparative cross-validation study in anti-programmed death ligand (αPD-L1)/anti-4-1BB-treated orthotopic PyMT mammary carcinoma-bearing hCD4-KI and WT mice, we detected 2-to 3-fold enhanced species-specific 89 Zr-hCD4-Mb or 89 Zr-mCD4-Mb uptake within CD4 + cell-enriched secondary lymphatic organs (lymph nodes and spleens).The 89 Zr-hCD4-Mb uptake in the PyMT tumors was more pronounced in hCD4-KI mice compared to the WT control littermates.Most importantly, MC38 adenocarcinoma-bearing mice treated with a combination of αPD-L1 and anti-lymphocyte-activation gene 3 (αLag-3) antibodies exhibited ~1.4-fold higher 89 Zr-mCD4-Mb uptake than mice that were not responsive to therapy or sham-treated mice.Conclusion: CD4 PET/MRI enabled monitoring of the CD4 + cell distribution in secondary lymphatic organs and the tumor microenvironment, capable of predicting sensitivity to CIT.Our imaging approach will provide deeper insights into the underlying molecular mechanisms of CD4-directed cancer immunotherapies in preclinical mouse models and is applicable for clinical translation.
The Early Perfusion Image Is Useful to Support the Visual Interpretation of Brain Amyloid-PET With 18F-Flutemetamol in Borderline Cases
Authors: Franziska L. Mathies, Fiona Heeman, Pieter Jelle Visser, Anouk den Braber, Maqsood Yaqub, Susanne Klutmann, Michael Schöll, Elsmarieke van de Giessen, Lyduine E. Collij, Ralph Buchert
Journal: Clinical Nuclear Medicine (2024)

Visual interpretation of brain amyloid-β (Aβ) PET can be difficult in individuals with borderline Aβ burden. Coregistration with individual MRI is recommended in these cases, which, however, is not always available. This study evaluated coregistration with the early perfusion frames acquired immediately after tracer injection to support the visual interpretation of the late Aβ-frames in PET with 18F-flutemetamol (FMM).
Porphyrin-grafted Lipid Microbubbles for the Enhanced Efficacy of Photodynamic Therapy in Prostate Cancer through Ultrasound-controlled <i>In Situ</i> Accumulation: Erratum
Authors: Yujia You, Xiaolong Liang, Tinghui Yin, Min Chen, Chen Qiu, Chuang Gao, Xiaoyou Wang, Yongjiang Mao, Enze Qu, Zhifei Dai, Rongqin Zheng
Journal: Theranostics (2024)

[This corrects the article DOI: 10.7150/thno.22469.].
Rbm24/Notch1 signaling regulates adult neurogenesis in the subventricular zone and mediates Parkinson-associated olfactory dysfunction
Authors: Ke Wang, Xing-Yang Liu, Sui-Feng Liu, Xiao-Xia Wang, Yi-Hua Wei, Jun-Rong Zhu, Jing Liu, Xiu Qin Xu, Lei Wen
Journal: Theranostics (2024)

Adult neurogenesis in the subventricular zone (SVZ) is essential for maintaining neural homeostasis, and its dysregulation contributes to anosmia and delayed tissue healing in neurological disorders, such as Parkinson's disease (PD). Despite intricate regulatory networks identified in SVZ neurogenesis, the molecular mechanisms dynamically maintaining neural stem/progenitor cells (NSPCs) in response to physiological and pathological stimuli remain incompletely elucidated.
The fecal microbiota of patients with primary biliary cholangitis (PBC) causes PBC-like liver lesions in mice and exacerbates liver damage in a mouse model of PBC
Authors: Huiyong Jiang, Ying Yu, Xiaoxiang Hu, Bingbing Du, Yini Shao, Feiyu Wang, Lifeng Chen, Ren Yan, Lanjuan Li, Longxian Lv
Journal: Gut Microbes (2024)

