Search Results (626)

Clear-cell renal cell carcinoma (ccRCC) accounts for the majority of kidney cancer diagnoses and exhibits widely variable clinical behaviour. The dataset described here was generated to support the discovery of robust biomarkers of tumour cell-cycle arrest and to inform the risk-stratified management of ccRCC. We assembled four independent cohorts including 480 patients from the UK arm of the SORCE adjuvant trial, 300 patients from a surgically treated series in Korea, 120 patients from a retrospective Scottish cohort, and a paired primary–metastatic cohort comprising 62 patients. Formalin-fixed paraffin-embedded nephrectomy specimens were processed for routine hematoxylin and eosin (H&E) histology, and for multiplex immunofluorescence (mIF). The mIF panels detect the cyclin-dependent kinase inhibitor p21^CDKN1a, the DNA replication licencing factor MCM2, endoglin/CD105, Lamin B1 and nuclear DNA (Hoechst). Whole-slide images (WSIs) were acquired at high resolution, and artificial-intelligence pipelines were used to segment nuclei, classify individual cells into arrested phenotypes, and calculate the fraction of cells. Accompanying metadata include demographics, tumour stage, grade, Leibovich score, treatment arm (sorafenib/placebo), relapse events, and disease-free survival. All images and derived tables are released under a CC0 licence via the BioImage Archive, ensuring unrestricted reuse. This multi-cohort dataset provides a rich resource for studying cell-cycle arrest and proliferation markers, training image-analysis algorithms, and developing prognostic signatures in RCC. Full article

Background/Objectives: IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide; it is characterized by a complex pathophysiology involving several inflammatory pathways. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway may be critical in this process. This study aimed to investigate the role of this pathway in IgAN and examine related tissue inflammatory markers. Methods: We analyzed 63 biopsy-confirmed patients with IgAN and performed immunohistochemical analysis on renal samples. A panel of antibodies targeting the JAK/STAT pathway, including JAK2, JAK3, p-STAT, STAT3, and MAPK/ERK, was used for this analysis. Six kidney tumor border samples were used as controls. Additionally, CD68 staining was used to evaluate tissue inflammation in the kidney biopsies. Results: Patients with IgAN showed a significantly higher cellular density of JAK3 staining at the glomerular level compared to controls, indicating JAK3 activation (p < 0.0002). Nevertheless, the correlation between JAK3 positivity in glomeruli and clinical parameters such as the initial and final estimated glomerular filtration rate (eGFR) and proteinuria was not statistically significant. Identical results were obtained with CD68+ macrophage counts in the glomerular compartment, which did not show any correlation with clinical parameters, while CD68+ tubulointerstitial staining demonstrated a significant correlation with both initial (p = 0.002) and final eGFRs (p = 0.0014), proteinuria (p = 0.010), and interstitial fibrosis (p < 0.001), as well as with renal disease progression (p = 0.005). Conclusions: Activation of the JAK/STAT pathway was observed in patients with IgAN relative to controls, notwithstanding the inability to assess the full pathway due to technical limitations. Macrophage CD68 staining in the tubulointerstitial area increased and was associated with clinical and laboratory parameters such as eGFR and proteinuria. Additionally, MEST-C histological parameters, such as segmental glomerulosclerosis (S0/S1), tubular atrophy/interstitial fibrosis (T0/T1/T2), and crescents (C0/C1/C2), were associated with a higher number of CD68+ cells. Full article

We report a rare case of primary renal adenosarcoma in a 26-year-old woman presenting with right flank pain. Contrast-enhanced computed tomography demonstrated a large, mixed solid and cystic mass confined to the renal pelvocalyceal system, closely mimicking a malignant renal tumor. Histopathologic examination revealed a biphasic tumor with phyllodiform architecture. Immunohistochemistry showed benign epithelial positivity for cytokeratin and focal malignant stromal positivity for smooth muscle actin and CD10; however, the tumor was negative for CD99, Wilm’s tumor protein, SS18-SSX, BCOR, and estrogen/progesterone receptors. These findings led to the diagnosis of primary renal adenosarcoma. This case highlights the diagnostic challenge of distinguishing this rare tumor from more common renal malignancies and underscores the importance of imaging–pathologic correlation. Full article

