tbuckley/cabot-search huggingface dataset:
Discovery of 2-deoxy glucose surfaced mixed layer dendrimer: a smart neuron targeted systemic drug delivery system for brain diseases
Authors: Anubhav Dhull, Zhi Zhang, Rishi Sharma, Aqib Iqbal Dar, Anu Rani, Jing Wei, Shamila Gopalakrishnan, Amanda Ghannam, Victoria Hahn, Anunay James Pulukuri, Stefanie Tasevski, Sara Moughni, Boyang Jason Wu, Anjali Sharma
Journal: Theranostics (2024)

The availability of non-invasive drug delivery systems capable of efficiently transporting bioactive molecules across the blood-brain barrier to specific cells at the injury site in the brain is currently limited.Delivering drugs to neurons presents an even more formidable challenge due to their lower numbers and less phagocytic nature compared to other brain cells.Additionally, the diverse types of neurons, each performing specific functions, necessitate precise targeting of those implicated in the disease.Moreover, the complex synthetic design of drug delivery systems often hinders their clinical translation.The production of nanomaterials at an industrial scale with high reproducibility and purity is particularly challenging.However, overcoming this challenge is possible by designing nanomaterials through a straightforward, facile, and easily reproducible synthetic process.Methods: In this study, we have developed a third-generation 2-deoxy-glucose functionalized mixed layer dendrimer (2DG-D) utilizing biocompatible and cost-effective materials via a highly facile convergent approach, employing copper-catalyzed click chemistry.We further evaluated the systemic neuronal targeting and biodistribution of 2DG-D, and brain delivery of a neuroprotective agent pioglitazone (Pio) in a pediatric traumatic brain injury (TBI) model. Results:The 2DG-D exhibits favorable characteristics including high water solubility, biocompatibility, biological stability, nanoscale size, and a substantial number of end groups suitable for drug conjugation.Upon systemic administration in a pediatric mouse model of traumatic brain injury (TBI), the 2DG-D localizes in neurons at the injured brain site, clears rapidly from off-target locations, effectively delivers Pio, ameliorates neuroinflammation, and improves behavioral outcomes.Conclusions: The promising in vivo results coupled with a convenient synthetic approach for the construction of 2DG-D makes it a potential nanoplatform for addressing brain diseases.
Single-cell analyses reveal evolution mimicry during the specification of breast cancer subtype
Authors: Zhi-Jie Gao, Huan Fang, Si Sun, Si-Qing Liu, Zhou Fang, Zhou Liu, Bei Li, Ping Wang, Sheng-Rong Sun, Xiang-Yu Meng, Qi Wu, Ce-Shi Chen
Journal: Theranostics (2024)

Background:The stem or progenitor antecedents confer developmental plasticity and unique cell identities to cancer cells via genetic and epigenetic programs.A comprehensive characterization and mapping of the cell-of-origin of breast cancer using novel technologies to unveil novel subtype-specific therapeutic targets is still absent.Methods: We integrated 195,144 high-quality cells from normal breast tissues and 406,501 high-quality cells from primary breast cancer samples to create a large-scale single-cell atlas of human normal and cancerous breasts.Potential heterogeneous origin of malignant cells was explored by contrasting cancer cells against reference normal epithelial cells.Multi-omics analyses and both in vitro and in vivo experiments were performed to screen and validate potential subtype-specific treatment targets.Novel biomarkers of identified immune and stromal cell subpopulations were validated by immunohistochemistry in our cohort.Results: Tumor stratification based on cancer cell-of-origin patterns correlated with clinical outcomes, genomic aberrations and diverse microenvironment constitutions.We found that the luminal progenitor (LP) subtype was robustly associated with poor prognosis, genomic instability and dysfunctional immune microenvironment.However, the LP subtype patients were sensitive to neoadjuvant chemotherapy (NAC), PARP inhibitors (PARPi) and immunotherapy.The LP subtype-specific target PLK1 was investigated by both in vitro and in vivo experiments.Besides, large-scale single-cell profiling of breast cancer inspired us to identify a range of clinically relevant immune and stromal cell subpopulations, including subsets of innate lymphoid cells (ILCs), macrophages and endothelial cells. Conclusion:The present single-cell study revealed the cellular repertoire and cell-of-origin patterns of breast cancer.Combining single-cell and bulk transcriptome data, we elucidated the evolution mimicry from normal to malignant subtypes and expounded the LP subtype with vital clinical implications.Novel immune and stromal cell subpopulations of breast cancer identified in our study could be potential therapeutic targets.Taken together, Our findings lay the foundation for the precise prognostic and therapeutic stratification of breast cancer.
Combined activation of artificial and natural ion channels for disrupting mitochondrial ion homeostasis towards effective postoperative tumor recurrence and metastasis suppression
Authors: Panqin Ma, Zheng Luo, Qi Wang, Ying Chen, Feng Liu, Changliang Ren, Caisheng Wu, Zibiao Li, Yun-Long Wu
Journal: Theranostics (2024)

