Search Results (442)

Concomitant sensitisation to non-specific lipid transfer proteins (nsLTPs) from olive pollen (Ole e 7) and peach (Pru p 3) has been observed in the south of Spain. In the search for reasons to explain this observation, we studied a potential causal relationship between Human Leukocyte Antigen (HLA) molecules and nsLTP sensitisation. For this purpose, eighteen Ole e 7-monosensitised (MONOLE) patients, 22 Pru p 3-monosensitised (MONPRU) patients, and 22 bisensitised (BI) patients were genotyped for HLA class II alleles. Complementarily, T-cell epitopes were predicted with the Immune Epitope Database analysis tool to test HLA epitope presentation. Our results showed a significant increase in DRB1*11 and DQB1*03 frequencies in MONPRU patients and DRB1*04 frequency in MONOLE patients. Additionally, T-cell epitope analysis revealed high binding affinity between the predicted Pru p 3 epitopes and DRB1*11 and between the predicted Ole e 7 epitopes and DRB1*04, suggesting that presentation of these epitopes may be favoured and predisposing individuals to sensitisation. Conversely, low DQB1*05 frequency and poor binding ability of predicted epitopes from both nsLTPs postulated this allele as a possible protective factor to sensitisation. Variations in the binding affinity between nsLTP epitopes and HLA molecules may underlie individual susceptibility to nsLTP allergy. Full article

Planning conservation for multiple species while accounting for habitat availability and connectivity under uncertain land-use changes presents a major challenge. This study proposes a protocol to identify strategic conservation areas by assessing the functional connectivity of key bird species under future land-use scenarios in the Chaco Serrano of Córdoba, Argentina. We modeled three land-use scenarios for 2050: business as usual, sustainability, and intensification. Using the Equivalent Connected Area index, we evaluated functional connectivity for Chlorostilbon lucidus, Polioptila dumicola, Dryocopus schulzii, Milvago chimango, and Saltator aurantiirostris for 1989, 2019, and 2050, incorporating information about habitat specialization and dispersal capacity to reflect differences in ecological responses. All species showed declining connectivity from 1989 to 2019, with further losses expected under future scenarios. Connectivity declines varied by species and were not always proportional to habitat loss, highlighting the complex relationship between land-use change and functional connectivity. Surprisingly, the sustainability scenario led to the greatest losses in connectivity, emphasizing that habitat preservation alone does not ensure connectivity. Using the Integral Connectivity Index, we identified habitat patches critical for maintaining connectivity, particularly those vulnerable under the business as usual scenario. With a spatial prioritization analysis we identified priority conservation areas to support future landscape connectivity. These findings underscore the importance of multispecies, connectivity-based planning and offer a transferable framework applicable to other regions. Full article

Background/Objective: This study aimed to evaluate the effectiveness of very early oral transition in Enterobacterales bloodstream infections (E-BSIs), identify factors associated with it, compare the effectiveness of different oral options, and assess its economic and ecological benefits. Methods: Retrospective, observational cohort study including monomicrobial E-BSI in clinically stable adult patients by day 3 of bacteremia with oral antibiotic options. Transition to oral antibiotics by day 3 or earlier (early oral (EO) group) was compared to later transition or remaining on intravenous therapy (nEO group). Early oral transition-associated factors were analyzed. Oral high-dose beta-lactams (BLs) were compared to quinolones (QLs) or trimethoprim/sulfamethoxazole (TS). Economic and ecological costs were assessed. Results: Of 345 E-BSI, 163 (47.2%) were in the EO group, characterized by more urinary tract infections (UTIs) and shorter hospital stays. The nEO group had higher Charlson Comorbidity Index (CCI), extended-spectrum beta-lactamase (ESBL) production, greater source control need, and longer time to clinical stability. There were no significant differences in mortality and relapse. UTIs were associated with early oral transition (OR 2.02, IC 95% 1.18–3.48), while higher CCI (0.85, 0.77–0.95), source control need (0.39, 0.19–0.85), longer time to clinical stability (0.51, 0.39–0.66), and ESBL isolates (0.39, 0.19–0.80) hindered this practice. High-dose BLs and QL/TS were equally effective. Early oral transition resulted in 38.794 KgCO₂eq reduction and EUR 269,557.99 savings. Conclusions: Very early oral transition at day 3 or before in stable E-BSI patients is effective, eco-sustainable, and cost-effective; UTI is related with the early oral switch, while comorbidities, ESBL production, source control need, or longer time to clinical stability hinder this practice. Full article

