Search Results (86)

Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage prostate cancer (PC), but the emergence of treatment resistance remains a major clinical challenge. Although the GST family has been implicated in drug resistance, the specific role of GSTM5 remains poorly understood. This study investigates whether GSTM5, alone or in combination with clinical variables, can improve patient stratification based on the risk of early treatment resistance. Methods: In silico analyses were performed to examine GSTM5’s role in protein interactions, molecular pathways, and gene expression. The rs3768490 polymorphism was genotyped in 354 patients with PC, classified by ADT response. Descriptive analysis and logistic regression models were applied to evaluate associations between genotype, clinical variables, and ADT response. GSTM5 expression related to the rs3768490 genotype and ADT response was also analyzed in 129 prostate tissue samples. Results: The T/T genotype of rs3768490 was significantly associated with a lower likelihood of early ADT resistance in both individual (p = 0.0359, Odd Ratios (OR) = 0.18) and recessive models (p = 0.0491, OR = 0.21). High-risk classification according to D’Amico was strongly associated with early progression (p < 0.0004; OR > 5.4). Combining genotype and clinical risk improved predictive performance, highlighting their complementary value in stratifying patients by treatment response. Additionally, GSTM5 expression was slightly higher in T/T carriers, suggesting a potential protective role against ADT resistance. Conclusions: The T/T genotype of rs3768490 may protect against ADT resistance by modulating GSTM5 expression in PC. These preliminary findings highlight the potential of integrating genetic biomarkers into clinical models for personalized treatment strategies, although further studies are needed to validate these observations. Full article

Background: Type 2 diabetes (T2D patients) have a 74% increased risk of heart failure (HF), but traditional HF biomarkers lack sensitivity in early disease detection. Increased epicardial adipose tissue volume (EATv) is associated with cardiovascular risk in T2D, and novel biomarkers such as growth differentiation factor 15 (GDF15), Galectin-3, and soluble suppression of tumorigenicity 2 (sST2) are inflammation biomarkers linked to HF. Methods: We investigated associations between EATv, inflammation biomarkers, and the effect of metabolic control in 14 healthy controls (HCs) and 36 newly diagnosed T2D patients both before (poor glycemic control, PGC) and after 12 months of glycemic optimization (good glycemic control, GGC). EATv indexed to body surface area (iEATv) was quantified by multidetector computed tomography, and biomarker levels were measured by immunoassays. Results: PGC patients had higher iEATv (59.53 ± 21.67 vs. 36.84 ± 16.57 cm³/m², p = 0.0017) and elevated GDF15, Galectin-3, and sST2 levels (all p < 0.05) than HC subjects. The glycemic optimization reduced iEATv (p = 0.0232) and sST2 (p = 0.048), while GDF15 and Galectin-3 remained unchanged. Multivariable analysis confirmed independent associations between iEATv, GDF15 (β = 0.27, p = 0.027) and sST2 (β = 0.29, p = 0.02). Conclusions: These results support the link between systemic inflammation, EAT expansion, and cardiac dysfunction, and they point to the role of epicardial fat in early HF risk of T2D patients. Full article

Spent coffee grounds (SCG) are produced in large quantities during coffee brewing, contributing to environmental concerns. Additionally, cationic dyes from textile, paper, and leather wastewater pose a major pollution issue. This study explores SCG as an adsorbent for methylene blue (MB) dye. A novel comparison of SCG cleaning methods with warm water, accelerated solvent extraction (ASE), supercritical fluid extraction (SFE), and ultrasound-induced cavitation (US) is presented. In addition, the chemical modifications of SCG using acetylation, acid (HNO₃), and base (KOH) treatment that have not been reported before are presented. ATR-FTIR confirmed the inclusion of functional groups, for example, the nitro group in SCG treated with HNO₃, and an increase in carboxylic groups in the samples treated with KOH and HNO₃. SEM analysis revealed a consistent porous texture across samples, with SCG-SFE, SCG-US, and SCG-HNO₃ showing smaller pores, and SCG-ASE displaying elongated cavities. Adsorption isotherm tests followed the Freundlich and Langmuir models, indicating favorable adsorption. The Langmuir maximum adsorption capacity (q_max) varied among cleaning methods from 65.69 mg/g (warm water) to 93.32 mg/g (SFE). In contrast, in base- and acid-treated SCG, a three- to four-fold increase in adsorption capacity was observed, with q_max values of 171.60 mg/g and 270.64 mg/g, respectively. These findings demonstrate that SCG washed with warm water and chemically treated achieves adsorption capacities comparable to other biosorbents reported in the literature. Therefore, SCG represents a promising, low-cost, and sustainable material for removing cationic dyes from wastewater, contributing to waste valorization and environmental protection. Full article

