Gated Mesoporous Silica Nanocarriers for a "Two-Step" Targeted System to Colonic Tissue.

Colon targeted drug delivery is highly relevant not only to treat colonic local diseases but also for systemic therapies. Mesoporous silica nanoparticles (MSNs) have been demonstrated as useful systems for controlled drug release given their biocompatibility and the possibility of designing gated systems able to release cargo only upon the presence of certain stimuli. We report herein the preparation of three gated MSNs able to deliver their cargo triggered by different stimuli (redox ambient (S1), enzymatic hydrolysis (S2), and a surfactant or being in contact with cell membrane (S3)) and their performance in solution and in vitro with Caco-2 cells. Safranin O dye was used as a model drug to track cargo fate. Studies of cargo permeability in Caco-2 monolayers demonstrated that intracellular safranin O levels were significantly higher in Caco-2 monolayers when using MSNs compared to those of free dye. Internalization assays indicated that S2 nanoparticles were taken up by cells via endocytosis. S2 nanoparticles were selected for in vivo tests in rats. For in vivo assays, capsules were filled with S2 nanoparticles and coated with Eudragit FS 30 D to target colon. The enteric coated capsule containing the MSNs was able to deliver S2 nanoparticles in colon tissue (first step), and then nanoparticles were able to deliver safranin O inside the colonic cells after the enzymatic stimuli (second step). This resulted in high levels of safranin O in colonic tissue combined with low dye levels in plasma and body tissues. The results suggested that this combination of enzyme-responsive gated MSNs and enteric coated capsules may improve the absorption of drugs in colon to treat local diseases with a reduction of systemic effects.

Gender, Sexuality, and Relationships in Young Hispanic People.

This study explores the relation between gender differences and sexuality among young Hispanic people. Eight hundred and forty young people from Spain and Mexico filled out a self-administered questionnaire about sexuality (sexual experience, sexual orientation, and sexual relationships) and gender (self-identification). Men in both Spain and Mexico more commonly report the practice of masturbation and vaginal sex, and are more likely to be unfaithful than women. Women in both countries report more steady partners and longer length of relationships. There were greater gender differences for Mexican men and women than for Spanish men and women in terms of sexual frequency, sexual orientation, and infidelity. Therefore, gender may play an important role in young people's sexuality, more so in Mexico than in Spain.

Self-Immolative Linkers as Caps for the Design of Gated Silica Mesoporous Supports.

A new hybrid material based on sulforhodamine B dye-loaded silica mesoporous nanoparticles capped with a self-immolative gate has been synthesized and characterized. The gated material's controlled release behavior is monitored under different pH conditions. Under acidic and neutral conditions, a low level of dye release is detected. However, at slightly basic pH, significant dye release occurs owing to deprotonation of the phenol moiety in the capping molecule, which results in its disassembly.

Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells.

We describe herein a Toll-like receptor 3 (TLR3) targeting delivery system based on mesoporous silica nanoparticles capped with the synthetic double stranded RNA polyinosinic-polycytidylic acid (poly(I:C)) for controlled cargo delivery in SK-BR-3 breast carcinoma cells. Our results show that poly(I:C)-conjugated nanoparticles efficiently targeted breast cancer cells due to dsRNA-TLR3 interaction. Such interaction also triggered apoptotic pathways in SK-BR-3, significantly decreasing cells viability. Poly(I:C) cytotoxic effect in breast carcinoma cells was enhanced by loading nanoparticles' mesopores with the anthracyclinic antibiotic doxorubicin, a commonly used chemotherapeutic agent.

Gated mesoporous silica nanoparticles for the controlled delivery of drugs in cancer cells.

In recent years, mesoporous silica nanoparticles (MSNs) have been used as effective supports for the development of controlled-release nanodevices that are able to act as multifunctional delivery platforms for the encapsulation of therapeutic agents, enhancing their bioavailability and overcoming common issues such as poor water solubility and poor stability of some drugs. In particular, redox-responsive delivery systems have attracted the attention of scientists because of the intracellular reductive environment related to a high concentration of glutathione (GSH). In this context, we describe herein the development of a GSH-responsive delivery system based on poly(ethylene glycol)- (PEG-) capped MSNs that are able to deliver safranin O and doxorubicin in a controlled manner. The results showed that the PEG-capped systems designed in this work can be maintained closed at low GSH concentrations, yet the cargo can be delivered when the concentration of GSH is increased. Moreover, the efficacy of the PEG-capped system in delivering the cytotoxic agent doxorubicin in cells was also demonstrated.

