Search Results (1,509)

In this work the production of poly(3-hexylthiophene) (P3HT) by electropolymerization using different materials as working electrodes is reported. Initially, the tests were carried out under atmospheric conditions with all the electrodes, and subsequently those that showed the best performance were selected to repeat the experiments in an inert atmosphere. The formation of the polymer film on the electrode surface was characterized by Fourier transform infrared spectroscopy (FT-IR) in the mid-infrared region (4000–400 cm⁻¹). This technique allowed the evaluation of the transmittance of P3HT deposited on the electrode surface. The presence of the polymer was confirmed by the appearance of characteristic absorption bands at 2920 cm⁻¹, 2850 cm⁻¹, 850 cm⁻¹ and 730 cm⁻¹. The absorption peaks found at 2920 cm⁻¹, 2850 cm⁻¹ and 850 cm⁻¹ show the presence of the typical functional groups of P3HT. These results suggest that the proposed method could represent a viable alternative for obtaining semiconductor polymers, avoiding the use of initiators with free radicals potentially harmful to human health. Full article

Background/Objectives: Colorectal carcinoma (CRC) is among the most commonly diagnosed cancers in both men and women. Although CRC mortality is generally decreasing, new therapeutic options are needed for unresponsive subgroups of CRC patients. Methods: A series of known and new tyrphostin derivatives was tested for their efficacy against three CRC cell lines with varying KRAS, p53, and/or BRAF statuses. Growth inhibition, apoptosis induction, and inhibition of EGFR and VEGFR-2 were investigated. Results: Tyrphostin A9, the known RG13022-related tyrphostin 1a and its dichlorido(p-cymene)ruthenium(II) complex 1b, and the new SF₅-substituted compounds 2a and 2b showed selective antiproliferative activity against KRAS-mutant HCT-116 CRC cells expressing wildtype p53, while p53-knockout HCT-116 and KRAS-wildtype BRAF/p53-mutant HT-29 CRC cells were distinctly less sensitive. In HCT-116 cells, only tyrphostin A9 increased mRNA expression of caspases 3 and 8, as well as the kinases MEK1 and MEK2, whereas 2a reduced caspase 8 mRNA levels. Tyrphostin A9 increased caspase 3 activity and induced apoptosis in HCT-116 p53-wildtype cells while simultaneously inhibiting the receptor tyrosine kinases EGFR and VEGFR-2 at low nanomolar concentrations. Conclusions: Tyrphostin A9 could be a promising therapeutic option for the treatment of KRAS-mutant CRC that expresses wildtype p53. Full article

Background: While hyperuricemia has been widely studied in cardiovascular and renal diseases, the prognostic impact of low serum uric acid (UA) remains unclear. Emerging evidence suggests hypouricemia may be linked to increased mortality and adverse outcomes. This study aimed to assess the relationship between low UA levels and poor outcomes, including mortality and intensive care unit (ICU) admission, in hospitalized patients. Methods: This retrospective cohort study included 1679 hospitalized patients (744 females, 935 males) from the Internal Medicine Clinic. Patients were categorized into normal and low UA groups based on sex-specific thresholds (male: <3.4 mg/dL, female: <2.4 mg/dL). The primary outcome was in-hospital mortality; secondary outcomes were ICU admission and discharge status. Logistic regression models adjusted for age, chronic kidney disease (CKD), hypertension (HT), and coronary artery disease (CAD). A Prognostic Uric Acid Score (PUAS) was developed using significant predictors and evaluated by Receiver Operating Characteristic (ROC) analysis. Results: Low UA levels were significantly associated with higher ICU admission and mortality (p = 0.012). Multivariate analysis identified age (OR: 1.032), low UA (OR: 2.285), and CKD (OR: 1.571) as predictors of poor prognosis. PUAS showed moderate performance (AUC: 0.664), with a cutoff score of 3.5 optimizing sensitivity and specificity. Conclusions: Low UA levels independently predict mortality and poor prognosis in hospitalized patients. These findings support routine UA monitoring and suggest hypouricemia may be a useful prognostic biomarker. Further studies are needed to understand clinical implications and guide UA-targeted interventions. Full article

