The EUropean PErioperative MEdical networking (EUPEMEN) project: recommendations for perioperative care in colorectal surgery. a quality improvement study.

BACKGROUND: Despite consensus supporting enhanced recovery programs, their full implementation in such a context is difficult due to conventional practices within various groups of professionals. The goal of the EUropean PErioperative MEdical Networking (EUPEMEN) project was to bring together the expertise and experience of national clinical professionals who have previously helped deliver major change programs in their countries and to use them to spread enhanced recovery after surgery protocols (ERAS) in Europe. The specific aim of this study is to present and discuss the key points of the proposed recommendations for colorectal surgery. MATERIALS AND METHODS: Five partners from university hospitals in four European countries developed the project as partners. Following a non-systematic review of the literature, the European consensus panel generated a list of recommendations for perioperative care in colorectal surgery. A list of recommendations was formulated and distributed to collaborators at each center to allow modifications or additional statements. These recommendations were then discussed in three consecutive meetings to share uniform ERAS protocols to be disseminated. RESULT: The working group developed (1) the EUPEMEN online platform to offer, free of charge, evidence-based standardized perioperative care protocols, learning activities, and assistance to health professionals interested in enhancing the recovery of their patients; (2) the preparation of the EUPEMEN Multimodal Rehabilitation manuals; (3) the training of the trainers to teach future teachers; and (4) the dissemination of the results in five multiplier events, one for each partner, to promote and disseminate the protocols. CONCLUSION: The EUPEMEN project allowed the sharing of the expertise of many professionals from four different European countries with the objective of training the new generations in the dissemination of ERAS protocols in daily clinical practice through a new learning system. This project was proposed as an additional training tool for all the enhanced recovery program teams.

Synthesis and toxicity assessment of Coffea arabica extract-derived gold nanoparticles loaded with doxorubicin in lung cancer cell cultures.

Cancer is the second leading cause of death worldwide, despite the many treatments available, cancer patients face side effects that reduce their quality of life. Therefore, there is a need to develop novel strategies to increase the efficacy of treatments. In this study, gold nanoparticles obtained by green synthesis with Coffea arabica green bean extract were loaded with Doxorubicin, (a highly effective but non-specific drug) by direct interaction and using commercial organic ligands that allow colloidal dispersion at physiological and tumor pH. Conjugation of these components resulted in stable nanohybrids at physiological pH and a tumor pH release dependent, with a particle size less than 40 nm despite having the ligands and Doxorubicin loaded on their surface, which gave them greater specificity and cytotoxicity in H69 tumor cells.

Modification of the physicochemical, functional, biochemical and structural properties of a soursop seed (Annona muricata L.) protein isolate treated with high-intensity ultrasound.

The obtained seeds from fruit processing are considered by-products containing proteins that could be utilized as ingredients in food manufacturing. However, in the specific case of soursop seeds, their usage for the preparation of protein isolates is limited. In this investigation a protein isolate from soursop seeds (SSPI) was obtained by alkaline extraction and isoelectric precipitation methods. The SSPI was sonicated at 200, 400 and 600 W during 15 and 30 min and its effect on the physicochemical, functional, biochemical, and structural properties was evaluated. Ultrasound increased (p < 0.05) up to 5 % protein content, 261 % protein solubility, 60.7 % foaming capacity, 30.2 % foaming stability, 86 % emulsifying activity index, 4.1 % emulsifying stability index, 85.4 % in vitro protein digestibility, 423.4 % albumin content, 83 % total sulfhydryl content, 316 % free sulfhydryl content, 236 % α-helix, 46 % ß-sheet, and 43 % ß-turn of SSPI, in comparison with the control treatment without ultrasound. Furthermore, ultrasound decreased (p < 0.05) up to 50 % particle size, 37 % molecular flexibility, 68 % surface hydrophobicity, 41 % intrinsic florescence spectrum, and 60 % random coil content. Scanning electron microscopy analysis revealed smooth structures of the SSPI with molecular weights ranging from 12 kDa to 65 kDa. The increase of albumins content in the SSPI by ultrasound was highly correlated (r = 0.962; p < 0.01) with the protein solubility. Improving the physicochemical, functional, biochemical and structural properties of SSPI by ultrasound could contribute to its utilization as ingredient in food industry.