The role of the gut microbiota in the occurrence and progression of primary biliary cholangitis (PBC) is not fully understood. First, the fecal microbiota of patients with PBC (
Promotion of osteochondral repair through immune microenvironment regulation and activation of endogenous chondrogenesis via the release of apoptotic vesicles from donor MSCs
Authors: Guangzhao Tian, Han Yin, Jinxuan Zheng, Rongcheng Yu, Zhengang Ding, Zineng Yan, Yiqi Tang, Jiang Wu, Chao Ning, Xun Yuan, Chenxi Liao, Xiang Sui, Zhe Zhao, Shuyun Liu, Weimin Guo, Quanyi Guo
Journal: Bioactive Materials (2024)

Utilizing transplanted human umbilical cord mesenchymal stem cells (HUMSCs) for cartilage defects yielded advanced tissue regeneration, but the underlying mechanism remain elucidated. Early after HUMSCs delivery to the defects, we observed substantial apoptosis. The released apoptotic vesicles (apoVs) of HUMSCs promoted cartilage regeneration by alleviating the chondro-immune microenvironment. ApoVs triggered M2 polarization in macrophages while simultaneously facilitating the chondrogenic differentiation of endogenous MSCs. Mechanistically, in macrophages, miR-100-5p delivered by apoVs activated the MAPK/ERK signaling pathway to promote M2 polarization. In MSCs, let-7i-5p delivered by apoVs promoted chondrogenic differentiation by targeting the eEF2K/p38 MAPK axis. Consequently, a cell-free cartilage regeneration strategy using apoVs combined with a decellularized cartilage extracellular matrix (DCM) scaffold effectively promoted the regeneration of osteochondral defects. Overall, new mechanisms of cartilage regeneration by transplanted MSCs were unconcealed in this study. Moreover, we provided a novel experimental basis for cell-free tissue engineering-based cartilage regeneration utilizing apoVs.
Monocyte Single-Cell Multimodal Profiling in Cardiovascular Disease Risk States
Authors: Alexander C. Bashore, Chenyi Xue, Eunyoung Kim, Hanying Yan, Lucie Y. Zhu, Huize Pan, Michael Kissner, Leila S. Ross, Hanrui Zhang, Mingyao Li, Muredach P. Reilly
Journal: Circulation Research (2024)

Monocytes are a critical innate immune system cell type that serves homeostatic and immunoregulatory functions. They have been identified historically by the cell surface expression of CD14 and CD16. However, recent single-cell studies have revealed that they are much more heterogeneous than previously realized.
Nucleic acid-based nanotherapeutics for treating sepsis and associated organ injuries
Authors: Huang-Ping Yu, Fu-Chao Liu, Yu-Kuo Chung, Ahmed Alalaiwe, Calvin T. Sung, Jia-You Fang
Journal: Theranostics (2024)

In recent years, gene therapy has been made possible with the success of nucleic acid drugs against sepsis and its related organ dysfunction.Therapeutics based on nucleic acids such as small interfering RNAs (siRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs), and plasmid DNAs (pDNAs) guarantee to treat previously undruggable diseases.The advantage of nucleic acid-based therapy against sepsis lies in the development of nanocarriers, achieving targeted and controlled gene delivery for improved efficacy with minimal adverse effects.Entrapment into nanocarriers also ameliorates the poor cellular uptake of naked nucleic acids.In this study, we discuss the current state of the art in nanoparticles for nucleic acid delivery to treat hyperinflammation and apoptosis associated with sepsis.The optimized design of the nanoparticles through physicochemical property modification and ligand conjugation can target specific organs-such as lung, heart, kidney, and liver-to mitigate multiple sepsis-associated organ injuries.This review highlights the nanomaterials designed for fabricating the anti-sepsis nanosystems, their physicochemical characterization, the mechanisms of nucleic acid-based therapy in working against sepsis, and the potential for promoting the therapeutic efficiency of the nucleic acids.The current investigations associated with nanoparticulate nucleic acid application in sepsis management are summarized in this paper.Noteworthily, the potential application of nanotherapeutic nucleic acids allows for a novel strategy to treat sepsis.Further clinical studies are required to confirm the findings in cell-and animal-based experiments.The capability of large-scale production and reproducibility of nanoparticle products are also critical for commercialization.It is expected that numerous anti-sepsis possibilities will be investigated for nucleic acid-based nanotherapeutics in the future.
Unlocking potential of oxytocin: improving intracranial lymphatic drainage for Alzheimer's disease treatment
Authors: Caihua Ye, Shengnan Wang, Lin Niu, Fan Yang, Guohe Wang, Siqi Wang, Jiamei Xie, Yihan Chen, Jinbo Qi, Hui Shen, Yan Dou, Junping Wang
Journal: Theranostics (2024)

