Towards efficient Ir(III) anticancer photodynamic therapy agents by extending π-conjugation on N

In this work we disclose a new family of biscyclometallated Ir(III) complexes of the general formula [Ir(C^N)2(N^N)]Cl (IrL1-IrL5), where HC^N is 1-phenyl-ß-carboline and N^N ligands (L1-L5) are different diimine ligands that differ from each other in the number of aromatic rings fused to the bipyridine scaffold. The photophysical properties of IrL1-IrL5 were thoroughly studied, and theoretical calculations were performed for a deeper comprehension of the respective variations along the series. All complexes exhibited high photostability under blue light irradiation. An increase in the number of aromatic rings led to a reduction in the HOMO-LUMO band gap causing a red-shift in the absorbance bands. Although all the complexes generated singlet oxygen (1O2) in aerated aqueous solutions through a photocatalytic process, IrL5 was by far the most efficient photosensitizer. Consequently, IrL5 was highly active in the photocatalytic oxidation of NADH. The formation of aggregates in DMSO at a high concentration (25 mM) was confirmed using different techniques, but was proved to be negligible in the concentration range of biological experiments. Moreover, ICP-MS studies proved that the cellular uptake of IrL2 and IrL3 is much better relative to that of IrL1, IrL4 and IrL5. The antiproliferative activity of IrL1-IrL5 was investigated in the dark and under blue light irradiation against different cancer cell lines. Complexes IrL1-IrL4 were found to be cytotoxic under dark conditions, while IrL5 turned out to be weakly cytotoxic. Despite the low cellular uptake of IrL5, this derivative exhibited a high increase of cytotoxicity upon blue light irradiation resulting in photocytotoxicity indexes (PI) up to 38. IrL1-IrL4 showed lower photocytotoxicity indexes ranging from 1.3 to 17.0. Haemolytic experiments corroborated the compatibility of our complexes with red blood cells. Confocal microscopy studies proved their accumulation in mitochondria, leading to mitochondrial membrane depolarization, and ruled out their localization in lysosomes. Overall, the mitochondria-targeted activity of IrL5, which inhibits considerably the viability of cancer cells upon blue light irradiation, allows us to outline this PS as a new alternative to traditional chemotherapeutic agents.

Treatment of Schatzker Type VI Tibia Fractures Using Circular External Fixation: State of the Art, Surgical Technique and Results.

BACKGROUND: Schatzker type VI tibia fractures are usually associated with infection and surgical wound-related problems. Circular external fixation (CEF) has been shown to minimize such complications. METHODS: We pose a retrospective study of patients with Schatzker type VI fractures treated with CEF. RESULTS: Twenty-two (22) patients were included (11M/11F) with a mean age of 60.1 ± 14.9 years. According to the AO/OTA classification, two fractures (9.1%) were A2, three (13.6%) were A3, and seventeen (77.3%) were C3. Three (13.6%) of them were open. The tissue damage observed in the nineteen (86.4%) closed fractures was classified according to Tscherne (four grade I, twelve grade II, and three grade III). The mean ex-fix time was 24.1 ± 5.1 weeks. None of the patients experienced deep infections, nonunion, or malunion. The mean ROM was 111.4 ± 17.8 degrees. Although stability was achieved in all cases, 50% of them suffered osteoarthritic degeneration. Four knees required TKR at a mean of 8.77 ± 5.58 years from trauma. The mean HHS knee score was 84.2 ± 10.3 points (excellent in fifteen (68.2%) cases, good in four (18.2%), and acceptable in three (13.6%)). The mean Rasmussen radiological score was 13.3 ± 3.5 (excellent in three (13.6%) cases, good in fifteen (68.2%), and acceptable in four (18.2%)). The mean SF-12 score was 35.1 ± 10.4 points on the physical scale and 53.0 ± 10.6 points on the mental scale. CONCLUSIONS: CEF has shown itself to be a valid treatment for patients with Schatzker type VI fractures, particularly for those where the fracture is comminuted, severely displaced, open, or associated with severe soft tissue damage.

