tbuckley/cabot-search huggingface dataset:
C-X-C motif chemokine receptor 4-directed PET signal in the arterial tree is not consistently linked to calcified plaque burden and cardiovascular risk
Authors: Aleksander Kosmala, Natalie Hasenauer, Sebastian E Serfling, Kerstin Michalski, Matthias Fröhlich, Niklas Dreher, Philipp E Hartrampf, Takahiro Higuchi, Andreas K Buck, Alexander Weich, Theresa Reiter, Rudolf A Werner
Journal: Theranostics (2024)

Purpose: To establish the extent, distribution and frequency of in-vivo vessel wall [68Ga]Ga-PentixaFor uptake and to determine its relationship with calcified atherosclerotic plaque burden (CAP) and cardiovascular risk factors (CVRF). Methods: 65 oncological patients undergoing [68Ga]Ga-PentixaFor PET/CT were assessed. Radiotracer uptake (target-to-background ratio [TBR]) and CAP burden (including number of CAP sites, calcification circumference and thickness) in seven major vessel segments per patient were determined. We then investigated associations of vessel wall uptake with CAP burden, cardiovascular risk (CVRF and European Society of Cardiology [ESC] SCORE2/SCORE2-OP risk chart) and image noise (determined by coefficient of variation [CoV] from unaffected liver parenchyma). Results: We identified 1292 sites of high focal [68Ga]Ga-PentixaFor uptake (PentixaFor+ sites) in the vessel wall in 65/65 (100%) patients, with concomitant calcification in 385/1292 (29.8%) sites. There were no significant associations between vessel wall uptake and CAP burden (number of PentixaFor+ sites: r ≤ 0.18, P ≥ 0.14; PentixaFor+ TBR: r ≤ 0.08, P ≥ 0.54). The number of PentixaFor+ sites showed a moderate correlation with cardiovascular risk (ESC SCORE2/SCORE2-OP, r = 0.30; number of CVRF, r = 0.26; P = 0.04, respectively), but failed to reach significance for PentixaFor+ TBR (r ≤ 0.18, P ≥ 0.22). In univariable regression analysis, body mass index (odds ratio [OR] 1.08, 95%-confidence interval [CI] 1.02-1.14) and CoV (OR, 1.07; CI, 1.05-1.10) were linked to TBR and the number of PentixaFor+ sites (P < 0.01, respectively), while injected activity was only associated with the latter imaging parameter (OR, 0.99; CI, 0.98-1.00; P = 0.04). In multivariable regression, injected activity (OR, 1.00; CI, 0.99-1.00) and CoV (OR, 1.06; CI, 1.06-1.07) remained significantly associated with the number of PentixaFor+ sites (P < 0.01, respectively). CoV, however, was the only parameter significantly linked to PentixaFor+ TBR on multivariable analysis (OR, 1.02; CI, 1.01-1.03; P < 0.01). Conclusion: On a visual and quantitative level, high focal [68Ga]Ga-PentixaFor uptake in the arterial tree was not consistently linked to vessel wall calcification or cardiovascular risk. Image noise, however, may account for a substantial portion of apparent vessel wall uptake.
Photobiomodulation: shining a light on depression
Authors: Lian Wang, Liwei Mao, Zhihai Huang, Jeffrey A Switzer, David C Hess, Quanguang Zhang
Journal: Theranostics (2024)

Depression is a prevalent public health issue, characterized by persistent low mood, impaired concentration, and diminished motivation. Photobiomodulation (PBM), which involves the application of red or near-infrared light, modulates physiological processes by enhancing cerebral blood flow, reducing inflammation, inhibiting apoptosis, and promoting neurogenesis. PBM can be administered transcranially or through systemic approaches, offering a potentially effective intervention for depression. This review discusses the characteristics of PBM, its underlying neurobiological mechanisms, and relevant physical parameters. Recent progress in both animal and clinical research underscores PBM's therapeutic potential for depression and emphasizes the need for further studies to establish a robust theoretical basis for standardized treatment protocols.
An enzyme-mimicking reactive oxygen species scavenger targeting oxidative stress-inflammation cycle ameliorates IR-AKI by inhibiting pyruvate dehydrogenase kinase 4
Authors: Wenfang He, Chenguang Ding, Ting Lin, Binqi Wang, Wenjing Wang, Zhichao Deng, Taian Jin, Yiwei Shang, Danna Zheng, Ting Bai, Mingzhen Zhang, Runqing Li, Juan Jin, Qiang He
Journal: Theranostics (2024)