The impediment to β-amyloid (Aβ) clearance caused by the invalid intracranial lymphatic drainage in Alzheimer's disease is pivotal to its pathogenesis, and finding reliable clinical available solutions to address this challenge remains elusive.
Endosome-microautophagy targeting chimera (eMIATAC) for targeted proteins degradation and enhance CAR-T cell anti-tumor therapy
Authors: Kunjian Lei, Jingying Li, Zewei Tu, Chuandong Gong, Junzhe Liu, Min Luo, Wenqian Ai, Lei Wu, Yishuang Li, Zhihong Zhou, Zhihao Chen, Shigang Lv, Minhua Ye, Miaojing Wu, Xiaoyan Long, Xingen Zhu, Kai Huang
Journal: Theranostics (2024)

Since oncogene expression products often exhibit upregulation or abnormally activated activity, developing a technique to regulate abnormal protein levels represent a viable approach for treating tumors and protein abnormality-related diseases.
Orexin neurons mediate temptation-resistant voluntary exercise
Authors: Alexander L. Tesmer, Xinyang Li, Eva Bracey, Cyra Schmandt, Rafael Polania, Daria Peleg-Raibstein, Denis Burdakov
Journal: Nature Neuroscience (2024)

Abstract Despite the well-known health benefits of physical activity, many people underexercise; what drives the prioritization of exercise over alternative options is unclear. We developed a task that enabled us to study how mice freely and rapidly alternate between wheel running and other voluntary activities, such as eating palatable food. When multiple alternatives were available, mice chose to spend a substantial amount of time wheel running without any extrinsic reward and maintained this behavior even when palatable food was added as an option. Causal manipulations and correlative analyses of appetitive and consummatory processes revealed this preference for wheel running to be instantiated by hypothalamic hypocretin/orexin neurons (HONs). The effect of HON manipulations on wheel running and eating was strongly context-dependent, being the largest in the scenario where both options were available. Overall, these data suggest that HON activity enables an eat–run arbitration that results in choosing exercise over food.
Tau in neurodegenerative diseases: molecular mechanisms, biomarkers, and therapeutic strategies
Authors: Xingyu Zhang, Jiangyu Wang, Zhentao Zhang, Keqiang Ye
Journal: Translational Neurodegeneration (2024)

Abstract The deposition of abnormal tau protein is characteristic of Alzheimer’s disease (AD) and a class of neurodegenerative diseases called tauopathies. Physiologically, tau maintains an intrinsically disordered structure and plays diverse roles in neurons. Pathologically, tau undergoes abnormal post-translational modifications and forms oligomers or fibrous aggregates in tauopathies. In this review, we briefly introduce several tauopathies and discuss the mechanisms mediating tau aggregation and propagation. We also describe the toxicity of tau pathology. Finally, we explore the early diagnostic biomarkers and treatments targeting tau. Although some encouraging results have been achieved in animal experiments and preclinical studies, there is still no cure for tauopathies. More in-depth basic and clinical research on the pathogenesis of tauopathies is necessary.
Intestinal epithelial damage-derived mtDNA activates STING-IL12 axis in dendritic cells to promote colitis
Authors: Yajie Cai, Shuo Li, Yang Yang, Shuni Duan, Guifang Fan, Jinzhao Bai, Qi Zheng, Yiqing Gu, Xiaojiaoyang Li, Runping Liu
Journal: Theranostics (2024)

The treatment of ulcerative colitis (UC) presents an ongoing clinical challenge. Emerging research has implicated that the cGAS-STING pathway promotes the progression of UC, but conflicting results have hindered the development of STING as a therapeutic target. In the current study, we aim to comprehensively elucidate the origins, downstream signaling and pathogenic roles of myeloid STING in colitis and colitis-associated carcinoma (CAC).