establishment-rat-model-acute-antibody-mediated-rejection-kidney

Establishment of Rat Model of Acute Antibody-Mediated Rejection in Kidney Transplantation

Acute antibody-mediated rejection (AAMR) remains a major obstacle to long-term graft survival in kidney transplantation. The pathophysiology of AAMR is ...

establishment-mouse-model-renal-fibrosis-via-unilateral-ischemia

Establishment of A Mouse Model of Renal Fibrosis <em>via</em> Unilateral Ischemia-Reperfusion Injury And Delayed Contralateral Nephrectomy

Renal ischemia-reperfusion injury (IRI) contributes to acute kidney injury (AKI) and is a major driver of progression to chronic kidney disease (CKD). A ...

The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital

Renal cell carcinoma is one of the most common malignancies worldwide, and kidney renal clear cell carcinoma (KIRC) is the most common histopathological type of renal cell carcinoma. However, the mechanism of KIRC progression remains poorly understood. Apolipoprotein M (ApoM) is a plasma apolipoprotein and a member of the lipid transport protein superfamily. Lipid metabolism is essential for tumor progression, and its related proteins can be used as therapeutic targets for tumors. ApoM influences the development of several cancers, but its relationship with KIRC remains unclear. In this study, we aimed to investigate the biological function of ApoM in KIRC and to reveal its potential molecular mechanisms. We found that ApoM expression was significantly reduced in KIRC and was strongly correlated with patient prognosis. ApoM overexpression significantly inhibited KIRC cell proliferation in vitro, suppressed the epithelial mesenchymal transition (EMT) of KIRC cells, and decreased their metastatic capacity. Additionally, the growth of KIRC cells was inhibited by ApoM overexpression in vivo. In addition, we found that overexpression of ApoM in KIRC attenuated Hippo-YAP protein expression and YAP stability and thus inhibited KIRC growth and progression. Therefore, ApoM may be a potential target for the treatment of KIRC.

ApoM suppresses kidney renal clear cell carcinoma growth and metastasis via the Hippo-YAP signaling pathway.

Rejection is the primary factor affecting the functionality of a kidney post-transplant, where its prompt prediction of risk significantly influences therapeutic strategies and clinical outcomes. Current graft health assessment methods, including serum creatinine measurements and transplant kidney puncture biopsies, possess considerable limitations. In contrast, urine serves as a direct indicator of the graft's degenerative stage and provides a more accurate measure than peripheral blood analysis, given its non-invasive collection of kidney-specific metabolite. This research entailed collecting fluorescent fingerprint data from 120 urine samples of post-renal transplant patients using hyperspectral imaging, followed by the development of a learning model to detect various forms of immunological rejection. The model successfully identified multiple rejection types with an average diagnostic accuracy of 95.56 %.Beyond proposing an innovative approach for predicting the risk of complications post-kidney transplantation, this study heralds the potential introduction of a non-invasive, rapid, and accurate supplementary method for risk assessment in clinical practice.

Fluorescence spectroscopic profiling of urine samples for predicting kidney transplant rejection.

Renal transplantation represents the foremost efficacious approach for ameliorating end-stage renal disease. Despite the current state of advanced renal transplantation techniques and the established postoperative immunosuppression strategy, a subset of patients continues to experience immune rejection during both the early and late postoperative phases, ultimately leading to graft loss. Consequently, the identification of immunobiomarkers capable of predicting the onset of immune rejection becomes imperative in order to facilitate early intervention strategies and enhance long-term prognoses. Upon reviewing the pertinent literature, we identified several indicators that could potentially serve as immune biomarkers to varying extents. These include the T1/T2 ratio, Treg/Th17 ratio, IL-10/TNF-α ratio, IL-33, IL-34, IL-6, IL-4, other cytokines, and NOX2/4.

Potential biomarkers for immune monitoring after renal transplantation.

