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Bladder cancer (BC) is a complex disease with patients showing widely variable responses to treatment. While immunotherapy has recently emerged as a promising alternative to the standard platinum-based chemotherapy, especially for platinum-resistant tumors, clinicians still lack reliable biomarkers to predict which patients will truly benefit from immunotherapy. This systematic review aimed to explore whether miRNAs could help decode the immune landscape of BC and serve as predictive biomarkers for immunotherapy response. A total of 3,272 articles were systematically screened on medical databases and narrowed down to 37 studies that examined the relationship between miRNAs, immune cell infiltration, and patient outcomes in BC. To further strengthen and validate our findings, we analyzed large-scale genomic data from The Cancer Genome Atlas (TCGA-BLCA). A total of 104 different miRNAs appeared to shape the BC immune microenvironment. Some studies also linked miRNA expression with clinical outcomes such as BCG therapy response and prognosis, while others dissected the molecular pathways. Further analyses established miR-155, miR-142, and miR-146b as key factors for CD4 memory T-cell and M1 macrophage infiltration. Notably, 49 miRNAs showed stage-specific expression differences in TCGA data, with 25 of them also significantly associated with progression-free interval or overall survival. miRNAs are emerging as powerful regulators of the immune microenvironment of BC. However, despite growing evidence, to date, no studies have directly explored miRNA profiles in driving immunotherapeutic decisions. Our findings highlight the need for prospective studies to translate these molecular insights into personalized treatment strategies.

Doxorubicin (DOX) is an effective anticancer drug, but its use is limited by dose-dependent heart toxicity. Quercetin is a natural antioxidant frequently studied for its beneficial properties. Moreover, a wide range of dietary supplements are available for human use. This in vivo study aimed to explore the potential cardioprotective effects of quercetin in chronic DOX treatment. A total of 32 Wistar rats were randomly divided into four groups: control, DOX, DOX/Q-50, and DOX/Q-100, treated with saline, 2.5 mg/kg body-weight DOX, 2.5 mg/kg body-weight DOX + 50 mg quercetin, and 2.5 mg/kg body-weight DOX + 100 mg quercetin, respectively, for two weeks. Rats were monitored using cardiac ultrasound (US) and markers for cardiac injury. Oxidative damage and ultrastructural changes in the heart were investigated. Chronic DOX treatment led to a decline in cardiac function and elevated values of NT pro-BNP, troponin I, and CK-MB. Quercetin treatment slightly improved certain US parameters, and normalized serum NT pro-BNP levels. Furthermore, DOX-induced SOD1 depletion with consequent Nrf2 activation and DNA damage as shown by an increase in γH2AX and 8HOdG. Quercetin treatment alleviated these alterations. Oral administration of quercetin alleviated serum markers associated with DOX-induced cardiotoxicity. Furthermore, it exhibited a favorable impact on the cardiac US parameters. This suggests that quercetin may have potential cardioprotective properties.

Background and Objectives: ST elevation myocardial infarction (STEMI), particularly when complicated by cardiogenic shock (CS), is a critical condition associated with high mortality rates. Identifying predictors of in-hospital mortality can enhance patient management and outcomes. Materials and Methods: This observational, retrospective case–control study included STEMI patients, both complicated and uncomplicated by CS. Additionally, demographics, clinical characteristics, laboratory data and in-hospital mortality rates were analysed for STEMI patients with CS and those without CS. Results: This study included a total of 101 patients with STEMI, of whom 51 (50.5%) had STEMI without CS and 50 (49.5%) had STEMI with CS. No significant differences were observed in demographic characteristics or STEMI risk factors between the two groups. Emergency coronarography was performed in 90.1% of the patients, with successful thrombolysis achieved in 24.5%. Patients with CS exhibited a significantly higher mortality (52%) than those without CS (11.76%). Univariate analysis identified white blood cell counts, CK-MB, CK levels, elevated creatinine and uric acid levels and a reduced left ventricular ejection fraction (LVEF) as predictors of mortality. Logistic regression analysis revealed that LVEF and CK-MB were independent predictors of in-hospital mortality in patients with STEMI and CS. Each 1% increase in LVEF was associated with a reduced mortality risk (HR = 0.89; 95% CI 0.81–0.98; p = 0.018), while elevated CK-MB levels were linked to an increased mortality risk (HR = 1; 95% CI 1–1.01; p = 0.014). Conclusions: Reduced systolic function and elevated CK-MB levels are key predictors of in-hospital mortality and outcomes in STEMI patients with CS. These findings underscore the importance of early identification and support the development of targeted management strategies aimed at improving outcomes in this high-risk population.