Rationale: Ischemia-reperfusion-induced acute kidney injury (IR-AKI), characterized by the abrupt decline in renal function, is distinguished by the intricate interplay between oxidative stress and inflammation. In this study, a reactive oxygen species (ROS) scavenger-CF@PDA was developed to effectively target antioxidant and anti-inflammatory pathways to disrupt the oxidative stress-inflammation cycle in IR-AKI. Methods: UV-vis absorption spectra, FTIR spectra, and TEM were employed to determine the successful construction of CF@P. ABTS, TMB, and NBT analyses were performed to detect the antioxidant ability and enzyme-mimicking ability of CF@P. In vitro and in vitro, the antioxidant/anti-inflammatory effect of CF@P was detected by MTT, qPCR, fluorescence, and flow cytometry. Multi-omics revealed the mechanism of CF@P in IR-AKI therapy, and molecular docking was further used to determine the mechanism. MRI and photoacoustic imaging were employed to explore the dual-mode imaging capacity of CF@P in IR-AKI management. Results: CF@P could disrupt the oxidative stress-inflammatory cascade by scavenging ROS, reducing pro-inflammatory cytokines, and modulation of macrophage polarization. Subsequent multi-omics indicated that the renal protective effects may be attributed to the inhibition of pyruvate dehydrogenase kinase 4 (PDK4). Metabolomics demonstrated that CF@P could improve the production of antioxidant compounds and reduce nephrotoxicity. Additionally, CF@P exhibited promising capabilities in T1-MRI and photoacoustic imaging for AKI management. Conclusions: Collectively, CF@P, possessing antioxidant/anti-inflammatory properties by inhibiting PDK4, as well as imaging capabilities and superior biocompatibility, holds promise as a therapeutic strategy for IR-AKI.
Metformin-based nanomedicines for reprogramming tumor immune microenvironment
Authors: Jieyu Liu, Xiaoling Li, Yinggang Li, Qiyong Gong, Kui Luo
Journal: Theranostics (2024)

Immunotherapy has transformed current cancer management, and it has achieved significant progress over last decades. However, an immunosuppressive tumor microenvironment (TME) diminishes the effectiveness of immunotherapy by suppressing the activity of immune cells and facilitating tumor immune-evasion. Adenosine monophosphate-activated protein kinase (AMPK), a key modulator of cellular energy metabolism and homeostasis, has gained growing attention in anti-tumor immunity. Metformin is usually considered as a cornerstone in diabetes management, and its role in activating the AMPK pathway has also been extensively explored in cancer therapy although the findings on its role remain inconsistent. Metformin in a nanomedicine formulation has been found to hold potential in reprogramming the immunosuppressive TME through immunometabolic modulation of both tumor and immune cells. This review elaborates the foundation and progress of immunometabolic reprogramming of the TME via metformin-based nanomedicines, offering valuable insights for the next generation of cancer therapy.
tRNA-derived small RNAs in disease immunity
Authors: Hongyuan Jia, Linling Zhang
Journal: Theranostics (2024)

Recently, members of a unique species of non-coding RNA, known as transfer RNA-derived small RNAs (tsRNAs) have been reported to serve multiple molecular functions, including in cells that mediate immunity. Because of their low molecular weights, tsRNAs were previously difficult to detect and were thus overlooked, until now. In this review, we delve into the biogenesis of tsRNAs and their diverse biological functions, ranging from transcriptional regulation to modulation of mRNA translation. We highlight the current evidence demonstrating their involvement in the immune response, as well as how tsRNAs modulate immunity to influence tumor growth and spread, autoimmune disease pathology and infection by pathogens. We surmise that tsRNAs are likely informative as diagnostic markers of cellular homeostasis and disease, and that therapeutic targeting of tsRNAs could be beneficial for a range of human diseases. Improved knowledge on the functions for tsRNAs in the mammalian immune system will enable us to leverage tsRNAs for their effective clinical use as treatments for human health challenges.
Silk fibroin-based hydrogels for cartilage organoids in osteoarthritis treatment
Authors: Congyi Shen, Ziyang Zhou, Ruiyang Li, Shike Yang, Dongyang Zhou, Fengjin Zhou, Zhen Geng, Jiacan Su
Journal: Theranostics (2024)

