Engineering a Surfactant Trap via Postassembly Modification of an Imine Cage.

Imine self-assembly stands as a potent strategy for the preparation of molecular organic cages. However, challenges persist, such as water insolubility and limited recognition properties due to constraints in the application of specific components during the self-assembly process. In this study, we addressed these limitations by initially employing a locking strategy, followed by a postassembly modification. This sequential approach enables precise control over both the solubility and host-guest properties of an imine-based cage. The resulting structure demonstrates water solubility and exhibits an exceptional capacity to selectively interact with anionic surfactants, inducing their precipitation. Remarkably, each cage precipitates 24 equiv of anionic surfactants even at concentrations much lower than the surfactant's critical micelle concentration (CMC), ensuring their complete removal. Molecular simulations elucidate how anionic surfactants specifically interact with the cage to facilitate aggregation below the surfactant CMC and induce precipitation as a micellar cross-linker. This innovative class of cages paves the way for the advancement of materials tailored for environmental remediation.

Role of Gut Microbiota in Dengue.

Dengue is a disease caused by a flavivirus (DENV) and transmitted by the bite of a mosquito, primarily the Aedes aegypti and Aedes albopictus species. Previous studies have demonstrated a relationship between the host gut microbiota and the evolution of dengue. It seems to be a bidirectional relationship, in which the DENV can affect the microbiota by inducing alterations related to intestinal permeability, leading to the release of molecules from microbiota dysbiosis that can influence the evolution of dengue. The role of angiotensin II (Ang II) in the microbiota/dengue relationship is not well understood, but it is known that the renin-angiotensin system (RAS) is present in the intestinal tract and interacts with the gut microbiota. The possible effect of Ang II on the microbiota/Ang II/dengue relationship can be summarised as follows: the presence of Ang II induced hypertension, the increase in angiotensinogen, chymase, and microRNAs during the disease, the induction of vascular dysfunction, the production of trimethylamine N-oxide and the brain/microbiota relationship, all of which are elements present in dengue that could be part of the microbiota/Ang II/dengue interactions. These findings suggest the potential use of Ang II synthesis blockers and the use of AT1 receptor antagonists as therapeutic drugs in dengue.

Deciphering the Concept of Solubility by Strategically Using the Counterion Effect in Charged Molecules.

Solubility is an essential concept in chemistry that describes the ability of a substance to dissolve in a particular solvent. Despite its importance in many fields of science, understanding the basic principles of solubility is challenging for many undergraduate students. Notably, students often encounter difficulties in comprehending the role of counterions when dealing with charged molecules. Here, we bring the opportunity to assimilate the key concepts of solubility regarding the role of counterions by developing a straightforward, cheap, and visually appealing experiment that focuses on the strategic use of counterions to control solubility. A student questionnaire delivered encouraging results with most of students giving positive feedback in both interest and training their hands-on skills. Hence, our experiment offers a proficient understanding of the solubility concept, thus preparing undergraduate students for advanced courses in the various subject areas of chemistry.

Highlights from the 57th Bürgenstock Conference on Stereochemistry 2024.

Herein, we share an overview of the scientific highlights from speakers at the latest edition of the longstanding Bürgenstock Conference.

Role of angiotensin II in cellular entry and replication of dengue virus.

Previous studies have demonstrated the relevance of several soluble molecules in the pathogenesis of dengue. In this regard, a possible role for angiotensin II (Ang II) in the pathophysiology of dengue has been suggested by the observation of a blockade of Ang II in patients with dengue, increased expression of molecules related to Ang II production in the plasma of dengue patients, increased expression of circulating cytokines and soluble molecules related to the action of Ang II, and an apparent relationship between DENV, Ang II effects, and miRNAs. In addition, in ex vivo experiments, the blockade of Ang II AT1 receptor and ACE-1 (angiotensin converting enzyme 1), both of which are involved in Ang II production and its function, inhibits infection of macrophages by DENV, suggesting a role of Ang II in viral entry or in intracellular viral replication of the virus. Here, we discuss the possible mechanisms of Ang II in the entry and replication of DENV. Ang II has the functions of increasing the expression of DENV entry receptors, creation of clathrin-coated vesicles, and increasing phagocytosis, all of which are involved in DENV entry. This hormone also modulates the expression of the Rab5 and Rab7 proteins, which are important in the endosomal processing of DENV during viral replication. This review summarizes the data related to the possible involvement of Ang II in the entry of DENV into cells and its replication.