Rationale: Pharmacological targeting of mitochondrial ion channels is developing as a new direction in cancer therapy.The opening or closing of these channels can impact mitochondrial function and structure by interfering with intracellular ion homeostasis, thereby regulating cell fate.Nevertheless, their abnormal expression or regulation poses challenges in eliminating cancer cells, and further contributes to metastasis, recurrence, and drug resistance.Methods: We developed an engineered mitochondrial targeted delivery system with self-reinforcing potassium ion (K + ) influx via amphiphilic mitochondrial targeting polymer (TMP) as carriers to co-deliver natural K + channel agonists (Dinitrogen oxide, DZX) and artificial K + channel molecules (5F8).Results: Using this method, DZX specifically activated natural K + channels, whereas 5F8 assembled artificial K + channels on the mitochondrial membrane, leading to mitochondrial K + influx, as well as oxidative stress and activation of the mitochondrial apoptotic pathway. Conclusion:The synergistic effect of 5F8 and DZX presents greater effectiveness in killing cancer cells than DZX alone, and effectively inhibited tumor recurrence and lung metastasis following surgical resection of breast cancer tumors in animal models.This strategy innovatively integrates antihypertensive drugs with artificial ion channel molecules for the first time to effectively inhibit tumor recurrence and metastasis by disrupting intracellular ion homeostasis, which will provide a novel perspective for postoperative tumor therapy.
PSMA-targeted radiotheranostics in modern nuclear medicine: then, now, and what of the future?
Authors: Mohamed Sallam, Nam-Trung Nguyen, Frank Sainsbury, Nobuo Kimizuka, Serge Muyldermans, Martina Benešová-Schäfer
Journal: Theranostics (2024)

In 1853, the perception of prostate cancer (PCa) as a rare ailment prevailed, was described by the eminent Londoner surgeon John Adams. Rapidly forward to 2018, the landscape dramatically altered. Currently, men face a one-in-nine lifetime risk of PCa, accentuated by improved diagnostic methods and an ageing population. With more than three million men in the United States alone grappling with this disease, the overall risk of succumbing to stands at one in 39. The intricate clinical and biological diversity of PCa poses serious challenges in terms of imaging, ongoing monitoring, and disease management. In the field of theranostics, diagnostic and therapeutic approaches that harmoniously merge targeted imaging with treatments are integrated. A pivotal player in this arena is radiotheranostics, employing radionuclides for both imaging and therapy, with prostate-specific membrane antigen (PSMA) at the forefront. Clinical milestones have been reached, including FDA- and/or EMA-approved PSMA-targeted radiodiagnostic agents, such as [
Distinctive tumorigenic significance and innovative oncology targets of SUMOylation
Authors: Heng Zhou, Na Deng, Yanshu Li, Xiaoyun Hu, Xue Yu, Shiheng Jia, Chen Zheng, Shan Gao, Huizhe Wu, Kai Li
Journal: Theranostics (2024)

