tbuckley/cabot-search huggingface dataset:
Revolutionizing drug delivery: low-intensity pulsed ultrasound (LIPUS)-driven deep penetration into hypoxic tumor microenvironments of cholangiocarcinoma
Authors: Sera Hong, Jaihwan Kim, Gujin Chung, Donghyuk Lee, Joon Myong Song
Journal: Theranostics (2024)

Hypoxia is a major obstacle in the treatment of solid tumors because it causes immune escape and therapeutic resistance. Drug penetration into the hypoxic regions of tumor microenvironment (TME) is extremely limited. This study proposes using the unidirectional fluid flow property of low-intensity pulsed ultrasound (LIPUS) to overcome drug penetration limitations in the TME. LIPUS is gaining attention as a therapeutic modality for cancer owing to its safety and efficacy.
Targeting cancer with precision: strategical insights into TCR-engineered T cell therapies
Authors: Pei Lin, Yunfan Lin, Zizhao Mai, Yucheng Zheng, Jiarong Zheng, Zihao Zhou, Xinyuan Zhao, Li Cui
Journal: Theranostics (2024)

T cell receptor-engineered T (TCR-T) cell therapies are at the forefront of cancer immunotherapy, offering a transformative approach that significantly enhances the ability of T cells to recognize and eliminate cancer cells. This innovative method involves genetically modifying TCRs to increase their affinity for tumor-specific antigens. While these enhancements improve the ability of T cells to recognize and bind to antigens on cancer cells, rigorous assessment of specificity remains crucial to ensure safety and targeted responses. This dual focus on affinity and specificity holds significant promise for the treatment of solid tumors, enabling precise and efficient cancer cell recognition. Despite rapid advancements in TCR engineering and notable progress in TCR screening technologies, as evidenced by the growing number of specific TCRs entering clinical trials, several technical and clinical challenges remain. These challenges primarily pertain to the specificity, affinity, and safety of engineered TCRs. Moreover, the accurate identification and selection of TCRs that are both effective and safe are essential for the success of TCR-T cell therapies in cancer treatment. This review provides a comprehensive examination of the theoretical foundations of TCR therapy, explores strategies for screening specific TCRs and antigens, and highlights the ongoing challenges in this evolving therapeutic landscape.
Phosphoglycerate mutase 1-mediated dephosphorylation and degradation of Dusp1 disrupt mitochondrial quality control and exacerbate endotoxemia-induced myocardial dysfunction
Authors: Rongjun Zou, Wanting Shi, Mingxian Chen, Miao Zhang, Dan Wu, Haixia Li, Hao Zhou, Yukun Li, Weihui Lu, Chao Li, Xiaoping Fan
Journal: Theranostics (2024)

Endotoxemia, caused by lipopolysaccharides, triggers systemic inflammation and myocardial injury by disrupting mitochondrial homeostasis. This study examines the roles of dual specificity phosphatase 1 (Dusp1) and phosphoglycerate mutase family member 1 (Pgam1) in this process.
Intranasal delivery of engineered extracellular vesicles loaded with miR-206-3p antagomir ameliorates Alzheimer's disease phenotypes
Authors: Dong Peng, Tingting Liu, Huahui Lu, Lei Zhang, Hongxia Chen, Yadong Huang, Bo Hu, Qihao Zhang
Journal: Theranostics (2024)

Rationale: The level of miR-206-3p in the plasma and temporal cortex is increased in Alzheimer's disease (AD) patients. miR-206-3p antagomir injected into hippocampus ameliorates cognitive deficits by enhancing the level of BDNF. However, the trauma caused by brain injection and susceptibility to degradation limit its application. Methods: To overcome these challenges, we constructed engineered extracellular vesicles derived from mesenchymal stem cell (MSC-EVs) loaded with miR-206-3p antagomir (MSC-EVs-anta) by electroporation technology, and explored the therapeutic effects of MSC-EVs-anta delivered by intranasal administration on AD mice. Transcriptome sequencing and LC-MS/MS proteomic analysis were employed to disclose the mechanism underlying the attenuation of AD phenotypes by MSC-EVs-anta. Results: MSC-EVs-anta had favorable neuroprotection by promoting neurite outgrowth in vitro. Following intranasal administration, MSC-EVs-anta improved learning and memory deficits, promoted hippocampal neurogenesis and synaptic plasticity, and alleviated Aβ deposition. Compared with MSC-EVs or miR-206-3p antagomir alone, MSC-EVs-anta showed superior therapeutic effects. Mechanistically, MSC-EVs-anta significantly upregulated brain-derived neurotrophic factor (BDNF) in AD mice, and activated the BDNF/TrkB signaling pathway. The data from two-omics analyses demonstrated that the differentially expressed proteins and genes significantly regulated by MSC-EVs-anta were primarily enriched in the pathways involved in neurogenesis and synapse. Conclusions: Our findings highlight the intranasal administration of MSC-EVs-anta as a promising strategy for the treatment of AD.
Advancing the clinical assessment of glomerular podocyte pathology in kidney biopsies via super-resolution microscopy and angiopoietin-like 4 staining
Authors: Xiaojing Liu, Suxia Wang, Gang Liu, Yan Wang, Shunlai Shang, Guming Zou, Shimin Jiang, Xuliang Wang, Li Yang, Wenge Li
Journal: Theranostics (2024)