This study aimed to assess phytochemical profiles and antioxidant activities of lyophilized black currant fruit juice (BCLJ) and its corresponding waste extract (BCLW) from the Čačanska crna variety, and to evaluate their antiproliferative properties. The main anthocyanins quantified through HPLC-DAD analysis were delphinidin-3-O-rutinoside and cyanidin-3-O-rutinoside, with significantly higher levels in BCLW. Antioxidant activity was examined using the DPPH and β-carotene/linoleic acid methods, with BCLW showing superior effects in both. Antiproliferative potential was evaluated by determining the Ki67 index in renal epithelial cells of rats treated with BCLJ or BCLW. Thirty healthy male rats were randomly assigned to five groups (n = 6) and administered BCLJ or BCLW orally for ten days, receiving 100, 200, and 300 mg/kg b.w. of BCLW (BCLW1, BCLW2, and BCLW3 groups, respectively) or 200 mg of BCLJ. Histopathological and immunohistochemical parameters were assessed in rats’ kidneys. Across all epithelial types (cortical proximal tubules, distal medullary proximal tubules, collecting ducts, and urothelial cells of the renal pelvis), the highest Ki67 indices were observed in control animals, particularly in collecting ducts and cortical proximal tubules. The lowest Ki67 values in cortical proximal tubules occurred in the BCLW2 group (p < 0.05 vs. control). These findings suggest that black currant preparations could be valuable functional ingredients. Full article

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, accounting for approximately 75–80% of all renal carcinomas, and is often diagnosed incidentally on abdominal imaging, such as abdominal ultrasound or CT scan. Among other types of renal cancer, ccRCC is recognized to be highly aggressive due to its metastatic potential, which leads to a poor prognosis and an increased mortality rate. The most common sites of ccRCC metastasis are the lung, lymph nodes, bone, liver, and adrenal glands. Clear cell RCC is the most frequent primary tumor associated with secondary pancreatic involvement, while overall, pancreatic metastases represent only 2–5% of all malignant pancreatic lesions. These metastases often occur many years after nephrectomy and may present as solitary or oligometastatic disease, frequently displaying a paradoxically favorable prognosis compared with other metastatic sites. The present narrative review we conducted emerged from presentations of ccRCC with pancreatic distant metastases, potentially labeled as primary pancreatic tumors on imaging studies, mimicking pancreatic neuroendocrine tumors due to the hypervascular nature of ccRCC. Four patients were investigated in our clinic for suspicious pancreatic lesions identified on CT imaging, involving both the head and body of the pancreas. The definitive diagnosis was established by performing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or fine-needle biopsy (FNB) and histopathological analysis of the collected tissue samples. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has emerged as a pivotal tool for obtaining tissue diagnosis, particularly when cross-sectional imaging is inconclusive. Through a synthesis of clinical data and literature, this article underscores the essential diagnostic role of EUS-guided tissue acquisition and its impact on therapeutic decision-making. Full article

Sepsis-associated acute kidney injury (S-AKI) is a frequent and life-threatening condition, characterized by rapid functional decline, which is followed by intense inflammation and tissue injury. Experimental lipopolysaccharide (LPS)-induced sepsis reproduces functional and morphological features of human S-AKI and enables investigation of melatonin which has numerous beneficial properties, such as antioxidant properties. In this study, the effects of melatonin (50 mg/kg) on kidney dysfunction, oxidative damage, inflammation, apoptosis, and histopathological alterations in a rat model of S-AKI induced by LPS application (10 mg/kg) were studied. Acute LPS exposure caused statistically significant (p ≤ 0.05) marked renal dysfunction, increased lipid and protein oxidation, suppression of antioxidant enzymes, enhanced NO/iNOS signaling, elevated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), activation of apoptotic pathways, and pronounced tubular and glomerular injury. Co-administration of melatonin statistically significantly (p ≤ 0.05) attenuated oxidative stress, reduced production of inflammatory cytokines, suppressed apoptosis, and ameliorated structural kidney damage, leading to partial restoration of renal function. These findings suggest that melatonin exerts renoprotective effects in S-AKI through combined antioxidant, anti-inflammatory, and anti-apoptotic actions, likely involving modulation of different signaling pathways. Full article