Protein SUMOylation, a post-translational modification, intricately regulates diverse biological processes including gene expression, cell cycle progression, signaling pathway transduction, DNA damage response, and RNA metabolism.This modification contributes to the acquisition of tumorigenicity and the maintenance of cancer hallmarks.In malignancies, protein SUMOylation is triggered by various cellular stresses, promoting tumor initiation and progression.This augmentation is orchestrated through its specific regulatory mechanisms and characteristic biological functions.This review focuses on elucidating the fundamental regulatory mechanisms and pathological functions of the SUMO pathway in tumor pathogenesis and malignant evolution, with particular emphasis on the tumorigenic potential of SUMOylation.Furthermore, we underscore the potential therapeutic benefits of targeting the SUMO pathway, paving the way for innovative anti-tumor strategies by perturbing this dynamic and reversible modifying process.
Stem cell-derived extracellular vesicles in the therapeutic intervention of Alzheimer's Disease, Parkinson's Disease, and stroke
Authors: Wantong Zhou, Xudong Wang, Yumeng Dong, Peifen Gao, Xian Zhao, Mengxia Wang, Xue Wu, Jiuheng Shen, Xin Zhang, Zhiguo Lu, Wenlin An
Journal: Theranostics (2024)

With the increase in the aging population, the occurrence of neurological disorders is rising.Recently, stem cell therapy has garnered attention due to its convenient sourcing, minimal invasiveness, and capacity for directed differentiation.However, there are some disadvantages, such as poor quality control, safety assessments, and ethical and logistical issues.Consequently, scientists have started to shift their attention from stem cells to extracellular vesicles due to their similar structures and properties.Beyond these parallels, extracellular vesicles can enhance biocompatibility, facilitate easy traversal of barriers, and minimize side effects.Furthermore, stem cell-derived extracellular vesicles can be engineered to load drugs and modify surfaces to enhance treatment outcomes.In this review, we summarize the functions of native stem cell-derived extracellular vesicles, subsequently review the strategies for the engineering of stem cell-derived extracellular vesicles and their applications in Alzheimer's disease, Parkinson's disease, and stroke, and discuss the challenges and solutions associated with the clinical translation of stem cell-derived extracellular vesicles.
Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis: Erratum
Authors: Haiou Yang, Haiyang Zhang, Yuchong Yang, Xinyi Wang, Ting Deng, Rui Liu, Tao Ning, Ming Bai, Hongli Li, Kegan Zhu, Jialu Li, Qian Fan, Guoguang Ying, Yi Ba
Journal: Theranostics (2024)

[This corrects the article DOI: 10.7150/thno.44419.].
Navigating new horizons: Prospects of NET-targeted radiopharmaceuticals in precision medicine
Authors: Takahiro Higuchi, Xinyu Chen, Rudolf A Werner
Journal: Theranostics (2024)