Use of Darvadstrocel (Allogenic Stem Cell Therapy) for Crohn's Fistulas in Real Clinical Practice: The National Project to Implement Mesenchymal Stem Cell for the Treatment of Perianal Crohn's Fistula (the PRIME Study).

BACKGROUND: Perianal fistulas may affect 15-50% of patients with Crohn's disease. Treatment is complex, requiring a multidisciplinary approach. Darvadstrocel (allogenic mesenchymal cells obtained from lipoaspirates) was approved in 2018 by the European and Spanish Agencies of Medicines and Medical Products as a treatment for fistulas in Crohn's disease. Recent European Crohn's and Colitis Organisation and Spanish Working Group on Crohn's Disease and Ulcerative Colitis guidelines state that darvadstrocel is effective with a favorable safety profile and a strong level of evidence (2). OBJECTIVE: Presenting real-world effectiveness data for darvadstrocel in a Spanish population. DESIGN: Observational retrospective cohort study with prospective data gathering. SETTINGS: Fourteen institutions. PATIENTS: From November 2019-April 2022, all patients (73) treated with darvadstrocel in these institutions were included, fulfilling the following criteria: 1) complex fistula/s in a patient with Crohn's disease; 2) failure of conventional and antitumor necrosis factor treatment; 3) absence of collections >2 cm confirmed by pelvic MRI scan at the time of surgery. INTERVENTIONS: Darvadstrocel treatment. MAIN OUTCOME MEASURES: Clinical response (closure of ≥50% of external openings), complete clinical closure (100% of external openings) and radiological closure (no fluid collection >2 cm, no edema or inflammation) evaluated 6 months after treatment. RESULTS: Clinical response was observed in 63 patients (86.3%), complete clinical closure in 50 patients (68.5%) and radiological closure in 45 patients (69.2%). Combined clinical and radiological response was observed in 41 patients (63.1%). Not all clinically healed patients had radiological closure and vice versa. No serious adverse events were reported. LIMITATIONS: Retrospective. CONCLUSIONS: Study results were consistent with those reported in previous clinical trials, real-world efficacy findings from the INSPIRE study (assessing darvadstrocel effectiveness in Europe, Israel, Switzerland, UK, and Japan) and previously published literature. Darvadstrocel was effective and demonstrated a favorable safety profile when used in normal clinical practice for treatment of fistulas in Crohn's disease. See Video Abstract.

Unraveling resistance mechanisms in combination therapy: A comprehensive review of recent advances and future directions.

Antimicrobial resistance is a global health threat. Misuse and overuse of antimicrobials are the main drivers in developing drug-resistant bacteria. The emergence of the rapid global spread of multi-resistant bacteria requires urgent multisectoral action to generate novel treatment alternatives. Combination therapy offers the potential to exploit synergistic effects for enhanced antibacterial efficacy of drugs. Understanding the complex dynamics and kinetics of drug interactions in combination therapy is crucial. Therefore, this review outlines the current advances in antibiotic resistance's evolutionary and genetic dynamics in combination therapies-exposed bacteria. Moreover, we also discussed four pivotal future research areas to comprehend better the development of antibiotic resistance in bacteria treated with combination strategies.

Nano-Regulation of Gene Expression in Chlamydomonas reinhardtii: Harnessing AuNPs for Remotely Switchable Lipid Biosynthesis via Antisense Oligonucleotides.

Antisense oligonucleotide (ASO)-mediated gene silencing has broad applications, spanning from biomedicine to agriculture, involving molecular biology, synthetic biology, and genetic manipulation. This research harnessed nanotechnology to augment ASO-mediated gene silencing, introducing a remotely switchable gene expression system for precise temporal control. We targeted lipid biosynthesis and accumulation enhancement in the photosynthetic eukaryote Chlamydomonas reinhardtii. Gold nanoparticles (AuNPs) transported double-stranded DNA (dsDNA), forming dsDNA-AuNP complexes. These complexes comprised 3'-thiolated sense strands attached to AuNPs and fluorescent antisense oligonucleotides. To avoid harmful laser effects on cells, we adopted a light-emitting diode (LED). Confocal microscopy confirmed dsDNA-AuNP internalization in C. reinhardtii. LED-triggered antisense release led to an 83% decrease in Citrate Synthase 2 (CIS 2) expression. Thiolated sense strand attachment postillumination inhibited antisense reannealing, enhancing gene silencing. This led to significant lipid body accumulation in cells, verified through fluorometric and fluorescence microscopy. This union of nanotechnology and ASO-mediated silencing provides gene regulation opportunities across sectors like biomedicine and agriculture. The system's remote switching capability underscores its potential in synthetic biology and genetic engineering. Our findings substantiate the utility of this approach for enhancing lipid biosynthesis in C. reinhardtii but also underscores its broader applicability to other organisms, fostering the development of novel solutions for pressing global challenges in energy, agriculture, and healthcare.

Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma.

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.

Ag-NP-Decorated Carbon Nanostructures: Synthesis, Characterization, and Antimicrobial Properties.

As the global urgency for effective antimicrobial agents intensifies, this work harnesses the widely demonstrated antimicrobial activity of silver nanoparticles (Ag-NPs) and proposes alternative synthesis approaches to metal-organic hybrid systems with antimicrobial activity. In this study, the proposed synthesis route involves decorating metallic nanoparticles into organic substrates without previous doping. The synthesis simultaneously uses polyethylene glycol for three crucial purposes: (1) acting as a mild reducing agent to generate Ag-NPs with a spherical shape and diameters ranging from 10 to just over 20 nm, (2) functioning as a dispersing agent for flakes of commercial nanostructured carbon supports, including reduced graphene oxide (rGO, ID-nano), and commercial carbon nanoplatelets from Sigma-Aldrich (GNPs, Sigma-Aldrich), and (3) serving as a promoter for the homogeneous anchoring of Ag-NPs in the carbon lattice without altering the conformation of the carbon lattice. This intricate interaction involves the π-orbitals from the sp2 hybridization honeycomb and the d-orbitals from the Ag-NPs, leading to the constructive rehybridization of rGO and GNPs. In our study, Ag-NPs/rGO are compared with a support lacking oxygenated groups in the lattice, such as commercial GNPs (Sigma-Aldrich), to produce Ag-NPs/GNPs. This comparison maintains constructive sp2 rehybridization, preserving the characteristic properties of rGO (ID-nano) and graphene nanoplatelets, including commercial GNPs (Sigma-Aldrich). Notably, oxygenated groups from rGO exhibit greater availability for exchanging oxo and hydroxy defects for Ag-NPs compared with GNPs (Sigma-Aldrich). The resulting Ag-NPs/rGO and Ag-NPs/GNP systems are thoroughly physicochemically characterized, employing techniques such as Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, scanning electron microscopy and energy dispersive X-ray spectroscopy, high-resolution transmission electron microscopy, and scanning transmission electron microscopy, revealing the successful integration of Ag-NPs with minimal alteration to the carbon lattice. Subsequent antimicrobial evaluation against Escherichia coli (E. coli) demonstrates significant activity, with Ag-NPs/rGO and Ag-NPs/GNPs registering similar minimum inhibitory concentrations of 50 µg mL-1. This study underscores the potential of our metal-organic hybrid systems as antimicrobial agents and provides insights into the constructive rehybridization process, paving the way for diverse applications in the biomedical and environmental fields.

OCT Imaging in Murine Models of Alzheimer's Disease in a Systematic Review: Findings, Methodology and Future Perspectives.

The murine models of Alzheimer's disease (AD) have advanced our understanding of the pathophysiology. In vivo studies of the retina using optical coherence tomography (OCT) have complemented histological methods; however, the lack of standardisation in OCT methodologies for murine models of AD has led to significant variations in the results of different studies. A literature search in PubMed and Scopus has been performed to review the different methods used in these models using OCT and to analyse the methodological characteristics of each study. In addition, some recommendations are offered to overcome the challenges of using OCT in murine models. The results reveal a lack of consensus on OCT device use, retinal area analysed, segmentation techniques, and analysis software. Although some studies use the same OCT device, variations in other parameters make the direct comparison of results difficult. Standardisation of retinal analysis criteria in murine models of AD using OCT is crucial to ensure consistent and comparable results. This implies the application of uniform measurement and segmentation protocols. Despite the absence of standardisation, OCT has proven valuable in advancing our understanding of the pathophysiology of AD.

[Quality of health information in Mexico in the OECD context: 2017-2021]. / Calidad de la información en salud de México en el contexto de la OCDE: 2017-2021.