Porcine epidemic diarrhea virus (PEDV) has emerged as a major pathogen responsible for porcine diarrheal diseases, causing outbreaks of severe diarrhea and high mortality in neonatal piglets, thereby inflicting severe economic losses on the global swine industry. Current commercial PED vaccines, comprising conventional inactivated and live attenuated formulations, have exhibited progressively diminished efficacy in the face of emerging PEDV variants. The development of high-efficiency vaccine platforms is therefore critical for PED control. This study engineered a cellular membrane nanovesicle (CMN)-based vaccine, which differs from existing inactivated or subunit vaccines by presenting the PEDV spike (S) protein on the cell membranes to mimic the bilayer phospholipid structure of the viral envelope. The full-length S protein (FS, aa 19-1309) or a truncated S protein fragment (TS, aa 19-726) was expressed in Expi293F cells, followed by extraction of cell membranes to assemble antigen-displaying CMN vaccines. Compared with commercial live attenuated vaccine, administration of the CMN vaccine elicited high-titer neutralizing antibodies and elevated IFN-γ-producing CD8⁺ T cells in murine studies. Safety assessments revealed no adverse effects on body weight, hepatic/renal function indices, or histopathological parameters in vaccinated mice. Furthermore, immunization of piglets elicited notable humoral and CD8⁺ T cell immune responses. Collectively, the strategy of CMN-based vaccine described herein delivers a potential PEDV vaccine platform, thereby offering a novel avenue for next-generation veterinary vaccine development. Full article

Kidney toxicity remains a major dose-limiting complication of radiation therapy and platinum-based chemotherapy, yet the molecular determinants of renal susceptibility and resilience to these genotoxic treatments are incompletely understood. Podocytes are particularly vulnerable to such insults, and emerging evidence implicates lipid dysregulation in podocyte injury. This study investigated the role of sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B), a podocyte-enriched lipid-modulating enzyme, in radiation- and cisplatin-induced nephrotoxicity. Using a doxycycline-inducible, podocyte-specific SMPDL3B transgenic mouse model, renal injury was assessed following focal kidney irradiation, cisplatin administration, or their combination through functional assays, histopathology, ultrastructural analysis, immunofluorescence, and targeted lipidomics. Combined radiation and cisplatin exposure markedly reduced podocyte SMPDL3B expression, accompanied by podocyte depletion, glomerular basement membrane remodeling, proteinuria, and impaired renal function. These structural and functional abnormalities were associated with the selective accumulation of long-chain ceramide-1-phosphate species. In contrast, podocyte-specific induction of SMPDL3B preserved glomerular architecture, maintained renal function, and prevented pathological ceramide-1-phosphate elevation. Collectively, these findings identify SMPDL3B as a key regulator of podocyte stability and lipid homeostasis during chemoradiation stress. Enhancing SMPDL3B activity may represent a mechanistically grounded strategy to mitigate treatment-induced kidney injury while preserving anticancer efficacy. Full article

Cisplatin (CDDP) is a cornerstone chemotherapeutic drug, yet its efficacy is frequently compromised by renal toxicity, primarily manifesting as acute kidney injury (AKI). Magnolol (MG) is a polyphenol from Magnolia officinalis and has been widely documented for its pronounced antioxidant and anti-inflammatory properties. This study evaluated the renoprotective effects of MG in a murine model of CDDP-induced AKI. Male C57BL/6 mice received MG (20 mg/kg) via daily intraperitoneal injection for four consecutive days, starting one day before a single CDDP injection. MG significantly reduced the serum concentrations of blood urea nitrogen and creatinine. Histopathological assessment revealed attenuated tubular damage and reduced expression of tubular injury markers. MG inhibited pro-inflammatory cytokines at both systemic and renal levels, alleviated endoplasmic reticulum stress, and suppressed activation of mitogen-activated protein kinase signaling pathways. Apoptotic damage was mitigated, as shown by the fewer TUNEL-positive cells and lowered expression of pro-apoptotic markers. In parallel, ferroptotic processes were alleviated through downregulation of pro-ferroptotic proteins and preservation of key antioxidant regulators. Importantly, MG restored nuclear factor erythroid 2-related factor 2 activity and upregulated downstream antioxidant effectors. These findings highlight the multi-targeted renoprotective actions of MG and support its possible utility as a therapeutic agent to prevent CDDP-induced renal injury. Full article

