Search Results (2,142)

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer subtype and, in most cases, it is incidentally diagnosed, as early-stage disease is often asymptomatic. Therefore, the identification of stable, noninvasive biomarkers is a major unmet clinical need. Urinary microRNAs (miRNAs) have emerged as promising candidates since they are extraordinarily stable in urine and show a close relationship with tumour biology. Methods: In this study, urinary expression levels of five miRNAs (miR-15a, miR-15b, miR-16, miR-210, and miR-let-7b) were analysed in RCC patients before surgery, 5 days after, and one month after surgery, and compared to healthy controls. Results: Non-parametric analyses revealed significant postoperative decreases for miR-15a (p = 0.002), miR-16 (p = 0.025), miR-210 (p = 0.030), and in the overall miRNA Sum (p = 0.002), suggesting that these miRNAs are directly linked to tumour presence. In the comparison between preoperative and one-month postoperative samples, miR-let-7b (p = 0.049) and the global miRNA Sum (p = 0.037) remained significantly reduced after intervention, indicating a partial normalisation of urinary miRNA profiles. Correlation analyses demonstrated positive associations between specific miRNAs and clinical parameters such as age, ischemia time, and surgical time, reinforcing their potential relevance to tumour biology and treatment response. Conclusions: These findings support urinary miRNAs as promising, minimally invasive biomarkers for ccRCC diagnosis and postoperative monitoring. 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

Background: Acute kidney injury (AKI) is a frequent and clinically relevant complication in cancer patients, with highly variable incidence. AKI increases morbidity and mortality, prolongs hospitalization, and may limit access to oncologic therapies. This study evaluated the incidence, risk factors, and outcomes of AKI in hospitalized cancer patients. Methods: We retrospectively analyzed patients admitted between 1 January 2016 and 31 December 2019. Individuals with cancer were identified and categorized into three groups: hematologic malignancies, solid cancers with metastases, and solid cancers without metastases. Demographic, clinical, and laboratory data were collected, and AKI was defined and staged according to KDIGO criteria, evaluating serum creatinine changes. Results: Among 56,390 hospitalized patients, 6723 (11.9%) had a cancer diagnosis. AKI incidence was significantly higher in cancer versus non-cancer patients (30.1% vs. 19.6%). Hematologic cancers showed the highest incidence (39.3%). Among hematologic patients, ICU admission, sepsis, and diabetes were strongly associated with AKI. In non-metastatic solid cancers, more conventional factors—including female sex, older age, sepsis, and ICU admission—were significant predictors. In contrast, in metastatic solid cancers, traditional AKI risk factors did not correlate with increased AKI occurrence. In cancer patients overall, AKI per se did not increase mortality risk; however, stage 3 AKI was associated with significantly higher mortality (HR 1.37, 95% CI 1.13–1.66, p < 0.001). Conclusions: AKI is common in hospitalized cancer patients, with specific patterns and heterogeneous risk factors and impact on outcomes. Implementation of tailored preventive strategies and early recognition are necessary to mitigate progression and improve clinical trajectories. Full article