Highly selective and sensitive detection of glutathione using mesoporous silica nanoparticles capped with disulfide-containing oligo(ethylene glycol) chains.

Mesoporous silica nanoparticles loaded with safranin O and capped with disulfide-containing oligo(ethylene glycol) chains were used for the selective and sensitive fluorimetric detection of glutathione.

Towards chemical communication between gated nanoparticles.

The design of comparatively simple and modularly configurable artificial systems able to communicate through the exchange of chemical messengers is, to the best of our knowledge, an unexplored field. As a proof-of-concept, we present here a family of nanoparticles that have been designed to communicate with one another in a hierarchical manner. The concept involves the use of capped mesoporous silica supports in which the messenger delivered by a first type of gated nanoparticle is used to open a second type of nanoparticle, which delivers another messenger that opens a third group of gated nanoobjects. We believe that the conceptual idea that nanodevices can be designed to communicate with one another may result in novel applications and will boost further advances towards cooperative systems with complex behavior as a result of the communication between simple abiotic individual components.

Antifeedant, antifungal and nematicidal compounds from the endophyte Stemphylium solani isolated from wormwood.

The continuous search for natural product-based biopesticides from fungi isolated from untapped sources is an effective tool. In this study, we studied a pre-selected fungal endophyte, isolate Aa22, from the medicinal plant Artemisia absinthium, along with the antifungal, insect antifeedant and nematicidal compounds present in the extract. The endophyte Aa22 was identified as Stemphylium solani by molecular analysis. The antifungal activity was tested by broth microdilution against Fusarium solani, F. oxysporum, F. moniliforme and Botrytis cinerea, the insect antifeedant by choice bioassays against Spodoptera littoralis, Myzus persicae and Rhopalosiphum padi and the in vitro mortality against the root-knot nematode Meloiydogyne javanica. The structures of bioactive compounds were determined on the basis of 1D and 2D NMR spectroscopy and mass spectrometry. The ethyl acetate extract obtained from the solid rice fermentation showed mycelial growth inhibition of fungal pathogens (EC50 0.08-0.31 mg/mL), was antifeedant to M. persicae (99%) and nematicidal (68% mortality). A bioguided fractionation led to the isolation of the new compound stempholone A (1), and the known stempholone B (2) and stemphol (3). These compounds exhibited antifeedant (EC50 0.50 mg/mL), antifungal (EC50 0.02-0.43 mg/L) and nematicidal (MLD 0.5 mg/mL) activities. The extract activities can be explained by 3 (antifungal), 1-3 (antifeedant) and 1 (nematicidal). Phytotoxicity tests on Lolium perenne and Lactuca sativa showed that the extract and 1 increased L. sativa root growth (121-130%) and 1 reduced L. perenne growth (48-49%). These results highlight the potential of the endophytic fungi Aa22 as biotechnological source of natural product-based biopesticides.

Bio-guided isolation of aromatic abietane diterpenoids from Salvia canariensis as biopesticides in the control of phytopathogenic fungi.

BACKGROUND: Biofungicides arise as a promising alternative to the indiscriminate use of harmful synthetic fungicides in crop management. RESULTS: The present study reports the bio-guided fractionation of an endemic plant from the Canary Islands, Salvia canariensis against the phytopathogens, Alternaria alternata, Botrytis cinerea, and Fusarium oxysporum. This procedure allowed identifying a series of diterpenoids with an abietane skeleton (1-5), which exhibited remarkable activity against the phytopathogenic fungi assayed. Their structures were established by means of spectroscopic and spectrometric methods, as well as comparison with reported data. Compounds 2 (carnosic acid), 4 (11-acetoxy carnosic acid) and 5 (11,12-diacetoxy carnosic acid) showed significant mycelium growth inhibition (%GI > 50 at 0.1 mg/mL concentration) on all the assayed fungi, and with a potency also higher than the positive control, Fosbel-Plus, a fungicide commonly used in agriculture. A preliminary structure-activity relationship is also discussed. CONCLUSIONS: These findings underline the aromatic abietane diterpenoids as promising eco-friendly alternatives to conventional fungicides to use in integrated pest management. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Selective and sensitive chromofluorogenic detection of the sulfite anion in water using hydrophobic hybrid organic-inorganic silica nanoparticles.