Dendrimers: Exploring Their Wide Structural Variety and Applications.

Dendrimers constitute a distinctive category of synthetic materials that bear resemblance to proteins in various aspects, such as discrete structural organization, globular morphology, and nanoscale dimensions. Remarkably, these attributes coexist with the capacity for facile large-scale production. Due to these advantages, the realm of dendrimers has undergone substantial advancement since their inception in the 1980s. Numerous reviews have been dedicated to elucidating this subject comprehensively, delving into the properties and applications of quintessential dendrimer varieties like PAMAM, PPI, and others. Nevertheless, the contemporary landscape of dendrimers transcends these early paradigms, witnessing the emergence of a diverse array of novel dendritic architectures in recent years. In this review, we aim to present a comprehensive panorama of the expansive domain of dendrimers. As such, our focus lies in discussing the key attributes and applications of the predominant types of dendrimers existing today. We will commence with the conventional variants and progressively delve into the more pioneering ones, including Janus, supramolecular, shape-persistent, and rotaxane dendrimers.

Tuning the Growth of Chiral Gold Nanoparticles Through Rational Design of a Chiral Molecular Inducer.

The bottom-up production of chiral gold nanomaterials holds great potential for the advancement of biosensing and nano-optics, among other applications. Reproducible preparations of colloidal nanomaterials with chiral morphology have been reported, using cosurfactants or chiral inducers such as thiolated amino acids. However, the underlying growth mechanisms for these nanomaterials remain insufficiently understood. We introduce herein a purposely devised chiral inducer, a cysteine modified with a hydrophobic chain, as a versatile chiral inducer. The amphiphilic and chiral features of this molecule provide control over the chiral morphology and the chiroptical signature of the obtained nanoparticles by simply varying the concentration of chiral inducer. These results are supported by circular dichroism and electromagnetic modeling as well as electron tomography to analyze structural evolution at the facet scale. Our observations suggest complex roles for the factors involved in chiral synthesis: the chemical nature of the chiral inducers and the influence of cosurfactants.

Surfactant Layers on Gold Nanorods.

ConspectusGold nanorods (Au NRs) are an exceptionally promising tool in nanotechnology due to three key factors: (i) their strong interaction with electromagnetic radiation, stemming from their plasmonic nature, (ii) the ease with which the resonance frequency of their longitudinal plasmon mode can be tuned from the visible to the near-infrared region of the electromagnetic spectrum based on their aspect ratio, and (iii) their simple and cost-effective preparation through seed-mediated chemical growth. In this synthetic method, surfactants play a critical role in controlling the size, shape, and colloidal stability of Au NRs. For example, surfactants can stabilize specific crystallographic facets during the formation of Au NRs, leading to the formation of NRs with specific morphologies.The process of surfactant adsorption onto the NR surface may result in various assemblies of surfactant molecules, such as spherical micelles, elongated micelles, or bilayers. Again, the assembly mode is critical toward determining the further availability of the Au NR surface to the surrounding medium. Despite its importance and a great deal of research effort, the interaction between Au NPs and surfactants remains insufficiently understood, because the assembly process is influenced by numerous factors, including the chemical nature of the surfactant, the surface morphology of Au NPs, and solution parameters. Therefore, gaining a more comprehensive understanding of these interactions is essential to unlock the full potential of the seed-mediated growth method and the applications of plasmonic NPs. A plethora of characterization techniques have been applied to reach such an understanding, but many open questions remain.In this Account, we review the current knowledge on the interactions between surfactants and Au NRs. We briefly introduce the state-of-the-art methods for synthesizing Au NRs and highlight the crucial role of cationic surfactants during this process. The self-assembly and organization of surfactants on the Au NR surface is then discussed to better understand their role in seed-mediated growth. Subsequently, we provide examples and elucidate how chemical additives can be used to modulate micellar assemblies, in turn allowing for a finer control over the growth of Au NRs, including chiral NRs. Next, we review the main experimental characterization and computational modeling techniques that have been applied to shed light on the arrangement of surfactants on Au NRs and summarize the advantages and disadvantages for each technique. The Account ends with a "Conclusions and Outlook" section, outlining promising future research directions and developments that we consider are still required, mostly related to the application of electron microscopy in liquid and in 3D. Finally, we remark on the potential of exploiting machine learning techniques to predict synthetic routes for NPs with predefined structures and properties.