Rationale: The tertiary structure of normal podocytes prevents protein from leaking into the urine. However, observing the complexity of podocytes is challenging because of the scale differences in their three-dimensional structure and the close proximity between neighboring cells in space. In this study, we explored podocyte-secreted angiopoietin-like 4 (ANGPTL4) as a potential morphological marker via super-resolution microscopy (SRM). Methods and Results: Specimens from patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), along with normal controls, were analyzed via immunofluorescence and immunohistochemistry to determine the expression and localization of ANGPTL4, confirming its extensive presence in podocytes across both healthy and diseased conditions. Immunoelectron microscopy revealed that ANGPTL4 is distributed throughout the podocyte cell body, primary processes, and foot processes. Compared with conventional podocyte markers such as nephrin and synaptopodin, ANGPTL4 excels in depicting the three-dimensional structure of podocytes via SRM imaging. We then refined a protocol using tyramide signal amplification staining and confocal microscopy to uniformly enhance podocyte fluorescence, facilitating the clinical assessment of biopsies. In patients diagnosed with MCD and FSGS, measurements of slit diaphragm density, primary process width, and foot process width were taken after further co-staining with nephrin to identify patterns of podocyte morphological alterations. Distinctive patterns of foot process effacement were identified in MCD and FSGS patients, with FSGS patients showing more pronounced podocyte injury. Conclusions: ANGPTL4 serves as a reliable morphological marker for podocyte analysis, offering enhanced visualization of their three-dimensional structure and facilitating the identification of distinct pathological changes in nephrotic syndrome patients.
A STING agonist prodrug reprograms tumor-associated macrophage to boost colorectal cancer immunotherapy
Authors: Aohua Deng, Renming Fan, Yongrui Hai, Junyan Zhuang, Bingjie Zhang, Xintong Lu, Wenhui Wang, Li Luo, Ge Bai, Lei Liang, Le Yang, Minggao Zhao, Gaofei Wei
Journal: Theranostics (2024)

Tumor-associated macrophages (TAMs) are abundant in colorectal cancer (CRC), correlating with immunosuppression and disease progression. Activation of the stimulator of interferon gene (STING) signaling pathway in TAMs offers a promising approach for CRC therapy. However, current STING agonists face challenges related to tumor specificity and administration routes.
Virus-like particle encapsulation of functional proteins: advances and applications
Authors: Xianxun Sun, Yindong Lian, Tao Tian, Zongqiang Cui
Journal: Theranostics (2024)

Proteins face several challenges in biomedicine, including issues with antibody production, degradation by proteases, rapid clearance by the kidneys, and short half-lives. To address these problems, various nano delivery systems have been developed, with virus-like particles (VLPs) emerging as a leading solution. VLPs, which are self-assembled protein complexes, offer effective encapsulation and transport of proteins. They provide enhanced stability, extended circulation time, preserved biological activity, improved targeting for therapies or imaging, and reduced side effects due to minimized systemic exposure. This review explores various methods for encapsulating proteins within VLPs. It assesses the benefits and limitations of each method and their applications in imaging, therapeutic enzyme delivery, vaccines, immunotherapy, nanoreactors, and biosensors. Future advancements in VLPs will depend on improving packaging methods, controlling protein loading, optimizing assembly techniques, and enhancing capsid design. The review also discusses current challenges and proposes solutions to advance the use of VLPs in various applications.
Recent advances in ferrocene-based nanomedicines for enhanced chemodynamic therapy
Authors: Gui-Long Wu, Senyou Tan, Xiaofeng Tan, Guodong Chen, Qinglai Yang
Journal: Theranostics (2024)

