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Renal fibrosis, especially tubulointerstitial fibrosis, is the inevitable outcome of all progressive chronic kidney diseases (CKDs) and exerts a great health burden worldwide. For a long time, interests in renal fibrosis have been concentrated on fibroblasts and myofibroblasts. However, in recent years, growing numbers of studies have focused on the role of tubular epithelial cells (TECs). TECs, rather than a victim or bystander, are probably a neglected mediator in renal fibrosis, responding to a variety of injuries. The maladaptive repair mechanisms of TECs may be the key point in this process. In this review, we will focus on the role of TECs in tubulointerstitial fibrosis. We will follow the fate of a tubular cell and depict the intracellular changes after injury. We will then discuss how the repair mechanism of tubular cells becomes maladaptive, and we will finally discuss the intercellular crosstalk in the interstitium that ultimately proceeds tubulointerstitial fibrosis.

Renal fibrosis is the common feature of all progressive kidney diseases and exerts great burden on public health worldwide. The maladaptive repair mechanism of tubular epithelial cells, an important mediator of renal fibrogenesis, manifests with partial epithelial–mesenchymal transition (EMT) and cell cycle arrest. The aim of this study is to investigate the possible correlation between partial EMT and cell cycle arrest, and elucidate the underlying mechanism. We examined human kidney allograft samples with interstitial fibrosis and three mice renal fibrosis models, unilateral ureter obstruction (UUO), ischemia–reperfusion injury, and Adriamycin nephropathy. The partial EMT process and p53–p21 axis were elevated in both human allograft with interstitial fibrosis, as well as three mice renal fibrosis models, and showed a time-dependent increase as fibrosis progressed in the UUO model. Snai1 controlled the partial EMT process, and led to parallel changes in renal fibrosis, G2/M arrest, and inflammation. p53–p21 axis arrested cell cycle at G2/M, and prompted partial EMT and fibrosis together with inflammation. NF-κB inhibitor Bay11-7082 disrupted the reciprocal loop between Snai1-induced partial EMT and p53–p21-mediated G2/M arrest. We demonstrated the reciprocal loop between partial EMT and G2/M arrest of TECs during renal fibrogenesis and revealed NF-κB-mediated inflammatory response as the underlying mechanism. This study suggests that targeting NF-κB might be a plausible therapeutic strategy to disrupt the reciprocal loop between partial EMT and G2/M arrest, therefore alleviating renal fibrosis.

Kidney transplantation is a life-saving strategy for patients with end-stage renal diseases. Despite the advances in surgical techniques and immunosuppressive agents, the long-term graft survival remains a challenge. Growing evidence has shown that the complement system, part of the innate immune response, is involved in kidney transplantation. Novel insights highlighted the role of the locally produced and intracellular complement components in the development of inflammation and the alloreactive response in the kidney allograft. In the current review, we provide the updated understanding of the complement system in kidney transplantation. We will discuss the involvement of the different complement components in kidney ischemia–reperfusion injury, delayed graft function, allograft rejection, and chronic allograft injury. We will also introduce the existing and upcoming attempts to improve allograft outcomes in animal models and in the clinical setting by targeting the complement system.

Eye semantic segmentation has a significant role in promoting biometric recognition. Most works improve the accuracy through designing complicated feature learning modules that usually require a high computation cost and are prone to over-fit. In this work, we propose a lightweight eye semantic segmentation method based on iterative learning, which only requires a small amount of labeled eye image data under visible light conditions. To be specific, we first propose a pseudo-label filtering strategy for eye semantic segmentation, which leverages a semi-supervised incremental learning technique to solve the problem of label scarcity. Besides, an attention-guided lightweight high-representation module is designed to boost precision while ensuring efficiency. Experiments on the Ubiris dataset show that the proposed method achieves state-of-the-art performance, with a mIoU of 86.18%.

Background Prostate cancer (PCa), one of the common malignant tumors, is the second leading cause of cancer-related deaths in men. The circadian rhythm plays a critical role in disease. Circadian disturbances are often found in patients with tumors and enable to promote tumor development and accelerate its progression. Accumulating evidence suggests that the core clock gene NPAS2 (neuronal PAS domain-containing protein 2) has been implicated in tumors initiation and progression. However, there are few studies on the association between NPAS2 and prostate cancer. The purpose of this paper is to investigate the impact of NPAS2 on cell growth and glucose metabolism in prostate cancer. Methods Quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining, western blot, GEO (Gene Expression Omnibus) and CCLE (Cancer Cell Line Encyclopedia) databases were used to analyze the expression of NPAS2 in human PCa tissues and various PCa cell lines. Cell proliferation was assessed using MTS, clonogenic assays, apoptotic analyses, and subcutaneous tumor formation experiments in nude mice. Glucose uptake, lactate production, cellular oxygen consumption rate and medium pH were measured to examine the effect of NPAS2 on glucose metabolism. The relation of NPAS2 and glycolytic genes was analyzed based on TCGA (The Cancer Genome Atlas) database. Results Our data showed that NPAS2 expression in prostate cancer patient tissue was elevated compared with that in normal prostate tissue. NPAS2 knockdown inhibited cell proliferation and promoted cell apoptosis in vitro and suppressed tumor growth in a nude mouse model in vivo. NPAS2 knockdown led to glucose uptake and lactate production diminished, oxygen consumption rate and pH elevated. NPAS2 increased HIF-1A (hypoxia-inducible factor-1A) expression, leading to enhanced glycolytic metabolism. There was a positive correlation with the expression of NPAS2 and glycolytic genes, these genes were upregulated with overexpression of NPAS2 while knockdown of NPAS2 led to a lower level. Conclusion NPAS2 is upregulated in prostate cancer and promotes cell survival by promoting glycolysis and inhibiting oxidative phosphorylation in PCa cells.