Dilution-induced gel-sol-gel-sol transitions by competitive supramolecular pathways in water.

Fascinating properties are displayed by synthetic multicomponent supramolecular systems that comprise a manifold of competitive interactions, thereby mimicking natural processes. We present the integration of two reentrant phase transitions based on an unexpected dilution-induced assembly process using supramolecular polymers and surfactants. The co-assembly of the water-soluble benzene-1,3,5-tricarboxamide (BTA-EG4) and a surfactant at a specific ratio yielded small-sized aggregates. These interactions were modeled using the competition between self-sorting and co-assembly of both components. The small-sized aggregates were transformed into supramolecular polymer networks by a twofold dilution in water without changing their ratio. Kinetic experiments show the in situ growth of micrometer-long fibers in the dilution process. We were able to create systems that undergo fully reversible hydrogel-solution-hydrogel-solution transitions upon dilution by introducing another orthogonal interaction.

Endothelial expression of the receptor for advanced glycation end products in experimental diabetes / Expresión endotelial del receptor para productos finales de glicación avanzada en diabetes experimental

The receptor for advanced glycation end products (RAGE) is implicated in the pathogenesis of several chronic diseases including diabetes. The interaction between RAGE and advanced glycation end products (AGEs) promotes gene expression, enhances the release of proinflammatory molecules and causes the generation of oxidative stress in numerous cell types. The aim of this investigation was to evaluate the effect of enalapril and losartan on RAGE expression in abdominal aortic endothelium of rats with experimentally induced diabetes. Male Sprague-Dawley rats, weighing approximately 150 - 200 g, were used. Diabetes was induced in 30 rats by intravenous administration of a single dose of 55 mg/kg body weight of streptozotocin (ETZ). The following groups were studied: control (n=10), diabetic (n=10), losartan-treated diabetic (n=10) and enalapril-treated diabetic (n=10) rats. RAGE expression in aortic endothelium was determined by indirect immunofluorescence. A significant increase in RAGE expression was observed in diabetic animals versus controls (p<0.001), there was a decrease in RAGE expression, in animals treated with losartan versus controls (p<0.01) and in those treated with enalapril (p<0.05) versus control and versus diabetes + vehicle. In conclusion, in the experimental model of ETZ-induced diabetes, there is an increase in RAGE expression at the level of the abdominal aortic endothelium, which can be reversed by treatment with losartan and/or enalapril, two drugs that block the renin-angiotensin system, suggesting its involvement in the molecular events related to vascular damage during diabetes.

El receptor para productos finales de glicación avanzada (RAGE) está implicado en la patogénesis de varias enfermedades crónicas incluyendo la diabetes. La interacción entre RAGE y los productos finales de glicación avanzada (AGEs), promueve la expresión génica, potencia la liberación de moléculas proinflamatorias y provoca la generación de estrés oxidativo en numerosos tipos de células. El objetivo de esta investigación fue evaluar el efecto del enalapril y el losartán sobre la expresión de RAGE en el endotelio de la aorta abdominal de ratas con diabetes inducida experimentalmente. Se utilizaron ratas Sprague-Dawley machos, con un peso aproximado de entre 150 - 200 g. La diabetes se indujo en 30 ratas mediante la administración intravenosa de una sola dosis de 55 mg/Kg de peso corporal de estreptozotocina (ETZ). Se estudiaron los siguientes grupos: ratas control (n=10), diabéticas (n=10), diabéticas tratadas con losartán (n=10) y diabéticas tratadas con enalapril (n=10). La expresión de RAGE en el endotelio aórtico se determinó por inmunofluorescencia indirecta. Se observó un incremento significativo en la expresión de RAGE en los animales diabéticos versus los controles (p<0.001), hubo una disminución en la expresión de RAGE, en los animales tratados con losartán versus los controles (p<0.01) y en los tratados con enalapril (p<0.05) versus control y versus diabetes + vehículo. En conclusión, en el modelo experimental de diabetes inducida por ETZ, existe un incremento en la expresión de RAGE a nivel del endotelio de la aorta abdominal, la cual puede revertirse mediante el tratamiento con losartán y/o enalapril, dos fármacos bloqueadores del sistema renina-angiotensina, lo cual sugiere la participación del mismo en los acontecimientos moleculares relacionados con el daño vascular durante la diabetes.