Malignant tumors have been a serious threat to human health with their increasing incidence. Difficulties with conventional treatments are toxicity, drug resistance, and recurrence. For this reason, non-invasive treatment modalities such as photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), and others have received much attention. Among them, Ferrocene (Fc)-based nanomedicines for enhanced Chemodynamic Therapy (ECDT) is a new therapeutic strategy based on the Fenton reaction. Based on ferrocene's good biocompatibility, potentiation in medicinal chemistry, and good stability of divalent iron ions, scientists are increasingly using it as a Fenton's iron donor for tumor therapy. Such ferrocene-based ECDT nanoplatforms have shown remarkable promise for clinical applications and have significantly increased the efficacy of CDT treatment. Ferrocene-based nanomedicines exhibit exceptional consistency owing to their low toxicity, high stability, enhanced bioavailability, and a multitude of advantages over conventional approaches to cancer treatment. As a consequence, a number of tactics have been investigated in recent years to raise the effectiveness of ferrocene-based ECDT. In this review, we detail the different forms and strategies used to enhance Ferrocene-based ECDT efficiency.
Targeting ion channels: innovative approaches to combat cancer drug resistance
Authors: Qian Shi, Zijing Yang, Huan Yang, Lihui Xu, Jing Xia, Jie Gu, Mengting Chen, Yan Wang, Xiaohong Zhao, Zehua Liao, Yiping Mou, Xidong Gu, Tian Xie, Xinbing Sui
Journal: Theranostics (2024)

Ion channels, as functional molecules that regulate the flow of ions across cell membranes, have emerged as a promising target in cancer therapy due to their pivotal roles in cell proliferation, metastasis, apoptosis, drug resistance, and so on. Recently, increasing evidence suggests that dysregulation of ion channels is a common characteristic of cancer cells, contributing to their survival and the resistance to conventional therapies. For example, the aberrant expression of sodium (Na
Membrane mechanics dictate axonal pearls-on-a-string morphology and function
Authors: Jacqueline M. Griswold, Mayte Bonilla-Quintana, Renee Pepper, Christopher T. Lee, Sumana Raychaudhuri, Siyi Ma, Quan Gan, Sarah Syed, Cuncheng Zhu, Miriam Bell, Mitsuo Suga, Yuuki Yamaguchi, Ronan Chéreau, U. Valentin Nägerl, Graham Knott, Padmini Rangamani, Shigeki Watanabe
Journal: Nature Neuroscience (2024)

Abstract Axons are ultrathin membrane cables that are specialized for the conduction of action potentials. Although their diameter is variable along their length, how their morphology is determined is unclear. Here, we demonstrate that unmyelinated axons of the mouse central nervous system have nonsynaptic, nanoscopic varicosities ~200 nm in diameter repeatedly along their length interspersed with a thin cable ~60 nm in diameter like pearls-on-a-string. In silico modeling suggests that this axon nanopearling can be explained by membrane mechanical properties. Treatments disrupting membrane properties, such as hyper- or hypotonic solutions, cholesterol removal and nonmuscle myosin II inhibition, alter axon nanopearling, confirming the role of membrane mechanics in determining axon morphology. Furthermore, neuronal activity modulates plasma membrane cholesterol concentration, leading to changes in axon nanopearls and causing slowing of action potential conduction velocity. These data reveal that biophysical forces dictate axon morphology and function, and modulation of membrane mechanics likely underlies unmyelinated axonal plasticity.
Recent advances of self-assembled nanoparticles in the diagnosis and treatment of atherosclerosis
Authors: Tuersun Aili, Jia-Bin Zong, Yi-Fan Zhou, Yu-Xiao Liu, Xiang-Liang Yang, Bo Hu, Jie-Hong Wu
Journal: Theranostics (2024)

Atherosclerosis remains a significant global health challenge, with its related conditions as the leading cause of death, underscoring the urgent need for enhanced diagnostic and therapeutic approaches. Recently, self-assembled nanoparticles (SANPs) have shown remarkable promise in treating atherosclerosis, attributed to their superior bioavailability, biodegradability, biocompatibility, and ease of functional modification. Numerous SANP variants, such as DNA origami, metal-organic frameworks (MOFs), nanozymes, peptide-based nanoparticles, and self-assembled prodrug nanoparticles, have been engineered, extending their utility in targeted drug delivery and imaging. Advances in fabrication technologies, including microfluidic techniques, allow for precise and scalable SANP production, while innovative nanoparticle designs-such as stimuli-responsive and carrier-free variants-enhance pharmacokinetic properties. The deployment of SANPs in atherosclerosis has introduced a range of diagnostic and therapeutic solutions, from non-invasive imaging and stimuli-responsive drug delivery to vaccination, theranostics, and biosensing. This review consolidates the recent progress in SANP applications for atherosclerosis, emphasizing their transformative potential in disease management.
High frequency of melanoma in <i>cdkn2b<sup>-/-</sup></i>/<i>tp53<sup>-/-</sup> Xenopus tropicalis</i>
Authors: Rensen Ran, Lanxin Li, Peng Cheng, Hongyi Li, Huanhuan He, Yonglong Chen, Jing Hang, Weizheng Liang
Journal: Theranostics (2024)