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30–40% of all non-Hodgkin lymphoma cases. Organs located DLBCL such as lymph node, stomach, gastrointestinal tract, or skin were reported. However, the adrenal gland DLBCL was not been well explored. We performed RNA sequencing of ten DLBCL samples from adrenal gland, integrated analyzed DLBCL RNA data from multiple organs, defined the new subtypes of adrenal gland DLBCL and explored their molecular signatures. The special expression pattern and microenvironment immunology scores of adrenal glands DLBCL were observed when compared with other organs. Natural killer T cells was predicted to significantly enrichment in adrenal gland DLBCL, canonical cancer pathways such as programmed death protein 1 signaling pathways, tumor necrosis factor signaling pathways and peptide antigen binding pathways were found to be correlated with adrenal gland DLBCL. Further analysis defined two distant adrenal gland DLBCL sub-type by RNA expression pattern. Our study revealed the special expression, defined the molecular subtype of adrenal gland DLBCL. These results expanded the organ related DLBCL data, provided the new knowledge of adrenal gland DLBCL expression profile.

Abstract Background: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. Methods: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. Results: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. Conclusions: 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.

Background Diabetic nephropathy leads to renal fibrosis via excessive ECM accumulation. Current therapies lack specificity, highlighting the need to identify targets like SRPK1, whose role in diabetic kidney fibrosis remains unclear. Methods We investigated SRPK1’s function using a streptozotocin-induced diabetic nephropathy mice model and administered the selective SRPK1 inhibitor SRPIN340. Histological, biochemical, and molecular analyses were performed to assess ECM deposition, renal function, and fibrotic marker expression. Additionally, Western blotting and immunohistochemistry were utilized to explore the involvement of the NF-κB/NLRP3 signaling pathway. Results SRPK1 expression was significantly elevated in fibrotic kidneys, correlating with increased ECM components (collagen I/III, fibronectin) and reduced renal function. SRPIN340 treatment markedly alleviated ECM accumulation, improved glomerular filtration rate, and suppressed fibrotic markers (α-SMA, TGF-β). Mechanistically, SRPK1 activation promoted NF-κB/NLRP3 pathway activation, leading to inflammatory cytokine release (IL-1β, TNF-α) and fibrosis. Inhibition of SRPK1 via SRPIN340 abrogated these effects, suggesting a causal role for SRPK1 in fibrotic progression. Conclusion SRPK1 activates NF-κB/NLRP3 pathway, promoting ECM synthesis and inflammation in diabetic nephropathy; SRPIN340 reduces fibrosis, highlighting SRPK1 as a therapeutic target. Key messages What is already known about this topic? Diabetic nephropathy (DN) is one of the major complications of diabetes, with its core pathological feature being renal interstitial fibrosis. SRPK1 (serine/arginine protein kinase 1) has been confirmed to participate in the progression of diseases such as pulmonary fibrosis and hepatic fibrosis by regulating RNA splicing and signaling pathways. However, its specific role in renal fibrosis remains unclear. What this study adds? This study demonstrates that SRPIN340, as an SRPK1 inhibitor, effectively alleviates renal fibrosis in animal models, thereby providing experimental evidence for the clinical translation of SRPK1-targeted therapies. How this study might affect research, practice, or policy? This study advocates for prioritizing SRPK1-targeted inhibitors in the development of future therapeutic strategies for chronic kidney disease (CKD), while urging interdisciplinary collaboration that synergizes pharmacological research, bioinformatics analysis, and clinical resources to expedite the advancement of SRPK1-based therapeutics.

[This corrects the article DOI: 10.3389/fimmu.2025.1663251.].[This corrects the article DOI: 10.3389/fimmu.2025.1663251.].

Acute rejection is a significant cause of impaired graft survival in the early post-transplantation period, and the early-stage immune cell dynamics with local intercellular communication during this process require further elucidation. We performed single-cell RNA sequencing (scRNA-seq) on CD45+ immune cells isolated from rat renal allografts during the early phase of acute rejection (days 0, 1, 3, and 7). Using unsupervised clustering, functional enrichment analysis, cellular trajectory inference, and intercellular communication network mapping, we delineated the immune cell dynamics and local communication networks at single-cell resolution. Our findings were subsequently validated through multiplex immunofluorescence and therapeutic intervention experiments. Macrophages constituted the dominant immune population during acute rejection. Sub-clustering analysis revealed a rapid expansion of the Isg15+Mac subset by post-transplant day 1, which persisted at elevated levels thereafter. Functional enrichment and trajectory inference demonstrated the pro-inflammatory properties of Isg15+Mac, implicating this subset in acute rejection. Cell-cell communication analysis identified Ccl3-Ccr5 ligand-receptor interactions between Isg15+Mac and T cells. Multiplex immunofluorescence confirmed abundance of Isg15+Mac within the allografts. Moreover, the acute rejection after kidney transplantation was alleviated by the FDA-approved Ccr5 blocker Maraviroc. Our study establishes an in-depth, early-stage immune landscape of renal transplantation, revealed that the Isg15+Mac subset activates T cells via the Ccl3-Ccr5 axis and thereby serves as a critical driver of acute rejection. And indicating that Maraviroc may potentially be a therapeutic candidate for transplant rejection.