Background: Given the pivotal role of diet in cardiovascular diseases (CVDs), there is a growing demand for new sources of bioactive phytochemicals that can contribute to CVD prevention and treatment. Previous research has unveiled the cardioprotective properties of several parts of sea buckthorn (Hippophae rhamnoides L.). For example, various fractions isolated from raw and roasted sea buckthorn seeds showed antioxidant properties in vitro. In addition, the serotonin-rich fraction obtained from roasted seed extract had the strongest antioxidant activity. However, it was unclear which chemical constituents contribute to the anti-platelet potential of sea buckthorn seeds. Methods: The anti-platelet activity of two fractions (fraction b and fraction c) from raw sea buckthorn seed extract, two fractions (fraction d and fraction g) from roasted sea buckthorn seed extract, and two chemical compounds—isorhamnetin 3-O-β-glucoside-7-O-α-rhamnoside (a major component of fraction b), and serotonin (5-HT, 5-hydroxytryptamine), present in fraction c was estimated in several in vitro assays. Results: Isorhamnetin 3-O-β-glucoside-7-O-α-rhamnoside significantly inhibited platelet activation. It lowered the exposition of the active form of GPIIb/IIIa on the surface of 20 μM ADP-stimulated platelets by about 26%. It also inhibited the exposition of P-selectin on the surface of 10 and 20 μM ADP-stimulated platelets. In addition, isorhamnetin 3-O-β-glucoside-7-O-α-rhamnoside (at 50 µg/mL) significantly prolonged the time of thrombus formation. The results also indicate that fractions d and g (from roasted seeds) are more effective anti-adhesive factors than fractions from raw sea buckthorn seeds. Conclusions: It can be suggested that sea buckthorn seeds can serve as a new source of anti-platelet compounds (especially derivatives of isorhamnetin) beneficial in CVD prevention and treatment; however, in vivo research is needed to clarify their mechanism of action, physiologically relevant concentrations, and therapeutic potential. Full article

Background: Suicide attempts often co-occur with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCH). Although impairments of the serotonin (5-HT) system have been associated with suicide attempts, it remains unclear whether these alterations reflect suicidal behavior or are confounded by underlying psychiatric diagnosis. This study used a genotype-informed dynamic model of the 5-HT presynapse to disentangle the effects of suicide attempts and psychiatric diagnosis. Methods: We applied a personalized dynamic model of the 5-HT presynapse to 392 psychiatric patients (with BD, MDD, or SCH), categorized by suicide attempt status, and 140 unaffected individuals. The model incorporated five variants across TPH2, SLC6A4, and MAOA genes simulating individual-specific concentration changes of five 5-HT-related molecular species. Model outputs were summarized by six statistical measures (mean, median, maximum, standard deviation, skewness, and kurtosis) and compared across groups. Results: No significant differences were found across groups defined by suicide attempt status and unaffected individuals. However, diagnosis significantly influenced 5-hydroxyindoleacetic acid (5-HIAA) mean, median, maximum, and standard deviation (all p < 0.05). BD patients had lower 5-HIAA levels than SCH patients (mean: p = 0.013; median: p = 0.013; maximum: p = 0.014; standard deviation: p = 0.014). MDD patients also showed lower 5-HIAA levels than SCH patients for the same measures, with differences approaching significance. No significant difference was observed between BD and MDD patients. A diagnosis-by-suicide attempt status interaction was observed for 5-HIAA skewness (p = 0.013). Conclusions: Model-derived 5-HT profiles were shaped primarily by diagnosis, while temporal dynamics of 5-HIAA, rather than its absolute levels, was associated with suicide attempt status. Thus, personalized dynamic modeling incorporating genetic variants may aid in detecting subtle molecular signatures across diagnoses and suicidal behavior. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by social/communication deficits and behavioral abnormalities, with neuronal apoptosis and immune-inflammatory dysregulation implicated in its pathogenesis. Marine-derived polysaccharides, particularly those from Enteromorpha prolifera (PEPs), exhibit neuroprotective and anti-inflammatory properties—yet their therapeutic potential for ASD remains unexplored. Major monosaccharide components of PEPs were identified as rhamnose, xylose, glucose, glucuronic acid, galactose, and ribose through ion chromatography analysis. Infrared spectroscopy confirmed PEPs as pyranose-type polysaccharides with α-glycosidic bonds and uronic acids, while gel permeation chromatography showed a predominant molecular weight of 3.813 kDa (83.919%). To explore the therapeutic potential of PEPs in ASD, a comprehensive method combining network pharmacology, molecular docking, and in vitro validation was conducted. A total of 235 ASD-related target proteins were predicted, with enrichment analyses indicating significant involvement in pathways such as neuroactive ligand–receptor interaction and the MAPK signaling pathway. In vitro assays using valproic acid (VPA)-induced HT22 neuronal cells showed that PEPs significantly attenuated apoptosis. Western blot analysis further confirmed the downregulation of HSP90AA1, cleaved CASP3/pro-CASP3, p-NF-κB1/NF-κB1, p-AKT1/AKT, and p-mTOR/mTOR, as well as the upregulation of IκBα after PEPs treatment. These findings suggest that PEPs exert neuroprotective effects through the modulation of apoptosis and inflammation-related signaling pathways, supporting their potential as a promising candidate for further study in ASD. Full article

