Mitochondrial dysfunction is a pivotal driver in the pathogenesis of acute kidney injury (AKI), chronic kidney disease (CKD), and congenital anomalies of the kidney and urinary tract (CAKUT). The kidneys, second only to the heart in mitochondrial density, rely on oxidative phosphorylation to meet the high ATP demands of solute reabsorption and filtration. Disrupted mitochondrial dynamics, such as excessive fission mediated by Drp1, exacerbate tubular apoptosis and inflammation in AKI models like ischemia–reperfusion injury. In CKD, persistent mitochondrial dysfunction drives oxidative stress, fibrosis, and metabolic reprogramming, with epigenetic mechanisms (DNA methylation, histone modifications, non-coding RNAs) regulating genes critical for mitochondrial homeostasis, such as PMPCB and TFAM. Epigenetic dysregulation also impacts mitochondrial–ER crosstalk, influencing calcium signaling and autophagy in renal pathology. Mitophagy, the selective clearance of damaged mitochondria, plays a dual role in kidney disease. While PINK1/Parkin-mediated mitophagy protects against cisplatin-induced AKI by preventing mitochondrial fragmentation and apoptosis, its dysregulation contributes to fibrosis and CKD progression. For instance, macrophage-specific loss of mitophagy regulators like MFN2 amplifies ROS production and fibrotic responses. Conversely, BNIP3/NIX-dependent mitophagy attenuates contrast-induced AKI by suppressing NLRP3 inflammasome activation. In diabetic nephropathy, impaired mitophagy correlates with declining eGFR and interstitial fibrosis, highlighting its diagnostic and therapeutic potential. Emerging therapeutic strategies target mitochondrial dysfunction through antioxidants (e.g., MitoQ, SS-31), mitophagy inducers (e.g., COPT nanoparticles), and mitochondrial transplantation, which mitigates AKI by restoring bioenergetics and modulating inflammatory pathways. Nanotechnology-enhanced drug delivery systems, such as curcumin-loaded nanoparticles, improve renal targeting and reduce oxidative stress. Epigenetic interventions, including PPAR-α agonists and KLF4 modulators, show promise in reversing metabolic reprogramming and fibrosis. These advances underscore mitochondria as central hubs in renal pathophysiology. Tailored interventions—ranging from Drp1 inhibition to mitochondrial transplantation—hold transformative potential to mitigate kidney injury and improve clinical outcomes. Additionally, dietary interventions and novel regulators such as adenogens are emerging as promising strategies to modulate mitochondrial function and attenuate kidney disease progression. Future research should address the gaps in understanding the role of mitophagy in CAKUT and optimize targeted delivery systems for precision therapies.
Benzoxazoles possess a wide range of therapeutic activities, including antimicrobial, antitumor, anti-inflammatory, and other. Using in silico and in vitro approaches, we determined the potential antitumor activity of benzoxazoles synthesized from thymoquinone in diffuse large B-cell lymphoma (DLBCL) cells. Molecular docking analysis showed strong binding affinities of benzoxazoles toward Akt and nuclear factor kappa B (NF-κB) protein targets that promote cancer cell proliferation and survival and whose expression is linked to tumorigenesis of activated B-cell (ABC) and germinal center B-cell (GCB) DLBCL subtypes. WST-8 assay showed the highest inhibitory activity of benzoxazole derivative bearing thiophene substituent in both DLBCL models. Western blot analysis indicated the inhibitory activity of selected compounds in HBL-1 cells, with decreased p-NF-κB and p-Akt protein expression, whereas treatment of DHL-4 cells stimulated the expression of p-Akt and p-NF-κB protein levels. These data suggest distinct, cell line-dependent activities of the substances that potentially act through diverse oncogenic signaling pathways in DLBCL cells and activation of compensatory cell mechanisms that could be an important step for combinatorial treatment approaches.