In water and wine: Chromofluorogenic detection of the sulfite anion in pure water was accomplished by using a new hybrid organic-inorganic material that contained a probe entrapped in hydrophobic biomimetic cavities. This material was used for the detection of sulfite in red wine.

Initial Impact of Perinatal Loss on Mothers and Their Partners.

(1) Background: Perinatal Loss affects one in ten women worldwide. It is known to have a deep impact on the physical and psychological wellbeing of the mother. Moreover, there is a lack of information in regard to gender differences. The role of culture, environment, personal characteristics, and gender is yet to be determined in most reports; (2) Objective and Methods: Our aim is to study the initial impact of perinatal losses in an unselected sample of couples, focusing on gender differences. We conducted a longitudinal prospective study with 29 mothers and 17 fathers. Upon discharge from the hospital, they filled out the Edinburgh Postnatal Depression Scale (EPDS), among others. After one-month post-loss, they performed the EPDS and the Short Version of the Perinatal Grief Scale. We used descriptive statistics for the sample and non-parametric tests for the comparison of gender; (3) Results: We found no gender differences in initial depressive symptoms, nor in depressive symptoms, perinatal grief symptoms, or grief level (total scores or complicated grief) one month after the loss; (4) Conclusions: we need to better understand the psychological evolution of couples in cases of perinatal loss without falling into preconceived ideas about the influence of gender.

Antifungal Potential of Canarian Plant Extracts against High-Risk Phytopathogens.

Phytopathogens are responsible for great losses in agriculture. In particular, Fusarium, Alternaria and Botrytis are fungal diseases that affect crops worldwide. In the search for eco-friendly solutions to pest control, plants and their chemo-biodiversity are promising sources of biopesticides for integrated pest management. The aim of the present study is to report the evaluation of sixteen plant species from the Canary Islands Archipelago against the phytopathogenic fungi Botrytis cinerea, Fusarium oxysporum, and Alternaria alternata. The plants were selected on the basis of their traditional uses in medicine and/or pest control, as well as on scientific studies reporting their uses in crop protection. Their growth inhibition (% I), in an in vitro test-assay on mycelium, was used to identify six ethanolic plant extracts displaying activity (% I > 30% at 1 mg/mL) against at least one of the assayed fungi. The most effective plant extracts were further fractionated by liquid−liquid partition, using solvents of increasing polarity. This procedure led to an improvement of the bioactivity against the phytopathogens, even affecting the hexane fraction from S. canariensis and achieving an 83.93% of growth inhibition at 0.5 mg/mL on B. cinerea. These findings identified five plant-derived extracts as potential candidates for the future development of new biofungicides, which could be applied in integrated pest management.

Nanoparticle-cell-nanoparticle communication by stigmergy to enhance poly(I:C) induced apoptosis in cancer cells.

Nanoparticle-cell-nanoparticle communication by stigmergy was demonstrated using two capped nanodevices. The first community of nanoparticles (i.e.S(RA)IFN) is loaded with 9-cis-retinoic acid and capped with interferon-γ, whereas the second community of nanoparticles (i.e.S(sulf)PIC) is loaded with sulforhodamine B and capped with poly(I:C). The uptake of S(RA)IFN by SK-BR-3 breast cancer cells enhanced the expression of TLR3 receptor facilitating the subsequent uptake of S(sulf)PIC and cell killing.

Megalanthine, a bioactive sesquiterpenoid from Heliotropium megalanthum, its degradation products and their bioactivities.

The new bioactive sesquiterpenoid (3R,6E)-2,6,10-trimethyl-3-(3-p-hydroxyphenylpropanoyloxy)-dodeca-6,11-diene-2,10-diol, named megalanthine, was isolated from the resinous exudates of Heliotropium megalanthum. The degradation products of this compound were identified. Several plant-defensive properties (insecticidal, antifungal, and phytotoxic) were evaluated after obtaining positive results in a preliminary etiolated wheat coleoptile bioassay. This bioassay showed the need to have both the phenolic and sesquiterpene moieties of the natural product present to achieve a biological effect. This result was confirmed in phytotoxicity bioassays. Megalanthine was ruled out as a significant plant-plant defense agent because of its lack of stability. The positive results recorded in the antifungal and antifeedant tests suggest, however, that this chemical is relevant in several ecological interactions involving H. megalanthum.

