Search Results (173)

In postmenopausal women, due to endocrine changes, there is an increase in oxidative stress (OS) that predisposes them to cardiovascular and metabolic alterations. Sixty-one percent of women in this stage require a primary therapeutic strategy to decrease OS. This study aimed to evaluate the effect of resveratrol and vitamin C on OS in postmenopausal women. A randomized, double-blind clinical trial was carried out. Forty-six postmenopausal women with insulin resistance (HOMA-IR > 2.5) were included and divided into three treatment groups: group A: resveratrol, n = 13; group B: resveratrol + vitamin C, n = 15; and group C: vitamin C, n = 14. Between before and after the antioxidants, group B showed a decrease of 33% in lipohydroperoxides (p = 0.02), and malondialdehyde (MDA) decreased by 26% (p = 0.0007), 32% (p = 0.0001), and 38% (p = 0.0001) in groups A–C, respectively. For protein damage, group B is the most representative, with a decrease of 39% (p = 0.0001). For total antioxidant capacity (TAC), there were significant increases of 30% and 28% in groups B and C, respectively. For HOMA-IR, there were no significant differences among the study groups. Supplementation with this combination of antioxidants significantly decreases markers of OS in postmenopausal women. In addition, it increases TAC by up to 30%. Full article

Tacrolimus (TAC) is a commonly used immunosuppressive drug in solid organ transplantation. Pharmacogenetics has been demonstrated before to be decisive in TAC pharmacotherapy. The CYP3A5*3 variant has been reported to be the main determinant of TAC dose requirements; however, other polymorphisms have also proven to be influential, especially in CYP3A5 non-expressor patients. The aim of this study is to evaluate the influence of genetic polymorphisms in TAC therapy in a cohort of Spanish transplant recipients. Genetic analysis including ten polymorphic variants was performed, and demographic and clinical data and pharmacotherapy of 26 patients were analyzed. No significant differences were found in weight-adjusted dose between CYP3A5 expressors and non-expressors (0.047 mg/kg vs. 0.044 mg/kg), while they were found for carriers of the CYP3A4*1B allele (0.101 mg/kg; p < 0.05). The results showed that patients with at least one CYP3A4*1B allele had a higher TAC dose and lower blood concentration. Dose-adjusted TAC blood levels were also lower in CYP3A4*1B carriers compared to non-carriers (0.72 ng/mL/mg vs. 2.88 ng/mL/mg). These results support the independence of CYP3A5*3 and CYP3A4*1B variants as determinants of dose requirements despite the linkage disequilibrium present between the two. The variability in genotype frequency between ethnicities may be responsible for the discrepancy found between studies. Full article

Background: Induction therapy with basiliximab is recommended in kidney transplant (KT) recipients with a low immunological risk (LIR) profile. Whether basiliximab is associated with a decreased risk of acute rejection (AR) and graft loss is controversial. Methods: In our institution, LIR patients (absence of anti-HLA antibodies before KT) are inducted with basiliximab in case of living-donor KT, while deceased-donor KT recipients receive no induction. Maintenance immunosuppression is similar, including a combination of tacrolimus (Tac), mycophenolate (MPA) and steroids. In this single-center retrospective study, we included all adult LIR patients who underwent KT between 1 January 2015 and 31 December 2022. Results: Of the 471 patients included, 354 received no induction and 117 received basiliximab. The median (IQR) number of HLA A-B-DR mismatches was 3 (2–3) and 2 (2–4) in the no induction group and the basiliximab group, respectively. The cumulative incidences in the no induction group vs. the basiliximab group of acute rejection and graft loss over 5 years post-KT were similar at 8.9% vs. 7.8% (p = 0.8) and 8.5% vs. 4.2% (p = 0.063), respectively. In multivariable Cox regression analysis, delayed graft function emerged as an independent risk factor for acute rejection (hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.23–6.13, p = 0.014) and graft loss (HR 9.32, CI 4.10–21.1, p < 0.001). Conclusions: Basiliximab did not provide any advantage in terms of rate of acute rejection and graft survival within 5 years post KT compared with a strategy without induction therapy in patients with a low immunological risk profile receiving triple maintenance immunosuppression Tac/MPA/steroids. Full article