Background: The Mini Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are the most commonly used scales to detect mild cognitive impairment in population-based epidemiologic studies. The aim of this study was to define which test is more reliable for early diagnosis of vascular dementia – MoCA or MMSE. Material and methodes: This prospective study included 274 patients with acute stroke, both sexes and all age groups. Patients were divided into groups: demented (DP) and non-demented (NDP). Each patient was underwent to a clinical examination and scoring with appropriate scales (MMSE and MoCA). Patients were tested on two times after discharge. Results: Out of the total number of patients, 171 (62.5%) of them were male, and 103 (37.5%) were female (p=0.339). First testing with the MMSE showed that 143 (52%) had mild or moderate dementia. Sixth months after stroke, the number of demented patients increased to 165 (60%). First testing with the MoCA scale showed that 183 (66%) had some degree of dementia, and after the sixth month 191 (69%). The MoCA recorded a greater number of patients with dementia in both, the first and second testing. MoCA is more sensitive than MMSE for detecting patient with vascular dementia 3 and 6 months after stroke (p=0.0004; p=0.01). Conclusion: The MoCA is more sensitive scale than the MMSE for detecting early stages of vascular dementia. It should be used in daily practice more often than the MMSE in order to make a timely diagnosis of the early stage of dementia. Keywords : vascular dementia, MMSE, MoCA
In order to complete the analysis of the water vapor diffusion problem, as well as the conditions for the appearance of mold, the paper investigates the cases when condensation occurs in the layer inside the structure while considering the increase in the humidity of the material in relation to its natural humidity. Additionally, the level of the average monthly humidity in relation to the critical relative humidity, as well as the temperature factor are investigated. The analysis was done on two materials that are most often used in our region – lightweight concrete (Siporex) block and normal concrete, in situations when thermal insulation is laid on the outside or on the inside of the structure. The calculation showed that for certain situations, already after a couple of years, the total humidity of the material exceeds the permitted values for the materials in question. It was also observed that in the case when moisture diffusion occurred adjacent to the insulating material, the total amount of condensed moisture exceeded the permitted value for which the appearance of mold is avoided.
Introduction: Physical activity has the potential to improve the physical and mental health of older adults, reducing the risk of joint pain and disability. Previous research suggests that regular muscle-strengthening exercise can enhance quality of life, however, chronic pain remains a challenge that negatively affects daily activities and social participation. Due to the importance of maintaining physical fitness in older age, tailored physical activity programs are recommended. Objective: Assess the impact of six physical activity treatments on pain, motor abilities, and quality of life in an elderly woman with chronic hip and knee joint pain. Case Report: The participant, a 74-year-old elderly woman, reported chronic hip and knee pain. Physical assessment included the Senior Fitness Test, Barthel Index, NRS pain scale, vital signs, and body composition analysis. After four weeks of therapy encompassing strength, stretching, and endurance exercises, no significant improvement in mobility was observed, but vital signs remained stable. The intensity of joint pain did not decrease. Conclusion: The results indicate that physical activity can have selective effects on various aspects of health in older adults, but combination with other therapies is necessary for more significant outcomes. Further research with larger samples and longer treatment durations is needed to better understand the effects of physical activity. Keywords: Senior Fitness Test, physiotherapy, physical exercise, quality of life
Introduction: Hepatitis B is a viral infection of the liver that can present as both an acute and chronic disease, caused by the hepatitis B virus (HBV). Despite the availability of an effective vaccine and antiviral therapies capable of suppressing viral replication , hepatitis B remains a significant public health concern. The aim of the study is to collect, statistically analyze, and compare data on age, gender, and the number of hepatitis B cases in the Herzegovina-Neretva (HNC) and Split-Dalmatia (SDC) Counties. Participants and methods: In this retrospective study, data were collected on the number of inhabitants and the number of registered patients with hepatitis B in the areas of these two counties, as well as demographic data of patients (age, gender) for the period from January 1, 2014, to December 31, 2024. Results: In HNC region, 11 individuals with hepatitis B were registered during the study period, with nearly equal numbers of women and men. The affected men were significantly younger than the women (p<0.05). In the SDC, 55 individuals with hepatitis B infection were registered during the same period, with significantly more men than women (p<0.05), while there was no statistically significant difference in the age of the patients (p>0.05). The average annual rate of reported hepatitis B infections in the observed period in the HNC was 0.42 %000, while in the SDC, it was 0.96 %000,. The overall notification rate of cases in the SDC was 12.21 %000,, significantly higher than in the HNC, where it was 4,66 %000, (p<0.05). Conclusion: It was determined that both counties have a low incidence rate of hepatitis B. The epidemiological data on hepatitis B obtained in this study are important for guiding prevention and treatment of the disease in the areas studied and contribute to one of the World Health Organization (WHO) goals, which is the elimination of hepatitis worldwide by 2030. Keywords: hepatitis B, incidence, elimination, Split-Dalmatia County, Herzegovina-Neretva County.