Osteoarthritis (OA) is a common joint disease characterized by cartilage degeneration. It can cause severe pain, deformity and even amputation risk. However, existing clinical treatment methods for cartilage repair present certain deficiencies. Meanwhile, the repair effect of cartilage tissue engineering is also unsatisfactory. Cartilage organoids are multicellular aggregates with cartilage-like three-dimensional structure and function. On the one hand, cartilage organoids can be used to explore the pathogenesis of OA by constructing disease models. On the other hand, it can be used as filler for rapid cartilage repair. Extracellular matrix (ECM)-like three-dimensional environment is the key to construct cartilage organoids. Silk fibroin (SF)-based hydrogels not only have ECM-like structure, but also have unique mechanical properties and remarkable biocompatibility. Therefore, SF-based hydrogels are considered as ideal biomaterials for constructing cartilage organoids. In this review, we reviewed the studies of cartilage organoids and SF-based hydrogels. The advantages of SF-based hydrogels in constructing cartilage organoids and the iterative optimization of cartilage organoids through designing hydrogels by using artificial intelligence (AI) calculation are also discussed. This review aims to provide a theoretical basis for the treatment of OA using SF-based biomaterials and cartilage organoids.
CXCR4-directed endoradiotherapy with [<sup>177</sup>Lu]Pentixather added to total body irradiation for myeloablative conditioning in patients with relapsed/refractory acute myeloid leukemia
Authors: Krischan Braitsch, Theo Lorenzini, Maike Hefter, Katrin Koch, Katharina Nickel, Jan C Peeken, Katharina S Götze, Wolfgang Weber, Anne Allmann, Calogero D'Alessandria, Julia Brosch-Lenz, Florian Bassermann, Martina Rudelius, Mareike Verbeek, Matthias Eiber, Peter Herhaus
Journal: Theranostics (2024)

Despite recent advances in the targeted therapy of AML, the disease continues to have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (alloSCT) remains to be the curative therapy option for fit patients with high-risk disease. Especially patients with relapsed or refractory (r/r) AML continue to have poor outcomes. Myeloablative total body irradiation (TBI) based conditioning can be used in AML patients refractory to multiple lines of standard therapy, but the optimal conditioning regimen remains unclear for patients considered to be chemotherapy- refractory. Feasibility of C-X-C-motif chemokine receptor 4 (CXCR4)-directed endoradiotherapy (ERT) has previously been demonstrated in AML patients with CXCR4 expression on leukemic blasts.
Tumor immunomodulation by nanoparticle and focused ultrasound alters gut microbiome in a sexually dimorphic manner
Authors: Akansha Singh, Sri Vidhya Chandrasekar, Vishnu Thayil Valappil, Joy Scaria, Ashish Ranjan
Journal: Theranostics (2024)

Local immunomodulation with nanoparticles (NPs) and focused ultrasound (FUS) is recognized for triggering anti-tumor immunity. However, the impact of these tumor immunomodulations on sex-specific microbiome diversity at distant sites and their correlation with therapeutic effectiveness remains unknown. Here, we conducted local intratumoral therapy using immunogenic cell death-enhancing Calreticulin-Nanoparticles (CRT-NPs) and FUS in male and female mice. We identified immune-related microbiome populations, aiming to translate our findings into clinical applications.
S100A proteins show a spatial distribution of inflammation associated with the glioblastoma microenvironment architecture
Authors: Blanca Cómitre-Mariano, Berta Segura-Collar, Gabriel Vellila-Alonso, Rubén Contreras, Aurelio Henandez-Lain, Manuel Valiente, Juan M Sepulveda, Stephen Garrett Marcus, Guillermo García-Posadas, Luis Jiménez-Roldán, Ángel Perez-Nuñez, Ricardo Gargini
Journal: Theranostics (2024)

Glioblastoma IDH wild type (GBM IDH wt) has a poor prognosis and a strongly associated with inflammatory processes. Inflammatory molecules generate positive feedback with tumor cells fueling tumor growth as well as recruitment of immune cells that promote aggressiveness. Although the role of many inflammatory molecules is well known, there are many macromolecules, such as the S100A proteins, whose role is only now beginning to be established.
MRI guided copper deprivator activated immune responses and suppressed angiogenesis for enhanced antitumor immunotherapy
Authors: Yinfeng Wang, Peng Wang, Huimin Li, Miao Yan, Feixue Ni, Li Zhang, Zhen Zhao, Wenjuan Gao, Guilong Zhang
Journal: Theranostics (2024)