Goals of the investigation:This work aimed to evaluate the neuroprotective effects of zinc oxide (ZnO) nanoparticles in an experimental mouse model of rotenone-induced PD and investigate the therapeutic effects of ZnO, cobalt ferrite nanoparticles, and their combination.Methods: The levels of dopamine, norepinephrine, epinephrine, and serotonin were assessed using ELISA in the control and experimental model of PD mice.The dopa-decarboxylase expression level was assayed by real-time PCR.The expression level of tyrosine hydroxylase (TH) was assessed by western blot analysis.Results: Our data showed that levels of dopamine decreased in PD mice compared to normal.ZnO NP increased dopamine levels in normal and PD mice (37.5% and 29.5%; respectively, compared to untreated mice).However, ZnO NP did not cause any change in norepinephrine and epinephrine levels either in normal or in PD mice.Levels of serotonin decreased by 64.0%, and 51.1% in PD mice treated with cobalt ferrite and dual ZnO-cobalt ferrite NPs; respectively, when compared to PD untreated mice.The mRNA levels of dopa-decarboxylase increased in both normal and PD mice treated with ZnO NP.Its level decreased when using cobalt ferrite NP and the dual ZnO-cobalt ferrite NP when compared to untreated PD mice.A significant decrease in TH expression by 0.25, 0.68, and 0.62 folds was observed in normal mice treated with ZnO, cobalt ferrite, and the dual ZnO-cobalt ferrite NP as compared to normal untreated mice.In PD mice, ZnO administration caused a non-significant 0.15-fold decrease in TH levels while both cobalt ferrite and the dual ZnO-cobalt ferrite NP administration caused a significant 0.3 and 0.4-fold decrease respectively when compared to untreated PD mice.Principal conclusion: This study reveals that ZnO NPs may be utilized as a potential intervention to elevate dopamine levels to aid in PD treatment.
Bioinspired cellular membrane-derived vesicles for mRNA delivery
Authors: Xiao Xu, Limei Xu, Jingzhi Wang, Caining Wen, Jiang Xia, Yuanmin Zhang, Yujie Liang
Journal: Theranostics (2024)

The rapid advancement of mRNA as vaccines and therapeutic agents in the biomedical field has sparked hope in the fight against untreatable diseases.Successful clinical application of mRNA therapeutics largely depends on the carriers.Recently, a new and exciting focus has emerged on natural cell-derived vesicles.These nanovesicles offer many functions, including enhanced drug delivery capabilities and immune evasion, thereby presenting a unique and promising platform for the effective and safe delivery of mRNA therapeutics.In this study, we summarize the characteristics and properties of biomimetic delivery systems for mRNA therapeutics.In particular, we discuss the unique features of cellular membrane-derived vesicles (CDVs) and the combination of synthetic nanovesicles with CDVs.
LINC00982-encoded protein PRDM16-DT regulates <i>CHEK2</i> splicing to suppress colorectal cancer metastasis and chemoresistance
Authors: Hui-Fang Hu, Lei Han, Jia-Ying Fu, Xuan He, Ji-Feng Tan, Qing-Ping Chen, Jing-Ru Han, Qing-Yu He
Journal: Theranostics (2024)

Metastasis is one of the key factors of treatment failure in late-stage colorectal cancer (CRC).Metastatic CRC frequently develops resistance to chemotherapeutic agents.This study aimed to identify the novel regulators from "hidden" proteins encoded by long noncoding RNAs (lncRNAs) involved in tumor metastasis and chemoresistance.Methods: CRISPR/Cas9 library functional screening was employed to identify the critical suppressor of cancer metastasis in highly invasive CRC models.Western blotting, immunofluorescence staining, invasion, migration, wound healing, WST-1, colony formation, gain-and loss-of-function experiments, in vivo experimental metastasis models, multiplex immunohistochemical staining, immunohistochemistry, qRT-PCR, and RT-PCR were used to assess the functional and clinical significance of FOXP3, PRDM16-DT, HNRNPA2B1, and L-CHEK2.RNA-sequencing, co-immunoprecipitation, qRT-PCR, RT-PCR, RNA affinity purification, RNA immunoprecipitation, MeRIP-quantitative PCR, fluorescence in situ hybridization, chromatin immunoprecipitation and luciferase reporter assay were performed to gain mechanistic insights into the role of PRDM16-DT in cancer metastasis and chemoresistance.An oxaliplatin-resistant CRC cell line was established by in vivo selection.WST-1, colony formation, invasion, migration, Biacore technology, gain-and loss-of-function experiments and an in vivo experimental metastasis model were used to determine the function and mechanism of cimicifugoside H-1 in CRC. Results:The novel protein PRDM16-DT, encoded by LINC00982, was identified as a cancer metastasis and chemoresistance suppressor.The down-regulated level of PRDM16-DT was positively associated with malignant phenotypes and poor prognosis of CRC patients.Transcriptionally regulated by FOXP3, PRDM16-DT directly interacted with HNRNPA2B1 and competitively decreased HNRNPA2B1 binding to exon 9 of CHEK2, resulting in the formation of long CHEK2 (L-CHEK2), subsequently promoting E-cadherin secretion.PRDM16-DT-induced E-cadherin secretion inhibited fibroblast activation, which in turn suppressed CRC metastasis by decreasing MMP9 secretion.Cimicifugoside H-1, a natural compound, can bind to LEU89, HIS91, and LEU92 of FOXP3 and significantly upregulated PRDM16-DT expression to repress CRC metastasis and reverse oxaliplatin resistance.Conclusions: lncRNA LINC00982 can express a new protein PRDM16-DT to function as a novel regulator in cancer metastasis and drug resistance of CRC.Cimicifugoside H-1 can act on the upstream of the PRDM16-DT signaling pathway to alleviate cancer chemoresistance.
Diagnostic performance and clinical impact of <sup>18</sup>F-AlF-NOTA-octreotide in a large cohort of patients with neuroendocrine neoplasms: A prospective single-center study
Authors: Guozhu Hou, Xin Cheng, Yi Yang, Dongbing Zhao, Guiqi Wang, Hong Zhao, Rong Zheng, Xuejuan Wang, Xiaoyuan Chen, Yihebali Chi, Jingjing Zhang
Journal: Theranostics (2024)