Risk factors and prognosis of catheter-related bloodstream infection in critically ill patients: a multicenter study.

OBJECTIVE: To assess the risk factors associated with CR-BSI development in critically ill patients with non-tunneled, non-cuffed central venous catheters (CVC) and the prognosis of the episodes of CR-BSI. Design and setting; prospective, observational, multicenter study in nine Spanish Hospitals. PATIENTS: All subjects admitted to the participating ICUs from October 2004 to June 2005 with a CVC. INTERVENTIONS: None. MEASUREMENT AND RESULTS: Overall, 1,366 patients were enrolled and 2,101 catheters were analyzed. Sixty-six episodes of CR-BSI were diagnosed. The incidence of CR-BSI was significantly higher in CVC compared with peripherically inserted central venous catheters (PICVC) without significant differences among the three locations of CVC. In the multivariate analysis, duration of catheterization and change over a guidewire were the independent variables associated with the development of CR-BSI whereas the use of a PICVC was a protective factor. Excluding PICVC, 1,598 conventional CVC were analyzed. In this subset, duration of catheterization, tracheostomy and change over a guidewire were independent risk factors for CR-BSI. A multivariate analysis of predictors for mortality among 66 patients with CRSI showed that early removal of the catheter was a protective factor and APACHE II score at the admission was a strong determinant of in-hospital mortality. CONCLUSIONS: Peripherically inserted central venous catheters is associated with a lower incidence of CR-BSI in critically ill patients. Exchange over a guidewire of CVC and duration of catheterization are strong contributors to CR-BSI. Our results reinforce the importance of early catheter removal in critically ill patients with CR-BSI.

A versatile drug delivery system targeting senescent cells.

Senescent cells accumulate in multiple aging-associated diseases, and eliminating these cells has recently emerged as a promising therapeutic approach. Here, we take advantage of the high lysosomal ß-galactosidase activity of senescent cells to design a drug delivery system based on the encapsulation of drugs with galacto-oligosaccharides. We show that gal-encapsulated fluorophores are preferentially released within senescent cells in mice. In a model of chemotherapy-induced senescence, gal-encapsulated cytotoxic drugs target senescent tumor cells and improve tumor xenograft regression in combination with palbociclib. Moreover, in a model of pulmonary fibrosis in mice, gal-encapsulated cytotoxics target senescent cells, reducing collagen deposition and restoring pulmonary function. Finally, gal-encapsulation reduces the toxic side effects of the cytotoxic drugs. Drug delivery into senescent cells opens new diagnostic and therapeutic applications for senescence-associated disorders.

Experiencias psicológicas de la pandemia covid en mujeres con depresión y/o ansiedad postparto: una serie de casos / Psychological experiences of covid pandemia in postpartum women with depression and anxiety: a case serie

Introducción: Las situaciones ambientales de estrés grave suponen un factor de riesgo conocido para el desarrollo de trastornos mentales durante el embarazo, especialmente emocionales. En este sentido la pandemia mundial del COVID-19 y el estado de emergencia y confinamiento subsiguiente, han podido tener un gran impacto psicológico en las mujeres embarazadas. Nuestro objetivo es realizar un análisis descriptivo de las percepciones de una serie de casos de mujeres embarazadas durante la pandemia COVID-19 que posteriormente han sido diagnosticadas con depresión/ansiedad postparto.Métodos: Descripción de 10 casos de mujeres adultas, embarazadas durante la pandemia y confinamiento, con depresión y/o ansiedad post-parto atendidas consecutivamente en el Programa de Salud Mental Perinatal de la Corporación Sanitaria Parc Taulí y en el Programa de Atención a la Salud Sexual y Reproductiva (ASSIR) del CAP San Fèlix. Todas las mujeres estaban en tratamiento psicológico (individual y grupal). Para medir el estrés específico, administramos el Pandemic-Related Pregnancy Stress Scale (PREPS) que evalúa la extensión y tipo de estrés relacionado con la pandemia en mujeres embarazadas, incluyendo 3 factores: Estrés relacionado con la preparación, Estrés relacionado con el miedo al contagio, y finalmente una dimensión relacionada con la resiliencia, denominada Valoración positiva. De forma opcional se incluyó una pregunta abierta sobre preocupaciones adicionales no incluidas en la Escala. Se realizó un análisis descriptivo y de contenido.Resultados: La mediana de las puntuaciones en las escalas de estrés de preparación y por miedo al contagio fue de 3,07 y 3,80 respectivamente, el 40% y el 50% puntuaron ≥4. La mediana de las puntuaciones en la escala de valoración positiva fue de 2,66, solo un caso puntuó ≥4. En el análisis de contenido de las frases libres, destacan la sensación de abandono, los sentimientos de soledad, desesperanza, miedo e incertidumbre. (AU)