Background: White spot lesions (WSLs) are characterized by enamel demineralization. Minimally invasive treatments using infiltrating resins, such as the commercially available Icon®, are recommended. The need for such treatments justifies ongoing research into developing materials that can address existing limitations regarding strength, durability, and biocompatibility. Objectives: This study aimed to synthesize and characterize four novel nanobiomaterials by evaluating their physicochemical properties and biocompatibility compared to the commercial material Icon®. Materials and methods: The recipes for the experimental nanobiomaterials NB3, NB6, NB3F, and NB6F contain varying proportions of TEGDMA, UDMA, HEMA, Bis-GMA, and HAF-BaF2 glass. Mechanical and physicochemical characteristics were evaluated, such as flexural strength, measured using the three-point test; water absorption and solubility; fluoride release; polymerization conversion; and residual monomers, assessed using High-Performance Liquid Chromatography (HPLC). In vitro cell viability was assessed via colorimetry using human dysplastic oral keratinocytes (DOKs). Results: NB6 and NB6F demonstrated the greatest polymerization potential. NB3 exhibited the lowest water absorption and solubility due to its hydrophobic nature. Additionally, the inclusion of UDMA enhanced the strength and elasticity of NB3 when compared to NB6. Among the samples with fluoride additives (NB3F and NB6F), the highest fluoride release on day 7 occurred with the material lacking UDMA. In contrast, the NB3F sample containing UDMA released the least amount of fluoride on the same day. In quantitative terms, NB3 and NB6F exhibited the lowest levels of residual monomers, whereas NB6 showed the highest levels. Both NB3 and NB6 were significantly better tolerated by the cells, showing higher cell viability compared to the commercial material Icon®. Conclusions: The materials’ mechanical and physicochemical properties varied with component proportions, enabling identification of a suitable formulation for targeted clinical applications. Biocompatibility tests showed that the experimental NB3 and NB6 were better tolerated than Icon®. Furthermore, the incorporation of filler particles improved the mechanical strength of the experimental nanobiomaterials.

Background: A debilitating complication of diabetes is diabetic peripheral neuropathy (DPN), for which effective therapy remains limited. In this research, we evaluated the effects of quercetin, pioglitazone, insulin, and a novel thiazolidine-2,4-dione derivative (TZDd) on the nerve functions in a streptozotocin (STZ)-induced rat model of DPN. Methods: In the experimental groups, STZ (60 mg/kg) was administered to Wistar rats to induce type 1 diabetic neuropathy, and the control and experimental DPN groups were treated with quercetin, pioglitazone, insulin, or TZDd for 5 weeks. The sensory and motor symptoms of DPN were evaluated via behavioral tests, nerve conduction velocity measurements, and electrophysiological assessment, and the synthesized TZDd was evaluated in silico for its pharmacokinetic, toxicological, and drug-likeness properties. Results: The diabetic rats developed DPN after 2 weeks of STZ administration, as evidenced by the significant reduction in the sensory and motor nerve conduction velocities (SNCVs and MNCVs) and increased mechanical hyperalgesia; on the other hand, quercetin, pioglitazone, insulin, and TZDd administration ameliorated the nerve functions of the DPN rats. In the in silico predictions, the novel TZDd exhibited no toxicity risks and demonstrated drug-like properties. Conclusions: Quercetin, pioglitazone, insulin, and TZDd showed neuroprotective effects that enhanced functional recovery in experimental DPN. These findings highlight that TZDd may represent a valuable compound with neuroprotective effects that could be used in DPN therapy and management.

Background and Objectives: The aim of this study was to evaluate the potential predictive value of VKORC1, CYP4F2, and GGCX polymorphisms, as well as other clinical and demographic factors, for 5-year mortality in patients with acute ischemic stroke (AIS). Materials and Methods: The study enrolled 252 patients who were consecutively hospitalized for AIS. Demographic data, comorbidities, and laboratory tests were collected. Genotyping of the VKORC1 rs9923231 (-1639G > A; VKORC1*2), CYP4F2 rs2108622 (1347C > T), and GGCX rs11676382 (12970C > G) polymorphisms was performed. Mortality was noted if it occurred within five years following the 30 days after discharge, using the National Health Insurance House registry. Results: Death was recorded in 71 (28.1%) patients. In multivariate analysis the following variables were independent variables associated with 5-year mortality: age > 72 years (OR 2.83 (95%CI 1.32; 6.08), p = 0.007), a lesion volume > 12.6 mL (OR 4.05 (95%CI 2.05; 7.99), p < 0.001), and an NIHSS score > 7 (OR—2.64 (95%CI 1.31; 5.31), p = 0.006). VKORC1 (-1639G > A) SNP m/m variant was only marginally associated with mortality. Conclusions: In this study which included AIS patients, VKORC1, CYP4F2, and GGCX polymorphisms did not independently predict mortality. The VKORC1 variant was only marginally associated with mortality, but this was attenuated after correction for multiple testing. Advanced age, NIHSS score, and the lesion volume were independent predictors of long-term mortality in AIS patients.