Purpose: Somatostatin receptor imaging with 18 F-AlF-NOTA-octreotide ( 18 F-AlF-OC) has shown promising performance in neuroendocrine neoplasms (NENs).In this study, we aim to investigate the diagnostic performance and clinical impact of 18 F-AlF-OC in a large prospective cohort of patients with NEN.Methods: Between January 2023 and November 2023, a total of 219 patients with confirmed or suspected NEN were enrolled prospectively and underwent 18 F-AlF-OC PET/CT at 2 h post-injection.The primary endpoint was the diagnostic performance, including sensitivity, specificity, and accuracy.An additional primary endpoint was the impact of 18 F-AlF-OC on clinical management.The reference standard was based on the results of histopathology or radiological follow-up.Results: 205 patients were included in the final analysis.The patient-level sensitivity, specificity, and accuracy of 18 F-AlF-OC PET/CT compared with contrast-enhanced CT/MRI were 90.5% vs. 81.8%,93.1% vs. 71.1%,and 91.2% vs. 79.4%,respectively.26 patients had tiny gastrointestinal NENs (smaller than 1 cm in diameter).The patient-based sensitivity of 18 F-AlF-OC PET/CT and contrast-enhanced CT/MRI were 61.5% (16/26) and 37.5% (9/24), respectively.The smallest diameter of gastrointestinal NEN detected by 18 F-AlF-OC PET/CT was 0.6 cm in the rectum, 0.3 cm in the stomach, and 0.5 cm in the duodenum. 18F-AlF-OC PET/CT results led to changes in clinical management in 19.5% of patients (40/205), owing mainly to new or unexpected findings compared to contrast-enhanced CT/MRI. Ivyspring International
Energy competition remodels the metabolic glucose landscape of psoriatic epidermal cells
Authors: Weiwei Liu, Jingwei Jiang, Zeming Li, Yang Xiao, Siyi Zhou, Dehuan Wang, Yi Zou, Tiantian Liu, Ke Li, Huan Liang, Nian'ou Wang, Xiao Xiang, Qiaoli Xie, Rixing Zhan, Jinwei Zhang, Xun Zhou, Li Yang, Cheng-Ming Chuong, Mingxing Lei
Journal: Theranostics (2024)