Objectives: To analyze the effects of the combination of Extra Virgin Olive Oil (EVOO) supplementation and a health-related lifestyle intervention on disease activity and cardiovascular disease risk factors in Systemic Lupus Erythematosus (SLE). Methods: A total of 38 women with SLE were randomly assigned to EVOO (n = 9) and EVOO combined with multicomponent health promotion and physical exercise program (EVOO + HRLI) (n = 15) or control (CG) (n = 14) groups for 24 weeks. Baseline and post-intervention assessments were performed, collecting data on disease activity, accrual damage, blood biochemical parameters, arterial stiffness parameters, Framingham risk score, anthropometric and body composition measurements, and cardiovascular risk factors. Results: No changes in disease activity were observed in any group after the intervention. For cardiovascular risk, significant differences were observed in the intervention groups for systolic and mean blood pressure, with greater reductions in the EVOO + HRLI (p = 0.036 vs. p < 0.001; p = 0.017 vs. p < 0.001, respectively). The EVOO group showed significant reductions in BFM and BFP (p = 0.042, p = 0.022, respectively). The EVOO+ HRLI group also showed significant reductions in triglycerides (p < 0.001), Aix brachial (p = 0.037), central systolic blood pressure (p < 0.001), central pulse pressure (p = 0.05), body mass index (p = 0.006), body fat mass and skeletal muscle mass (p = 0.039) after the intervention. Conclusions: Our findings suggest that a multidisciplinary program integrating nutritional interventions, health education, and the promotion of regular physical activity in SLE patients has the potential to significantly improve cardiovascular risk factors and body composition parameters. Thus, integrating this approach into clinical practice alongside usual pharmacological treatments would be beneficial for SLE patients. Clinical Trial Registration: NCT05261529. Full article

Background: Increased epicardial adipose tissue (EAT) volume is a common feature in type 2 diabetes (T2DM) which is directly associated with heart failure and advanced atherosclerosis. We aimed to evaluate lipoprotein-related biomarkers of EAT volume in T2DM patients before and after glycemic control. Methods: This study included 36 T2DM patients before and after optimization of glycemic control and on 14 healthy controls (HCs). EAT volume was measured using computed tomography imaging indexed to the body surface area (iEAT). Biochemical and lipid profiles were determined using commercial methods. Lipoproteins were isolated by ultracentrifugation, and variables of lipoprotein function were assessed. Multivariable regression analysis was used to find variables independently associated with iEAT. Results: iEAT was higher in T2DM than in controls and decreased with glycemic optimization. HDLs from T2DM had less apoA-I and cholesterol and more apoC-III and triglycerides. LDLs from T2DM had more triglycerides and apoB and smaller sizes than those from HCs. Significant correlations were found between iEAT and age, BMI, HbA1c, GGT, VLDLc, triglycerides, LDL size, apoA-I in HDL, and apoC-III in HDL. In the multivariable regression analysis, age, LDL size, and GGT associations remained statistically significant, and predicted 50% of the variability in EAT volume. ROC analysis using these variables showed an AUC of 0.835. Conclusions: Qualitative characteristics of lipoproteins were altered in T2DM. Multivariable analysis showed that LDL size and GGT plasma levels were independently associated with iEAT volume, suggesting that these variables might be useful biomarkers for stratifying T2DM patients with increased EAT volume. Full article