Melanoma, the deadliest form of skin cancer characterized by high therapy resistance, has undergone extensive investigation through the utilization of BRAF
FBLN7 mediates vascular smooth muscle cell phenotype switching and vascular remodeling in hypertension
Authors: Guoqing Yao, Xuehui Zheng, Yang Hu, Yuan Zhao, Binghui Kong, Yun Ti, Pei Li Bu
Journal: Theranostics (2024)

Rationale: Arterial remodeling serves as a pivotal mechanism underlying the development of diseases such as hypertension. Fibulin-7 (FBLN7), an adhesion protein, remains enigmatic regarding its role in these pathological processes. This study aims to explore whether FBLN7 influences vascular remodeling and its underlying mechanisms. Methods: We generated FBLN7 knockout mice and smooth muscle-specific FBLN7 overexpression mice. Vascular remodeling models were established by administering angiotensin II (Ang II) for 28 days. RNA sequencing, western blot, and immunofluorescence assays were employed to investigate the biological function of FBLN7 in vascular smooth muscle cells (VSMCs). The interaction mechanism between FBLN7 and cell membrane receptors was explored through mass spectrometry analysis, co-immunoprecipitation techniques and molecular dynamics simulations. Results: Bioinformatics analysis revealed an upregulation of FBLN7 expression in the vascular remodeling model, with FBLN7 predominantly localized in VSMCs. Subsequent in vivo validation demonstrated that FBLN7 knockout attenuated Ang II-induced vascular remodeling, reducing aortic wall thickness and collagen formation. Conversely, VSMC-specific overexpression of FBLN7 via AAV vectors exacerbating the remodeling phenotype. Functionally speaking, FBLN7 potentiates Ang II-mediated phenotypic transformation. Mechanistically, FBLN7 interacts with the extracellular and transmembrane domains of syndecan-4 (SDC4) via its C-terminal region, affecting SDC4 signaling and dimer formation. This interaction inhibits SDC4-mediated activation of the Rho-associated protein kinase pathway, subsequently reducing nuclear translocation of myocardin-related transcription factor A, leading to decreased transcription of genes associated with the contractile VSMCs phenotype. Conclusions: These findings reveal FBLN7 promotes the transition of VSMCs from a contractile to a synthetic phenotype, thereby aggravating vascular remodeling. This provides further insights into the pathogenesis of vascular remodeling and potential therapeutic strategies.
Targeting macrophage circadian rhythms with microcurrent stimulation to activate cancer immunity through phagocytic defense
Authors: Yuya Yoshida, Tomohito Tanihara, Keika Hamasaki, Fumiaki Tsurusaki, Taiki Fukuda, Satoka Adachi, Yuma Terada, Kaita Otsuki, Naoki Nishikawa, Kohei Fukuoka, Ryotaro Tsukamoto, Kengo Hamamura, Kosuke Oyama, Akito Tsuruta, Kouta Mayanagi, Satoru Koyanagi, Shigehiro Ohdo, Naoya Matsunaga
Journal: Theranostics (2024)

Macrophage phagocytosis plays a role in cancer immunotherapy. The phagocytic activity of macrophages, regulated by circadian clock genes, shows time-dependent variation. Intervening in the circadian clock machinery of macrophages is a potentially novel approach to cancer immunotherapy; however, data on this approach are scarce. Microcurrent stimulation (MCS) promotes inflammation, proliferation, and remodeling, suggesting its potential to modulate macrophage function; however, its application has been limited. In this study, we investigated the impact of MCS on macrophage phagocytosis of cancer cells using mouse/human macrophage cell lines and various mouse/human cancer cell lines.
Low <i>PPP2R2A</i> expression promotes sensitivity to CHK1 inhibition in high-grade serous ovarian cancer
Authors: Zhaojun Qiu, Deepika Sigh, Yujie Liu, Chandra B Prasad, Nichalos Bean, Chunhong Yan, Zaibo Li, Xiaoli Zhang, Goutham Narla, Analisa DiFeo, Qi-En Wang, Junran Zhang
Journal: Theranostics (2024)