Contrast-induced acute kidney injury (CIAKI) has emerged as the third most prevalent etiology of clinically acquired acute kidney injury, with a lack of specific preventive and therapeutic strategies. Rubia Cordifolia L. (madder root), a medicinal herb with a long-standing history and extensive clinical application, exhibits multiple pharmacological activities. This study aimed to clarify the renal protective effect of Rubia cordifolia L. dichloromethane extract (RCDE) on CIAKI modeling rats and investigate potential anti-apoptotic and autophagy-inducing effects molecular mechanisms. In this study, RCDE constituents were identified by UPLC-Q-TOF-MS. A CIAKI rat model was established to evaluate the nephroprotective effect of RCDE. The results showed that RCDE high-dose group significantly decreased serum SCr and BUN levels, attenuated renal histopathological damage, and modulated oxidative stress markers by decreasing MDA and CAT while increasing SOD, compared with the model group. It downregulated the expressions of Bcl-2, caspase-3 and p62, upregulated the expressions of Bax, Beclin1 and reduced the LC3B-II/LC3B-I ratio in renal tissues. Molecular docking indicates that anthraquinone compounds are probably the principal active constituents of RCDE. This study provides experimental evidence for the intervention efficacy of RCDE against CIAKI. Full article

Background/Objectives: Kidney cancer (RC) is a significant global health burden. Renal cell carcinoma (RCC) is the most common form of kidney cancer. Its predominant histological subtype is clear cell renal cell carcinoma (ccRCC), which is frequently diagnosed at an advanced local stage or with metastases. Detecting cancer at an early stage significantly increases the likelihood of a cure; therefore, research on new markers and a thorough understanding of tumor biology are essential. This study investigated the significance of aromatase (ARO), cathepsin S (CTSS), and matrix metalloproteinase 1 (MMP-1) as potential biomarkers in ccRCC. Methods: ARO, CTSS, and MMP-1 concentrations in plasma were determined using SPRi biosensors. Appropriate antibodies were used as biorecognition molecules in the biosensors. The samples analyzed came from 60 patients with histopathologically confirmed clear cell renal cell carcinoma (ccRCC) and from 26 patients diagnosed with chronic cystitis or benign prostatic hyperplasia (BPH). Results: A statistically significant increase (p < 0.00001) in the concentration of all proteins compared with the control samples was observed at the T3–T4 stage. The ARO concentration was already statistically significantly higher at the T1–T2 stage (p < 0.00001). The ROC curve for aromatase demonstrated high sensitivity and specificity for detecting ccRCC, with a cut-off point of 7.53 ng mL⁻¹. A moderate positive correlation was also found between the concentrations of the three tested substances in renal cancer, which may indicate potential interactions in the tumor’s pathogenesis. Conclusions: SPRI testing has been shown to be an alternative to standard methods for detecting potential ccRCC markers. The biosensors used in the study can simultaneously determine ARO, CTSS, and MMP-1. The results obtained suggest the potential importance of these proteins in the development of ccRCC, and our work proposes a new diagnostic technique that may aid in the diagnosis of ccRCC. Full article