Delayed Graft Function (DGF) is a prevalent complication in kidney transplantation (KT) that significantly affects allograft function and patient prognosis. Early and precise identification of DGF is crucial for improving post-transplant outcomes. In this study, we present KGnet, a predictive model leveraging hyperspectral imaging (HSI) to assess delayed graft function status. We analyzed 72 zero-hour biopsy samples from transplanted kidneys with confirmed pathological diagnoses, capturing spectral data across a wavelength range of 400 to 1000 nm. By examining spectral signatures related to tissue oxygenation, perfusion, and metabolic states, our approach enabled the detection of subtle biochemical changes indicative of DGF risk. The preprocessed spectral data were input into KGnet, achieving a prediction accuracy of 94 % for DGF occurrence, significantly outperforming existing predictive models. This study identifies key spectral signatures associated with DGF, allowing for precise risk prediction even before clinical symptoms emerge. Leveraging HSI for early detection introduces a novel pathway for individualized post-transplant management, offering substantial potential to enhance kidney transplantation outcomes and patient quality of life. These findings highlight significant clinical and research implications for the broader application of HSI in transplant medicine.

Using hyperspectral imaging to predict the occurrence of delayed graft function.

Microplastic (MP) contamination in human tissues is an emerging environmental and clinical concern, yet its relevance to organ transplantation remains poorly understood. This study characterized MPs in kidney transplantation-associated donor tissues and examined their relationship with early postoperative blood pressure (BP) in recipients. Tissue samples, including kidney, adrenal gland, renal artery, renal vein, and ureter, were collected from 28 kidney transplant donors. MPs were extracted from each tissue and analyzed using a multimodal strategy: pyrolysis-gas chromatography-mass spectrometry for polymer quantification, laser direct infrared spectroscopy (LD-IR) for particle identification, and scanning electron microscopy (SEM) for morphological assessment. Polyethylene (PE) and polyvinyl chloride (PVC) were consistently the most abundant polymers by mass, with PE concentrations ranging from 25.7 to 98.9 μg/g and PVC from 31.2 to 65.4 μg/g across tissues. LD-IR analysis showed that kidney tissue contained 293 MP particles (6 polymer types), adrenal gland 2017 (9 polymer types), renal artery 881 (8 polymer types), renal vein 1528 (10 polymer types), and ureter 1672 (10 polymer types). MPs measuring 20-100 μm accounted for 47.1-54.9 % of its content across tissues, while 100-500 μm MPs comprised 45.1-52.9 %. Postoperative BP was assessed 15 days post-transplantation. While moderate, tissue-specific correlations between certain MP types and BP were observed (e.g., natural rubber in adrenal glands, polycarbonate in renal arteries, polypropylene in renal veins, and butadiene rubber in ureters), most associations were not statistically significant. Negative values were obtained for linear regression and FDR correction, emphasizing the preliminary nature of the results. This highlights the need for further investigation of the clinical impact of MP.

Microplastic contamination in kidney transplant donor tissues and its association with early post-transplant blood pressure changes in recipients: A multi-modal analytical study.

Methylglyoxal (MG), which is a highly reactive dicarbonyl compound, has been increasingly recognized due to its role in the pathogenesis of kidney injury, particularly in diseases such as diabetic nephropathy and hypertensive nephropathy. MG promotes advanced glycation end product (AGE) formation and directly impairs cell function. MG levels are significantly increased in various renal diseases. This study aimed to investigate the relationship between MG and ferroptosis, which is a form of cell death involving iron-dependent lipid peroxidation (LPO), during kidney injury. Animal and cellular experiments were conducted to verify that ferroptosis occurred after MG treatment, and RNA sequencing (RNA-Seq) was performed to analyse changes in gene expression profiles after MG exposure. A mouse model that mimicked human kidney injury was established by administering folic acid, and the MG and D-lactate levels in serum and tissues were measured.  experiments involved treating human HK-2 renal tubular epithelial cells (TECs) with MG and assessing markers of cytotoxicity, oxidative stress, and ferroptosis. MG levels were significantly increased in serum and renal tissues from patients with renal injury and from model mice. In HK-2 cells, MG treatment induced cytotoxicity, increased intracellular reactive oxygen species (ROS) levels, triggered ferroptosis by increasing LPO, and decreased glutathione (GSH) levels. These findings suggest a potential association between MG accumulation and kidney injury and indicate that MG promotes ferroptosis specifically in renal TECs. This study provides new insights into the molecular mechanisms underlying MG-induced kidney injury and potential directions for developing new therapeutic strategies.

Methylglyoxal induces oxidative stress and ferroptosis of renal tubular epithelial cells in acute and chronic kidney injury mice.