Mortality and Costs of Cardiac Implantable Electronic Device (CIED) Infections According to the Therapeutic Approach: A Single-Center Cohort Study.

Background: Cardiac device infections are serious adverse events associated with considerable morbidity and mortality, significant costs, and increased healthcare utilization. The aim of this study is to calculate the costs of treatment of cardiac implantable electrostimulation device (CIED)-related infections for different types of infection (local or systemic) and therapeutic approaches. Patients and Methods: Single-center cohort (1985-2018). The costs of the CIED-related infections were analyzed according to initial treatment (antimicrobial treatment exclusively, local approach, or transvenous lead extraction (TLE)). Total costs (including those for hospitalization stay, drugs, extraction material, and newly implanted devices) were assigned to each case until its final resolution. Results: A total of 380 cases (233 local and 147 systemic infections) were analyzed. The average cost of systemic infection was EUR 34,086, mainly due to hospitalization (78.5%; mean: 24 ± 14 days), with a mortality rate of 10.8%. Local infection had a mortality rate of 2.5% (mainly related to the extraction procedure) and an average cost of EUR 21,790, which was higher in patients with resynchronization therapy devices and defibrillators (46% of total costs). Surgical procedures limited to the pocket for local infections resulted in a high rate of recurrence (87%), evolved to systemic infections in 48 patients, and had a higher cost compared to TLE (EUR 42,978 vs. EUR 24,699; p < 0.01). Conclusions: The costs of treating CIED-related infections are high and mainly related to the type of treatment and length of hospitalization. Complete device removal is always the most effective approach and is a cost-saving strategy.

Topical Meloxicam Hydroxypropyl Guar Hydrogels Based on Low-Substituted Hydroxypropyl Cellulose Solid Dispersions.

Meloxicam (MX) is a poorly water-soluble drug with severe gastrointestinal side effects. Topical hydrogel of hydroxypropyl guar (HPG) was formulated using a solid dispersion (SD) of MX with hydroxypropyl cellulose (LHPC) as an alternative to oral administration. The development of a solid dispersion with an adequate MX:LHPC ratio could increase the topical delivery of meloxicam. Solid dispersions showed high MX solubility values and were related to an increase in hydrophilicity. The drug/polymer and polymer/polymer interactions of solid dispersions within the HPG hydrogels were evaluated by SEM, DSC, FTIR, and viscosity studies. A porous structure was observed in the solid dispersion hydrogel MX:LHPC (1:2.5) and its higher viscosity was related to a high increase in hydrogen bonds among the -OH groups from LHPC and HPG with water molecules. In vitro drug release studies showed increases of 3.20 and 3.97-fold for hydrogels with MX:LHPC ratios of (1:1) and (1:2.5), respectively, at 2 h compared to hydrogel with pure MX. Finally, a fitting transition from zero to first-order model was observed for these hydrogels containing solid dispersions, while the n value of Korsmeyer-Peppas model indicated that release mechanism is governed by diffusion through an important relaxation of the polymer.

The differential expressions of aquaporins underline the diverse strategies of cucumber and tomato against salinity and zinc stress.

Salinity and excess zinc are two main problems that have limited agriculture in recent years. Aquaporins are crucial in regulating the passage of water and solutes through cells and may be essential for mitigating abiotic stresses. In the present study, the adaptive response to moderate salinity (60 mM NaCl) and excess Zn (1 mM ZnSO4 ) were compared alone and in combination in Cucumis sativus L. and Solanum lycopersicum L. Water relations, gas exchange and the differential expression of all aquaporins were analysed. The results showed that cucumber plants under salinity maintained the internal movement of water through osmotic adjustment and the overexpression of specific PIPs aquaporins, following a "conservation strategy". As tomato has a high tolerance to salinity, the physiological parameters and the expression of most aquaporins remained unchanged. ZnSO4 was shown to be stressful for both plant species. While cucumber upregulated 7 aquaporin isoforms, the expression of aquaporins increased in a generalized manner in tomato. Despite the differences, water relations and transpiration were adjusted in both plants, allowing the RWC in the shoot to be maintained. The aquaporin regulation in cucumber plants facing NaCl+ZnSO4 stress was similar in the two treatments containing NaCl, evidencing the predominance of salt in stress. However, in tomato, the induced expression of specific isoforms to deal with the combined stress differed from independent stresses. The results clarify the key role of aquaporin regulation in facing abiotic stresses and their possible use as markers of tolerance to salinity and heavy metals in plants.