Background: Rhabdoid tumor of the kidney (RTK) is a highly aggressive pediatric malignancy characterized by biallelic SMARCB1 loss, resulting in aberrant MYC pathway activation and cell cycle regulation. MYC-activated tumors are vulnerable in splicing functions and sensitive to splicing inhibitors. Therefore, in this study, cyclin-dependent kinase 11 (CDK11), which regulates both cell cycle and RNA splicing, was tested as a therapeutic target in RTK. Methods: CDK11A/B expression was analyzed using the TARGET-RT database. The therapeutic efficacy of the CDK11 inhibitor OTS964 was evaluated in two RTK cell lines (G401 and JMU-RTK-2) and a JMU-RTK-2 xenograft mouse model. Cytotoxicity, apoptosis, cell cycle, and RNA splicing were examined using the Sulforhodamine B assay, immunoblotting, flow cytometry, and RT-PCR. Results: CDK11B, but not CDK11A, was significantly upregulated in RTK and correlated with the poor survival. OTS964 inhibited RTK cell growth in vitro with the IC50 of 33.1 nM (G401) and 19.3 nM (JMU-RTK-2) and significantly prolonged survival in vivo (median survival: 46.5 vs. 37.0 days, p < 0.01) without marked toxicity. Mechanistically, OTS964 induced G2/M cell cycle arrest and p53 upregulation, disrupted RNA splicing via SF3B1 dephosphorylation, and ultimately led to apoptosis through caspase-3 activation. Conclusions: CDK11 inhibition by OTS964 effectively suppresses RTK growth through cell cycle arrest and RNA splicing inhibition, leading to apoptosis. OTS964 shows potent anti-tumor activity and tolerability, supporting CDK11 as a promising therapeutic target for RTK and related SMARCB1-deficient cancers. Full article

Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and is marked by pronounced intra-tumoural heterogeneity that complicates therapeutic response. Patient-derived organoids offer a physiologically relevant model to capture this diversity and evaluate treatment effects. When integrated with spatial transcriptomics, they might enable the mapping of spatially resolved transcriptional and isoform-level changes within the tumour microenvironment. Methods: We established a robust workflow for generating patient-derived ccRCC organoids, that are not passaged and retain original cellular components. These retain key features of the original tumours, including cancer cell, stromal, and immune components. Results: Spatial transcriptomic profiling revealed multiple transcriptionally distinct regions within and across organoids, reflecting the intrinsic heterogeneity of ccRCC. Isoform-level analysis identified spatially variable expression of glutaminase (GLS) isoforms, with heterogeneous distributions of both the GAC and KGA variants. Treatment with NUC-7738, a phosphoramidate derivative of 3′-deoxyadenosine, induced marked transcriptional remodelling of organoids, including alterations in ribosomal and mitochondrial gene expression. Conclusions: This study demonstrates that combining long-read spatial transcriptomics with patient-derived organoid models provides a powerful and scalable approach for dissecting gene and isoform-level heterogeneity in ccRCC and for elucidating spatially resolved transcriptional responses to novel therapeutics. Full article

Evaluating the activity of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in tryptophan (Trp) metabolism, is important because IDO is involved in immune tolerance and drives the production of Trp metabolites implicated in psychiatric disorders and cancer. This study aimed to design and develop a novel fluorescent l-Trp derivative to fluorometrically monitor Trp-catabolizing enzyme activity via IDO. To evaluate IDO activity in vivo, 7-N,N-dimethylamino-2,1,3-benzoxadiazole (DBD), a fluorophore, was covalently bound at the 5-position of the indole ring in Trp to produce 5-DBD-l-Trp. An in vivo microdialysis (MD) study was conducted using the kidneys of Sprague–Dawley rats. Specifically, 5.0 μM 5-DBD-l-Trp in phosphate-buffered Ringer’s solution was infused into the rats, and the MD sample was analyzed via high-performance liquid chromatography with fluorescence detection. In the MD sample, two fluorescence peaks other than 5-DBD-l-Trp were observed during the 5-DBD-l-Trp infusion, and the main metabolite peak was proposed to be 5-DBD-kynurenine, verified by liquid chromatography-tandem mass spectrometry. The intensity of the fluorescent peak was significantly attenuated by co-infusion with an IDO inhibitor, 1-methyl-d-Trp. These results suggest that 5-DBD-l-Trp may be metabolized by renal IDO and can be used to evaluate IDO activity in vivo. Full article