Background: Copper plays an important role in the regulation of PD-L1, suggesting that reducing copper levels within tumors may enhance anti-cancer immunotherapy. Methods: Tumor microenvironment responsive copper nanodeprivator (TMECN) was developed for enhancing immunotherapy of tumor via the cross-link of mercaptopolyglycol bipyridine and dimercaptosuccinic acid modifying FePt nanoalloy using the disulfide bond. Results: Upon entering tumor cells, the disulfide bond in TMECN is cleaved by the overexpressed glutathione, exposing abundance of sulfhydryl groups. Next, TMECN actively captured copper ions in the cancer cells, which triggered the self-assembly of TMECN. The reduced copper not only inhibited tumor neovascularization and PD-L1 transcription but also promoted the ubiquitination and degradation of PD-L1, blocking tumor immune escape. In addition, TMECN catalyzed Fenton reaction and produced reactive oxygen species (ROS) in cancer cells, inducing immunogenic cell death (ICD) of tumor. The inhibition of PD-L1 and the activation of ICD synergistically promoted cytotoxic T lymphocyte infiltration for tumor, evoked robust antitumor immune responses. In addition, the self-assembly of TMECN in tumor induced T1 to T2 switchable contrast imaging, which significantly improved accurate diagnosis of tumor. Conclusion: TMECN could effectively inhibit tumor growth and metastases, meanwhile improve MRI contrast enhancement of tumor. The project will offer a simple strategy for enhancing MRI-guided antitumor immunotherapy.
Engineering nanosystems for regulating reproductive health in women
Authors: Qinrui Fu, Lejun Fu
Journal: Theranostics (2024)

Reproductive health-related diseases have a significant impact on the well-being of millions of women worldwide, severely compromising their quality of life. Women encounter unique challenges in terms of reproductive health, including gynecological diseases and malignant neoplasms prior to pregnancy, as well as complications during pregnancy that greatly undermine their physical and mental health. Despite recent advancements in the field of female reproduction, substantial challenges still persist. To address these challenges, nanotechnology-based diagnostic and therapeutic strategies have emerged to provide intelligent detection and treatment for pathologies related to women's reproductive health. Although some progress has been made with nanotherapeutics in this domain, its application is still nascent due to the delicate and intricate nature of the female reproductive system. This review comprehensively presents the latest advancements in nanomedicine for regulating woman's reproductive health. Firstly, based on the time period of onset, nanomedicine applications are categorized into four subcategories: 1) preconception diseases such as polycystic ovary syndrome, endometriosis, and gynecologic malignancy treatment; 2) pregastrulation period diseases including placenta accreta spectrum disorders and ectopic pregnancy; 3) mid-term pregnancy diseases like preeclampsia; and 4) late pregnancy diseases such as deep vein thrombosis during pregnancy. The systematic introduction covers the progress made by nanomedicine in various disease areas. Finally, this article discusses the challenges faced by these nanomedicines from research to clinical translation while also highlighting future directions.
Metabolism of cancer cells and immune cells in the initiation, progression, and metastasis of cancer
Authors: Mingxia Jiang, Huapan Fang, Huayu Tian
Journal: Theranostics (2024)

The metabolism of cancer and immune cells plays a crucial role in the initiation, progression, and metastasis of cancer. Cancer cells often undergo metabolic reprogramming to sustain their rapid growth and proliferation, along with meeting their energy demands and biosynthetic needs. Nevertheless, immune cells execute their immune response functions through the specific metabolic pathways, either to recognize, attack, and eliminate cancer cells or to promote the growth or metastasis of cancer cells. The alteration of cancer niches will impact the metabolism of both cancer and immune cells, modulating the survival and proliferation of cancer cells, and the activation and efficacy of immune cells. This review systematically describes the key characteristics of cancer cell metabolism and elucidates how such metabolic traits influence the metabolic behavior of immune cells. Moreover, this article also highlights the crucial role of immune cell metabolism in anti-tumor immune responses, particularly in priming T cell activation and function. By comprehensively exploring the metabolic crosstalk between cancer and immune cells in cancer niche, the aim is to discover novel strategies of cancer immunotherapy and provide effective guidance for clinical research in cancer treatment. In addition, the review also discusses current challenges such as the inadequacy of relevant diagnostic technologies and the issue of multidrug resistance, and proposes potential solutions including bolstering foundational cancer research, fostering technological innovation, and implementing precision medicine approaches. In-depth research into the metabolic effects of cancer niches can improve cancer treatment outcomes, prolong patients' survival period and enhance their quality of life.
Inhibiting autophagy selectively prunes dysfunctional tumor vessels and optimizes the tumor immune microenvironment
Authors: Wanting Hou, Chaoxin Xiao, Ruihan Zhou, Xiaohong Yao, Qin Chen, Tongtong Xu, Fujun Cao, Yulin Wang, Xiaoying Li, Ouying Yan, Xiaolin Ai, Cheng Yi, Dan Cao, Chengjian Zhao
Journal: Theranostics (2024)