Background: Our research team analyzed the microRNA (miRNA)-197-3p involved in cardioprotection, and we demonstrated that the overexpression of miRNA-197-3p could be linked to a higher risk of cardiac damage. Recent research indicated that miRNA-197-3p inhibits the effector proteins of the anaesthetic preconditioning mechanism of halogenated drugs. In this scenario, we proposed to determine the role of miRNA-197-3p in cardiac injury and its effects on myocardial conditioning under halogenated exposure. Hypothesis: Patients having myocardial revascularization surgery have increased heart damage due to postoperative miRNA-197-3p upregulation. Methods: Human cardiac myocytes (HCMs) were used in an in vitro hypoxia/reperfusion (H/R) model. The miRNA-197-3p-MIMIC was transfected into the HCMs. Three H/R-induced HCM groups were performed: negative MIMIC-control transfected, MIMIC transfected, and non-transfected. Each H/R cell group was exposed to Propofol (P), Sevoflurane (S), or non-exposed. Healthy cell cultures were the control group. ELISA assays were used to assess the Akt1 and p53 cell secretion capacity, and the Next Generation Sequencing assay was used to measure the differential expression of miRNA targets. Results: The secretion capacity of H/R-induced HCMs transfected with the MIMIC was higher under sevoflurane exposure regarding Akt-1 cytokine (I/R + S: 0.80 ± 0.06 ng/mL; I/R + P: 0.45 ± 0.28 ng/mL; p > 0.05), and lower regarding p53 cytokine (I/R + S: 38.62 ± 6.93 ng/mL; I/R + P: 43.34 ± 15.20 ng/mL; p > 0.05) compared to propofol. In addition, a significant gene overexpression of five miRNAs, in the sevoflurane group, was linked to cardioprotection: miRNA-29-3p, 24-3p, 21-3p, 532, and miRNA-335-5p. Conclusions: miRNA-197-3p inhibits the cardioprotection induced by halogenated exposure and can be considered a biomarker of cardiac damage. Additional research is required to validate our findings in other clinical settings. Full article

Background: Recent research highlights the potential role of sex-specific variations in cardiovascular disease. The gut microbiome has been shown to differ between the sexes in patients with cardiovascular risk factors. Objectives: The main objective of this study is to analyze the differences between women and men in the relationship between gut microbiota and measures of arterial stiffness. Methods: We conducted a cross-sectional study in Spain, selecting 180 subjects (122 women, 58 men) aged between 45 and 74. Subjects with arterial stiffness were identified by the presence of at least one of the following: carotid–femoral pulse wave velocity (cf-PWV) above 12 mm/s, cardio–ankle vascular index (CAVI) above nine, or brachial–ankle pulse wave velocity (ba-PWV) above 17.5 m/s. All other cases were considered subjects without arterial stiffness. The composition of the gut microbiome in fecal samples was determined by 16S rRNA sequencing. Results: We found that women have a more diverse microbiome than men (Shannon, p < 0.05). There is also a significant difference in gut microbiota composition between sexes (Bray–Curtis, p < 0.01). Dorea, Roseburia, and Agathobacter, all of them short-chain fatty-acid producers, were more abundant in women’s microbiota (log values > 1, p-value and FDR < 0.05). Additionally, Blautia was more abundant in women when only the subjects with arterial stiffness were considered. According to logistic regression, Roseburia was negatively associated with arterial stiffness in men, while Bifidobacterium and Subdoligranulum were positively related to arterial stiffness. Conclusions: In the Spanish population under study, women had higher microbiome diversity and potentially protective genera. The host’s gender determines the influence of the same bacteria on arterial stiffness. Trial Registration Number: NCT03900338. Full article

Saquinavir is a drug used as an HIV treatment, with recent reports of new uses. It has poor aqueous solubility and very low oral bioavailability. However, when prepared in a eutectic mixture with the natural bioenhancer, piperine, it demonstrated improvements in these drawbacks. Therefore, considering that EMs can be easily produced and scaled-up, it could potentially be used in new pharmaceutical formulations. For this purpose, an analytical method capable of quantifying SQV in the presence of PIP is required for quality control purposes. In this context, UV–Vis equipment is simpler to use and cheaper than HPLC, and it is commonly available in most laboratories. Therefore, a derivative spectrophotometry method at 245 nm was developed and validated to quantify SQV. The method showed good linearity from 0.5 to 100.0 mg/L, with a limit of detection and limit of quantification of 0.331 mg/L and 0.468 mg/L, respectively. Furthermore, it was precise, accurate, and demonstrated good specificity up to a 1:4.3 SQV:PIP ratio. Consequently, the results demonstrate that the method can be employed for SQV quantification in the presence of PIP as an economical and simple technique. This contribution could be the basis for a quality control technique for these types of products. Full article