Background: This study investigates the global burden of early-onset bladder cancer (EOBC) from 1990 to 2021, highlighting regional disparities and the growing role of metabolic risk factors. Early-onset bladder cancer (EOBC), diagnosed before age 50, is an emerging global health concern. While less common than kidney cancer, EOBC contributes substantially to mortality and disability-adjusted life years (DALYs), with marked sex disparities. Its global epidemiology remains unassessed systematically. Methods: Using GBD 1990–2021 data, we analyzed EOBC incidence, prevalence, mortality, and DALYs across 204 countries in individuals aged 15–49. Trends were examined via segmented regression, EAPC, and Bayesian age-period-cohort modeling. Inequality was quantified using SII and CI. Decomposition and SDI-efficiency frontier analyses were introduced. Results: From 1990 to 2021, EOBC incidence rose 62.2%, prevalence 73.1%, deaths 15.3%, and DALYs 15.8%. Middle-SDI regions bore the highest burden. Aging drove trends in high-SDI areas and population growth in low-SDI regions. Over 25% of high-SDI countries underperformed in incidence/prevalence control. Smoking remained the leading risk factor, with rising hyperglycemia burdens in high-income areas. Males carried over twice the female burden, peaking at age 45–49. Conclusions: EOBC shows sustained global growth with middle-aged concentration and significant regional disparities. Structural inefficiencies highlight the need for enhanced screening, early warning, and tailored resource allocation. Full article

Acute kidney injury (AKI) remains a major clinical challenge, with high morbidity and limited therapeutic options. In recent years, mitochondria have gained considerable attention as key regulators of the metabolic and immune responses during renal injury. Beyond their classical role in ATP production, mitochondria participate directly in inflammatory signaling, releasing mitochondrial DNA and other DAMPs that activate pathways such as TLR9, cGAS–STING, and the NLRP3 inflammasome. At the same time, immune cells recruited to the kidney undergo significant metabolic shifts that influence whether injury progresses or resolves. Increasing evidence also shows that immune-modulating therapies, including immune checkpoint inhibitors and innovative cell-based immunotherapies, can influence mitochondrial integrity, thereby altering renal susceptibility to injury. This review first summarizes the established knowledge on mitochondrial dysfunction in AKI, with emphasis on distinct mechanistic pathways activated by chemotherapy and immunotherapy. It then discusses emerging mitochondrial-targeted therapeutic strategies, logically integrating preclinical insights with data from ongoing and proposed clinical trials to present a coherent translational outlook. 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

Aim: To analyse the importance of inflammation in the disease burden and prognosis of patients with type 2 diabetes (T2DM) and atrial fibrillation (AF). We assessed these patients according to their neutrophil-to-lymphocyte ratio (NLR) values, examining their baseline characteristics and their prognosis at one year of follow-up based on a prospective AF registry in Spain (Sumamos-FA-SEMI). Methods: A prospective, multicentre, observational study of patients with AF (Sumamos-FA-SEMI) was conducted. We categorised the patients into four groups according to the presence of T2DM and NLR levels with a reference cut-off point of three. We compared the characteristics of the four groups and evaluated the prognosis using the mean values of all-cause mortality and all-cause mortality plus readmissions during a year of follow-up. Results: We analysed 1071 patients, 482 of whom had T2DM. This group had significantly higher rates of obesity and comorbidities. Groups with an NLR greater than three points had a higher prevalence of cancer, lower HDL cholesterol levels, and more albuminuria. Other inflammatory markers, such as C-reactive protein, were also higher in these groups. Regarding prognosis, groups (both with and without T2DM) with an NLR greater than three had significantly higher mortality, with a higher probability in those without T2DM (HR 3.58, 95% CI: 1.99–6.43, p < 0.00). In terms of mortality and readmissions, only the group without T2DM and with an NLR greater than three had significantly higher mortality (HR 2.19, 95% CI: 1.51–3.19, p < 0.00). Conclusions: Among atrial fibrillation patients, the combination of T2DM and high inflammation (NLR) was linked to higher comorbidity, worse metabolic and kidney disease, and the poorest prognosis. Surprisingly, the highest risk of readmission or death was in non-T2DM patients with higher NLR levels, suggesting that T2DM treatments may mitigate risk. Full article