Progression of aortic stenosis (AS) is aggravated by type 2 Diabetes Mellitus (T2DM) and kidney dysfunction (KD). Oxidative stress is one of the main mechanisms that triggers AS and is also disturbed among subjects with T2DM and KD. Consequently, we studied the redox homeostasis in four groups of patients, also classifying each patient based on their kidney function: control subjects, T2DM, AS, and AS+T2DM. Free reduced thiols in plasma were analyzed using a colorimetric assay, and the redox state of human serum albumin (HSA) was assessed by immunodetection and PEG-PCMal labeling. Lower levels of thiols were evident in patients with AS and AS+T2DM, while reduced and mildly oxidized HSA was more abundant in T2DM and AS+T2DM patients, reflecting less protection against oxidation. Moreover, the thiol levels decreased as KD increased in patients with AS and AS+T2DM. Differences also exist in reduced and mildly oxidized HSA between patients with normal and severely impaired kidney function, whereas AS patients with severe KD had more strongly oxidized HSA. Our results confirm an imbalance in oxidative stress associated with AS that is aggravated by the coexistence of T2DM and KD. Moreover, T2DM treatment might mitigate this dysfunction, opening the door to new therapeutic approaches for these patients. Full article

The MAM domain-containing glycosylphosphatidylinositol anchor 1 (MDGA1) gene, which encodes a protein involved in synaptic inhibition, has been identified as a potential risk gene for restless legs syndrome. A recent study in the Chinese population described increased MDGA1 methylation levels in patients with idiopathic RLS (iRLS) compared to healthy controls. In this study, we investigated the possible association between the most common variants in the MDGA1 gene and the risk for iRLS in a Caucasian Spanish population. We assessed the frequencies of MDGA1 rs10947690, MDGA1 rs61151079, and MDGA1 rs79792089 genotypes and allelic variants in 263 patients with idiopathic RLS and 280 healthy controls using a specific TaqMan-based qPCR assay. We also analyzed the possible influence of the genotype frequencies on several variables, including age at the onset of RLS, gender, a family history of RLS, and response to drugs commonly used in the treatment of RLS. The frequencies of the genotypes and allelic variants of the three common missense SNVs studied did not differ significantly between RLS patients and controls, neither in the whole series nor when analyzing each gender separately; were not correlated with age at onset and the severity of RLS assessed by the International Restless Legs Syndrome Study Group Rating Scale (IRLSSGRS); and were not related to a family history of RLS or the pharmacological response to dopamine agonists, clonazepam, or gabaergic drugs. Our findings suggest that common missense SNVs in the MDGA1 gene are not associated with the risk of developing idiopathic RLS in Caucasian Spanish people. Full article

Bursera bipinnata (DC.) Engl. (B. bipinnata), commonly known as “copal chino,” is a widely distributed Mexican tree found in transitional zones between pine-oak and deciduous forests. It is valued for its high-quality copal resin, traditionally used in ceremonies and offerings. Additionally, B. bipinnata is recognized for its significant value in traditional medicine, particularly in treating ailments associated with inflammation. In this work, the inhibition of nitric oxide (NO) production of the volatile fraction and resin of B. bipinnata in LPS-stimulated RAW 264.7 macrophage cells were demonstrated. In contrast, the volatile fraction exhibited 37.43 ± 7.13% inhibition at a concentration of 40 µg/mL. Chromatographic analyses of the total resin enabled the chemical characterization of eleven pentacyclic triterpenes belonging to the ursane, oleanane, and lupane series, as well as eight monoterpenes. Notably, the structures of compounds 15, 17, and 29–35 are reported for the first time from the resin of Bursera bipinnata. The anti-inflammatory activity observed for B. bipinnata resin in this study may be attributed to its high content of the triterpenes α-amyrin (15, 29.7%) and 3-epilupeol (17, 38.1%), both known for their anti-inflammatory properties. These findings support the traditional use of this copal resin. Full article

Background: Vaccines represent one of the most affordable and efficient tools for controlling infectious diseases; however, the development of efficacious vaccines against complex pathogens remains a major challenge. Adjuvants play a relevant role in enhancing vaccine-induced immune responses. One such molecule is interferon-stimulated gene 15 (ISG15), a key modulator of antiviral immunity that acts both through ISGylation-dependent mechanisms and as a cytokine-like molecule. Methods: In this study, we assessed the immunostimulatory potential of ISG15 as an adjuvant in Modified Vaccinia virus Ankara (MVA)-based vaccine candidates targeting Zika virus (ZIKV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Early innate responses and immune cell infiltration were analyzed in immunized mice by flow cytometry and cytokine profiling. To elucidate the underlying mechanism of action of ISG15, in vitro co-infection studies were performed in macrophages. Finally, we evaluated the magnitude and functional quality of the elicited antigen-specific cellular immune responses in vivo. Results: Analysis of early innate responses revealed both platform- and variant-specific effects. ISG15AA preferentially promoted natural killer (NK) cell recruitment at the injection site, whereas ISG15GG enhanced myeloid cell infiltration in draining lymph nodes (DLNs), particularly when delivered via MVA. Moreover, in vitro co-infection of macrophages with MVA-based vaccine vectors and the ISG15AA mutant led to a marked increase in proinflammatory cytokine production, highlighting a dominant role for the extracellular, ISGylation-independent functions of ISG15 in shaping vaccine-induced immunity. Notably, co-infection of ISG15 with MVA-ZIKV and MVA-SARS-CoV-2 vaccine candidates enhanced the magnitude of antigen-specific immune responses in both vaccine models. Conclusions: ISG15, particularly in its ISGylation-deficient form, acts as a promising immunomodulatory adjuvant for viral vaccines, enhancing both innate and adaptive immune responses. Consistent with previous findings in the context of Human Immunodeficiency virus type 1 (HIV-1) vaccines, this study further supports the potential of ISG15 as an effective adjuvant for vaccines targeting viral infections such as ZIKV and SARS-CoV-2. Full article

