tbuckley/cabot-search huggingface dataset:
The m6A modification of SOX18 leads to increased PTX3 and cardiomyocyte pyroptosis in sepsis-induced cardiomyopathy
Authors: He Sun, Xinan Qiao, Xiangyan Peng, Hanzhao Zhu, Liyun Zhang, Liqing Jiang, Longteng Wang, Chao Xue, Jian Yang, Wei Yi, Bin Zhang, Jincheng Liu, Weixun Duan
Journal: Theranostics (2025)

Rationale: Sepsis-induced cardiomyopathy (SIC) is a rapidly progressing condition with poor prognosis in the absence of effective therapeutic interventions. Cardiomyocyte pyroptosis is a critical factor contributing to cardiac dysfunction in SIC. Currently, research on this mechanism remains unclear. Methods: We performed LPS-induced primary mouse cardiomyocyte modeling and mouse SIC modeling. Through mRNA-Seq, we found significant pyroptosis in the cardiac tissue of SIC mice. Further confocal microscopy and immunoprecipitation results confirmed that PTX3 is an important participant in cardiomyocyte pyroptosis. We then used ChIP and dual-luciferase reporter assays to confirm that SOX18 exerts a transcriptional repression effect on PTX3. M6A-Seq and RNA stability assays confirmed that the m6A modification mediated/recognized by RBM15/YTHDF2 is a crucial factor in the changes of SOX18 in SIC. Results: Our experiments demonstrated that the abnormally elevated PTX3 in SIC plays a key role in mediating pyroptosis. Under physiological conditions, PTX3 transcription is repressed by SOX18. However, during septic cardiomyopathy, SOX18 stability is compromised by RBM15/YTHDF2-mediated m6A modification, leading to increased PTX3 levels and the subsequent induction of cardiomyocyte pyroptosis. Conclusion: In summary, we have delineated the RBM15/YTHDF2-SOX18-PTX3 axis in SIC. It provides a new approach for the treatment of cardiomyocyte pyroptosis in SIC and for improving prognosis.
Phenylboronic acid in targeted cancer therapy and diagnosis
Authors: Mila Radan, Ivana Carev, Mladen Miloš, Marina Tranfić Bakić
Journal: Theranostics (2025)

Over the past few decades, phenylboronic acid (PBA) and its derivatives have gained attention for their biological activity. More recently, they have gained interest for their application in targeted cancer therapy, owing to their ability to selectively and reversibly bind to sialic acids on the cell surface through the formation of boron ester bonds. Initially, the research was focused on the antitumor properties of simple PBA derivatives. However, it has since expanded to include more complex nanomaterials and drug-delivery systems that exploit the unique properties of PBA for enhanced therapeutic efficacy. This paper presents a comprehensive review of the physico-chemical background of PBA-based drugs in cancer therapy, provides insight into recent advancements in PBA-based systems for targeted drug delivery and their role in improving antitumor efficacy, and offers a perspective on future research and development in the field.
NIR light-driven nanomotor with cascade photodynamic therapy for MRSA biofilm eradication and diabetic wound healing
Authors: Yuanyuan Deng, Jia Zheng, Jianghua Li, Bo Liu, Ke Chen, Yiling Xu, Liu Deng, Huixia Liu, You-Nian Liu
Journal: Theranostics (2025)

