Acute Response of Hepatocyte MRP2 Internalization as an Indicator of Ischemia-reperfusion Injury in Liver Transplantation

Transplantation · 2025-05-05 · 2 citations

BACKGROUND: The introduction of normothermic machine perfusion (NMP) offers new opportunities to evaluate liver graft viability before liver transplantation (LT). Under ischemic stress, multidrug resistance-associated protein 2 (MRP2) translocates from the hepatocyte membrane to the cytoplasm, resulting in loss of function. METHODS: We measured the cytoplasmic proportion of MRP2 (MRP2 internalization index, MII) by immunofluorescence colocalization analysis using CD13 as a canalicular membrane marker. RESULTS: The data showed that MII significantly correlated with ischemia time in both in situ ischemia-reperfusion injury and NMP rat models (R 2 = 0.331, P < 0.0001; R 2 = 0.632, P < 0.0001, respectively). Perfusate levels of liver injury markers at the end of NMP showed a significant positive correlation with MII for aspartate aminotransferase (R² = 0.444, P = 0.0013) and arginase 1 (R² = 0.637, P < 0.0001). Conversely, bile production exhibited a significant inverse correlation with MII (R² = 0.618, P < 0.0001). The maximum transport rate of MRP2 ( Vmax,MRP2 ), derived from kinetic modeling of sodium fluorescein biliary excretion, showed a significant inverse correlation with ischemia time (R 2 = 0.326, P = 0.0086) and MII (R 2 = 0.554, P = 0.0002). In human LT, MII values from donor liver biopsies preLT correlated significantly with peak postLT serum aminotransferase levels (R 2 = 0.398, P = 0.0007). CONCLUSIONS: MRP2 is a putative biomarker for the assessment of hepatic ischemia-reperfusion injury. The biliary excretion kinetics of sodium fluorescein reflects MRP2-mediated transport activity, providing a novel diagnostic method for predicting liver graft viability after LT.

Leveraging Contrast Agent Kinetics for Robust Reflectance Mode Fluorescence Tomography

2025-04-14

Fluorescence Image Guided Surgery utilizes continuous wave epi-fluorescence measurements on the tissue surface to locate targets such as tumors or lymph nodes, but precise 3D localization of deep targets remains intractable due to the illposedness of the associated inverse problem. We propose a Fluorescence Diffuse Optical Tomography scheme which leverages the different contrast agent kinetics in malignant vs normal tissue and reconstructs the 3D tumor location from a time series of epi-fluorescence measurements. We conduct sequential synthetic experiments, which mimic the differential uptake and release profile of fluorescent dye ICG in tumors vs normal tissue and demonstrate for the first time that the proposed method can robustly recover targets up to 1cm deep and in the presence of realistic tumor-to-background ratios.

The Molecular Epidemiology of Colorectal Cancer Study

immuneACCESS · 2025-05-15

The Molecular Epidemiology of Colorectal Cancer Study (MECC) is a population-based study of incident CRC cases and healthy controls recruited from northern Israel from 1998 through 2017. After QC, 2,750 CRC cases with T cell receptor clonality and abundance data were derived from immunoSEQ assays.

Advances in noninvasive imaging for detecting radiation-induced lung injury (RILI)

International Journal of Radiation Biology · 2025-07-15 · 4 citations

The imaging modalities reviewed have potential to not only provide early identification of RILI but may also provide mechanistic insights into the progression of RILI via noninvasive detection of characteristic RILI mechanisms including: inflammation, vascular damage, cell death, oxidative stress, and fibrosis.

Abstract 4469: Multimodal liposomal organic nanoparticle for immunomodulation and photodynamic combinatorial therapy for triple negative breast cancer

Cancer Research · 2025-04-21

Background: IL-12 is a potent cytokine with promising pre-clinical efficacy in solid tumors, including triple-negative breast cancer (TNBC), by enhancing anti-tumor immunity through Treg reprogramming and boosting CD8+ T cell function. However, its clinical use is limited by systemic toxicity and challenges in targeted tumor delivery. Combining IL-12 with photodynamic therapy (PDT) represents a potential solution to these issues, optimizing therapeutic outcomes. Concept &amp; Novelty: We developed a cationic tetra-lipid organic nanoparticle to co-encapsulate IL-12 and HPPH (a photosensitizer; λmax = 658 nm). Efficient IL-12 encapsulation has been challenging due to steric hindrance and hydrophilic nature. To overcome this, we employed a bipolar solvent system (CHCl3:CH3OH, 2:1), achieving 98% IL-12 loading. The self-assembly of IL-12 in methanol enables its complexation with chloroform, forming hydrogen-bonding through synergistic solvation that enhances encapsulation efficiency. Methodology: (a) Liposomal nanoparticle (LNP) Synthesis: The cationic core lumen for IL-12 encapsulation in LNP was achieved by dissolving DPPC, cholesterol, and DOTAP in a 13:5:1 molar ratio in CHCl3. IL-12 (2 mg/mL in CH3OH) was added and stirred for 1 hour. Subsequently, DSPE-PEG-2000-NH2 conjugated with HPPH and DiR in CHCl3 added dropwise and stirred under inert conditions. Solvent removed to form lipid cake (15 mg/L total lipid concentration), and hydrated with PBS. LNP achieved with sonication and multiple freeze/thaw cycles. Purified with centrifugation-dialysis. (b) In-Vivo: 4T1 murine model of breast cancer was developed with 20 Balb/c mice. Double-blind segregation in 5 groups (1 test + 4 control) was done. The test group received intravenous (i.v.) injections of IL-12 and HPPH-loaded LNP (IL-12@LNP-DiR@HPPH) and treated with laser. The control groups received either/or free IL-12/IL-12@LNP-DiR/LNP/No treatment. The biodistribution of LNP was monitored through time-dependent IVIS imaging. Results &amp; Discussion: We synthesized 92 nm IL-12@LNP-DiR@HPPH nanoparticles with surface charge of 0-0.4 mV, indicating stability for biological use. After intravenous injection, maximum DiR fluorescence was observed at tumor site at 6 hours. At this time point, photodynamic therapy with IL-12@LNP-DiR@HPPH resulted in 80-94% tumor volume regression and increased cytolytic T cell presence in the tumor, compared to controls. No toxicity, ulceration, or metastasis was observed in the treatment group during the therapeutic window. Conclusion: We present a novel platform that addresses the challenge of multiple drug loading including efficient loading of IL-12 and successful delivery to the tumor site. A crosstalk between IL-12-mediated immune response and photo-triggered ROS generation promises a potential therapeutic strategy for TNBC with interventions. Citation Format: Sayantan Sinha, Dhruv Bhatnagar, Anne Frei, Heather Himburg, Amit Joshi. Multimodal liposomal organic nanoparticle for immunomodulation and photodynamic combinatorial therapy for triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4469.