Cyclosporine A in hospitalized COVID-19 pneumonia patients to prevent the development of interstitial lung disease: a pilot randomized clinical trial.

Post-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908-8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).

Physicochemical and pharmacotechnical characterization of Prussian blue for future Prussian blue oral dosage forms formulation.

Ferric hexacyanoferrate, Fe4 [Fe(CN)6]3 · xH2O, known as Prussian blue (PB), has proven its effectiveness as an antidote in cases of accidental poisoning or poisoning caused by radioactive materials such as cesium (Cs) and thallium (Tl); which due to their solubility in water, when absorbed by the human body, cause serious damage to vital organs. The local development of a drug with PB as an active ingredient arises as a response to the civil and military needs established within the Ministry's pharmacy request for national defense. This fact contemplates the circumstances related to public health protection in the nuclear, radiological, biological and chemical (NRBQ) of the emergency institutions in health and national security. In this paper and by using various analytical techniques, the characterization of the locally synthesized PB with pharmaceutical quality has been described, as a first step to predict its behavior in the preparation of a drug that contains it as an active ingredient. The research findings demonstrate that locally synthesized PB is suitable for use in oral dosage forms, enabling the local development of drug formulations incorporating PB, thus being able to potentially become a main resource in the treatment of Cs and Tl poisoning in any accidental or intended of the population. This development opens up the possibility of creating drug formulations that incorporate PB at a local level, making it a potentially significant resource in the treatment of Cs and Tl poisoning. The ability to locally produce and utilize PB in oral dosage forms could be crucial in addressing cases of accidental or intentional exposure within the population. This advancement not only contributes to the scientific understanding of PB but also holds promising implications for practical applications in public health and emergency situations.

Predictive usefulness of qSOFA, NEWS and GYM scores in the elderly patient: EDEN-5 study.

OBJECTIVE: To analyze the prognostic accuracy of the scores NEWS, qSOFA, GYM used in hospital emergency department (ED) in the assessment of elderly patients who consult for an infectious disease. METHODS: Data from the EDEN (Emergency Department and Elderly Need) cohort were used. This retrospective cohort included all patients aged ≥65 years seen in 52 Spanish EDs during two weeks (from 1-4-2019 to 7-4-2019 and 30/3/2020 to 5/4/2020) with an infectious disease diagnosis in the emergency department. Demographic variables, demographic variables, comorbidities, Charlson and Barthel index and needed scores parameters were recorded. The predictive capacity for 30-day mortality of each scale was estimated by calculating the area under the receiver operating characteristic (ROC) curve, and sensitivity and specificity were calculated for different cut-off points. The primary outcome variable was 30-day mortality. RESULTS: 6054 patients were analyzed. Median age was 80 years (IQR 73-87) and 45.3% women. 993 (16,4%) patients died. NEWS score had better AUC than qSOFA (0.765, 95CI: 0.725-0.806, versus 0.700, 95%CI: 0.653-0.746; P < .001) and GYM (0.716, 95%CI: 0.675-0.758; P = .024), and there was no difference between qSOFA and GYM (P = .345). The highest sensitivity scores for 30-day mortality were GYM ≥ 1 point (85.4%) while the qSOFA score ≥2 points showed high specificity. In the case of the NEWS scale, the cut-off point ≥4 showed high sensitivity, while the cut-off point NEWS ≥ 8 showed high specificity. CONCLUSION: NEWS score showed the highest predictive capacity for 30-day mortality. GYM score ≥1 showed a great sensitivity, while qSOFA ≥2 scores provide the highest specificity but lower sensitivity.