Cellular senescence plays a critical role in tumorigenesis and is recognized as a hallmark of colorectal cancer (CRC). Emerging evidence suggests that 5-fluorouracil (5-FU)-induced senescence may contribute to chemoresistance and tumor recurrence. Here, we investigated the effect of 5-FU on colon cancer cell senescence and whether MM-129 (pyrazolo[4,3-e]tetrazolo[4,5-b][1,2,4]triazine sulfonamide) can antagonize this activity. Senescence was identified by the expression of senescence-associated β-galactosidase (SA-β-gal) and cyclin-dependent kinase inhibitor 1A (p21) using qPCR, microscopy, flow cytometry, and immunohistochemistry. We also measured interleukin 6 (IL-6) and tumor necrosis factor (TNF-α) as key SASP cytokines, along with E-cadherin (CDH1), a marker of epithelial integrity. The SIRT1/STAT3 pathway was evaluated to elucidate the mechanism of MM-129′s action. MM-129 counteracted 5-FU-induced senescence in colon cancer models, reducing p21 levels in zebrafish xenografts and the number of SA-β-gal-positive cells in vitro and in tumor tissues from DLD-1 and HT-29 mouse xenografts. MM-129 also inhibited senescence-associated responses by suppressing SASP cytokines (IL-6, TNF-α) and restoring E-cadherin (CDH1), and it modulated the SIRT1/STAT3 axis, which may underlie the observed senotherapeutic effects. In conclusion, MM-129 represents a novel senotherapeutic candidate. By modulating the SIRT1/STAT3 axis, it may suppress the SASP and weaken pro-survival signaling, thereby facilitating selective clearance of senescent cells. Integrating senotherapeutics with conventional cancer therapies may enhance efficacy and open new avenues for translational research. Full article

Background: Despite anatomically successful surgical correction, postoperative hypertension remains a significant concern in patients with coarctation of the aorta, even when repair is performed during infancy. Inflammation and neurohormonal activation have been proposed as contributing mechanisms. Objective: To investigate the association between preoperative inflammatory biomarkers—specifically the interleukin-6 (IL-6) to tumor necrosis factor-alpha (TNF-α) ratio—and the development of hypertension in patients with successful isolated coarctation of the aorta repair under one year of age. Methods: This observational study included 42 infants with isolated CoA. Clinical, echocardiographic, and biochemical parameters were analyzed. Preoperative plasma levels of IL-6, TNF-α, von Willebrand factor (vWF), and renin were measured. Patients were classified based on hypertensive status at 2-year follow-up. Univariate and multivariate logistic regression analyses were performed to identify predictors of postoperative hypertension. Results: Hypertension was diagnosed in 16 out of 41 patients (39%) at follow-up. A preoperative IL-6/TNF-α ratio > 2 was an independent predictor in multivariate analysis for postoperative HT (OR = 6.1, 95% CI = 6.23–9.31, p = 0.02). Conclusions: In this small single-center cohort, an elevated IL-6/TNF-α ratio was associated with postoperative hypertension after coarctation repair. These exploratory findings should be considered hypothesis-generating and warrant confirmation in larger, multicenter studies. Full article