Cardiac transplantation is the preferred treatment option for patients with chronic heart failure. However, acute rejection remains as a the significant challenge that leads to cardiac allograft dysfunction, resulting from immune system activation and reactive oxygen species (ROS) production by inflammatory cells. Current immunosuppressive regimens have limitations, such as systemic administration, toxicity, and inefficient inhibition of B cells, macrophages, and natural killer (NK) cells. Targeted immunosuppressant delivery via nanomaterials is a promising approach for sustained release within allografts, significantly enhancing drug efficiency. Manganese dioxide (MnO) possesses the characteristics of chemotaxis towards inflammatory sites, scavenging ROS, and facilitating drug transport. In this study, tacrolimus (FK506)-loaded MnO nanoparticles (NPs) are synthesized via in-situ polymerization, using polydopamine (PDA) as an intermediate. The resulting FK506@MnO/PDA NPs exhibit excellent safety and cytocompatibility. This targeted delivery system significantly increases FK506 accumulation in murine cardiac allografts, effectively mitigating acute rejection and prolonging allograft survival. Furthermore, the mechanism by which FK506@MnO/PDA NPs alleviate acute rejection is investigated, validating that FK506 release inhibits T-cell activation while modulating the inflammatory environment by reducing oxidative stress and scavenging ROS. Fluorescence imaging demonstrates that FK506@MnO/PDA NPs exhibit prolonged retention and more pronounced accumulation in cardiac allografts compared with free FK506. This study presents a novel strategy for immunosuppressive therapy following cardiac transplantation, potentially improving allograft prognosis.

Targeted tacrolimus delivery via manganese dioxide nanoparticles for mitigating acute allograft rejection in murine cardiac transplantation.

Organ transplantation improves survival and quality of life in end-stage organ failure, but rejection remains a key barrier to long-term graft success. While current immunosuppression primarily targets adaptive immunity, its limitations and side effects necessitate alternative therapeutic strategies. Macrophages infiltrate grafts extensively, which are involved in antigen presentation function, ischemia-reperfusion injury, and both acute and chronic rejection processes. Notably, their polarization toward an anti-inflammatory phenotype may alleviate rejection and potentially contribute to graft immune tolerance. In this review, we will give an overview on macrophage phenotypes and their functional diversity in allograft rejection. Also, we will discuss emerging strategies to modulate macrophage polarization, including therapies exploiting their dual regulatory capacity, nanoparticle-based targeting systems, gene therapies, and microRNA-mediated regulation. A deeper understanding of macrophage biology in transplantation could enable more sophisticated anti-rejection approaches, whose integration with conventional immunosuppression may ultimately enhance long-term graft outcomes.

Macrophage polarization in organ transplantation rejection and targeted therapeutic strategies.

Atypical hemolytic uremic syndrome (aHUS) is a severe post-transplant complication associated with a high risk of graft loss and mortality. Based on its pathophysiological mechanism, aHUS can be classified into recurrent aHUS (reactivation post-transplantation) and  aHUS (new-onset disease after transplantation). This study reports a case of a 52-year-old kidney transplant recipient who developed recurrent aHUS 10 months post-transplantation, triggered by SARS-CoV-2 infection. Genetic analysis revealed mutations in complement-related genes CFHR and C3. Following the diagnosis, the patient received a course of eculizumab induction therapy (900 mg/week for the first 4 weeks), followed by long-term maintenance therapy (900 mg every 2 weeks). Significant clinical improvement was observed, including stabilization of blood pressure, normalization of hemoglobin and lactate dehydrogenase (LDH) levels, an increase in platelet count, and a urine output exceeding 2,000 mL per day. The patient continued regular follow-up after discharge, with stable graft function. This case highlights the potential role of SARS-CoV-2 and other infections as triggers for aHUS recurrence in kidney transplant recipients and further supports the efficacy of eculizumab in treating recurrent aHUS. Furthermore, this study underscores the importance of precise immune risk stratification and early intervention in the effective management of aHUS recurrence.

Case Report: Effective use of eculizumab in treating recurrent atypical HUS following renal transplantation triggered by SARS-CoV-2 infection.