Objective: Diabetic kidney disease (DKD) is characterized by podocyte injury and impaired autophagy. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) exhibit therapeutic potential for DKD, yet their mechanisms remain unclear. This study investigated whether BMSC-Exos restore podocyte autophagy via the miR-143-3p/Bcl-2/Beclin1 axis to delay DKD progression. Methods: A high-glucose (HG)-induced podocyte injury model was established using mouse podocytes (MPC5). Autophagy-related proteins (Beclin1, Bcl-2, LC3) and the injury marker desmin were analyzed by Western blot and immunofluorescence (IF). High-throughput sequencing identified BMSC-Exos-enriched miRNAs, with the miR-143-3p/Bcl-2 targeting relationship validated by dual-luciferase reporter assays. BMSCs transfected with miR-143-3p mimic or inhibitor were used to assess exosomes effects on autophagy and podocin expression. In vivo, DKD mice received tail vein injections of modified BMSC-Exos, followed by evaluation of physiological parameters, biochemical indices, and renal histopathology. Results: BMSC-Exos were successfully isolated and characterized. Fluorescence microscopy confirmed exosomes internalization by HG-treated MPC5 cells. BMSC-Exos upregulated Beclin1 and LC3-II while downregulating Bcl-2 and desmin, indicating enhanced autophagy. High-throughput sequencing revealed miR-143-3p enrichment in BMSC-Exos, and Bcl-2 was confirmed as a direct target of miR-143-3p. Exosomes from miR-143-3p mimic-transfected BMSCs further promoted autophagy and podocin expression. In DKD mice, BMSC-Exos reduced blood glucose, urinary albumin-to-creatinine ratio (UACR), and ameliorated renal damage, whereas miR-143-3p inhibition attenuated these effects. Conclusions: BMSC-Exos deliver miR-143-3p to target Bcl-2, thereby activating Beclin1-mediated autophagy and ameliorating DKD. This study elucidates a novel autophagy regulatory mechanism supporting BMSC-Exos as a cell-free therapy for DKD. Full article

Background: As a widely used chemotherapeutic agent, cisplatin frequently induces acute kidney injury (AKI), which severely compromises patient survival and limits its clinical use. While the natural flavonoid diosmetin (Dio) shows promise in mitigating cisplatin-induced nephrotoxicity, its clinical translation is challenged by poor solubility, low bioavailability, and incompletely elucidated mechanisms. This study aimed to overcome these limitations by developing a novel drug delivery system using the microalgae Dunaliella salina (D. salina, Ds) to load Dio (Ds-Dio), thereby enhancing its efficacy and exploring its therapeutic potential. Methods: We first characterized the physicochemical properties of Ds and Dio, and then Ds-Dio complex was synthesized via co-incubation. Its nephroprotective efficacy and safety were systematically evaluated in a cisplatin-induced mouse AKI model by assessing renal function (serum creatinine, blood urea nitrogen), injury biomarkers, histopathology, body weight, and organ index. The underlying mechanism was predicted by network pharmacology and subsequently validated experimentally. Results: The novel Ds-Dio delivery system has been successfully established. In the AKI model, Ds-Dio significantly improved renal function and exhibited a superior protective effect over Dio alone; this benefit is attributed to the enhanced bioavailability provided by Ds carrier. In addition, Ds-Dio also demonstrated safety performance, with no evidence of toxicity to major organs. Network pharmacology analysis predicted the involvement of PI3K/AKT pathway, which was experimentally verified. Specifically, we confirmed that Ds-Dio alleviates AKI by modulating the PI3K/AKT pathway, resulting in concurrent suppression of NF-κB-mediated inflammation and activation of NRF2-dependent antioxidant responses. Conclusions: This study successfully developed a microalgae-based drug delivery system, Ds-Dio, which significantly enhances the nephroprotective efficacy of Dio against cisplatin-induced AKI. The nephroprotective mechanism is associated with modulation of the PI3K/AKT pathway, resulting in the simultaneous attenuation of oxidative stress and inflammation. Full article