Urban parks and cemeteries constitute hot spots of bird diversity in urban areas. However, the seasonal dynamics of their bird communities have been scarcely explored at large scales. This study aims to analyze the drivers of urban bird assemblage seasonality in urban parks and cemeteries comparing assemblages during breeding and non-breeding seasons in the Neotropical Region. Since cemeteries have less human disturbance than urban parks, we expected differences in bird community seasonality between habitats. The seasonal change of species composition was partitioned into species turnover and nestedness. At large scales, the seasonal change of species composition was positively related to temperature seasonality and was higher in the Northern Hemisphere. At the landscape scale, the seasonal change of composition decreased in sites located in the most urbanized areas. At the local scale, sites with the highest habitat diversity and pedestrian traffic had the lowest seasonal change of composition. The species turnover was higher in the Northern Hemisphere, augmented with increasing annual temperature range, and decreased in urban parks. The species nestedness was positively related to habitat diversity. Our results showed that a multi-scale framework is essential to understand the seasonal changes of bird communities. Moreover, the two components of seasonal composition dissimilarity showed contrasting responses to environmental variables. Although the surrounding urbanization lowered the seasonal dynamics of urban green areas, cemeteries seem to conserve more seasonal changes than urban parks. Thus, urban cemeteries help to conserve the temporal dynamics of bird communities in cities. Full article

Background: The effects of anesthetic drugs on myocardial cells have been a subject of research for the last 50 years. The clinical benefits of halogenated agents, particularly sevoflurane, have been demonstrated in cardiac surgery patients. These benefits are due to the action of different enzymes and a variety of molecular pathways mediated by the action of small noncoding RNAs (sRNA) such as microRNAs (miRNAs). However, the modulation potential induced by anesthetic drugs on the miRNA expression and their cardioprotective effects is unknown. Objective: To analyze the variation in the expression of a panel of miRNAs induced by halogenated agents to identify their cardioprotective effects. Aims: Variations in the expression of specific miRNAs induce the potential cardioprotective effects of halogenated agents. Methods: An ischemia/reperfusion (I/R) in vitro model of primary human cardiac myocytes (HCMs) was performed. Four study groups were performed: control group (standard culture conditions), I/R group (without hypnotic drugs exposition), I/R-propofol group (I/R-P), and I/R-sevoflurane group (I/R-S). The secretion of p53 and Akt1 cytokines was quantified in the different cell study groups using an Enzyme-Linked ImmunoSorbent Assay, and the differentially expressed miRNAs were identified carrying out a complete genomic sequencing using the Next Generation Sequencing (NGS). Results: HCMs subjected to the I/R procedure and exposed to sevoflurane showed lower secretion levels of p53 factor and higher levels of Akt-1 cytokine compared to HCMs exposed to propofol (p53: I/R-S: 10.43 ± 0.91 ng/mL; I/R-P: 137.92 ± 7.53 ng/mL; p > 0.05); (Akt1: I/R-S: 0.62 ± 0.12 ng/mL; I/R-P: 0.23 ± 0.05 ng/mL; p > 0.05). The miRNA gene expression analysis (NGS) showed significantly increased expression of the hsa-miR-140-5p and hsa-miR-455-5p, both miRNAs associated with cardiac function; the hsa-miR-98-5p and hsa-miR-193a-5p, both related to apoptosis inhibition; and the hsa-let-7d-5p associated with myocardial protection. This increase was observed in the HCMs group exposed to sevoflurane in comparison to the propofol group. Conclusions: Sevoflurane-induced miRNAs overexpression confers cardioprotection through various mechanisms at the DNA level and the different signaling pathways levels, such as Akt/ERK. Full article