Introduction: Adults over 65 years of age have the highest mortality rate from lower respiratory tract infections caused by influenza. People who live with or care for patients in risk groups, such as healthcare workers, should be vaccinated. Low influenza vaccination rates among certain at-risk groups contribute to the burden of disease and remain a major public health challenge. The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on seasonal influenza. Aim: Investigate the coverage of influenza vaccination among adults at the Health Center of the Split-Dalmatia County in Vrgorac. Materials and methods: A retrospective analysis was conducted. Data on influenza vaccinations from January 01, 2019 to December 31, 2024 at the Health Center of the Split-Dalmatia County in Vrgorac were analyzed from the electronic immunization database. The following variables were included in the analysis: vaccination coverage by year, subject category (older than 65, chronically ill, healthcare worker, other), and subject gender. Results: A total of 2090 doses of influenza vaccine for adults were consumed. The most vaccine doses were consumed in 2020, 512 doses, and the fewest vaccine doses were consumed in the last two years, 257 and 296, respectively (p<0.05). The largest number of patients was over 65 years old, 1214, 833 were chronic patients, while 26 were healthcare workers (p<0.05). Conclusion: A statistically significantly lower consumption of vaccine doses was found during and after the end of the COVID-19 pandemic compared to the time before the pandemic. Healthcare workers were statistically significantly less vaccinated against influenza compared to other groups. Keywords: Influenza, human flu, vaccination, immunization, vaccines
Cytochrome P450 (CYP450) enzymes are pivotal in the metabolism of numerous anticancer agents, with CYP3A4 being the predominant isoform involved. Inhibition of CYP450 enzymes is a major mechanism underlying clinically significant drug-drug interactions (DDIs), particularly in oncology, where polypharmacy is frequent. This review aims to provide a comprehensive and critical overview of CYP450 enzyme inhibition, focusing specifically on the impact of kinase inhibitors (KIs) and poly adenosine diphosphate-ribose polymerase (PARP) inhibitors. A systematic review of the current literature was conducted, focusing on the molecular mechanisms of CYP450 inhibition, including reversible, time-dependent, mechanism-based, and pseudo-irreversible inhibition. Specific attention was given to the inhibitory profiles of clinically relevant KIs and PARP inhibitors, with analysis of pharmacokinetic consequences and regulatory considerations. Many KIs, such as abemaciclib and ibrutinib, demonstrate time-dependent or quasi-irreversible inhibition of CYP3A4, while PARP inhibitors like olaparib and rucaparib exhibit moderate reversible and time-dependent CYP3A4 inhibition. These inhibitory activities can significantly alter the pharmacokinetics of co-administered drugs, leading to increased risk of toxicity or therapeutic failure. Regulatory guidelines now recommend early identification of time-dependent and mechanism-based inhibition using physiologically based pharmacokinetic) (PBPK) modeling. CYP450 inhibition by KIs and PARP inhibitors represents a critical but often underappreciated challenge in oncology pharmacotherapy. Understanding the mechanistic basis of these interactions is essential for optimizing treatment regimens, improving patient safety, and supporting personalized oncology care. Greater clinical vigilance and the integration of predictive modeling tools are necessary to mitigate the risks associated with CYP-mediated DDIs.
Using direct hydrogen reduction in a rotary kiln without smelting and the dissolving of solid residues under high pressure in an autoclave, this study investigates pyrometallurgical and hydrometallurgical techniques for decarbonizing and recovering precious metals from bauxite residue. The aim of this paper is to provide decarbonizing methods for removing iron from bauxite residue, a Bayer process by-product that cannot be disposed of in an environmentally responsible way. Hydrogen is being researched as a cleaner substitute for conventional carbon-based reductive melting, which produced large CO₂ emissions. A rotary kiln's hydrogen reduction process recovers 99.9% of the iron as iron, which can then be separated from the solid residue that contains other valuable metals using magnetic separation. In contrast to very stable oxides like titanium oxide, silica, and aluminum oxide, we found that hydrogen can reduce iron oxide from bauxite residues to metallic iron. Sulfuric acid leaching of titanium, iron, and aluminum is highly effective when done in an autoclave at high pressure.
Dissolution of water-insoluble drugs is an important challenge in drug delivery. Adsorbing water-insoluble drugs onto nanoporous carriers such as zeolites can improve drug dissolution. The drug molecules adsorbed in a thin layer onto nanoporous carriers are fully exposed to the solvent, enhancing the dissolution process. This presentation will give new insights into the adsorption of water-insoluble letrozole drug onto the nanoporous clinoptilolite zeolite from a nanoscale-science point of view based on experimental and theoretical considerations. Adsorption of the letrozole drug on clinoptilolite zeolite will be conducted from the colloidal dispersion state. The amount of letrozole adsorbed in a monolayer will be evidenced by thermogravimetric measurements, while optical spectroscopy techniques will reveal the interactions of the letrozole drug on the nanoporous zeolite framework. Positive adsorption energy at the letrozole-clinoptilolite interface calculated using density functional theory models suggests a small affinity for letrozole adsorption, suggesting the letrozole release is more favorable than the adsorption process. Thus, this presentation will show new possibilities in adsorption and dissolution of water-insoluble drugs.