Dysfunctional tumor vasculature, hypoxia, and an immunosuppressive microenvironment are significant barriers to effective cancer therapy. Autophagy, which is critical for maintaining cellular homeostasis and apoptosis resistance, is primarily triggered by hypoxia and nutrient deprivation, conditions prevalent in dysfunctional tumor vessels due to poor circulation. However, the role of autophagy in dysfunctional tumor endothelial cells and its impact on treatment and the tumor microenvironment (TME) remain poorly understood. Methods: We used multiplex immunofluorescence and transgene-based imaging to characterize autophagy in endothelial cells from clinical tumor samples, zebrafish xenograft tumors, and murine models. Using a zebrafish xenograft vasculature platform, we analyzed the effects of autophagy inhibitors on the structure and function of the tumor vasculature. In mice, we investigated autophagy inhibition via endothelial-specific autophagy gene knockout (Atg7 iECKO) and the autophagy inhibitor SBI-0206965 and evaluated the synergistic effects of combining SBI-0206965 with low-dose chemotherapy (5-fluorouracil, 5-FU) or PD-1 antibody. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro under hypoxic, glucose-deprived, and serum-free conditions to simulate dysfunctional tumor endothelial cells and to explore the mechanisms by which autophagy inhibition optimizes tumor vasculature. Results: Elevated autophagy was observed in tumor endothelial cells within the dysfunctional vasculature. Autophagy inhibition, through either genetic knockout or pharmacological inhibition, selectively prunes dysfunctional vessels and improves vascular function. It also stimulates the formation of a perivascular immune niche, thereby optimizing the tumor immune microenvironment (TiME). Furthermore, combining the autophagy inhibitor SBI-0206965 with low-dose 5-FU or PD-1 antibody potentiated the anti-tumor effects. Mechanistic studies have indicated that autophagy acts as a protective response to the hypoxic and nutrient-deprived TME, while its inhibition, mediated by p53 activation, promotes tumor endothelial cell apoptosis in dysfunctional tumor vessels, further optimizing the structure and function of the tumor vasculature. Conclusions: Targeting endothelial cell autophagy is a promising strategy for remodeling the dysfunctional tumor vasculature, optimizing the TiME, and boosting the efficacy of chemotherapy and immunotherapy.
Advancements in GelMA bioactive hydrogels: Strategies for infection control and bone tissue regeneration
Authors: Lei Huang, Ziyao Guo, Xiaoxia Yang, Yinchun Zhang, Yiyun Liang, Xiaxue Chen, Xiaoling Qiu, Xuan Chen
Journal: Theranostics (2024)

Infectious bone defects present a significant clinical challenge, characterized by infection, inflammation, and subsequent bone tissue destruction. Traditional treatments, including antibiotic therapy, surgical debridement, and bone grafting, often fail to address these defects effectively. However, recent advancements in biomaterials research have introduced innovative solutions for managing infectious bone defects. GelMA, a three-dimensional network of hydrophilic polymers that can absorb and retain substantial amounts of water, has attracted considerable attention in the fields of materials science and biomedical engineering. Its distinctive properties, such as biocompatibility, responsiveness to stimuli, and customisable mechanical characteristics make GelMA an exemplary scaffold material for bone tissue engineering. This review aims to thoroughly explore the current literature on antibacterial and osteogenic strategies using GelMA hydrogels for the restoration of infected bones. It discusses their fabrication methods, biocompatibility, antibacterial effectiveness, and bioactivity. We conclude by discussing the existing challenges and future research directions in this field, with the hope of inspiring further innovations in the synthesis, modification, and application of GelMA-based hydrogels for infection control and bone tissue regeneration.
Orchestrating the frontline: HDAC3-miKO recruits macrophage reinforcements for accelerated myelin debris clearance after stroke
Authors: Jiaying Li, Chenran Wang, Yue Zhang, Yichen Huang, Ziyu Shi, Yuwen Zhang, Yana Wang, Shuning Chen, Yiwen Yuan, He Wang, Leilei Mao, Yanqin Gao
Journal: Theranostics (2024)

White matter has emerged as a key therapeutic target in ischemic stroke due to its role in sensorimotor and cognitive outcomes. Our recent findings have preliminarily revealed a potential link between microglial HDAC3 and white matter injury following stroke. However, the mechanisms by which microglial HDAC3 mediates these effects remain unclear.
Optical coherence tomography (OCT) and OCT angiography: Technological development and applications in brain science
Authors: Luyao Yang, Pengyu Chen, Xiaofei Wen, Qingliang Zhao
Journal: Theranostics (2024)

Brain diseases are a leading cause of disability and death worldwide. Early detection can lead to earlier intervention and better outcomes for patients. In recent years, optical coherence tomography (OCT) and OCT angiography (OCTA) imaging have been widely used in stroke, traumatic brain injury (TBI), and brain cancer due to their advantages of