High-grade serous ovarian cancer (HGSOC), the most lethal epithelial ovarian cancer subtype, faces persistent challenges despite advances in the therapeutic use of PARP inhibitors. Thus, innovative strategies are urgently needed to improve survival rates for this deadly disease. Checkpoint kinase 1 (CHK1) is pivotal in regulating cell survival during oncogene-induced replication stress (RS). While CHK1 inhibitors (CHK1i's) show promise as monotherapy for ovarian cancer, a crucial biomarker for effective stratification in clinical trials is lacking, hindering efficacy improvement and toxicity reduction. PP2A B55α, encoded by
RNA nanotherapeutics for hepatocellular carcinoma treatment
Authors: Yihang Yuan, Weijie Sun, Jiaqi Xie, Ziheng Zhang, Jing Luo, Xiangfei Han, Yongfu Xiong, Yang Yang, Yang Zhang
Journal: Theranostics (2024)

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, particularly due to the limited effectiveness of current therapeutic options for advanced-stage disease. The efficacy of traditional treatments is often compromised by the intricate liver microenvironment and the inherent heterogeneity. RNA-based therapeutics offer a promising alternative, utilizing the innovative approach of targeting aberrant molecular pathways and modulating the tumor microenvironment. The integration of nanotechnology in this field, through the development of advanced nanocarrier delivery systems, especially lipid nanoparticles (LNPs), polymer nanoparticles (PNPs), and bioinspired vectors, enhances the precision and efficacy of RNA therapies. This review highlights the significant progress in RNA nanotherapeutics for HCC treatment, covering micro RNA (miRNA), small interfering RNA (siRNA), message RNA (mRNA), and small activating RNA (saRNA) mediated gene silencing, therapeutic protein restoration, gene activation, cancer vaccines, and concurrent therapy. It further comprehensively discusses the prevailing challenges within this therapeutic landscape and provides a forward-looking perspective on the potential of RNA nanotherapeutics to transform HCC treatment.
Clinical-grade human dental pulp stem cells improve adult hippocampal neural regeneration and cognitive deficits in Alzheimer's disease
Authors: Wei Xiong, Wenting She, Ye Liu, Heng Zhou, Xinxin Wang, Fang Li, Ruohan Li, Junnan Wang, Dongdong Qin, Shuili Jing, Xingxiang Duan, Cailei Jiang, Chun Xu, Yan He, Zhihao Wang, Qingsong Ye
Journal: Theranostics (2024)

Background: Disrupted hippocampal functions and progressive neuronal loss represent significant challenges in the treatment of Alzheimer's disease (AD). How to achieve the improvement of pathological progression and effective neural regeneration to ameliorate the intracerebral dysfunctional environment and cognitive impairment is the goal of the current AD therapy. Methods: We examined the therapeutic potential of clinical-grade human derived dental pulp stem cells (hDPSCs) in cognitive function and neuropathology in AD. Specifically, we investigated the effect of neural crest-specific derived hDPSCs on endogenous neural regeneration and long-term efficacy following a single transplantation in the triple-transgenic mouse model (3xTg-AD). Results: Our research demonstrated that a single administration of clinical-grade hDPSCs yielded dramatic short-term therapeutic benefits (5 weeks) and sustained partial efficacy (6 months) with respect to improving cognitive impairment and delaying typical pathological progression in 3xTg-AD mice. Intriguingly, exogenous hDPSCs were robustly self-differentiated into newborn functional neurons in the hippocampus of 3xTg-AD mice. The foremost evidence is provided that hDPSCs promote endogenic neural regeneration by enhancing the activation of the Wnt/β-catenin pathway, which may contribute to stabilizing the hippocampal neural network to reverse memory deficits. Conclusion: These findings highlight the multifunctional potential of hDPSCs in AD treatment, which enhances cognition through alleviating neuropathology and providing neural regenerative driving force. Understanding these multiplicity effects is critical to advancing the clinical translation of stem cell-based therapies for AD.
<i>Ex vivo</i> enhancement of CD8+ T cell activity using functionalized hydrogel encapsulating Tonsil-derived lymphatic endothelial cells
Authors: Heesun Hong, Chan Hum Park, Ji Seung Lee, Kyunghee Kim, Sudarshini Nath, Moon Sik Oh, Sol Kim, Chul Hee Lee, Ki Hyun Kim, Woo Hee Choi, Kyu Young Choi, Hae Sang Park, Ok Joo Lee, In-Sun Hong, Soon Hee Kim
Journal: Theranostics (2024)