Deactivation of a dimeric DNA-binding peptide through a palladium-mediated self-immolative cleavage.

Herein, we describe an approach for the on-demand disassembly of dimeric peptides using a palladium-mediated cleavage of a designed self-immolative linker. The utility of the strategy is demonstrated for the case of dimeric basic regions of bZIP transcription factors. While the dimer binds designed DNA sequences with good affinities, the peptide-DNA complex can be readily dismounted by addition of palladium reagents that trigger the cleavage of the spacer, and the release of unfunctional monomeric peptides.

Diabetes, heart damage, and angiotensin II. What is the relationship link between them? A minireview.

Cardiovascular complications are the main cause of mortality and morbidity in the diabetic patients, in whom changes in myocardial structure and function have been described. Numerous molecular mechanisms have been proposed that could contribute to the development of a cardiac damage. In this regard, angiotensin II (Ang II), a proinflammatory peptide that constitutes the main effector of the renin-angiotensin system (RAS) has taken a relevant role. The aim of this review was to analyze the role of Ang II in the different biochemical pathways that could be involved in the development of cardiovascular damage during diabetes. We performed an exhaustive review in the main databases, using the following terms: angiotensin II, cardiovascular damage, renin angiotensin system, inflammation, and diabetes mellitus. Classically, the RAS has been defined as a complex system of enzymes, receptors, and peptides that help control the blood pressure and the fluid homeostasis. However, in recent years, this concept has undergone substantial changes. Although this system has been known for decades, recent discoveries in cellular and molecular biology, as well as cardiovascular physiology, have introduced a better understanding of its function and relationship to the development of the diabetic cardiomyopathy.

Polifarmacia en Chile: una investigación descriptiva / Polipharmacy in Chile: a descriptive research

La polifarmacia es un término que, si bien no existe un consenso, se considerará como el uso concomitante de cinco o más medicamentos ya sean recetados o no por un profesional. Con respecto a ésta, se ha visto que se ha acrecentado en los últimos años tanto en Chile como en el mundo. En la presente investigación descriptiva se realizó un análisis de la Encuesta Nacional de Salud de Chile (ENS) 2016-17 y se comparó con los resultados obtenidos en la Encuesta Nacional de Salud 2009-10 y con la Encuesta sobre Salud, Envejecimiento y Jubilación Europea para de esta forma realizar un recuento objetivo sobre el aumento de esta condición en Chile. Al caracterizar a los grupos más afectados, se vio que en Chile la mayor prevalencia se daba en población adulta mayor sobre 65 años, mujeres y personas con escolaridad menor a 8 años cursados. Esto da cuenta del nivel del problema y la necesidad de una visión médica holística para el especial abordaje de la multimorbilidad, pues la polifarmacia trae consigo a su vez riesgos para la salud como lo son el aumento de las reacciones adversas e interacciones medicamentosas, riesgo de hospitalización, mayor deterioro del estado funcional, incremento de alteraciones cognitivas y mayores costos monetarios para el sistema de salud.

Polypharmacy is a term that, although there is no official definition, is understood as the concomitant use of five or more medications, regardless of whether they are prescribed by a professional. Regarding this phenomenon, an increase can be observed in recent years both in Chile and on a global level. This present descriptive research draws on an analysis of the National Health Survey (ENS) from 2016-17 and a comparison with the National Survey of Health from 2009-10 and with Survey of Health, Ageing and Retirement in Europe in order to carry out an objective count on the increase of this phenomenon. When characterizing the most affected groups, this paper shows that in Chile the highest prevalence can be found in the older adult population over 65 years of age, women and people with less than 8 years of schooling. These results reveal the dimension of the issue, and the need for a holistic medical vision to pay particular attention to multiple morbidities since polypharmacy brings with it health risks such as increased adverse reactions and drug interactions, risk of hospitalization, further deterioration of functional status, increase in cognitive alterations and higher monetary costs for the health system

Introducing Hyaluronic Acid into Supramolecular Polymers and Hydrogels.