Objectives/Background: Vitamin D-binding protein (VDBP) and free vitamin D are new markers that are being studied as a possible markers of vitamin D status. The main aim of our study was to analyze the VDBP genotype and quantify the levels of free vitamin D in a sample of cystic fibrosis (CF) patients. Methods: We conducted a multicenter, cross-sectional, and prospective study including patients with CF and exocrine pancreatic insufficiency who were clinically stable. We investigated vitamin D levels (total and free) and the different VDBP haplotypes. Free vitamin D levels were measured using an electro-chemiluminescence assay. Results: A sample of 48 patients was obtained (52% male; median age 13.8 years). The most common allele of VDBP was Gc1s (72%) > Gc2 (52%) > Gc1f (27%). The median calcidiol was 21.2 ng/mL (IR 15.3–26.9), and 81% had levels in the insufficiency range: 23 patients (48%) below 20 ng/mL, and 16 (33%) between 20 and 30 ng/mL. The median free vitamin D level was 4.2 pg/mL (IR 3.9–5.6). A positive correlation was observed between calcidiol and free vitamin D levels (r = 0.871; p < 0.0001). After adjustment for season, vitamin D supplementation, sex, and CF-related diabetes, patients with Gc1f polymorphism had a lower risk of vitamin D deficiency, OR 0.22 (95% CI 0.05–0.99), and p = 0.027. A negative linear trend was observed between the polymorphisms grouped into three categories (Gc1/Gc1, Gc1/Gc2, and Gc2/Gc2, in that order) and vitamin D and free vitamin D levels (p = 0.025 and p = 0.033, respectively). Conclusion: In CF, as in the general population, the most common VDBP haplotype in the Caucasian race is Gc1s. VDBP polymorphisms influence serum vitamin D and free vitamin D levels in CF patients. There is a good correlation between free vitamin D and calcidiol levels, suggesting that measuring the latter in CF does not seem to provide any additional benefit. Full article

Background: In susceptible hosts, SARS-CoV2-induced hyperinflammation accounts for an increased mortality. The search of adjuvant immunomodulatory therapies has been ongoing ever since the pandemic outbreak. Aim: Our purpose was to evaluate the efficacy of cyclosporin A (CsA) as an add-on therapy to the standard of care (SoC) in patients with severe COVID-19 pneumonia. Methods: We conducted a randomized clinical trial in patients admitted to eight Spanish tertiary hospitals. Patients were stratified into two severity categories and randomized in a 1:1 ratio to receive a corticosteroid-based standard therapy with or without CsA. The primary endpoint was FiO2 recovery by Day 12 without relapses. Results: 109 patients were included and randomized, and 98 of them considered for the mITT population (51 assigned to the CsA + SoC group and 47 to the SoC group). A total of 35 (68.6%) patients from the CsA + SoC group and 32 (71.1%) patients from the SoC group reached the primary endpoint in the mITT analysis. No differences were found after stratification into age groups, in the severity level at admission, or in a combination of both. Overall, the time to FiO2 normalization was 7.4 days vs. 7.9 days in the experimental and control groups, respectively. Global mortality was 8.2%. Severe adverse events were uncommon and equally distributed between arms. Conclusion: The addition of CsA did not show differences over a corticosteroid-based treatment in the clinical course of the included patients. A better identification of candidates who will benefit from receiving immunomodulatory drugs is necessary in future studies. Full article

The aim of the present study was to evaluate skin temperature (Tsk) asymmetries, using infrared thermography, in professional padel players before (PRE), after (POST) and 10 min after training (POST10), and their relationship with perceptual variables and training characteristics. Thermal images were taken of 10 players before, after and 10 min after a standardized technical training. After training, Tsk of the dominant side was higher than before training in the anterior forearm (30.8 ± 0.4 °C vs. 29.1 ± 1.2 °C, p < 0.01; ES = 1.9), anterior shoulder (31.6 ± 0.6 °C vs. 30.9 ± 0.6 °C, p < 0.05; ES = 1.0) posterior arm (29.5 ± 1.0 °C vs. 28.3 ± 1.2 °C, p < 0.05; ES = 1.0), and posterior forearm (30.8 ± 0.9 °C vs. 29.3 ± 1.6 °C, p < 0.05; ES = 1.1). Likewise, these differences were significant POST10 in the anterior arm, anterior forearm, anterior shoulder, posterior arm and posterior forearm. Comparing the different moments of measurement (PRE, POST and POST10), the temperature was higher POST10 in all the regions analyzed except for the shoulder, abdominals, and lower back. Also, correlations were found between fatigue variation and temperature variation between limbs (Tsk dominance), and no correlation was found except between age and posterior thigh (|r| = 0.69; p < 0.05), and between the racket mass and anterior knee (|r| = 0.81; p < 0.01). In conclusion, infrared thermography allows monitoring of skin asymmetries between limbs in professional padel players, but these asymmetries were not related to overall fatigue variation, overall pain variation, years of experience and training hours. Full article