Synthesis, antioxidant and neuroprotective analysis of diversely functionalized α-aryl-N-alkyl nitrones as potential agents for ischemic stroke therapy.

Herein, we report the synthesis, antioxidant and biological evaluation of 32 monosubstituted α-arylnitrones derived from α-phenyl-tert-butyl nitrone (PBN) in the search for neuroprotective compounds for ischemic stroke therapy, trying to elucidate the structural patterns responsible for their neuroprotective activity. Not surprisingly, the N-tert-butyl moiety plays beneficious role in comparison to other differently N-substituted nitrone groups. It seems that electron donor substituents at the ortho position and electron withdrawing substituents at the meta position of the aryl ring induce good neuroprotective activity. As a result, (Z)-N-tert-butyl-1-(2-hydroxyphenyl)methanimine oxide (21a) and (Z)-N-tert-butyl-1-(2-(prop-2-yn-1-yloxy)phenyl)methanimine oxide (24a) showed a significant increase in neuronal viability in an experimental ischemia model in primary neuronal cultures, and induced neuroprotection and improved neurodeficit score in an in vivo model of transient cerebral ischemia. These results showed that nitrones 21a and 24a are new effective small and readily available antioxidants, and suitable candidates for further structure optimization in the search for new phenyl-derived nitrones for the treatment of ischemic stroke and related diseases.

Phototoxicity of cyclometallated Ir(III) complexes bearing a thio-bis-benzimidazole ligand, and its monodentate analogue, as potential PDT photosensitisers in cancer cell killing.

Two novel cyclometallated iridium(III) complexes have been prepared with one bidentate or two monodentate imidazole-based ligands, 1 and 2, respectively. The complexes showed intense emission with long lifetimes of the excited state. Femtosecond transient absorption experiments established the nature of the lowest excited state as 3IL state. Singlet oxygen generation with good yields (40% for 1 and 82% for 2) was established by detecting 1O2 directly, through its emission at 1270 nm. Photostability studies were also performed to assess the viability of the complexes as photosensitizers (PS) for photodynamic therapy (PDT). Complex 1 was selected as a good candidate to investigate light-activated killing of cells, whilst complex 2 was found to be toxic in the dark and unstable under light. Complex 1 demonstrated high phototoxicity indexes (PI) in the visible region, PI > 250 after irradiation at 405 nm and PI > 150 at 455 nm, in EJ bladder cancer cells.

The Golgi complex of dopaminergic enteric neurons is fragmented in a hemiparkinsonian rat model.

Since gastrointestinal disorders are early consequences of Parkinson's disease (PD), this disease is clearly not restricted to the central nervous system (CNS), but also significantly affects the enteric nervous system (ENS). Large aggregates of the protein α-synuclein forming Lewy bodies, the prototypical cytopathological marker of this disease, have been observed in enteric nervous plexuses. However, their value in early prognosis is controversial. The Golgi complex (GC) of nigral neurons appears fragmented in Parkinson's disease, a characteristic common in most neurodegenerative diseases. In addition, the distribution and levels of regulatory proteins such as Rabs and SNAREs are altered, suggesting that PD is a membrane traffic-related pathology. Whether the GC of enteric dopaminergic neurons is affected by the disease has not yet been analyzed. In the present study, dopaminergic neurons in colon nervous plexuses behave as nigral neurons in a hemiparkinsonian rat model based on the injection of the toxin 6-OHDA. Their GCs are fragmented, and some regulatory proteins' distribution and expression levels are altered. The putative mechanisms of the transmission of the neurotoxin to the ENS are discussed. Our results support the possibility that GC structure and the level of some proteins, especially syntaxin 5, could be helpful as early indicators of the disease. RESEARCH HIGHLIGHTS: The Golgi complexes of enteric dopaminergic neurons appear fragmented in a Parkinson's disease rat model. Our results support the hypothesis that the Golgi complex structure and levels of Rab1 and syntaxin 5 could be helpful as early indicators of the disease.

Development of Pharmacological Strategies with Therapeutic Potential in Ischemic Stroke.