Chemotherapy-induced senescence (CIS) contributes to tumor persistence and relapse. In this study, we investigated the senolytic activity of piceatannol (PCT) in 5-fluorouracil (5FU)-induced senescent colorectal cancer (CRC) cells. Senescence was established in P53-proficient HCT116 cells and normal colon fibroblasts (CCD18Co) following prolonged 5FU exposure, as shown by increased SA-β-gal activity, upregulation of P16, P21, and P53, mitochondrial depolarization, and enhanced oxidative stress. Subsequent PCT treatment selectively induced apoptosis in senescent populations, while non-senescent or p53-mutant, senescence-resistant HT29 cells were minimally affected. This effect was prevented by N-acetylcysteine, indicating a redox-sensitive mechanism. Mechanistically, PCT triggered mitochondrial depolarization and AIF-associated, caspase-independent apoptosis without increasing ROS. Morphological analysis with MitoTracker and quantitative morphometry using Fiji confirmed a fragmented mitochondrial network, characterized by reduced form factor, length, and number per cell. Western blotting revealed downregulation of fusion proteins (MFN1, MFN2), decreased FIS1, stable DRP1, and marked upregulation of the DRP1 adaptor MFF, consistent with suppressed fusion and enhanced fission competence. Together, these findings demonstrate that PCT selectively targets chemotherapy-induced senescent CRC cells through mitochondrial fragmentation and AIF-dependent apoptosis, highlighting its potential as an adjuvant strategy to limit the long-term burden of therapy-induced senescence. Full article

Background: Despite its use in patients awaiting heart transplant (HT), the impact of continuous inotropic support on short-term complications and long-term transplant outcomes remains unclear. This study evaluated inotrope use at the time of HT on perioperative complications and post-transplant survival, comparing outcomes at 30 days, 1 year, and 10 years with mechanical circulatory support (MCS) strategies including ECMO, IABP, and VADs. Methods: A retrospective analysis of the United Network for Organ sharing (UNOS) registry was performed, stratifying patients based on bridge strategy at the time of transplant: inotropes, ECMO, IABP, or VADs. Baseline characteristics, perioperative complications, and 30-day, 1-year, and 10-year post-transplant survival outcomes were analyzed across groups. Survival was assessed using Kaplan–Meier and Cox proportional hazards models. Results: Among the 11,801 heart transplant patients included, 9330 were on inotropes, 372 were on ECMO, 1072 received an IABP, and 1027 had VADs. Inotrope-bridged patients had significantly lower 30-day and 1-year mortality rates compared to the ECMO, IABP, and VAD groups. They also experienced reduced incidences of post-transplant dialysis and stroke. At 10 years, the inotrope group demonstrated superior long-term survival, with significantly lower mortality risk compared to ECMO (HR: 1.81; CI: 1.49–2.20, p < 0.001), IABP (HR: 1.19; CI: 1.06–1.32, p = 0.005), and VAD (HR: 1.18; CI: 1.10–1.27, p < 0.001). Conclusions: Continuous use of inotropes after waitlisting is associated with lower short, intermediate, and long-term mortality and does not lead to worse outcomes compared to ECMO, IABP, and VAD support. When mechanical support is not an option, inotropic therapy remains a viable and effective strategy. Full article