OBJECTIVE: To evaluate the health information system (HIS) of Mexico according to the information reported to the Organization for Economic Co-operation and Development (OECD). The ultimate goal is to identify the improvements that should be considered. METHOD: Health indicators published by the OECD (2017 to 2021) are analyzed according to 11 thematic groups. Coverage (quantity and type of indicators reported by thematic group) and quality of information were assessed, according to OECD guidelines. RESULTS: Mexico reported annually 14 of 378 indicators (3.7%), and discontinuously 204. In no group were all indicators reported annually, except for the two on COVID-19. Three out of 88 were reported annually on use of services; and none on health status, quality of care and pharmaceutical market. Twelve indicators (5.5% of those reported by Mexico, 3.2% of the full OECD set) had optimal quality and annual reporting. 57.7% of the reported indicators had at least one quality defect. CONCLUSIONS: Within the framework of the standards set by the OECD, of which Mexico is a member, the Mexican HIS presents significant deficits in coverage and quality of information. These results should be considered to implement improvement initiatives.

ZnO Decorated Graphene-Based NFC Tag for Personal NO2 Exposure Monitoring during a Workday.

This paper presents the integration of a sensing layer over interdigitated electrodes and an electronic circuit on the same flexible printed circuit board. This integration provides an effective technique to use this design as a wearable gas measuring system in a target application, exhibiting high performance, low power consumption, and being lightweight for on-site monitoring. The wearable system proves the concept of using an NFC tag combined with a chemoresistive gas sensor as a cumulative gas sensor, having the possibility of holding the data for a working day, and completely capturing the exposure of a person to NO2 concentrations. Three different types of sensors were tested, depositing the sensing layers on gold electrodes over Kapton substrate: bare graphene, graphene decorated with 5 wt.% zinc oxide nanoflowers, or nanopillars. The deposited layers were characterized using FESEM, EDX, XRD, and Raman spectroscopy to determine their crystalline structure, morphological and chemical compositions. The gas sensing performance of the sensors was analyzed against NO2 (dry and humid conditions) and other interfering species (dry conditions) to check their sensitivity and selectivity. The resultant-built wearable NFC tag system accumulates the data in a non-volatile memory every minute and has an average low power consumption of 24.9 µW in dynamic operation. Also, it can be easily attached to a work vest.

La débil garantía constitucional del derecho a la protección de la salud en España: una propuesta de reforma / A frágil garantia constitucional do direito à proteção da saúde na Espanha: uma proposta de reforma / The weak constitutional guarantee of the right to health protection in Spain: a reform proposal

Objetivo: discutir el derecho a la protección de la salud en España y su no inclusión en la categoría de derecho fundamental. Metodología: Revisión crítica de documentos normativos españoles e internacionales - Constitución, leyes y tratados internacionales - desde la perspectiva del análisis de la salud como un derecho fundamental. Resultados: La garantía y efectividad del derecho a la salud en España no son satisfactorias, ya que a partir de la regulación legislativa y, a menudo, administrativa del tema, surgen reclamaciones jurídicas bien definidas y exigibles ante los órganos jurisdiccionales, como derechos subjetivos individuales. Esto faculta al legislador introducir retrocesos significativos en la determinación del alcance del derecho a la salud. Conclusión: Se impone una reforma constitucional que signifique la reconfiguración de un derecho y su inclusión en la lista de aquellos considerados fundamentales en la Sección 1ª del Capítulo II del Título I de la Constitución, a fin de dotarlo de un contenido esencial, vinculante para el legislador y para que él mismo sea beneficiario de una garantía jurisdiccional directa y máxima, tanto ordinaria como extraordinaria ante el Tribunal Constitucional.

Objetivo: discutir o direito à proteção da saúde na Espanha e o seu não enquadramento na categoria de direito fundamental. Metodologia: revisão crítica de documentos normativos espanhóis e internacionais ­ Constituição, Leis e tratados internacionais na perspectiva de análise da saúde como um direito fundamental. Resultados: a garantia e efetividade do direito à saúde na Espanha não são satisfatórios visto que a partir da regulamentação legislativa e, muitas vezes, administrativa do tema, surgem reivindicações jurídicas bem definidas e exigíveis perante os órgãos judiciais, como direitos subjetivos individuais. Isso permite ao legislador introduzir retrocessos significativos na determinação do alcance do direito à saúde. Conclusão: Impõe-se uma reforma constitucional que signifique a reconfiguração de um direito e sua inclusão na lista daqueles considerados fundamentais na Seção 1ª do Capítulo II do Título I da Constituição, a fim de dotá-lo de um conteúdo essencial, vinculativo para o legislador e para que ele mesmo seja beneficiário de uma garantia jurisdicional direta e máxima, tanto ordinária quanto extraordinária perante o Tribunal Constitucional.