This study explores the effectiveness of electrocoagulation (EC) for removing toxic hexavalent chromium (Cr(VI)) from industrial wastewater using iron and aluminum electrodes in both batch and continuous modes. Iron electrodes demonstrated superior performance, achieving up to 99.8% Cr(VI) removal in batch mode at an optimal current density of 5 mA/cm2, while continuous operation at 50 L/h achieved comparable removal after 30 minutes, with slightly lower efficiency due to reduced retention time. The lowest specific energy consumption (2.82 kWh/kg Cr(VI)) was also recorded under these optimal conditions, highlighting economic feasibility. Fourier-transform infrared (FTIR) analysis of the sludge confirmed the reduction of Cr(VI) to the less toxic Cr(III), primarily in the form of Cr(OH)3. Characteristic peaks indicate Cr-O vibrations in chromium hydroxide, while the presence of hydroxyl (-OH) groups confirms the formation of iron hydroxide complexes that facilitate Cr(VI) adsorption and precipitation. Additional spectral features suggest the presence of iron oxides, further supporting the electrocoagulation mechanism involving the generation of coagulant species in situ. Overall, the results affirm EC as a highly efficient and cost-effective treatment method, particularly suitable for large-scale applications.
Introduction: The aim of this study was to assess the antioxidant activity of cinnamon extracts obtained using different solvents (ethanol, methanol, acetone, water) and their mixtures with water. Additionally, the phenolic and flavonoid contents were analyzed to investigate their correlation with antioxidant activity. Materials and Methods: Cinnamon extracts were prepared using pure solvents (ethanol, methanol, acetone, water) and their mixture with water in different proportions. The total phenolic and flavonoid contents, as well as the antioxidant activity of the obtained extracts, were analyzed. Results and Discussion: The results showed that the extracts obtained from mixtures of ethanol and water had a high content of phenols and flavonoids, with the 40:10 ethanol-to-water mixture yielding the highest phenolic (240.69 mg/g) and flavonoid (0.275 mg/g) contents. Similarly, methanol and its mixtures with water showed variations in the content of these components, with pure methanol providing the highest values (252.12 mg/g for phenols and 0.2212 mg/g for flavonoids). Regarding antioxidant activity, ethanol extracts and their mixtures with water achieved the best results, with the 20:30 ethanol-to-water mixture displaying the highest antioxidant potential (937.775 µmol TE/g). Methanol-water mixtures, particularly in the 40:10 ratio, also exhibited high activity (928.675 µmol TE/g). Acetone extracts and their mixtures with water had somewhat lower values, while water-based extracts showed the lowest antioxidant activity (192.9 µmol TE/g). Conclusion: These results indicate a significant potential of solvent mixtures, particularly acetone-water mixtures, in enhancing bioactivity and antioxidant effects.
Accurate reconstruction of latent environmental fields from sparse and indirect observations is a foundational challenge across scientific domains-from atmospheric science and geophysics to public health and aerospace safety. Traditional approaches rely on physics-based simulators or dense sensor networks, both constrained by high computational cost, latency, or limited spatial coverage. We present the Temporal Radiation Operator Network (TRON), a spatiotemporal neural operator architecture designed to infer continuous global scalar fields from sequences of sparse, non-uniform proxy measurements. Unlike recent forecasting models that operate on dense, gridded inputs to predict future states, TRON addresses a more ill-posed inverse problem: reconstructing the current global field from sparse, temporally evolving sensor sequences, without access to future observations or dense labels. Demonstrated on global cosmic radiation dose reconstruction, TRON is trained on 22 years of simulation data and generalizes across 65,341 spatial locations, 8,400 days, and sequence lengths from 7 to 90 days. It achieves sub-second inference with relative L2 errors below 0.1%, representing a>58,000X speedup over Monte Carlo-based estimators. Though evaluated in the context of cosmic radiation, TRON offers a domain-agnostic framework for scientific field reconstruction from sparse data, with applications in atmospheric modeling, geophysical hazard monitoring, and real-time environmental risk forecasting.
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