Sesquiterpenes, flavonoids, shikimic acid derivatives and pyrrolizidine alkaloids from Senecio kingii Hook.

Twenty-four compounds including eleven eremophilanolides (1-11), one eremophilane (13), five shikimic acid derivatives (14-18), six flavonoids (19-24), and the macrocyclic unsaturated pyrrolizidine alkaloid integerrimine (25) were isolated from Senecio kingii, an endemic species from the Magallanes Region (Chile). Compounds 3, 5, 6, 8-11 and 13-18 have not been previously reported as natural products. Their molecular structures were determined by NMR spectroscopic analysis and comparison with published NMR data. An X-ray-analysis of compound 3 has been performed. Their insecticidal and antifungal activities were tested, being compound 3 the strongest insect antifeedant. Compounds 6, 9 and 18 were moderate antifungals.

Sexual behaviors in male sex workers in Spain: modulating factors.

This study analyzed how the culture of origin, educational level, sexual orientation, and experience of male sex workers may mediate their commercial sexual behaviors. A total of 100 Spanish agency male sex workers were interviewed. Most of them were young men, Latin American, homosexual, and had middle-level education. Our results showed that cultural differences and sexual orientation could influence male sex workers when engaging in sexual behaviors with their clients. Social and health projects with male sex workers may have to take into account sexual myths and taboos related to sexual orientation and cultural differences.

Subclinical hypothyroidism and cardiovascular risk.

BACKGROUND: Subclinical hypothyroidism (SCH) has been suggested to be associated with increased cardiovascular risk by different mechanisms. Several cardiovascular risk factors have been analysed, but yielded controversial results. OBJECTIVES: We aimed to analyse whether there are differences in several cardiovascular risk markers, such as lipids, inflammatory parameters: plasma viscosity (PV), fibrinogen and C reactive protein (CRP); homocysteine (Hcy) and red blood cell distribution width (RDW), when comparing SCH and controls. We also analysed which of these parameters predict SCH risk and constitute independent markers. METHODS: We determined PV in a Fresenius capillary plasma viscosimeter, Hcy by a chemiluminiscent enzyme immunoassay, and biochemical and haematological parameters by conventional laboratory methods in 58 SCH outpatients and 58 controls matched for age and gender. RESULTS: SCH patients did not show statistical differences for glucose, lipids or leucocytes (p > 0.05). However, patients showed a higher prevalence for use of hypolipidaemic drugs, body mass index (BMI), thyroid stimulating hormone (TSH), PV, CRP, fibrinogen, Hcy and RDW (p < 0.05). RDW correlated with inflammation parameters: PV (r = 0.331, p < 0.05), fibrinogen (r = 0.424, p < 0.05), CRP (r = 0.433, p < 0.01) and leucocytes (r = 0.613, p < 0.01). None of the cardiovascular markers correlated with the TSH levels (p > 0.05) In the unadjusted logistic regression analyses, BMI ≥28 kg/m2, RDW ≥14%, Hcy ≥12 µm/L, fibrinogen ≥400 mg/dL and MCV ≤88 fL increased SCH risk, but only RDW ≥14% and fibrinogen ≥400 mg/dL independently increased this risk in the adjusted logistic regression analyses (OR = 4.68, 95% CI 1.20-18.30 P = 0.026; OR = 3.48, 95% CI 1.08-11.23 P = 0.037). CONCLUSION: SCH patients show a higher cardiovascular risk, characterised by increased PV, fibrinogen, Hcy and RDW. However, only fibrinogen ≥400 mg/dL and RDW ≥14% are independent predictors of SCH.