Objective: to discuss the right to health protection in Spain and its non-inclusion in the category of fundamental rights. Methodology: Critical review of Spanish and international normative documents - Constitution, laws, and international treaties - from the perspective of analyzing health as a fundamental right. Results: The guarantee and effectiveness of the right to health in Spain are not satisfactory, as from the legislative and often administrative regulation of the topic, well-defined and enforceable legal claims arise before judicial bodies, as individual subjective rights. This allows the legislator to introduce significant setbacks in determining the scope of the right to health. Conclusion: A constitutional reform is necessary to reconfigure a right and include it in the list of those considered fundamental in Section 1 of Chapter II of Title I of the Constitution, in order to endow it with an essential content, binding for the legislator, and so that it itself benefits from direct and maximum jurisdictional guarantee, both ordinary and extraordinary, before the Constitutional Court.

Glaucoma: from pathogenic mechanisms to retinal glial cell response to damage.

Glaucoma is a neurodegenerative disease of the retina characterized by the irreversible loss of retinal ganglion cells (RGCs) leading to visual loss. Degeneration of RGCs and loss of their axons, as well as damage and remodeling of the lamina cribrosa are the main events in the pathogenesis of glaucoma. Different molecular pathways are involved in RGC death, which are triggered and exacerbated as a consequence of a number of risk factors such as elevated intraocular pressure (IOP), age, ocular biomechanics, or low ocular perfusion pressure. Increased IOP is one of the most important risk factors associated with this pathology and the only one for which treatment is currently available, nevertheless, on many cases the progression of the disease continues, despite IOP control. Thus, the IOP elevation is not the only trigger of glaucomatous damage, showing the evidence that other factors can induce RGCs death in this pathology, would be involved in the advance of glaucomatous neurodegeneration. The underlying mechanisms driving the neurodegenerative process in glaucoma include ischemia/hypoxia, mitochondrial dysfunction, oxidative stress and neuroinflammation. In glaucoma, like as other neurodegenerative disorders, the immune system is involved and immunoregulation is conducted mainly by glial cells, microglia, astrocytes, and Müller cells. The increase in IOP produces the activation of glial cells in the retinal tissue. Chronic activation of glial cells in glaucoma may provoke a proinflammatory state at the retinal level inducing blood retinal barrier disruption and RGCs death. The modulation of the immune response in glaucoma as well as the activation of glial cells constitute an interesting new approach in the treatment of glaucoma.

Handling Patient Emergencies During Radiopharmaceutical Therapy.

PURPOSE: Radiopharmaceutical therapy (RPT) is a rapidly growing treatment modality. Though uncommon, patients may experience complications during their RPT treatment, which may trigger a rapid response from the hospital team. However, members of this team are typically not familiar with precautions for radiation safety. During these events, it is important to prioritize the patient's health over all else. There are some practices that can help minimize the risk of radiation contamination spread and exposure to staff while tending to the patient. METHODS AND MATERIALS: We formed a team to develop a standard protocol for handling patient emergencies during RPT treatment. This team consisted of an authorized user, radiation safety officer, medical physicist, nurse, RPT administration staff, and a quality/safety coordinator. The focus for developing this standardized protocol for RPT patient emergencies was 3-fold: (1) stabilize the patient; (2) reduce radiation exposure to staff; and (3) limit the spread of radiation contamination. RESULTS: We modified our hospital's existing rapid response protocol to account for the additional staff and tasks needed to accomplish all 3 of these goals. Each team member was assigned specific responsibilities, which include serving as a gatekeeper to restrict traffic, managing the crash cart, performing chest compressions, timing chest compressions, documenting the situation, and monitoring/managing radiation safety in the area. We developed a small, easy-to-read card for rapid response staff to read while they are en route to the area so they can be aware of and prepare for the unique circumstances that RPT treatments present. CONCLUSIONS: Though rapid response events with RPT patients are uncommon, it is important to have a standardized protocol for how to handle these situations beforehand rather than improvise in the moment. We have provided an example of how our team adapted our hospital's current rapid response protocol to accommodate RPT patients.