In this study, we analyze the extent to which thin hard coatings can serve as tribological protective layers for the selected plastic substrate materials PA12 (polyamide 12) und PEEK (polyetheretherketone), with and without fiber reinforcement. The approximately 1 µm thick coating variants ta-C, ta-C:N, and ta-C:B, which were applied using the laser arc process, are investigated. In oscillating sliding wear tests against a steel ball in an air atmosphere without lubricant, the wear of the coating and counter body is compared to analogous coating variants applied in parallel to AISI 52100 steel. The ta-C-based coatings show good adhesion strength and basic suitability as wear protection layers on the plastic substrates in the tribological tests. However, there are variations depending on the coating type and substrate material. The use of a Cr interlayer and its thickness also plays an important role. It is demonstrated that by coating under conditions where the uncoated plastic substrate would normally fail, a similarly good performance as with analogously coated steel substrates can be achieved by ta-C:N. Full article

This study aimed to investigate the antioxidant and anti-inflammatory activities mechanism of Artemisia dracunculus (A. dracunculus) and Artemisia abrotanum (A. abrotanum) ethanol extracts in acute rat inflammation induced in Wistar male rats with turpentine oil. The characterization of the polyphenolic compounds in the extracts was conducted using UV–Vis and Fourier-transform infrared spectroscopy and high-performance liquid chromatography coupled with mass spectrometry techniques. The antioxidant activity of the extracts was evaluated in vitro by DPPH, FRAP, H₂O₂, and NO scavenging tests and in vivo by measuring the total oxidative status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), 8-hydroxy-deoxyguanosine (8-Oxo-dG), advanced oxidation protein products (AOPP), malondialdehyde (MDA), nitric oxide (NO), 3-nitrotyrosine (3NT), and total thiols (SH). Inflammation was evaluated by measuring nuclear factor-kB-p65 (NfkB-p65) and NLRP3 inflammasome activation with IL-1β, IL-18, and gasdermin D. Liver and renal toxicity was determined following transaminases (ALT and AST), creatinine, and urea. The experimental results indicated that A. dracunculus and A. abrotanum ethanol extracts have moderate in vitro antioxidant activity and had in vivo antioxidant activity and an anti-inflammatory effect by NfkB-p65, IL-1b, IL-18, and gasdermin D serum level reduction. The antioxidant activity correlated with the chemical composition of the extracts. These results bring evidence-based use of A. dracunculus and A. abrotanum’s in traditional and contemporary medicine. Full article

Background and Objectives: In this study, we aimed to investigate the effects of bosentan, an endothelin receptor antagonist, on endothelin-1 (ET-1), hypoxia-inducible factor-1 (HIF-1), nuclear factor-kappa B (NF-κB), and tumor necrosis factor (TNF)-α as inflammation markers, pro-oxidant antioxidant balance (PAB), and total antioxidant capacity (TAC) levels as oxidative stress parameters in lung tissues of rats in an experimental model of pulmonary contusion (PC) induced by blunt thoracic trauma. Materials and Methods: Thirty-seven male Sprague-Dawley rats were divided into five groups. C: The control group (n = 6) consisted of unprocessed and untreated rats. PC3 (n = 8) underwent 3 days of PC. PC-B3 (n = 8) received 100 mg/kg bosentan and was given orally once a day for 3 days. The PC7 group (n = 7) underwent 7 days of PC, and PC-B7 (n = 8) received 100 mg/kg bosentan and was given orally once a day for 7 days. Results: ET-1, NF-κB, TNF-α, HIF-1α, and PAB levels were higher, while TAC activity was lower in all groups compared with the control (p < 0.05). There was no significant difference in ET-1 and TNF-α levels between the PC-B3 and PC-B7 groups and the control group (p < 0.05), while NF-κB, HIF-1α, and PAB levels were still higher in both the PC-B3 and PC-B7 groups than in the control group. Bosentan decreased ET-1, NF-κB, TNF-α, HIF-1α, and PAB and increased TAC levels in comparison to the nontreated groups (p < 0.05). Conclusions: Bosentan decreased the severity of oxidative stress in the lungs and reduced the inflammatory reaction in rats with PC induced by blunt thoracic trauma. This suggests that bosentan may have protective effects on lung injury mechanisms by reducing hypoxia, inflammation, and oxidative stress. If supported by similar studies, bosentan can be used in both pulmonary and emergency clinics to reduce ischemic complications, inflammation, and oxidative stress in some diseases that may be accompanied by ischemia. Full article