Boron is a trace element with multifaceted chemical and biological properties that underpin its emerging relevance in human health and medicinal chemistry. Although present in organisms at very low concentrations, boron participates in key physiological processes, including mineral metabolism, bone homeostasis, hormonal regulation, immune modulation, and redox balance. Its unique electronic structure—characterized by electron deficiency and the ability to form multi-center bonds—gives rise to diverse allotropic, cluster, and coordination chemistries, enabling the formation of biologically active complexes and therapeutic agents. Dietary boron, derived mainly from plant-based foods, is efficiently absorbed and predominantly excreted by the kidneys, showing a strong correlation between intake and urinary levels. Current evidence suggests beneficial effects of boron on bone mineral density, cognitive function, inflammation, antioxidant defenses, and metabolic regulation, although the precise molecular mechanisms remain partially understood. In medicinal chemistry, a broad spectrum of boron-containing compounds—including borates, boronic acids, boronated amino acids, carboranes, and metallacarboranes—has gained clinical and preclinical importance. These compounds serve as enzyme inhibitors, antimicrobial and anti-inflammatory agents, metabolic modulators, and critical boron carriers in boron neutron capture therapy (BNCT), which leverages the neutron-capture properties of ¹⁰B for targeted cancer treatment. Advances in synthesis, functionalization, and nanocarrier design have expanded the therapeutic potential of boron-based molecules. Ongoing research aims to optimize their selectivity, biodistribution, safety, and diagnostic integration. Overall, boron represents a versatile and rapidly developing component of modern biomedical science, with promising implications for oncology, infectious diseases, metabolic disorders, and precision medicine. Full article

Background and Clinical Significance: Kidney transplant recipients have a 2–4-fold higher cancer risk than the general population. The sequential occurrence of multiple myeloma (MM) and native-kidney renal cell carcinoma (RCC) is rare and creates competing priorities between anti-myeloma efficacy and allograft preservation. Case Presentation: A 54-year-old woman with a 2020 living-donor kidney transplant presented in 2024 with bone pain and shoulder swelling. Low-dose whole-body CT showed multiple punched-out osteolytic lesions. Work-up revealed IgG-κ M-protein 38.5 g/L and 25% clonal plasma cells; cytogenetics showed a complex karyotype (R-ISS III). First-line bortezomib/cyclophosphamide/dexamethasone (VCd) was given while maintaining tacrolimus plus low-dose steroid. After four cycles, she achieved very good partial response (M-protein 42.3 to 5.6 g/L) with stable graft function. Follow-up imaging detected a large exophytic mass in the native right kidney; nephrectomy confirmed papillary RCC, type II. Later, the myeloma progressed with epidural extension causing cord compression. Second-line daratumumab/carfilzomib/dexamethasone (DKd) and palliative spine radiotherapy were initiated. The course was complicated by opportunistic infection and pancytopenia, and the patient died in January 2025. Conclusions: Vigilant post-transplant cancer surveillance—including native-kidney RCC—tailored immunosuppression, and multidisciplinary coordination are critical. VCd with tacrolimus may be feasible when graft preservation is prioritized; however, relapsed high-risk MM on DKd carries substantial infectious risk and a guarded prognosis. Full article