The use of supramolecular polymers to construct functional biomaterials is gaining more attention due to the tunable dynamic behavior and fibrous structures of supramolecular polymers, which resemble those found in natural systems, such as the extracellular matrix. Nevertheless, to obtain a biomaterial capable of mimicking native systems, complex biomolecules should be incorporated, as they allow one to achieve essential biological processes. In this study, supramolecular polymers based on water-soluble benzene-1,3,5-tricarboxamides (BTAs) were assembled in the presence of hyaluronic acid (HA) both in solution and hydrogel states. The coassembly of BTAs bearing tetra(ethylene glycol) at the periphery (BTA-OEG4) and HA at different ratios showed strong interactions between the two components that led to the formation of short fibers and heterogeneous hydrogels. BTAs were further covalently linked to HA (HA-BTA), resulting in a polymer that was unable to assemble into fibers or form hydrogels due to the high hydrophilicity of HA. However, coassembly of HA-BTA with BTA-OEG4 resulted in the formation of long fibers, similar to those formed by BTA-OEG4 alone, and hydrogels were produced with tunable stiffness ranging from 250 to 700 Pa, which is 10-fold higher than that of hydrogels assembled with only BTA-OEG4. Further coassembly of BTA-OEG4 fibers with other polysaccharides showed that except for dextran, all polysaccharides studied interacted with BTA-OEG4 fibers. The possibility of incorporating polysaccharides into BTA-based materials paves the way for the creation of dynamic complex biomaterials.

In situ immunopathological events in human cervical intraepithelial neoplasia and cervical cancer: Review.

Neoplasia of the cervix represents one of the most common cancers in women. Clinical and molecular research has identified immunological impairment in squamous intraepithelial cervical lesions and cervical cancer patients. The in-situ expression of several cytokines by uterine epithelial cells and by infiltrating leukocytes occurs during the cervical intraepithelial neoplasia and cervical cancer. Some of these cytokines can prevent and others can induce the progression of the neoplasm. The infiltrating leukocytes also produce cytokines and growth factors relate to angiogenesis, chemotaxis, and apoptosis capable of modulating the dysplasia progression. In this review we analyzed several interleukins with an inductive effect or blocking effect on the neoplastic progression. We also analyze the genetic polymorphism of some cytokines and their relationship with the risk of developing cervical neoplasia. In addition, we describe the leukocyte cells that infiltrate the cervical uterine tissue during the neoplasia and their effects on neoplasia progression.

Acute post-streptococcal glomerulonephritis: analysis of the pathogenesis.

Increasing evidence supports a central role of the immune system in acute post streptococcal glomerulonephritis (APSGN), but the current view of how streptococcal biology affects immunity, and vice versa, remains to be clarified. Renal glomerular immune complex deposition is critical in the initiation of APSGN; however, mechanisms previous to immune complex formation could modulate the initiation and the progression of the disease. Initial and late renal events involved in the nephritis can also be related to host factors and streptococcal factors. In this review we describe the mechanisms reported for the APSGN pathogenesis, the interactions of streptococcal products with renal cells and leukocytes, the possible effects of different nephritogenic antigens in the renal environment and the possibility that APSGN is not just due to a single streptococcal antigen and its antibody; instead, kidney damage may be the result of different factors acting at the same time related to both streptococcus and host factors. Addressing these points should help us to better understand APSGN physiopathology.

Stimuli-Responsive DNA Binding by Synthetic Systems.