Retrograde axonal neurodegeneration along the visual pathway—either direct or trans-synaptic—has already been demonstrated in multiple sclerosis (MS), as well as in compressive, vascular, or posttraumatic lesions of the visual pathway. Optical coherence tomography (OCT) can noninvasively track macular and optic nerve changes occurring as a result of this phenomenon. Our paper aimed to review the existing literature regarding hemimacular atrophic changes in the ganglion cell layer identified using OCT examination in MS patients without prior history of optic neuritis. Homonymous hemimacular atrophy has been described in post-chiasmal MS lesions, even in patients with normal visual field results. Temporal and nasal macular OCT evaluation should be performed separately in all MS patients, in addition to an optic nerve OCT evaluation and a visual field exam.

Gold nanoparticles (Au-NPs) have been explored as potential vectors for enhancing the antitumor efficacy of doxorubicin (DOX) while minimizing its cardiotoxic effects. However, the impacts of DOX Au-NPs on cardiac function and oxidative stress remain inadequately understood. This study aimed to explore the effects of DOX Au-NPs in comparison to free DOX, focusing on oxidative stress markers, inflammation, ultrastructural changes, and cardiac function. Male rats were divided into the following four groups: control, citrate Au-NPs, DOX, and DOX Au-NPs. Cardiac function was assessed using echocardiography, and oxidative stress was evaluated through Nrf2, malondialdehyde (MDA) and superoxide dismutase (SOD) levels, and the GSH/GSSG ratio. The ultrastructure of cardiac tissue was assessed by transmission electron microscopy (TEM). Rats treated with DOX Au-NPs exhibited significant cardiac dysfunction, as indicated by a reduction in fractional shortening and ejection fraction. Oxidative stress markers, including elevated MDA levels and a reduced GSH/GSSG ratio, were significantly worse in the DOX Au-NP group. SOD levels decreased, indicating compromised antioxidant defenses. Citrate Au-NPs also caused some alterations in cardiac function and ultrastructure but without other molecular alterations. DOX Au-NPs failed to mitigate cardiotoxicity, instead exacerbating oxidative stress and cardiac dysfunction. DOX Au-NPs possess cardiotoxic effects, necessitating further investigation into alternative nanoparticle formulations or therapeutic combinations to ensure both efficacy and safety in cancer treatment.

Ovarian cancer (OC) poses significant treatment challenges due to late-stage diagnosis and a complex tumor microenvironment contributing to therapy resistance. We optimized a U-CUP perfusion-based bioreactor method to culture patient-derived primary and metastatic OC specimens, demonstrating that perfusion better preserves cancer cell viability and proliferation, both when fresh and slow-frozen tissues were used. Perfused cultures maintained key microenvironment components, including cancer-associated fibroblasts, endothelial and immune cells. Genetic analysis confirmed the retention in culture of tumor-specific driver mutations. We hence challenged ad hoc generated cisplatin-sensitive and resistant OC cells with cisplatin during growth in U-CUP, validating our system for the testing of drug response. Finally, treatment of slow-frozen OC tissues with carboplatin/paclitaxel revealed different degrees of response to treatment, as indicated by variations in tumor necrosis and number of residual PAX8 + cells, providing the bases for the prompt evaluation of OC standard chemotherapy efficacy in our ex vivo system.

Stroke is a leading cause of death and severe disability worldwide. Rapid diagnosis is critical to ensure the timely administration of medical treatment. Given that in some cases CT scans fail to show the classic clinical signs of stroke, we aimed to evaluate the diagnostic capacity of adiponectin levels and their association with the clinical parameters of patients with acute ischemic stroke (AIS). Adiponectin was measured within 24 h (T1) and 48 h (T2) of AIS onset in 70 patients. A total of 68 control cases were included in the study. Adiponectin levels were significantly higher in the AIS patients than in the controls (16.64 (3.79; 16.69) vs. 3.78 (3.79; 16.69); p < 0.001), with an accuracy of 0.98 (AUC = 0.99). Lower levels were seen in males and in AIS patients with obesity. Higher levels of adiponectin at T1 were associated with a moderate/severe NIHSS score at patient discharge. Moreover, higher levels of borderline significance were seen in patients who died within 12 months of their AIS episode (p = 0.054). Adiponectin may be a useful biomarker for the identification of AIS patients who do not present classic CT signs and could be used to stratify severe cases. Further studies are needed to validate these results.