Empowering Sustainable Human Capital for Digital Circular Economy in the Gulf Cooperation Council HealthCare Sector

2025-01-01

Drug Delivery in Retinoblastoma

International Ophthalmology Clinics · 2025-09-25 · 1 citations

Retinoblastoma is considered a prototype pediatric malignancy as retinoblastoma research has been instrumental in advancing our knowledge of cancer genetics, tumor suppressor genes, and the development of new treatment approaches. Also, retinoblastoma boasts one of the highest survival rates among pediatric cancers, with survival rates often exceeding 90% in developed countries. The research focus is shifting towards improved globe and vision salvage. Also, there is emphasis on advancing treatments that are tailored based on individual patient characteristics, including tumor genetics and molecular markers, to improve outcomes and minimize side effects.

Image-guided in vivo evaluation and comparison of bone-targeting peptides for therapeutic intervention

Drug Delivery and Translational Research · 2025-09-15

Selection of Bone-Targeting Peptides for Therapeutic Intervention: An In Vivo Evaluation and Comparison Study

bioRxiv (Cold Spring Harbor Laboratory) · 2024-12-16

Abstract Hydroxyapatite (HA)-binding peptides are emerging as promising candidates for bone-targeted therapies due to their strong affinity for mineralized tissues and biocompatibility. However, most studies to date have focused on in vitro characterization, providing limited insight into their in vivo performance. This study bridges that gap by evaluating the in vivo behavior of HA-binding peptides D8, E8, YD8, and YE8 using fluorescence imaging to assess their biodistribution in healthy and pathological bone environments. In healthy animal models, D8 demonstrated the strongest binding across mineralized tissues, including the skull, femur, and tibia, while YD8 showed moderate binding. In contrast, E8 and YE8 exhibited limited localization influenced by peptide dosage and binding kinetics. Pathological models, including defective tibia and osteogenesis imperfecta (OIM) mice, revealed preferential accumulation of D8 and YD8 in structurally compromised regions, underscoring their potential for targeting diseased bone microenvironments. Fluorescence imaging, enhanced by spectral unmixing algorithms, proved effective for assessing peptide localization and distribution. These findings highlight the utility of HA-binding peptides for bone-targeted therapies and emphasize the importance of in vivo studies in advancing their therapeutic and diagnostic applications. This work provides a foundation for optimizing peptide designs to improve specificity and efficacy in bone repair and regeneration.

Strategic Adoption of Artificial Intelligence for Human Resource Management Practices Transforming Healthcare Sector

The International Journal of Education Management and Sociology · 2024-05-21 · 7 citations

The incorporation of Artificial Intelligence (AI) technology into several industries has significantly impacted the usual workflows and processes in recent years, including the healthcare industry. Human Resource Management (HRM) is essential in healthcare businesses as it is responsible for the recruitment, training, and the retention of skilled staff members who are capable of providing high-quality patient care. This paper investigates different methods in which AI is used in HRM in the healthcare industry on the basis of existing research in the area. It analyzes how AI affects recruitment, talent management, workforce optimization, and employee well-being. This paper also discusses the challenges and future prospects of AI-driven approaches in HRM practices. It explores how these approaches are changing the way healthcare organizations operate and improving patient outcomes. The results provide some valuable contributions to the field of artificial intelligence in the healthcare sector. Initially, the chapter gives a factual foundation for the current presumptions on the implementation and difficulties of artificial intelligence in the healthcare domain. Further, it shows how artificial intelligence provides numerous opportunities to expedite Human Resource operations by offering automated applicant screening, customized learning systems, optimizing the workforce and enhancing employee engagement. Although AI has the capacity to revolutionize HRM practices in the healthcare industry, it also presents some challenges and obstacles. In order to ensure that AI-driven solutions promote fairness, transparency, and equity, it is crucial to address issues such as algorithmic bias, privacy of data and the impact on the human workforce in a deliberate manner. In addition, healthcare firms need to invest funds for implementing rigorous cyber security measures in order to ensure the privacy of patient and employee data from cyber-attacks and potential breaches.