Therapeutic electrical stimulation, such as transcranial cortical stimulation and peripheral somatosensory stimulation, is used to improve motor function in patients with stroke. We hypothesized that these stimulations exert neuroprotective effects during the subacute phase of ischemic stroke by regulating novel common signaling pathways. Male C57BL/6J mouse models of ischemic stroke were treated with high-definition (HD)-transcranial alternating current stimulation (tACS; 20 Hz, 89.1 A/mm²), HD-transcranial direct current stimulation (tDCS; intensity, 55 A/mm²; charge density, 66,000 C/m²), or electroacupuncture (EA, 2 Hz, 1 mA) in the early stages of stroke. The therapeutic effects were assessed using behavioral motor function tests. The underlying mechanisms were determined using transcriptomic and other biomedical analyses. All therapeutic electrical tools alleviated the motor dysfunction caused by ischemic stroke insults. We focused on electrically stimulating common genes involved in apoptosis and cell death using transcriptome analysis and chose 11 of the most potent targets (Trem2, S100a9, Lgals3, Tlr4, Myd88, NF-kB, STAT1, IL-6, IL-1β, TNF-α, and Iba1). Subsequent investigations revealed that electrical stimulation modulated inflammatory cytokines, including IL-1β and TNF-α, by regulating STAT1 and NF-kB activation, especially in amoeboid microglia; moreover, electrical stimulation enhanced neuronal survival by activating neurotrophic factors, including BDNF and FGF9. Therapeutic electrical stimulation applied to the transcranial cortical- or periphery-nerve level to promote functional recovery may improve neuroprotection by modulating a common neuronal death pathway and upregulating neurotrophic factors. Therefore, combining transcranial cortical and peripheral somatosensory stimulation may exert a synergistic neuroprotective effect, further enhancing the beneficial effects on motor deficits in patients with ischemic stroke. Full article

Ultra-high temperature ceramics (UHTCs) have been widely applied in many fields. In order to enhance the comprehensive properties of TaB₂-based UHTCs, the first collaborative use of fine TaC particles and dispersed multi-walled carbon nanotubes (MWCNTs) was employed via spark plasma sintering (SPS) at 1700 °C. The derived UHTCs exhibited an average grain size of 1.3 μm, a relative density of 98.6%, an elastic modulus of 386.3 GPa, and a nano hardness of 21.7 GPa, leading to a greatly improved oxidation resistance with a lower linear ablation rate at −3.3 × 10⁻² μm/s, and a markedly reinforced ablation resistance with mass ablation rate of −1.3 × 10⁻³ mg/(s·cm²). The enhanced ablation resistance was attributable to the physical pinning effect, sealing effect and self-healing effect. Thus, this study provides a potential strategy for preparation of UHTCs with bettered ablation resistance and physical properties. Full article

Knowledge of the microbiota present in food processing environments is a significant advance that will allow for better evaluation of the risk of food contamination and a better design of the procedures for sanitization. The levels of microbial group indicators of hygienic quality were determined in different areas of the slaughter lines of two poultry slaughterhouses in the northwest of Spain (22 surfaces in each slaughterhouse were studied). The average microbial levels (cfu/cm²) were 2.15 × 10² ± 4.26 × 10² (total aerobic counts, TAC), 1.99 × 10² ± 5.00 × 10² (psychrotrophic microorganisms), 3.10 × 10⁰ ± 1.37 × 10¹ (enterobacteria), 3.96 × 10⁰ ± 2.55 × 10¹ (coliforms), 1.80 × 10⁻¹ ± 7.79 × 10⁻¹ (enterococci), and 1.12 × 10⁻¹ ± 3.35 × 10⁻¹ (vancomycin-resistant enterococci, VRE). TAC and psychrotrophic microorganisms were the most abundant groups in all samples (p < 0.05). The counts of both microbial groups were higher (p < 0.05) in samples of Slaughterhouse A than in those of Slaughterhouse B. Microbial loads for the rest of the bacteria were not influenced by the slaughterhouse sampled (p > 0.05). All 44 samples showed TAC and psychrotrophic microorganisms. Colonies of the rest of the microbial groups were only found in 26 samples (59.1% of the total). The isolates (one from each sample) were identified with MALDI-TOF and PCR. Gram-negative bacteria (all Enterobacteriaceae) were isolated in 23 samples, and Gram-positive bacteria were isolated in 16 (9 Enterococcus spp., 2 Enterococcus spp. and VRE, 3 VRE, 1 Enterococcus spp. and Listeria spp., and 1 Listeria spp.). The resistance of the strains to 11 (Enterococcus spp.) or 17 (Enterobacteriaceae) antibiotics was determined (disk diffusion, CLSI), finding an average of 2.05 ± 2.06 resistances per strain (3.46 ± 2.27 if reduced susceptibility reactions are included). A total of 37.3% of the Enterobacteriaceae isolates had a gene for resistance to beta-lactam antibiotics (bla_TEM, bla_CTX-M-15, bla_KPC, bla_CMY-2 or bla_NDM). The high prevalence of resistant bacteria and resistance genes highlights the need to establish measures to control the spread of antibiotic resistance in poultry slaughterhouses. The findings of this work could contribute to the design of more effective sanitation procedures. Full article