Follicular helper T (Tfh), B and regulatory T (Treg) cells are involved in the pathogenesis of chronic rejection (CR) after transplantation. Dihydroartemisinin (DHA) is an antimalarial drug with anti-inflammatory activity; however, the effects and mechanisms of DHA on Tfh, B and Treg cells have not been comprehensively elucidated. The aim of this study was to investigate the effect of DHA on Tfh, B and Treg cells and its preventive effect on CR. In vitro assays demonstrated that DHA not only blocks the induction of Tfh cells and alleviates their supportive effect on B cell differentiation but also directly suppresses B cell activation, differentiation and antibody production. Additionally, DHA promotes the induction of Treg cells and enhances their stability in an inflammatory environment. In vivo studies showed that DHA effectively alleviated CR by suppressing neointimal hyperplasia, myocardial injury and interstitial fibrosis and reducing inflammatory cell infiltration and C4d deposition in allografts. Moreover, DHA decreased the levels of Tfh, germinal centre Tfh, B, germinal centre B, IgG-producing and plasma cells in recipients but increased Treg cell levels in recipients and allografts. Mechanistically, we confirmed that DHA inhibits Tfh cells by blocking IL-2-inducible T cell kinase signalling, suppresses B cells by blocking Bruton's tyrosine kinase signalling, and enhances Treg cells by blocking mTOR signalling while promoting STAT5 signalling. In conclusion, our results verified that DHA inhibits Tfh and B cells and enhances Treg cells to attenuate CR in mice, highlighting its potential applicability in the development of robust treatment options.

Dihydroartemisinin Alleviates Chronic Allograft Rejection by Inhibiting Tfh and B Cells While Promoting Treg Cells in Murine Cardiac Transplantation.

Accurate differentiation between adrenocortical tumors (ACTs) and pheochromocytomas (PHEOs) remains challenging in intraoperative pathology. This study proposes a hyperspectral-deep-learning fusion framework integrating spectral and spatial features for rapid, label-free diagnosis. Using Savitzky-Golay-filtered hyperspectral data (400-1000 nm) and a lightweight dual-branch convolutional network, the model achieved an AUC of 0.96 and an accuracy of 92.8%. Mutual information-based band selection and mid-level feature fusion enhanced efficiency, while Grad-CAM and spectral sensitivity analyses revealed interpretable wavelength-feature associations corresponding to lipid and hemoglobin absorption. The proposed system demonstrates strong potential for real-time, interpretable intraoperative discrimination between cortical and medullary adrenal tumors, supporting precision endocrine surgery.

ArticleTotal : 2	Year
Publication title	2026
Publication title	2026

Article	Year
ApoM suppresses kidney renal clear cell carcinoma growth and metastasis via the Hippo-YAP signaling pathway. Archives of biochemistry and biophysics\| PubMed ID: 37211224	2023
Fluorescence spectroscopic profiling of urine samples for predicting kidney transplant rejection. Photodiagnosis and photodynamic therapy\| PubMed ID: 38244654	2024
Potential biomarkers for immune monitoring after renal transplantation. Transplant immunology\| PubMed ID: 38679337	2024
Using hyperspectral imaging to predict the occurrence of delayed graft function. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy\| PubMed ID: 39486235	2025
Microplastic contamination in kidney transplant donor tissues and its association with early post-transplant blood pressure changes in recipients: A multi-modal analytical study. Journal of hazardous materials\| PubMed ID: 40902535	2025
Methylglyoxal induces oxidative stress and ferroptosis of renal tubular epithelial cells in acute and chronic kidney injury mice. Frontiers in cell and developmental biology\| PubMed ID: 41049288	2025
Targeted tacrolimus delivery via manganese dioxide nanoparticles for mitigating acute allograft rejection in murine cardiac transplantation. Biomaterials\| PubMed ID: 41056839	2026
Macrophage polarization in organ transplantation rejection and targeted therapeutic strategies. Transplant immunology\| PubMed ID: 41110609	2025
Case Report: Effective use of eculizumab in treating recurrent atypical HUS following renal transplantation triggered by SARS-CoV-2 infection. Frontiers in medicine\| PubMed ID: 41267868	2025
Dihydroartemisinin Alleviates Chronic Allograft Rejection by Inhibiting Tfh and B Cells While Promoting Treg Cells in Murine Cardiac Transplantation. Immunology\| PubMed ID: 41437677	2025
Hyperspectral-Deep-Learning Fusion for Rapid Differentiation of Adrenocortical Tumors and Pheochromocytomas. Journal of biophotonics\| PubMed ID: 41633611	2026

Zhe Yang

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