Background: Chronic inflammation drives colorectal cancer (CRC) progression, with PAR-2, a G-protein coupled receptor, linking extracellular inflammatory signals to tumor-promoting pathways via ERK1/2 phosphorylation, calcium mobilization, TNF-α upregulation, and apoptosis suppression. While curcumin has notable anti-inflammatory and anti-cancer properties, its effects on PAR-2 signaling in inflammation-driven CRC remain underexplored. Objective: This study investigates how curcumin modulates PAR-2 expression and downstream oncogenic signaling in inflammation-driven CRC cells and explores its potential direct interaction with PAR-2 at the structural level. Methods: HT 29 and Caco-2 CRC cell lines were exposed to lipopolysaccharide (LPS) to induce an inflammatory phenotype, followed by treatment with curcumin at 50 µM and 100 µM. PAR-2 and PAR-1 expression, along with downstream markers including ERK1/2, p-ERK, TNF-α, caspase-8, cleaved caspase-8, caspase-3, Bcl 2, and Bax, were analyzed by Western blot and quantitative PCR. Calcium mobilization was assessed using Fluo-4 dye-based fluorescence imaging. Apoptosis was quantified using MTT viability assays, AO/EtBr dual staining, and Annexin V/PI flow cytometry. In parallel, AlphaFold-predicted structural models of PAR-2 were used to perform molecular docking with curcumin using CB-Dock2, to identify potential binding pockets and assess binding energetics. Results: Curcumin selectively downregulated PAR-2—but not PAR-1—at both transcript and protein levels in a dose-dependent manner. This downregulation was accompanied by suppression of ERK phosphorylation and calcium signaling, inhibition of TNF-α secretion, and reversal of the anti-apoptotic signaling axis (Bcl 2 downregulation and Bax and caspase-3/-8 upregulation). Functional assays confirmed enhanced apoptosis in curcumin-treated cells. Computational docking revealed a high-affinity binding interaction between curcumin and the transmembrane domain of PAR-2, supporting the hypothesis of direct G-Protein-Coupled Receptor (GPCR) modulation. Conclusions: Our findings reveal that curcumin targets the PAR-2/ERK/TNF-α axis and reactivates apoptotic pathways in inflammation-driven CRC, establishing it as a potent, mechanistically validated candidate for therapeutic repurposing in CRC. Full article

Intermediate-temperature (IT) proton-exchange membranes (PEMs) play vital roles in hydrogen and direct liquid fuel cells, electrolyzers, and other electrochemical membrane reactors at elevated temperatures of higher than 150 °C. This article reports the fabrication and performance assessment of a type of new IT polymer–inorganic composite (PIC) PEMs that were made of cerium ultraphosphate (CeP₅O₁₄-CUP) as the durable solid-state proton conductor and undoped polybenzimidazole (PBI) as the high-temperature (HT) polymeric binder. The proton conductivity and electrochemical performance of the PIC PEMs were characterized at 200 °C with varying membrane thickness, processing parameters, and operating conditions using a single-stack hydrogen fuel cell connected to a fuel cell test station. Experimental results show that the PIC membranes (with CUP of 75 wt.%) carried high mechanical flexibility and strength as well as noticeably reduced water uptake of 4.4 wt.% compared to pristine PBI membranes of 14.0 wt.%. Single-stack hydrogen fuel cell tests at 200 °C in a humidified hydrogen and air environment showed that the proton conductivity of the PIC PEMs was measured up to 0.105 S/cm, and the electrochemical performance exhibited its dependence upon the membrane thickness with the power density of up to 191.7 mW/cm². Discussions are made to explore performance dependence and improvement strategies. The present study expects the promising future of the IT-PIC-PEMs for broad applications in high-efficiency electrochemical energy conversion and value-added chemical production at elevated temperatures of 200 °C or higher. Full article