Background: Diabetic wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) are challenging to heal due to biofilm formation, which impairs conventional antibiotics with limited penetration and severe side effects. Near-infrared (NIR)-driven nanomotors with autonomous motion and photothermal effects show promise for antibacterial therapy but often lack targeted specificity. Lysostaphin (Ly), an enzyme targeting bacterial cell walls, offers excellent potential against drug-resistant MRSA. Methods: A novel NIR-driven CSIL nanomotor has fabricated by co-loading indocyanine green (ICG) and lysostaphin onto spinous yolk-shell structured C/SiO2@C nanoparticles. The autonomous motion, biofilm penetration, and antibacterial efficacy of CSIL nanomotors are evaluated in vitro, while their biofilm eradication and wound healing performance are assessed in an MRSA-infected diabetic mouse model using a cascade photodynamic therapy (CPDT) strategy. Results: CSIL nanomotors exhibit photothermal and photodynamic properties with MRSA-targeting specificity. They can effectively eradicate MRSA biofilms both in vitro and in vivo, suppress virulence and biofilm-related genes, thus promoting diabetic wound healing by shaping a microenvironment dominated by M2 macrophages. The CPDT strategy is able to avoid excessive ROS production and thermal damage, enabling safe and effective therapy. Conclusion: CSIL nanomotors, with integrated photothermal, photodynamic, and MRSA-targeting properties, represent a novel, efficient and targeted approach to antibacterial therapy in diabetic wounds, offering significant advantages over conventional antibiotics.
Therapeutic potential of FAPI RLT in oncology: A systematic review
Authors: Saad Ruzzeh, Ahmed Saad Abdlkadir, Diana Paez, Keon W Kang, Tadashi Watabe, Serin Moghrabi, Andrew M Scott, Akram Al-Ibraheem
Journal: Theranostics (2025)

Rationale: This systematic review aims to examine the safety and efficacy of fibroblast activation protein inhibitor (FAPI) radioligand therapy (RLT) for various epithelial neoplasms. Methods: PubMed, Web of Science, and Scopus databases were searched up to Jan 4, 2025, for studies involving FAPI RLT in various cancers. Data extraction focused on exploring safety and efficacy of FAPI RLT. Results: Overall, 27 studies involving a total of 144 patients who received FAPI RLT were included in this systematic review. [177Lu]Lu-FAPI was employed in 21 studies, with 225 cycles administered to 95 patients at a median dose of 6.8 GBq/cycle. Six non-randomized clinical investigations using [177Lu]Lu-FAPI reported disease control rates ranging from 18.2% to 83.3%. Only three studies documented a cumulative total of six patients who experienced grade 3 or 4 toxicity post [177Lu]Lu-FAPI RLT. Of 16 case reports utilizing [177Lu]Lu-FAPI, nine achieved disease control across various cancer types, with no reported adverse events. Four studies employed [90Y]Y-FAPI, totaling 103 cycles in 42 patients at a median dose of 6.7 GBq/cycle. Three non-randomized clinical investigations reported disease control rates of 50% to 82%, with two studies documenting eight high-grade toxicity events. Furthermore, a successful administration of [90Y]Y-FAPI was employed in a single reported case involving multiple primary neoplasms with no reported adverse events. However, the patient did not achieve disease control post [90Y]Y-FAPI. A cohort study utilized 53 [213Bi]Bi-FAPI-46 injections following a fractionated dose regimen in six cancer patients, achieving a 33.3% disease control rate without reported adverse events. One case report described dual radionuclide therapy using two cycles with a cumulative 20 GBq [153Sm]Sm-FAPI and a third 8 GBq [90Y]Y-FAPI cycle in a lung cancer patient, resulting in stable disease for eight months. Conclusion: FAPI RLT is a promising and safe therapeutic agent in oncology, with potential benefits achieved on short-term basis. However, its long-term efficacy and safety require further research with larger, controlled studies, considering the currently observed variations in patient populations, cancer types, and methodologies within reviewed studies.
Recent advances and prospects of nanoparticle-based drug delivery for diabetic ocular complications
Authors: Siqi Wang, Hongyu Yang, Jiaying Zheng, Aiyang Tong, Sen Mu, Dongkai Wang, Ming Zhao, Ji Li
Journal: Theranostics (2025)