The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes of vitamin B12 absorption and its transport between cells. FUT2 gene polymorphisms are associated with vitamin B12 levels in the body. Vitamin B12 deficiency associated with hyperhomocysteinemia is a major risk factor for cardiovascular diseases (CVDs), which are one of the main causes of death in patients after kidney transplantation. The aim of our study was to determine the impact of the rs602662 (G>A) polymorphism of the FUT2 gene on the functionality of transplanted kidneys and the risk of CVD in patients after kidney transplantation. The study included 402 patients treated with immunosuppression (183 patients taking cyclosporine (CsA) and 219 patients taking tacrolimus (TAC)). The analysis of the FUT2 rs602662 (G>A) polymorphism was performed using real-time PCR. Patients with CsA were more likely to be underweight (1.64% vs. 0.91%) and obese (27.87% vs. 15.98%), while those taking TAC were more likely to be of normal weight (39.27%) or overweight (43.84%). No statistically significant differences were observed comparing the mean blood pressure, both systolic and diastolic. The renal profile showed a higher median urea nitrogen concentration in patients with CsA (26.45 mg/dL (20.60–35.40) vs. 22.95 mg/dL (17.60–33.30), p = 0.004). The observed frequency of rs602662 alleles of the FUT2 gene was similar in the analyzed groups. The A allele was present in 43.7% of patients with CsA and 41.1% of those taking TAC (OR = 0.898; 95% CI: 0.678–1.189; p = 0.453). In the group with CsA, the GG genotype was present in 32.2% of patients, the GA in 48.1% and the AA in 19.7%. A similar distribution was obtained in the TAC group: GG—33.8%, GA—50.2%, and AA—16.0%. An association of genotypes containing the G allele with a higher incidence of hypertension was observed. The G allele was present in 65% of people with hypertension and in 56% of patients with normal blood pressure (p = 0.036). Moreover, the evaluation of the renal parameters showed no effect of the FUT2 polymorphism on the risk of organ rejection because the levels of creatinine, eGFR, potassium, and urea nitrogen were prognostic of successful transplantation. Our results suggest that the rs6022662 FUT2 polymorphism may influence the risk of cardiovascular diseases. Full article

A congested match and training schedule could alter internal load, and this could be reflected in biomarkers of stress and immunity in elite futsal players. The aim of this study was to analyze the effects of a congested match and training schedule on internal load and levels of total protein, total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index, and the concentrations of salivary immunoglobulin A (SIgA) in 17 professional players from the same Portuguese elite futsal club (age: 23.07 ± 6.76 years old; height: 1.75 ± 0.06 m; body mass: 75.47 ± 7.47 kg; experience in playing in elite: 5.38 ± 2.03 years) who performed 5 matches and 16 training sessions in a period of 27 days. The salivary content of total protein, TOS, TAC, oxidative stress index, and SIgA were calculated before and after the training sessions and the unofficial matches under study. Saliva sampling was conducted 10 min before each match or training session and 40 min after (post-match and post-training). The MANOVA of repeated measures showed a significant difference for total protein and SIgA (p < 0.01). Total protein (sphericity = 0.007; statistical power = 0.818) and SIgA (sphericity = 0.018; statistical power = 0.693) are highly correlated with the time factor. The main findings revealed several key points: (a) There was a significant increase in total protein, SIgA, and TAC during acute load (pre- vs. post-session) in both training and match contexts. Specifically, total protein and SIgA displayed notable increments in both training and match settings, while TAC exhibited significant increases exclusively during matches. (b) No changes in TOS and oxidative stress index were observed during acute load in either training or match contexts. (c) A positive trend was noted between the chronic load during a congested week of the precompetitive season and the decrease in total protein and SIgA levels. (d) Additionally, a positive correlation between internal training loads and oxidative/antioxidant responses was found, as expressed by the oxidative stress index, without significant differences (p-value > 0.05) in acute and chronic loads during congested matches and training schedules. Full article