Medical treatment of coronavirus 19 disease (COVID-19) is a therapeutic challenge. The available data strongly suggest that calcifediol treatment may reduce the severity of COVID-19, and corticosteroids are the treatment of choice worldwide for severe COVID-19. Both have a very similar action profile, and their combined use in patients may modify the contribution of each administered compound. Objective: To evaluate how treatment with calcifediol and/or corticosteroids in medical practice modified the need for ICU admission, death, or poor prognosis of patients hospitalized with COVID-19 during the first outbreaks. Design, patients and setting: A retrospective observational cohort study of patients admitted for COVID-19 to the Pneumology Unit of the Hospital Universitario Reina Sofía (Córdoba, Spain). Interventions: Patients were treated with calcifediol or/and corticosteroids with the best available therapy and standard care, according to clinical practice guidelines. Measurements: Admission to the intensive care unit (ICU) or death during hospitalization and poor prognosis. Results: Seven hundred and twenty-eight patients were included. According to the treatment received, they were included in four groups: calcifediol (n = 68), glucocorticoids (n = 112), both (n = 510), or neither (n = 38). Of the 578 patients treated with calcifediol, 88 were admitted to the ICU (15%), while of the 150 not treated with calcifediol, 39 required ICU admission (26%) (p < 0.01). Among the patients taking calcifediol without glucocorticoids, only 4 of 68 (5.8%) required ICU admission, compared to 84 of 510 (16.5%) treated with both (p = 0.022). Of the 595 patients who had a good prognosis, 568 (82.01%) had received treatment with calcifediol versus the 133 patients with a poor prognosis, of whom 90 (67.66%) had received calcifediol (p < 0.001). This difference was not found for corticosteroids. Interpretation: The treatment of choice for hospitalized patients with moderate or mild COVID-19 could be calcifediol, not administering corticosteroids, until the natural history of the disease reaches a stage of hyperinflammation. Full article

Chronic wounds, especially those that are hard-to-heal, constitute a serious public-health problem. Although progress has been made in the development of wound dressings for healing, there is little high-quality evidence of their efficacy, with no evidence of superiority in the use of one hydrogel over another. To evaluate the superiority of a hydrogel (EHO-85), containing Olea europaea leaf extract (OELE), over a standard hydrogel (SH), the promotion and/or improvement of healing of difficult-to-heal wounds was compared in a prospective, parallel-group multicenter, randomized, observer-blinded, controlled trial (“MACAON”). Non-hospitalized patients with pressure, venous or diabetic foot-ulcers difficult-to-heal were recruited and treated with standard care, and EHO-85 (n = 35) or VariHesive (n = 34) as SH. Wound-area reduction (WAR; percentage) and healing rate (HR; mm²/day) were measured. EHO-85 showed a statistically significant superior effect over VariHesive. At the end of the follow-up period, the relative WAR decreased by 51.6% vs. 18.9% (p < 0.001), with a HR mean of 10.5 ± 5.7 vs. 1.0 ± 7.5 mm²/day (p = 0.036). EHO-85 superiority is probably based on its optimal ability to balance the ulcer bed, by modulating pH and oxidative stress. That complements the wetting and barrier functions, characteristics of conventional hydrogels. These results support the use of EHO-85 dressing, for treatment of hard-to-heal ulcers. Trial Registration AEMPS:PS/CR623/17/CE. Full article