Diabetes mellitus (DM) is a chronic metabolic disorder that significantly affects various organ systems. The systemic effects of DM lead to numerous complications, with ocular manifestations being of particular concern due to their severity and impact on quality of life. Hyperglycemia-induced ocular damage often results in a range of lesions, including diabetic retinopathy (DR), keratopathy, cataracts, and glaucoma. These conditions impose considerable physical discomfort on patients and place a substantial economic burden on healthcare systems. The advent of nanotechnology has facilitated the development of innovative therapeutic strategies for managing diabetic ocular complications. This review highlights several common ocular complications associated with DM, focusing on their pathogenesis and treatment strategies. Emphasis is placed on the innovative applications and potential of nanotechnology in treating diabetic ocular complications.
Plasma extracellular vesicles from recurrent GBMs carrying LDHA to activate glioblastoma stemness by enhancing glycolysis
Authors: Xin Zhang, JunJie Li, Yiyao Huang, Anming Yang, Xiaoliu Liu, Yunhao Luo, Hao Tian, Minghui Wen, Chengzong Zhong, Bin Peng, Haitao Sun, Lei Zheng
Journal: Theranostics (2025)

Rationale: Glioblastoma multiforme (GBM) is the most aggressive primary malignant brain tumor in adults, characterized by high invasiveness and poor prognosis. Glioma stem cells (GSCs) drive GBM treatment resistance and recurrence, however, the molecular mechanisms activating intracranial GSCs remain unclear. Extracellular vesicles (EVs) are crucial signaling mediators in regulating cell metabolism and can cross the blood-brain barrier (BBB). This study aimed to elucidate how EV cargo contributes to the intracranial GSC state and validate a non-invasive diagnostic strategy for GBM relapse. Methods: We isolated plasma extracellular vesicles (pl-EVs) from three groups: recurrent GBM patients post-resection, non-recurrent GBM patients post-resection, and healthy individuals. Newly diagnosed GBM patients served as an additional control. EVs were characterized and co-cultured with primary GBM cell lines to assess their effect on tumor stemness. EV cargo was analyzed using proteomics to investigate specific EV subpopulations contributing to GBM relapse. Based on these findings, we generated engineered LDHA-enriched EVs (LDHA-EVs) and co-cultured them with patient-derived organoids (PDOs). Metabolomics was performed to elucidate the underlying signal transduction pathways. Results: Our study demonstrated that pl-EVs from recurrent GBM patients enhanced aerobic glycolysis and stemness in GBM cells. Proteomic analysis revealed that plasma EVs from recurrent GBMs encapsulated considerable amounts of the enzyme lactate dehydrogenase A (LDHA). Mechanistically, LDHA-loaded EVs promoted glycolysis, induced cAMP/ATP cycling, and accelerated lactate production, thereby maintained the GSC phenotype. Concurrently, post-surgical therapy-induced stress-modulated hypoxia in residual tumors, promoted LDHA-enriched EV release. Clinically, high levels of circulating LDHA-positive EVs correlated with increased glycolysis, poor therapeutic response, and shorter survival in recurrent GBM patients. Conclusion: Our study highlights LDHA-loaded EVs as key mediators promoting GSC properties and metabolic reprogramming in GBM. These findings provide insights into recurrence mechanisms and suggest potential liquid biopsy approaches for monitoring and preventing GBM relapse.
Active microneedle patch equipped with spontaneous bubble generation for enhanced rheumatoid arthritis treatment
Authors: Ting Liu, Jintao Fu, Ziyang Zheng, Minglong Chen, Wenhao Wang, Chuanbin Wu, Guilan Quan, Xin Pan
Journal: Theranostics (2025)