ABCG2 is a crucial ATP-binding cassette (ABC) transporter involved in multidrug resistance and essential physiological and pharmacological processes. In recent years, multiple ABCG2 structures have been resolved using cryo-electron microscopy (cryo-EM), providing significant insights into its conformational states during its transport cycle. However, even more than 25 years after its description, a high-resolution X-ray crystallographic structure is still unavailable, limiting the understanding of its dynamic transitions, as well as leaving aspects of the transport cycle unresolved and open to discussion. Given the complexity of ABCG2, a multidisciplinary approach is essential in order to fully elucidate its mechanism. This review compiles recent advances in ABCG2 structural biology, highlights unresolved controversies, and explores future directions to bridge the gap between structure and function. Moving forward, integrating multiple structural and functional approaches will be key to uncovering the intricate workings of this enigmatic transporter. In particular, detailed structural insights will be crucial to identifying new ABCG2 substrates and designing selective inhibitors, with important implications for therapeutic development. Full article

This study investigates the use of hop cone residues as a sustainable alternative to peat in seed coating formulations for the delivery of biocontrol agents such as Trichoderma. Some native isolates, T. velutinum T029 and T. harzianum T019 and T059, were tested for their development on peat and hop residues using qPCR. The results showed significantly higher fungal growth in hop cones, indicating their value as a carbon-rich substrate. Seed germination tests on various species showed that hop-based coatings did not inhibit germination and in some cases improved it. Field trials confirmed that bean seeds coated with hops 24 h before sowing outperformed those coated with peat, particularly in integrated production systems, in terms of germination. The results of this study suggest a new area of research: using hop residues in sustainable seed treatments could promote the valorization of agricultural residues, while improving crop establishment and reducing the dependence on synthetic inputs. Full article

Cryptosporidium spp. oocysts are highly resistant to conventional disinfection methods and have been associated with foodborne outbreaks linked to unpasteurized fruit and vegetable juices. This study aimed to evaluate the effectiveness of Pulsed Electric Fields (PEF) in permeabilizing Cryptosporidium oocysts in water, apple juice, and carrot juice. Oocysts were exposed to monopolar square-wave pulses (3 µs) at electric field strengths ranging from 15 to 35 kV/cm, with treatment times up to 180 µs, and application temperatures between 25 °C and 60 °C. Membrane permeabilization was assessed using propidium iodide uptake via fluorescence microscopy and flow cytometry. Results showed that oocyst permeabilization increased with electric field strength, treatment time, and temperature, with up to 90% permeabilization achieved at 35 kV/cm and 45 °C. Carrot juice treatments yielded higher permeabilization levels than apple juice, attributed to greater electrical conductivity and energy input. Temperatures below 60 °C alone had negligible effects, but synergistically enhanced PEF efficacy. These findings demonstrate that PEF, particularly when combined with mild heat, is a promising non-thermal technology for reducing Cryptosporidium viability in beverages, offering an effective alternative for improving the microbiological safety of minimally processed juices while preserving sensory and nutritional quality. Full article

Introduction: This article aims to provide an updated overview of the scientific knowledge regarding the interplay between the Mediterranean diet (MedD), sustainability, and cardiovascular and metabolic health. Methodology: A systematic review was conducted following the PRISMA guidelines, succeeded by a narrative synthesis of data extracted from original research articles in English and Spanish. These articles, indexed in the Scopus and PubMed databases from inception to 31 December 2024, addressed the relationship between MedD, sustainability, and cardiovascular and metabolic health. The methodological quality of the included studies was assessed for bias using the JBI critical appraisal tools. This review was registered in PROSPERO (ID CRD42024476408). Results: The search identified 11 relevant articles. A primary focus on obesity was evident (nine articles), followed by chronic inflammation and metabolic syndrome (two articles each), and cardiovascular health (one article). Regarding sustainability, climate change was the most frequently addressed concern (eight articles). Discussion: A clear trend emerged, indicating a direct association between environmental sustainability, positive health outcomes, and adherence to the MedD. These findings underscore the benefits of the MedD, demonstrating its potential not only to reduce the environmental impact but also to improve health markers such as BMI, metabolic syndrome risk, and chronic inflammation levels. Full article