Capacitive immunosensing at gold nanoparticle-decorated reduced graphene oxide electrodes fabricated by one-step laser nanostructuration.

Nanostructured electrochemical biosensors have ushered in a new era of diagnostic precision, offering enhanced sensitivity and specificity for clinical biomarker detection. Among them, capacitive biosensing enables ultrasensitive label-free detection of multiple molecular targets. However, the complexity and cost associated with conventional fabrication methods of nanostructured platforms hinder the widespread adoption of these devices. This study introduces a capacitive biosensor that leverages laser-engraved reduced graphene oxide (rGO) electrodes decorated with gold nanoparticles (AuNPs). The fabrication involves laser-scribed GO-Au3+ films, yielding rGO-AuNP electrodes, seamlessly transferred onto a PET substrate via a press-stamping methodology. These electrodes have a remarkable affinity for biomolecular recognition after being functionalized with specific bioreceptors. For example, initial studies with human IgG antibodies confirm the detection capabilities of the biosensor using electrochemical capacitance spectroscopy. Furthermore, the biosensor can quantify CA-19-9 glycoprotein, a clinical cancer biomarker. The biosensor exhibits a dynamic range from 0 to 300 U mL-1, with a limit of detection of 8.9 U mL-1. Rigorous testing with known concentrations of a pretreated CA-19-9 antigen from human fluids confirmed their accuracy and reliability in detecting the glycoprotein. This study signifies notable progress in capacitive biosensing for clinical biomarkers, potentially leading to more accessible and cost-effective point-of-care solutions.

Use of Novel Homochiral Thioureas Camphor Derived as Asymmetric Organocatalysts in the Stereoselective Formation of Glycosidic Bonds.

We synthesized six new camphor-derived homochiral thioureas 1-6, from commercially available (1R)-(-)-camphorquinone. These new compounds 1-6 were evaluated as asymmetric organocatalysts in the stereoselective formation of glycosidic bonds, with 2,3,4,6-tetra-O-benzyl-D-glucopyranosyl and 2,3,4,6-tetra-O-benzyl-D-galactopyranosyl trichloroacetimidates as donors, and several alcohols as glycosyl acceptors, such as methanol, ethanol, 1-propanol, 1-butanol, 1-octanol, iso-propanol, tert-butanol, cyclohexanol, phenol, 1-naphtol, and 2-naphtol. Optimization of the asymmetric glycosylation reaction was achieved by modifying reaction conditions such as solvent, additive, loading of catalyst, temperature, and time of reaction. The best result was obtained with 2,3,4,6-tetra-O-benzyl-D-galactopyranosyl trichloroacetimidates, using 15 mol% of organocatalyst 1, in the presence of 2 equiv of MeOH in solvent-free conditions at room temperature for 1.5 h, affording the glycosidic compound in a 99% yield and 1:73 α:ß stereoselectivity; under the same reaction conditions, without using a catalyst, the obtained stereoselectivity was 1:35 α:ß. Computational calculations prior to the formation of the products were modeled, using density functional theory, M06-2X/6-31G(d,p) and M06-2X/6-311++G(2d,2p) methods. We observed that the preference for ß glycoside formation, through a stereoselective inverted substitution, relies on steric effects and the formation of hydrogen bonds between thiourea 1 and methanol in the complex formed.

RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages.

Macrophage activation is a complex process with multiple control elements that ensures an adequate response to the aggressor pathogens and, on the other hand, avoids an excess of inflammatory activity that could cause tissue damage. In this study, we have identified RND3, a small GTP-binding protein, as a new element in the complex signaling process that leads to macrophage activation. We show that RND3 expression is transiently induced in macrophages activated through Toll receptors and potentiated by IFN-γ. We also demonstrate that RND3 increases NOTCH signaling in macrophages by favoring NOTCH1 expression and its nuclear activity; however, Rnd3 expression seems to be inhibited by NOTCH signaling, setting up a negative regulatory feedback loop. Moreover, increased RND3 protein levels seem to potentiate NFκB and STAT1 transcriptional activity resulting in increased expression of proinflammatory genes, such as Tnf-α, Irf-1, or Cxcl-10. Altogether, our results indicate that RND3 seems to be a new regulatory element which could control the activation of macrophages, able to fine tune the inflammatory response through NOTCH.

Light-Responsive and Dual-Targeting Liposomes: From Mechanisms to Targeting Strategies.

In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.