Rationale: Skin cells actively metabolize nutrients to ensure cell proliferation and differentiation.Psoriasis is an immune-disorder-related skin disease with hyperproliferation in epidermal keratinocytes and is increasingly recognized to be associated with metabolic disturbance.However, the metabolic adaptations and underlying mechanisms of epidermal hyperproliferation in psoriatic skin remain largely unknown.Here, we explored the role of metabolic competition in epidermal cell proliferation and differentiation in psoriatic skin.Methods: Bulk-and single-cell RNA-sequencing, spatial transcriptomics, and glucose uptake experiments were used to analyze the metabolic differences in epidermal cells in psoriasis.Functional validation in vivo and in vitro was done using imiquimod-like mouse models and inflammatory organoid models.Results: We observed the highly proliferative basal cells in psoriasis act as the winners of the metabolic competition to uptake glucose from suprabasal cells.Using single-cell metabolic analysis, we found that the "winner cells" promote OXPHOS pathway upregulation by COX7B and lead to increased ROS through glucose metabolism, thereby promoting the hyperproliferation of basal cells in psoriasis.Also, to prevent toxic damage from ROS, basal cells activate the glutathione metabolic pathway to increase their antioxidant capacity to assist in psoriasis progression.We further found that COX7B promotes psoriasis development by modulating the activity of the PPAR signaling pathway by bulk RNA-seq analysis.We also observed glucose starvation and high expression of SLC7A11 that causes suprabasal cell disulfide stress and affects the actin cytoskeleton, leading to immature differentiation of suprabasal cells in psoriatic skin.Conclusion: Our study demonstrates the essential role of cellular metabolic competition for skin tissue homeostasis.
Mesenchymal stem cell-derived apoptotic vesicles ameliorate impaired ovarian folliculogenesis in polycystic ovary syndrome and ovarian aging by targeting WNT signaling
Authors: Yu Fu, Manjin Zhang, Bingdong Sui, FeiFei Yuan, Wenbo Zhang, Yashuang Weng, Lei Xiang, Can Li, Longquan Shao, Yong You, Xueli Mao, Haitao Zeng, Di Chen, Meijia Zhang, Songtao Shi, Xuefeng Hu
Journal: Theranostics (2024)

Rationale: It has been emergingly recognized that apoptosis generates plenty of heterogeneous apoptotic vesicles (apoVs), which play a pivotal role in the maintenance of organ and tissue homeostasis.However, it is unknown whether apoVs influence postnatal ovarian folliculogenesis.Methods: Apoptotic pathway deficient mice including Fas mutant (Fas mut ) and Fas ligand mutant (FasL mut ) mice were used with apoV replenishment to evaluate the biological function of apoVs during ovarian folliculogenesis.Ovarian function was characterized by morphological analysis, biochemical examination and cellular assays.Mechanistical studies were assessed by combinations of transcriptomic and proteomic analysis as well as molecular assays.CYP17A1-Cre; Axin1 fl/fl mice was established to verify the role of WNT signaling during ovarian folliculogenesis.Polycystic ovarian syndrome (PCOS) mice and 15-month-old mice were used with apoV replenishment to further validate the therapeutic effects of apoVs based on WNT signaling regulation.Results: We show that systemic administration of mesenchymal stem cell (MSC)-derived apoptotic vesicles (MSC-apoVs) can ameliorate impaired ovarian folliculogenesis, PCOS phenotype, and reduced birth rate in Fas mut and FasL mut mice.Mechanistically, transcriptome analysis results revealed that MSC-apoVs downregulated a number of aberrant gene expression in Fas mut mice, which were enriched by kyoto encyclopedia of genes and genomes (KEGG) pathway analysis in WNT signaling and sex hormone biosynthesis.Furthermore, we found that apoptotic deficiency resulted in aberrant WNT/β-catenin activation in theca and mural granulosa cells, leading to responsive action of dickkopf1 (DKK1) in the cumulus cell and oocyte zone, which downregulated WNT/β-catenin expression in oocytes and, therefore, impaired ovarian folliculogenesis via Ivyspring International