Acute ischemic stroke constitutes a health challenge with great social impact due to its high incidence, with the social dependency that it generates being an important source of inequality. The lack of treatments serving as effective neuroprotective therapies beyond thrombolysis and thrombectomy is presented as a need. With this goal in mind, our research group's collaborative studies into cerebral ischemia and subsequent reperfusion concluded that there is a need to develop compounds with antioxidant and radical scavenger features. In this review, we summarize the path taken toward the identification of lead compounds as potential candidates for the treatment of acute ischemic stroke. Evaluations of the antioxidant capacity, neuroprotection of primary neuronal cultures and in vivo experimental models of cerebral ischemia, including neurological deficit score assessments, are conducted to characterize the biological efficacy of the various neuroprotective compounds developed. Moreover, the initial results in preclinical development, including dose-response studies, the therapeutic window, the long-term neuroprotective effect and in vivo antioxidant evaluation, are reported. The results prompt these compounds for clinical trials and are encouraging regarding new drug developments aimed at a successful therapy for ischemic stroke.

Modification of Gene Expression of Tomato Plants through Foliar Flavonoid Application in Relation to Enhanced Growth.

The exogenous application of phenolic compounds is increasingly recognized as a valuable strategy for promoting growth and mitigating the adverse effects of abiotic stress. However, the biostimulant effect under optimal conditions has not been thoroughly explored. In this study, we investigated the impact of foliar application of flavonoids, specifically CropBioLife (CBL), on tomato plants grown under controlled conditions. Our study focused on determining growth parameters, such as cell size, and assessing the concentration of hormones. Principal component analysis (PCA) from all physiological variables was determined. Additionally, we utilized high-throughput mRNA-sequencing technology and bioinformatic methodologies to robustly analyze the transcriptomes of tomato leaves regulated by flavonoids. The findings revealed that CBL primarily influenced cell enlargement by 60%, leading to increased growth. Furthermore, CBL-treated plants exhibited higher concentrations of the hormone zeatin, but lower concentrations of IAA (changes of 50%). Moreover, RNA-seq analysis indicated that CBL-treated plants required increased mineral transport and water uptake, as evidenced by gene expression patterns. Genes related to pathways such as fatty acid degradation, phenylpropanoid biosynthesis, and ABC transporters showed regulatory mechanisms governing internal flavonoid biosynthesis, transport, and tissue concentration, ultimately resulting in higher flavonoid concentrations in tomato leaves.

Clinical complications after a traumatic brain injury and its relation with brain biomarkers.

We aimed to find out which are the most frequent complications for patients who suffer a traumatic brain injury (TBI) and its relation with brain biomarker levels. We conducted a hospital cohort study with patients who attended the Hospital Emergency Department between 1 June 2018 and 31 December 2020. Different variables were collected such as biomarkers levels after 6 h and 12 h of TBI (S100, NSE, UCHL1 and GFAP), clinical and sociodemographic variables, complementary tests, and complications 48 h and 7 days after TBI. Qualitative variables were analysed with Pearson's chi-square test, and quantitative variables with the Mann-Whitney U test. A multivariate logistic regression model for the existence of complications one week after discharge was performed to assess the discriminatory capacity of the clinical variables. A total of 51 controls and 540 patients were included in this study. In the TBI group, the mean age was 83 years, and 53.9% of the patients were male. Complications at seven days were associated with the severity of TBI (p < 0.05) and the number of platelets (p = 0.016). All biomarkers except GFAP showed significant differences in their distribution of values according to gender, with significantly higher values of the three biomarkers for women with respect to men. Patients with complications presented significantly higher S100 values (p < 0.05). The patient's baseline status, the severity of the TBI and the S100 levels can be very important elements in determining whether a patient may develop complications in the few hours after TBI.

Bacterial molecular machinery in the Martian cryosphere conditions.