Rationale: The utilization of dissolving microneedles (MNs) facilitates the painless delivery of pharmaceuticals via the transdermal route. However, conventional MNs rely on passive diffusion through the gradual dissolving of the matrix, which can impede the therapeutic efficacy of the delivered drugs. Methods: In this study, we present the development of a novel degradable active MNs platform. This platform employs sodium bicarbonate and citric acid loaded in a dissolving MNs patch as a built-in motor for deeper and faster intradermal payload delivery. The sodium bicarbonate microparticles and citric acid undergo a chemical reaction when in contact with tissue fluid, resulting in the rapid formation of explosive carbon dioxide bubbles. This provides the necessary force to break through dermal barriers and enhance payload delivery. Results: The results demonstrated that the active MNs possessed excellent mechanical properties, rapid detachment characteristics, and superior drug release kinetics. Furthermore, the drug permeation behavior of active MNs exhibited enhanced permeation and distribution in skin-mimicking gel and porcine skin when compared to conventional passive MNs. In vivo experiments employing a rat model of rheumatoid arthritis showed that active MNs achieved superior therapeutic efficacy compared to passive MNs. Conclusions: This universal and effective autonomous dynamic microneedle delivery technology is straightforward to prepare and ultilize, and has the potential to improve the therapeutic efficacy of drugs, offering significant prospects for a diverse range of therapeutic applications.
Acetylation-regulated DUSP1 deficiency contributes to renal fibrosis progression
Authors: Shaobo Wang, Bo Zhang, Yaqin Wang, Qigang Lan, Liangjing Lv, Tangli Xiao, Yan Li, Mengying Yao, Jun Zhang, Cheng Wang, Yinghui Huang, Jinghong Zhao, Jiachuan Xiong
Journal: Theranostics (2025)

Rationale: The irreversible damage of renal fibrosis has been widely recognized as a critical factor in the progression of chronic kidney disease (CKD) to end-stage kidney failure. This necessitates investigation into its precise mechanisms. Dual-specificity phosphatase 1 (DUSP1), a regulator of mitogen-activated protein kinase (MAPK) pathways, is linked to diseases such as cancer and immune disorders, but its role in renal fibrosis is unclear. This study aimed to clarify the role of DUSP1 in renal fibrosis, identify the intrinsic mechanisms involved, and provide a theoretical basis for the clinical translation of a new target for renal fibrosis treatment. Methods: We characterized DUSP1 expression in kidney tissues from unilateral ureteral obstruction (UUO) mice and patients with CKD using histological analysis. We established a UUO-induced renal fibrosis model using DUSP1 knockout mice. The role and mechanism of DUSP1-mediated inhibition of renal fibrosis was evaluated both in vivo and in vitro. Finally, we performed virus-mediated gene transfer, RNA-Seq, immunohistochemistry, western blotting, and qPCR to further analyze our findings. Results: We found that DUSP1, a crucial dephosphorylating enzyme, was remarkably reduced in renal tubular epithelial cells (RTECs) in mice and patients with CKD. This reduction was inversely correlated with kidney function and severity of renal fibrosis. DUSP1 deficiency exacerbated UUO-induced renal fibrosis in mice, whereas overexpression of DUSP 1 reduces fibrogenesis in human renal tubular epithelial (HK-2) cells treated with transforming growth factor-β1 in vitro. Mechanistically, deletion of DUSP1 promotes the nuclear translocation of Smad3, a crucial mediator of renal fibrosis, primarily through dephosphorylation at its 423/425 residue. Interestingly, we observed that DUSP1 is primarily regulated by acetylation modification, which is accompanied by an increased expression of histone deacetylase 1 (HDAC1) under UUO conditions. Furthermore, HDAC1 inhibition reversed the decrease in DUSP1 and the dephosphorylation of Smad3 in RTECs. Finally, the use of HDAC1 inhibitors or adeno-associated virus-mediated DUSP1 overexpression in RTECs significantly ameliorated UUO-induced renal injury and fibrosis. Conclusion: These results demonstrate that DUSP1 deficiency accelerates renal fibrosis through Smad3 nuclear translocation, modulated by HDAC1-driven acetylation. HDAC1 inhibition or DUSP1 overexpression significantly alleviated renal damage, highlighting DUSP1's therapeutic potential in combating CKD progression.
Ginsenoside Rg1 Inhibits Glucagon-Induced Hepatic Gluconeogenesis through Akt-FoxO1 Interaction: Erratum
Authors: Qun Liu, Fei-Ge Zhang, Wen-Song Zhang, An Pan, Yi-Lin Yang, Jin-Feng Liu, Ping Li, Bao-Lin Liu, Lian-Wen Qi
Journal: Theranostics (2025)