DNA is the molecule responsible for the storage and transmission of the genetic information in living organisms. The expression of this information is highly regulated. In eukaryotes, it is achieved mainly at the transcription level thanks to specialized proteins called transcription factors (TFs) that recognize specific DNA sequences, thereby promoting or inhibiting the transcription of particular genes. In many cases, TFs are present in the cell in an inactive form but become active in response to an external signal, which might modify their localization and DNA binding properties or modulate their interactions with the rest of the transcriptional machinery. As a result of the crucial role of TFs, the design of synthetic peptides or miniproteins that can emulate their DNA binding properties and eventually respond to external stimuli is of obvious interest. On the other hand, although the B-form double helix is the most common DNA secondary structure, it is not the only one with an essential biological function. Guanine quadruplexes (GQs) have received considerable attention due to their critical role in the regulation of gene expression, which is usually associated with a change in the GQ conformation. Thus, the development of GQ probes whose properties can be controlled using external signals is also of significant relevance.In this Account, we present a summary of the recent efforts toward the development of stimuli-responsive synthetic DNA binders with a particular emphasis on our own contributions. We first introduce the structure of B and GQ DNAs, and some of the main factors underlying their selective recognition. We then discuss some of the different approaches used for the design of stimulus-mediated DNA binders. We have organized our discussion according to whether the interaction takes place with duplex or guanine quadruplex DNAs, and each section is divided according to the nature of the stimulus (i.e., physical or chemical). Regarding physical stimuli, light (through the incorporation of photolabile protecting groups or photoisomerizable agents) is the most common input for the activation/deactivation of DNA binding events. With respect to chemical signals, the use of metals (through the incorporation of metal-coordinating groups in the DNA binding agent) has allowed the development of a wide range of stimuli-responsive DNA binders. More recently, redox-based systems have also been used to control DNA interactions.This Account ends with a "Conclusions and Outlook" section highlighting some of the general lessons that have been learned and future directions toward further advancing the field.

Angiotensin II Induces Increased Myocardial Expression of Receptor for Advanced Glycation End Products, Monocyte/Macrophage Infiltration and Circulating Endothelin-1 in Rats With Experimental Diabetes.

OBJECTIVES: It is known that the receptor for advanced glycation end products (RAGE) activation is involved in the pathogenesis of cardiovascular disease in diabetes. Previous studies have shown the presence of angiotensin II (Ang II) in diabetes, suggesting a role for this hormone during the disease. However, the association between RAGE and Ang II during pathologic cardiac remodelling after streptozotocin (STZ)-induced diabetes remains unclear. Because Ang II is capable of inducing pro-inflammatory events, blocking its production (enalapril), and its action on its receptor (losartan) could decrease inflammatory events in the myocardium in this experimental model of diabetes. Thus, the aim of this study was to assess the association between RAGE expression, inflammatory events and Ang II in the myocardium during STZ-induced diabetes. METHODS: Diabetes was induced by intravenous injection of STZ in Sprague-Dawley rats. Myocardial expressions of RAGE, monocyte/macrophage (ED-1-positive cells) infiltration and the intercellular adhesion molecule-1 were determined by histochemical methods. Levels of circulating endothelin-1 (ET-1) were determined by enzyme-linked immunoassay. Effects of Ang II included blocking using losartan (15 mg/kg body weight per day by gastric gavage) or enalapril (18 mg/kg body weight per day by gastric gavage). RESULTS: Increased expression of both RAGE and ED-1 was seen in the myocardium, but expression of myocardial vascular intercellular adhesion molecule-1 remained unchanged. Circulating levels of ET-1 in STZ rats were increased. Renin‒angiotensin system inhibition decreased expression of myocardial RAGE, ED-1 and ET-1. CONCLUSIONS: The present findings suggest a role for Ang II in myocardial inflammation in STZ-induced diabetes mediated by RAGE and ET-1.

Micelle-directed chiral seeded growth on anisotropic gold nanocrystals.

Surfactant-assisted seeded growth of metal nanoparticles (NPs) can be engineered to produce anisotropic gold nanocrystals with high chiroptical activity through the templating effect of chiral micelles formed in the presence of dissymmetric cosurfactants. Mixed micelles adsorb on gold nanorods, forming quasihelical patterns that direct seeded growth into NPs with pronounced morphological and optical handedness. Sharp chiral wrinkles lead to chiral plasmon modes with high dissymmetry factors (~0.20). Through variation of the dimensions of chiral wrinkles, the chiroptical properties can be tuned within the visible and near-infrared electromagnetic spectrum. The micelle-directed mechanism allows extension to other systems, such as the seeded growth of chiral platinum shells on gold nanorods. This approach provides a reproducible, simple, and scalable method toward the fabrication of NPs with high chiral optical activity.