The exploration of Mars is one of the main objectives of space missions since the red planet is considered to be, or was in the past, potentially habitable. Although the surface of Mars is now dry and arid, abundant research suggests that water covered Mars billions of years ago. Recently, the existence of liquid water in subglacial lakes has been postulated below the South pole of Mars. Until now, experiments have been carried out on the survival of microorganisms in Martian surface conditions, but it remains unknown how their adaptation mechanisms would be in the Martian cryosphere. In this work, two bacterial species (Bacillus subtilis and Curtobacterium flacumfaciens) were subjected to a simulated Martian environment during 24 h using a planetary chamber. Afterward, the molecular machinery of both species was studied to investigate how they had been modified. Proteomes, the entire set of proteins expressed by each bacterium under Earth (named standard) conditions and Martian conditions, were compared using proteomic techniques. To establish this evaluation, both the expression levels of each protein, and the variation in their distribution within the different functional categories were considered. The results showed that these bacterial species followed a different strategy. The Bacillus subtilis resistance approach consisted of improving its stress response, membrane bioenergetics, degradation of biomolecules; and to a lesser extent, increasing its mobility and the formation of biofilms or resistance endospores. On the contrary, enduring strategy of Curtobacterium flacumfaciens comprised of strengthening the cell envelope, trying to protect cells from the extracellular environment. These results are especially important due to their implications for planetary protection, missions to Mars and sample return since contamination by microorganisms would invalidate the results of these investigations.

Frequency of Helicobacter pylori Infection in Patients Requiring GI Endoscopy in Seven Units in Three Antioquia Subregions

Aim: To determine the frequency of Helicobacter pylori and sociodemographic factors, life habits, and personal and family history of gastroduodenal diseases in patients who required and were taken to GI endoscopy (symptomatic or by screening) in seven endoscopy units in three Antioquia subregions. Materials and methods: A cross-sectional study conducted between 2016 and 2018 included 272 participants. Sociodemographic factors, life habits, and personal and family history were related to H. pylori infection. Descriptive statistics and bivariate analysis were performed to establish the association between the variables, and multivariate analysis (binomial regression) was used to adjust the prevalence ratios of the associated factors. A p-value ≤ 0.05 was considered statistically significant. Results: The frequency of H. pylori infection was 55.9%, with differences by subregion (Valle de Aburrá metropolitan area: 54.3%, Oriente: 64%, and Urabá: 79.2%). Factors associated with H. pylori infection were male sex (adjusted prevalence ratio [APR] = 1.26; 95% confidence interval [CI] = 1.04-1.52), age 18-55 years (APR = 1.62; CI 95% = 1.22-2.16), absence of drinking water (APR = 1.40; 95% CI: 1.15-1.72) and educational level below university (APR = 1.73; 95% CI% = 1.26-2.38). Conclusion: The frequency of H. pylori was higher than in other recent studies because different diagnostic tests were used for its detection, and differences were found in the frequency of infection by region, which is explained by the heterogeneity in the populations analyzed. This study suggests the need to improve the population's living conditions to reduce H. pylori and direct measures of primary prevention of the infection, especially in family groups, men, individuals between 18 and 55 years old without drinking water, and with an educational level lower than university.