Background and Rationale: Tinospora crispa (L.) Hook.f. & Thomson (T. crispa) is a climbing medicinal plant with long-standing ethnopharmacological use, particularly in inflammatory and hepatic disorders and cancer-related conditions. There is a knowledge gap regarding how wild versus cultivated ecotypes differ in chemotype, bioactivity, and safety, and how this might support or refine traditional use. Study Objectives: This study aimed to compare wild and cultivated ecotypes of T. crispa from the Nile Delta (Egypt) in terms of quantitative and qualitative phytochemical profiles; selected in vitro biological activities (especially antioxidant and cytotoxic actions); genetic markers potentially associated with metabolic variation; and short-term oral safety in an animal model. Core Methodology: Standardized extraction of plant material from wild and cultivated ecotypes. Determination of total phenolics, total flavonoids, and major phytochemical classes (alkaloids, tannins, terpenoids). Metabolomic characterization using UHPLC-ESI-QTOF-MS, supported by NMR, to confirm key compounds such as berberine, palmatine, chlorogenic acid, rutin, and borapetoside C. In vitro bioassays including: Antioxidant activity (e.g., radical-scavenging assay with EC₅₀ determination). Cytotoxicity against human cancer cell lines, with emphasis on HepG2 hepatoma cells and calculation of IC₅₀ values. Targeted genetic analysis to detect single-nucleotide polymorphisms (SNPs) in the gen1 locus that differentiate ecotypes. A 14-day oral toxicity study in rats, assessing liver and kidney function markers and performing histopathology of liver and kidney tissues. Principal Results: The wild ecotype showed a 43–65% increase in total flavonoid and polyphenol content compared with the cultivated ecotype, as well as substantially higher levels of key alkaloids, particularly berberine (around 12.5 ± 0.8 mg/g), along with elevated chlorogenic acid and borapetoside C. UHPLC-MS and NMR analyses confirmed the identity of the main bioactive constituents and defined a distinct chemical fingerprint for the wild chemotype. Bioassays demonstrated stronger antioxidant activity of the wild extract than the cultivated one and selective cytotoxicity of the wild extract against HepG2 cells (IC₅₀ ≈ 85 µg/mL), being clearly more potent than extracts from cultivated plants. Genetic profiling detected a C → T SNP within the gen1 region that differentiates the wild ecotype and may be linked to altered biosynthetic regulation. The 14-day oral toxicity study (up to 600 mg/kg) revealed no evidence of hepatic or renal toxicity, with biochemical markers remaining within physiological limits and normal liver and kidney histology. Conclusions and Future Perspectives: The wild Nile-Delta ecotype of T. crispa appears to be a stress-adapted chemotype characterized by enriched levels of multiple bioactive metabolites, superior in vitro bioactivity, and an encouraging preliminary safety margin. These findings support further evaluation of wild T. crispa as a candidate source for standardized botanical preparations targeting oxidative stress-related and hepatic pathologies, while emphasizing the need for: More comprehensive in vivo efficacy studies. Cultivation strategies that deliberately maintain or mimic beneficial stress conditions to preserve phytochemical richness. Broader geographical and genetic sampling to assess how generalizable the present chemotypic and bioactivity patterns are across the species. Full article

Metabolic acidosis is common after kidney transplantation and has been linked to adverse renal outcomes. However, its relationship with histological injury in kidney allografts remains poorly characterized. We aimed to explore the association between metabolic acidosis and histopathological features in kidney allograft biopsies. This single-center, cross-sectional observational study included 63 adult kidney transplant recipients who underwent clinically indicated allograft biopsies. Metabolic acidosis was defined as a serum bicarbonate level < 22 mmol/L at the time of biopsy. Histological lesions were assessed according to the Banff classification. Lesion severity was evaluated using descriptive statistics, nonparametric comparisons, ordinal logistic regression, and multivariable logistic regression models adjusted for renal function, proteinuria, and time from transplantation. Sensitivity analyses additionally adjusted for hemoglobin and donor-related variables. Patients with metabolic acidosis exhibited numerically higher severity scores for both acute inflammatory lesions and chronic histological changes, including total inflammation and interstitial fibrosis/tubular atrophy (IFTA). Across ordinal analyses and multivariable regression models, consistent directional trends toward a greater histological injury burden were observed among acidotic patients; however, none of these associations reached statistical significance, and confidence intervals were wide. Sensitivity analyses yielded directionally consistent effect estimates. In this biopsy-based analysis, metabolic acidosis showed consistent directional trends toward a higher burden of inflammatory and chronic histological lesions, although these findings did not reach statistical significance. Full article