[This corrects the article DOI: 10.7150/thno.18788.].
THSD4 promotes hair growth by facilitating dermal papilla and hair matrix interactions
Authors: Miaomiao Wang, Mengyue Wang, Jingwei Jiang, Ke Li, Huan Liang, Nian'ou Wang, Yi Zou, Dehuan Wang, Siyi Zhou, Yuchun Tang, Wang Wu, Weiming Qiu, Xinxin Li, Xusheng Wang, Qiaoli Xie, Xiao Xiang, Wei Zhou, Li Yang, Cheng-Ming Chuong, Mingxing Lei
Journal: Theranostics (2025)

Introduction: Aging causes striking changes in the extracellular matrix (ECM) in hair follicles, which has a profound influence on hair growth. How the ECM of dermal papilla (DP), the master regulator of hair growth, changes during aging remains largely unknown. Methods: Herovici staining, Western Blotting and immunofluorescence were used to assess DP ECM and protein expression in hair follicles. Bulk and single cell RNA-sequencing were used to analyze gene expression and predict upstream and downstream regulators of target genes. Skin organoid and mouse models were used for functional validation of molecular mechanisms. Results: Aged follicle DP shows drastic depletion of ECM in which Thrombospondin Type 1 Domain Containing 4 (Thsd4) is highly downregulated. THSD4 is specifically expressed in the interface between DP and hair matrix (HM). It promotes hair growth by enhancing the interaction between dermal (DP) and epithelial cells (HM) through the SDC4-THSD4-CXCL1 signaling axis in both skin organoids and mouse models. Murine dorsal hair follicles show upregulated THSD4, enhanced DP-HM interaction, and hair growth following exposure to low temperature. Conclusions: THSD4 is a key micro- and macro-environmental mediator to promote hair growth by facilitating epidermal-mesenchymal interactions during aging. These findings demonstrate the therapeutic potential of low-temperature treatment for treating unwanted hair loss.
Endoscopic “combined-arms approach” for the management of a giant intraductal papillary mucinous neoplastic lesion of the bile duct
Authors: Theodor Voiosu, Andrei Mihai Voiosu, Mihaela Maria Birligea, Andrea Tringali, Istvan Hritz, Bogdan Mateescu, Marc Barthet
Journal: Endoscopy (2025)

An intraductal papillary mucinous neoplastic lesion (IPMN) of the bile duct is a rare, difficult-to-treat disease causing complex strictures of the biliary tree. For patients who are not amenable to radical surgery, maintaining patent bile ducts requires an individualized approach, with endoscopists sometimes resorting to outside-the-box solutions to provide long-term drainage [1]. We report the case of a 77-year-old patient failing conventional drainage with multiple plastic stents who presented with recurrent bouts of cholangitis and a newly developed intrahepatic cystic lesion ([Fig. 1])
Dual targeting PET tracer [<sup>68</sup>Ga]Ga-PSFA-01 in patients with prostate cancers: A pilot exploratory study
Authors: Yue Li, Lili Guan, Xiaoyang Zhang, Jia Li, Xinlin Wang, Wenbo Li, Lu Xu, Shuang Liu, Zhaobing Tang, Mengchao Cui, Hua Pang
Journal: Theranostics (2025)