Objetivo: determinar la frecuencia de Helicobacter pylori y la presencia de factores sociodemográficos, hábitos de vida y antecedentes personales y familiares de enfermedades gastroduodenales en pacientes que requirieron y fueron llevados a endoscopia digestiva (sintomáticos o por tamización) en siete unidades de endoscopia de tres subregiones de Antioquia. Materiales y métodos: estudio transversal realizado entre 2016 y 2018 que incluyó a 272 participantes. Los factores sociodemográficos, hábitos de vida, antecedentes personales y familiares se relacionaron con la infección por H. pylori. Se realizó estadística descriptiva y análisis bivariado para establecer la asociación entre las variables y el análisis multivariado (regresión binomial) para ajustar las razones de prevalencia de los factores asociados. Un valor p ≤ 0,05 se consideró estadísticamente significativo. Resultados: la frecuencia de infección por H. pylori fue de 55,9%, con diferencias por subregión (área metropolitana del Valle de Aburrá: 54,3%, oriente: 64% y Urabá: 79,2%). Los factores asociados a la infección por H. pylori fueron sexo masculino (razón de prevalencia ajustada [RPA] = 1,26; intervalo de confianza [IC] del 95% = 1,04-1,52), edad de 18-55 años (RPA = 1,62; IC 95% = 1,22-2,16), ausencia de agua potable (RPA = 1,40; IC 95%: 1,15-1,72) y nivel educativo inferior al universitario (RPA = 1,73; IC 95% = 1,26-2,38). Conclusión: la frecuencia de H. pylori fue mayor que en otros estudios recientes porque se emplearon diferentes pruebas diagnósticas para su detección y se demostraron diferencias en la frecuencia de la infección por región, lo cual se explica por la heterogeneidad en las poblaciones analizadas. Este estudio sugiere la necesidad de mejorar las condiciones de vida de la población para reducir la infección por H. pylori y dirigir medidas de prevención primaria de la infección especialmente en los grupos familiares, en hombres, individuos entre 18 y 55 años, sin agua potable y con un nivel educativo inferior al universitario.

Evaluation of the Bioaccessible Fraction of T-2 Toxin from Cereals and Its Effect on the Viability of Caco-2 Cells Exposed to Tyrosol.

The bioaccessibility of mycotoxins is an important factor that has to be considered when assessing the risk they pose to human health. Bioactive compounds like phenolics could play a protective role against the toxic effects of contaminants. In this work, the bioaccessible fraction of the T-2 toxin (T-2) contained in breakfast cereals and its effect on the viability of Caco-2 cells were investigated. Furthermore, the effect of tyrosol (a polyphenol abundant in EVOO) on T-2-induced cytotoxicity was evaluated in the same cell line. After standardized in vitro gastrointestinal digestion, the T-2 toxin was released from T-2-spiked breakfast cereals and further quantified by UHPLC-MS/MS. The bioaccessible fraction of T-2 was 51 ± 4%. The cell viability study was performed by pre-treating the cells for 24 h with tyrosol (25, 50 and 100 µM) and subsequently adding T-2 at 15 nM or by treating the cells with a combination of tyrosol and T-2. In the simultaneous treatment, 25 µM tyrosol prevented the toxic effects produced by the exposure to T-2 at 15 nM; however, cytotoxic effects were observed for the other combinations tested. The pre-treatment of Caco-2 cells with tyrosol did not attenuate the cytotoxic effects caused by exposure to T-2. These results suggest that tyrosol at low concentrations (25 µM) could exert a cytoprotective effect on Caco-2 cells against 15 nM T-2 when administered simultaneously with T-2. However, more studies are required to corroborate this hypothesis.

Dihydropyrimidinase-Related Protein 2 Is a New Partner in the Binding between 4E-BP2 and eIF4E Related to Neuronal Death after Cerebral Ischemia.

Transient cerebral ischemia induces neuronal degeneration, followed in time by secondary delayed neuronal death that is strongly correlated with a permanent inhibition of protein synthesis in vulnerable brain regions, while protein translational rates are recovered in resistant areas. In the translation-regulation initiation step, the eukaryotic initiation factor (eIF) 4E is a key player regulated by its association with eIF4E-binding proteins (4E-BPs), mostly 4E-BP2 in brain tissue. In a previous work, we identified dihydropyrimidinase-related protein 2 (DRP2) as a 4E-BP2-interacting protein. Here, using a proteomic approach in a model of transient cerebral ischemia, a detailed study of DRP2 was performed in order to address the challenge of translation restoration in vulnerable regions. In this report, several DRP2 isoforms that have a specific interaction with both 4E-BP2 and eIF4E were identified, showing significant and opposite differences in this association, and being differentially detected in resistant and vulnerable regions in response to ischemia reperfusion. Our results provide the first evidence of DRP2 isoforms as potential regulators of the 4E-BP2-eIF4E association that would have consequences in the delayed neuronal death under ischemic-reperfusion stress. The new knowledge reported here identifies DRP2 as a new target to promote neuronal survival after cerebral ischemia.