Breast cancer is a disease with a high incidence and mortality rate worldwide. There is a growing interest in the search for alternative treatments with a good cytotoxic effect but fewer adverse effects, because paclitaxel and cis-platinum treatments present severe adverse effects. The aim of this study was evaluating the antitumor activity of ethyl acetate extract of Ballota hirsuta Benth (EAB) in breast cancer cell lines. The ${\mathrm{I}\mathrm{C}}_{50}$ of EAB is 49.3 μg/mL and 3.7 μg/mL in 2D and 375 μg/mL and 135 μg/mL in 3D in the MCF-7 and MDA-MB-231 cell lines, respectively. It arrested the cell cycle in the G1 phase and decreased CDK4 activity by 86%, increasing the p53 protein levels. During the in silico analysis, the compounds interacted with the IGF-R1, CDK1, CDK2, TNFR1, MLKL, MMP2, MMP9, E-cadherin and N-cadherin proteins, which are involved in necroptosis, invasion and the cell cycle. It decreased the ATP levels in 3D by 87% at 600 μg/mL in MCF-7 and 99% at 250 μg/mL in MDA-MB-231; induced apoptosis by increasing the activity of caspases-3/7, -8 and -9; inhibited invasion and enhanced the effect of cisplatin and paclitaxel in combination with EAB. The results show the antitumor potential of EAB as a possible adjuvant in breast cancer therapy. Full article

Imidacloprid, a systemic neonicotinoid insecticide, exerts its neurotoxic effects by binding to nicotinic acetylcholine receptors in the central nervous system. In this study, we examined the effects of commercial imidacloprid formulations on the growth of Chlorella vulgaris and other algal species, comparing these responses with those induced by plant hormones. Our results demonstrate that formulated imidacloprid stimulates C. vulgaris growth at concentrations as low as 7.82 μM, with a more pronounced effect than certain phytohormones. We observed similar growth-enhancing effects in other algal species exposed to imidacloprid. Notably, pure imidacloprid induced equivalent growth responses in C. vulgaris, confirming that the observed stimulation results from the active ingredient itself rather than formulation adjuvants. Given its insecticidal mode of action, potential worst-case aquatic contamination scenarios with imidacloprid may lead to significant increases in algal biomass through both direct (growth stimulation) and indirect (reduction of zooplankton grazing pressure) mechanisms. Full article

Cannabis remains the most widely used illicit drug worldwide, identifying it is a routine procedure in forensic toxicology. Due to its widespread use, there is a need for analytical methods that can detect it in biological samples. Hair is of particular interest in forensic toxicology as it is the only biological sample that enables retrospective analysis of consumption. In addition, collecting hair is non-invasive, and the specimens can be stored at room temperature. However, the sample preparation process for hair is tedious and multi-step. To address this issue, this study introduces a novel approach to preparing hair samples for analysis, based on air-assisted liquid–liquid microextraction (AALLME). This technique is a modification of dispersive liquid–liquid microextraction (DLLME), which eliminates the need for dispersants and chlorinated organic solvents as extractants. Both techniques offer sustainable alternatives to conventional liquid–liquid extraction (LLE) and solid-phase extraction (SPE), making them of interest in forensic toxicology. This study is the first to report the application of AALLME to the hair matrix. A mixture of cyclohexane and ethyl acetate (9:1) was used as the extractant solvent. Gas chromatography–mass spectrometry (GC–MS) was then used to determine and quantify THC. The method was validated according to FDA guidelines and demonstrated good linearity within the 0.01–4 ng/mg range. The limits of detection (LOD) and quantification (LOQ) were 0.008 and 0.01 ng/mg, respectively. Finally, the applicability of the method was evaluated by analyzing hair samples received by the Forensic Toxicology Service. Full article

Prenylated chalcones have garnered attention as potential anticancer agents due to their ability to modulate multiple cancer-related pathways. In this study, we synthesized and evaluated nine novel prenylated chalcone derivatives for their antiproliferative effects against castration-resistant prostate cancer (CRPC) cell lines, DU145 and PC3. Among these, compounds 6d and 7j demonstrated potent cytotoxic activity, with IC₅₀ values comparable to cisplatin, and exhibited selective toxicity towards cancer cells over non-tumorigenic RWPE-1 cells. Mechanistic investigations revealed that these compounds induce apoptosis via mitochondrial membrane depolarization and increased late apoptotic events. Flow cytometry confirmed activation of both early and late apoptotic pathways. These findings highlight the potential of chalcone derivatives 6d and 7j as promising therapeutic candidates for CRPC treatment and support further development of chalcone-based molecules in precision oncology. Full article