Purpose: To assess the effectiveness of [68Ga]Ga-PSFA-01 PET/CT in detecting primary tumors and metastatic lesions in patients with prostate cancer (PCa), and to compare the results with those from [68Ga]Ga-PSMA-11 PET/CT and [68Ga]Ga-FAPI-04 scans. Methods: Patients with histologically proven PCa were prospectively recruited and underwent [68Ga]Ga-PSFA-01 PET/CT, of which: 25 participants also underwent [68Ga]Ga-PSMA-11 PET/CT scan, 5 patients also underwent [68Ga]Ga-FAPI-04 PET/CT scan, 3 patients underwent three modalities imaging. To assess the expression of PSMA and FAP, we obtained a pathological tissue section from a patient and performed immunohistochemical staining analysis. SUVmax-PSFA, SUVmax-PSMA, SUVmax-FAPI and the number of detected lesions were compared by using the Wilcoxon signed-rank test, and the Mc-Nemar test was used to compare detectivity. Correlation between SUVmax-PSFA and prostate cancer related clinical indicators was demonstrated with Spearman's ratio. A visual assessment was made to compare the detectability of primary tumors and metastases in different regions. Results: A total of 33 patients with a median age of 70 years (range: 52-89 years) were enrolled. Including 13 patients for initial staging and 20 for recurrence detection. [68Ga]Ga-PSFA-01 demonstrated superior performance in both patient-based and lesion-based analyses than [68Ga]Ga-PSMA-11 PET/CT. However, [68Ga]Ga-PSFA-01 depicted lower uptake in primary tumors (11.13 ± 7.04 vs. 15.44 ± 9.25, p = 0.009), bone metastases (8.50 ± 5.0 vs. 12.43 ± 9.55, p < 0.001) and metastases in other sites (6.05 ± 3.29 vs. 10.73 ± 8.74, p = 0.028) , lower tumor to background ratio (TBR) than [68Ga]Ga-PSMA-11 PET/CT (2.86 ± 1.50 vs. 9.50 ± 5.62, p < 0.001). [68Ga]Ga-PSFA-01 PET/CT showed more lesions (24 vs. 13, p = 0.18), higher uptake (primary tumors, 10.27 ± 2.42 vs. 7.32 ± 0.17, p = 0.109; bone metastases, 8.14 ± 5.98 vs.4.52 ± 1.22, p = 0.128; pelvic lymph nodes, 5.4 ± 2.83 vs.4.19 ± 1.39, p = 0.655) than [68Ga]Ga-FAPI-04 PET/CT. There was also a significantly positive correlation between SUVmax-PSFA of prostate lesions with the tPSA levels (r = 0.468, p = 0.016) and fPSA levels (r = 0.518, p = 0.04), a significantly negative correlation with the free-to-total prostate-specific antigen ratio (FPSAR) (r = -0.608, p = 0.012). Conclusion: [68Ga]Ga-PSFA-01 PET/CT demonstrated higher detection rates and visual assessment efficacy compared to [68Ga]Ga-PSMA-11 PET/CT in PCa patients. While preliminary data suggest that [68Ga]Ga-PSFA-01 may also outperform [68Ga]Ga-FAPI-04 PET/CT, the sample size for [68Ga]Ga-FAPI-04 (n = 5) is limited, and further studies are needed to confirm these findings.
Zwitterionic lipid nanoparticles for efficient siRNA delivery and hypercholesterolemia therapy with rational charge self-transformation
Authors: Ruichen Zhao, Jing Guo, Ziqi Liu, Yusheng Zhang, Jiamin Zuo, Songzhang Lv, Xianyu Li, Wenlong Yao, Xin Zhang
Journal: Theranostics (2025)

Rationale: Effective delivery of small interfering RNA (siRNA) remains a significant challenge in treating hypercholesterolemia due to biocompatibility, cellular uptake, and endosomal escape issues. Rational regulation of carrier surface charge contributes to efficient siRNA delivery in vivo. Methods: This study introduces zwitterionic lipid nanoparticles (ZwiLNPs) as a novel solution to these challenges. By leveraging the unique properties of zwitterionic polymers, we achieved robust siRNA encapsulation and targeted delivery. The design of ZwiLNPs facilitates charge self-transformation in response to physiological conditions, which enhances their biocompatibility and cellular uptake efficiency. Result: In vivo studies demonstrated significant liver-targeting capabilities of ZwiLNPs, with improved endosomal escape following cellular internalization. Comparative analyses confirmed that ZwiLNPs outperform conventional lipid nanoparticles in terms of both cellular uptake and endosomal release. Conclusion: These findings position ZwiLNPs as a promising platform for RNA interference therapies, particularly for hypercholesterolemia and other lipid-related disorders.