Background/Objectives: This study examined the efficacy of essential amino acid (EAA) supplementation on changes in behavior and hippocampal neurotrophin, dopaminergic and serotonergic markers to a volume overload stress resembling an overtraining syndrome. Methods: Thirty-two 3-month-old male C57Bl/6J mice were randomized into four groups: Resistance training (RT), resistance training with overtraining (RTO), resistance training with overtraining and EAA (RTOEAA), or control. Mice in RTOEAA received EAA supplementation (1.5 g·kg·day⁻¹), while the other groups received a sham treatment. A 5-week resistance training protocol was employed. Training volume was increased two-fold during the final two weeks for RTO and RTOEAA to cause the OTS. EAA intervention for RTOEAA occurred during the OTS. Results: A significant decline in the maximum resistance carrying load in RTO compared to RT (p = 0.002) and RTOEAA (p = 0.029) confirmed that the animals in that group were overtrained. Significantly greater average latency times for RTO compared to RT (p = 0.009) and C (p = 0.05) indicated that the OTS caused spatial memory deficits in animals that were not supplemented. These latter changes may have been related to the significant declines in brain derived neurotrophic (BDNF) expression and elevations in dopamine 1 receptor (D1R) expressions. Increased resiliency for RTOEAA may have been related to the effect of EAA on stimulating significant increases in the expression of hippocampal tyrosine receptor kinase B (TrkB) and serotonin receptors (5-HT1A). Conclusions: EAA supplementation during a resistance model of overtraining appeared to provide increased resiliency to OTS by maintaining neurotrophin expression and enhancing serotonergic adaptation. Full article

The development of thin-film organic solar cells (TFOSCs) is pivotal for advancing sustainable energy technologies because of their potential for low-cost, lightweight, and flexible photovoltaic applications. In this study, silver-doped copper sulfide (CuS/Ag) metal nanoparticles (MNPs) were successfully synthesized via a wet chemical method. These CuS/Ag MNPs were incorporated at varying concentrations into a poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) blend, serving as the active layer to enhance the photovoltaic performance of the TFOSCs. The fabricated TFOSC devices were systematically evaluated based on the optical, electrical, and morphological characteristics of the active layer. By varying the concentration of CuS/Ag MNPs, the influence of nanoparticle doping on photocurrent generation was investigated. The device incorporating 1% CuS/Ag MNPs exhibited the highest power conversion efficiency (PCE) of 5.28%, significantly outperforming the pristine reference device, which achieved a PCE of 2.53%. This enhancement is attributed to the localized surface plasmon resonance (LSPR), which augments charge transport and increases optical absorption. The CuS/Ag MNPs were characterized using ultraviolet–visible (UV-Vis) absorption spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy-dispersive dispersion (EDX) analysis. These findings underscore the potential of CuS/Ag MNPs in revolutionizing TFOSCs, paving the way for more efficient and sustainable solar energy solutions. Full article

The development of non-toxic, novel anti-tumor alternatives that target key hallmark events of tumor progression is of a high priority for cancer therapy. Natural compounds, such as Essential oils (EOs) derived from plant extracts are a mixture of chemical components known for their diverse pharmacological properties, including anticancer potential. For this purpose, we investigated the antitumor activity of Eucalyptus globulus essential oil (EEO) and its major constituents against colorectal cancer cells in vitro. EEO significantly reduced the viability of colon cancer LS174 cells, induced caspase-dependent apoptosis and triggered cell cycle arrest by modulating the expression of several effectors involved in these processes. Mechanistically, EEO exhibited its activity by targeting p38, SAPK/JNK, ERK1/2, and AKT kinases in LS174 cells. Considering the pivotal role of p53 status in mediating the response to anticancer therapies, we further investigated the effects of Eucalyptol, 3-Cyclohexene-1-methanol, α-Pinene, and α-Terpineol, identified as major components of EEO, on the viability of human colon adenocarcinoma LS174 (wild type p53) and HT29 (mutant p53) cell lines. Interestingly, we highlighted for the first time that 3-Cyclohexene-1-methanol exhibited the most anti-proliferative activity against both tumor cells irrespective to their p53 status. It exerted its effect by inducing apoptotic cell death, disturbing cell cycle progression along with reducing the phosphorylation of key components of the proliferation and survival pathways p38, ERK1/2, and AKT kinases. Our results suggest that Eucalyptus essential oil and its component, 3-Cyclohexene-1-methanol represent promising multi-targeting candidates for colorectal cancer therapy. Full article