Bryophyllum pinnatum (BP) is a medicinal plant used to treat many conditions when taken as a leaf juice, leaves in capsules, as an ethanolic extract, and as herbal tea. These preparations have been chemically analyzed except for decoctions derived from boiled green leaves. In preparation for a clinical trial to validate BP tea as a treatment for kidney stones, we used NMR and MS analyses to characterize the saturation kinetics of the release of metabolites. During boiling of the leaves, (a) the pH decreased to 4.8 within 14 min and then stabilized; (b) regarding organic acids, citric and malic acid were released with maximum release time (t_max) = 35 min; (c) for glycoflavonoids, quercetin 3-O-α-L-arabinopyranosyl-(1 → 2)-α-L-rhamnopyranoside (Q-3O-ArRh), myricetin 3-O-α-L-arabinopyranosyl-(1 → 2)-α-L-rhamnopyranoside (M-3O-ArRh), kappinatoside, myricitrin, and quercitrin were released with t_max = 5–10 min; and (d) the total phenolic content (TPC) and the total antioxidant capacity (TAC) reached a t_max at 55 min and 61 min, respectively. In summary, 24 g of leaves boiled in 250 mL of water for 61 min ensures a maximal release of key water-soluble metabolites, including organic acids and flavonoids. These metabolites are beneficial for treating kidney stones because they target oxidative stress and inflammation and inhibit stone formation. Full article

The combination of vitamin A and D derivatives with classical chemotherapeutic treatments results in more satisfactory outcomes. The use of drug combinations, such as 9cUAB130 with carboplatin and cisplatin with TAC-101, shows enhanced cytotoxic effects and reductions in ovarian tumor volume compared to single-drug treatments. Combining cisplatin with calcitriol and progesterone increases VDR expression, potentially enhancing the effectiveness of anticancer therapy in ovarian cancer. The effectiveness of vitamin derivatives in anticancer treatment may vary depending on the characteristics of the tumor and the cell line from which it originated. An increase in thiamine intake of one unit is associated with an 18% decrease in HPV infection. Higher intake of vitamin C by 50 mg/day is linked to a lower risk of cervical neoplasia. Beta-carotene, vitamin C, and vitamin E are associated with risk reductions of 12%, 15%, and 9% in endometrial cancer, respectively. A balanced daily intake of vitamins is important, as both deficiency and excess can influence cancer development. It has been observed that there is a U-shaped relationship between group B vitamins and metabolic markers and clinical outcomes. Full article

This study investigates the strategic decision-making abilities of large language models (LLMs) via the game of Tic-Tac-Toe, renowned for its straightforward rules and definitive outcomes. We developed a mobile application coupled with web services, facilitating gameplay among leading LLMs, including Jurassic-2 Ultra by AI21, Claude 2.1 by Anthropic, Gemini-Pro by Google, GPT-3.5-Turbo and GPT-4 by OpenAI, Llama2-70B by Meta, and Mistral Large by Mistral, to assess their rule comprehension and strategic thinking. Using a consistent prompt structure in 10 sessions for each LLM pair, we systematically collected data on wins, draws, and invalid moves across 980 games, employing two distinct prompt types to vary the presentation of the game’s status. Our findings reveal significant performance variations among the LLMs. Notably, GPT-4, GPT-3.5-Turbo, and Llama2 secured the most wins with the list prompt, while GPT-4, Gemini-Pro, and Mistral Large excelled using the illustration prompt. GPT-4 emerged as the top performer, achieving victory with the minimum number of moves and the fewest errors for both prompt types. This research introduces a novel methodology for assessing LLM capabilities using a game that can illuminate their strategic thinking abilities. Beyond enhancing our comprehension of LLM performance, this study lays the groundwork for future exploration into their utility in complex decision-making scenarios, offering directions for further inquiry and the exploration of LLM limits within game-based frameworks. Full article

The aim of this in vivo study was to investigate the effects of a novel mycotoxin detoxifier whose formulation includes clay (bentonite and sepiolite), phytogenic feed additives (curcumin and silymarin) and postbiotics (yeast products) on the health, performance and redox status of weaned piglets under the dietary challenge of fumonisins (FUMs). The study was conducted in duplicate in the course of two independent trials on two different farms. One hundred and fifty (150) weaned piglets per trial farm were allocated into two separate groups: (a) T1 (control group): 75 weaned piglets received FUM-contaminated feed and (b) T2 (experimental group): 75 weaned piglets received FUM-contaminated feed with the mycotoxin-detoxifying agent from the day of weaning (28 days) until 70 days of age. Thiobarbituric acid reactive substances (TBARSs), protein carbonyls (CARBs) and the overall antioxidant capacity (TAC) were assessed in plasma as indicators of redox status at 45 and 70 days of age. Furthermore, mortality and performance parameters were recorded at 28, 45 and 70 days of age, while histopathological examination was performed at the end of the trial period (day 70). The results of the present study reveal the beneficial effects of supplementing a novel mycotoxin detoxifier in the diets of weaners, including improved redox status, potential hepatoprotective properties and enhanced growth performance. Full article