Objectives: To determine the incidence of delayed methotrexate elimination (DME) and acute kidney injury (AKI) and their associations with clinical outcomes in patients receiving high-dose methotrexate (HDMTX) for cancer treatment. Methods: The HDMTX European Registry collected medical records data from 12 institutions in 5 European countries to investigate the clinical practice patterns of healthcare providers utilizing HDMTX for cancer treatment. Cancer types included were acute lymphoblastic leukemia (ALL), primary central nervous system lymphoma (PCNSL), non-Hodgkin lymphoma (NHL), osteosarcoma, and other CNS cancers. Primary endpoints were the incidence of DME and AKI; secondary endpoints were clinical outcomes, including hospital length of stay (LOS), delay in the subsequent course of treatment, methotrexate dose reduction, and omission of next course of treatment. Associations between the primary and secondary endpoints were analyzed with Chi-square and Wilcoxon rank-sum tests. Results: Among the 2501 total HDMTX courses analyzed, DME occurred in 302 courses (12.1%), and AKI in 384 courses (15.4%). DME incidence was highest in courses for PCNSL (18.2%) and NHL (17.2%); AKI incidence was highest in ALL courses (21.0%). Incidence of DME and AKI varied by age and methotrexate infusion duration among the different cancer types. Occurrence of DME was associated with longer delays prior to the next course of treatment, longer hospital LOS, and more frequent methotrexate dose reductions and dose omissions. Conclusions: While HDMTX is a very effective and safe treatment, administration of efficacious doses of methotrexate can lead to AKI and DME, and no single or combination of patient or treatment factors was found to reliably predict their occurrence. Thus, diligent monitoring of methotrexate levels is imperative for early detection and prompt management of nephrotoxicity in all settings where HDMTX treatment is administered. Full article

Background/Objectives: Research on noble metal nanoparticles (NPs) has increased over the past three decades, with advancements in synthesis techniques refining their physicochemical characteristics, including size, shape, and surface chemistry. Bimetallic NPs (BNPs) offer synergistic properties contributed by both metals. Gold (Au) and palladium (Pd) NPs possess low toxicity, high biocompatibility and loading, ease of synthesis and surface modification. Doxorubicin (DOX) and 5-fluorouracil (5-FU) are potent chemotherapeutic drugs but are rapidly metabolised in the body, producing severe side effects, limiting their use. Hence, innovative strategies to mitigate this is needed. Methods: In this study, AuPd NPs in a core-shell formation were chemically synthesized. The AuPd NPs were conjugated to 5-FU and DOX-encapsulated CS complexes and decorated with the targeting moiety transferrin (Tf). Results: Transmission electron microscopy and nanoparticle tracking analysis confirmed that the BNPs were spherical, with an average size of 73.4 nm. Functionalized BNPs were able to encapsulate more than 70% of 5-FU and DOX, resulting in a controlled drug release profile at pH 4.2. Cytotoxicity levels in human cancer cells, HeLa (cervical carcinoma) and MCF-7 (breast adenocarcinoma), as well as in non-cancer HEK293 (embryonic kidney) cells, revealed that the Tf-targeted nanocomplexes were HeLa cell-specific, with no significant cytotoxicity in the HEK293 cells. Tf-mediated cellular uptake was confirmed by receptor competition studies in the HeLa cells. Apoptosis and oxidative stress analysis confirmed cell death by apoptosis, consistent with the action of 5-FU and DOX. Conclusions: This study highlighted the potential of this BNP-nanocomplex as a suitable vehicle for drug delivery. Full article

Active propelled micro robots (MRs) represent a transformative shift in biomedical engineering, engineered to navigate physiological environments by converting chemical, acoustic, or magnetic energy into mechanical propulsion. Unlike passive delivery systems limited by diffusion and systemic clearance, MRs offer autonomous mobility, enabling precise penetration and retention in hard-to-reach tissues. This review provides comprehensive analysis of MR technologies within urology, a field uniquely suited for microrobotic intervention due to the urinary tract’s anatomical accessibility and fluid-filled nature. We explore how MRs address critical therapeutic limitations, including the high recurrence of kidney stones and the rapid washout of intravesical bladder cancer therapies. The review categorizes propulsion mechanisms optimized for the urinary environment, such as urea-fueled nanomotors and magnetic swarms. Furthermore, we detail emerging applications, including bioresorbable acoustic robots for tumor ablation and magnetic grippers for minimally invasive biopsies. Finally, we critically assess the path toward clinical translation, focusing on challenges in biocompatibility, real-time tracking (MRI, MPI, photoacoustic imaging), and the regulatory landscape for these advanced combination products. Full article