The Glycan Structure Dictionary-a dictionary describing commonly used glycan structure terms.

Recent technological advances in glycobiology have resulted in a large influx of data and the publication of many papers describing discoveries in glycoscience. However, the terms used in describing glycan structural features are not standardized, making it difficult to harmonize data across biomolecular databases, hampering the harvesting of information across studies and hindering text mining and curation efforts. To address this shortcoming, the Glycan Structure Dictionary has been developed as a reference dictionary to provide a standardized list of widely used glycan terms that can help in the curation and mapping of glycan structures described in publications. Currently, the dictionary has 190 glycan structure terms with 297 synonyms linked to 3,332 publications. For a term to be included in the dictionary, it must be present in at least 2 peer-reviewed publications. Synonyms, annotations, and cross-references to GlyTouCan, GlycoMotif, and other relevant databases and resources are also provided when available. The purpose of this effort is to facilitate biocuration, assist in the development of text mining tools, improve the harmonization of search, and browse capabilities in glycoinformatics resources and help to map glycan structures to function and disease. It is also expected that authors will use these terms to describe glycan structures in their manuscripts over time. A mechanism is also provided for researchers to submit terms for potential incorporation. The dictionary is available at https://wiki.glygen.org/Glycan_structure_dictionary.

Exploring the conformational dynamics of PD1 in complex with different ligands: What we can learn for designing novel PD1 signaling blockers?

Activation of T cells triggers the expression of regulatory molecules like the programmed cell death 1 (PD1) protein. The association of PD1 with the natural ligands PDL1 and PDL2 induces an inhibitory signal that prevents T cells from proliferating and exerting effector functions. However, little is known about how the binding of the ligands induce the PD1 inhibitory signal over T cells effector functions. Here, we explore the dynamics of PD1 free, and in complex with different PDL1 variants as well as the therapeutic antibodies nivolumab and pembrolizumab in order to assess the conformational changes in PD1 related to the signaling process. Our simulations suggest a pre-conformational selection mechanism for the binding of the different PDL1 variants, while an induced-fit model fits better for the molecular recognition process of the therapeutic antibodies. A deep analysis of the changes on PD1 movement upon the binding to different ligands revealed that as larger is the difference in the conformation adopted by loop C'D with respect to the complex with PDL1 is higher the ligand ability to reduce the PD1 inhibitory signaling. This behavior suggests that targeting specific conformations of this loop can be useful for designing therapies able to recover T cells effector functions.

Concentration trend study on foaming properties for native soy protein isolate treated by ultrasound and heating.

Given the non-linearity of many protein properties with a short range of concentration which cannot be predicted a priori, and due to the lack of references in the food industry, we proceeded to analyze the foaming ones. The existing bibliography belongs to other fields of research but it is scarcely found for this area. For the food industry, ultrasound is considered one of the most environment-friendly processing. In addition, heating combination would alter their results considerably by synergistic or additive phenomena. Native soy protein isolate was obtained in our laboratory to use it as starting material; ultrasound with temperature was applied at 2, 4 and 6%w/w protein concentrations. Therefore, the objective of this paper was to determine the effect of ultrasound+temperature (50 or 90 °C) simultaneously applied, on the foamability by relating with the relative viscoelasticity, aggregates particle size distribution and their surface charge by zeta potential. The results indicated that treatments promoted changes on the functional parameters depending on the protein concentration. The analysis showed that at 4%wt/wt was adequate to improve foam formation and stability at same time. Dynamic rheology of continuous phase was relation with foamability showing the higher relative viscoelasticity at 4% of concentration after the combined treatment. Light scattering studies could partially explain this observation, taking into account both, the bulk viscosity and the low number of large particles formed after treating. Surface charge was increased for all concentrations equally leading to the aggregates formation of greater colloidal stability for all concentration and treatment conditions investigated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1007/s13197-020-04954-w).

Efficacy of direct current generated by multiple-electrode arrays on F3II mammary carcinoma: experiment and mathematical modeling.

BACKGROUND: The modified Gompertz equation has been proposed to fit experimental data for direct current treated tumors when multiple-straight needle electrodes are individually inserted into the base perpendicular to the tumor long axis. The aim of this work is to evaluate the efficacy of direct current generated by multiple-electrode arrays on F3II mammary carcinoma that grow in the male and female BALB/c/Cenp mice, when multiple-straight needle electrodes and multiple-pairs of electrodes are inserted in the tumor. METHODS: A longitudinal and retrospective preclinical study was carried out. Male and female BALB/c/Cenp mice, the modified Gompertz equation, intensities (2, 6 and 10 mA) and exposure times (10 and 20 min) of direct current, and three geometries of multiple-electrodes (one formed by collinear electrodes and two by pair-electrodes) were used. Tumor volume and mice weight were measured. In addition, the mean tumor doubling time, tumor regression percentage, tumor growth delay, direct current overall effectiveness and mice survival were calculated. RESULTS: The greatest growth retardation, mean doubling time, regression percentage and growth delay of the primary F3II mammary carcinoma in male and female mice were observed when the geometry of multiple-pairs of electrodes was arranged in the tumor at 45, 135, 225 and 325o and the longest exposure time. In addition, highest direct current overall effectiveness (above 66%) was observed for this EChT scheme. CONCLUSIONS: It is concluded that electrochemical therapy may be potentially addressed to highly aggressive and metastic primary F3II murine mammary carcinoma and the modified Gompertz equation may be used to fit data of this direct current treated carcinoma. Additionally, electrochemical therapy effectiveness depends on the exposure time, geometry of multiple-electrodes and ratio between the direct current intensity applied and the polarization current induced in the tumor.

Quantitative assessment of extracellular IL-1 regulation.

IL-1 system is involved in the induction and maintenance of chronic inflammation associated with several autoimmune diseases and cancer, mainly due to its capacity to promote the secretion of inflammatory mediators. For this reason, several intracellular and extracellular mechanisms for this system have been fixed during the evolution. In spite of the large description of molecular interactions between IL-1 ligands and receptors, little is known about the relevance and limits of the extracellular regulatory mechanims in different scenarios. To tackle this problem, we developed and calibrated a mathematical model including all the known interactions between IL-1 ligands and IL-1Rs and calibrate it with experimental data of IL-1 binding to different cells. The model predicts that, independently on the IL-1Rs expression, IL-1α has more ability than IL-1ß to induce IL-1 signaling, which suggests that both ligands can be equally relevant for the IL-1 related inflammation. On the other hand, at the cell level, IL-1 signaling is mainly controlled by IL-1R1 and IL-1R3 and not by IL-1R2. Moreover, the soluble form of IL-1R1 and IL-1RA have the highest capacity to prevent IL-1α while IL-1R2 and IL-1R1 and IL-1RA have a similar capacity to prevent IL-1ß signaling. The soluble IL-1R3 has the lowest capacity to prevent IL-1 signaling and preferentially inhibits cells with low number of IL-1R3. In general, model predictions suggest several ways in which IL-1 controlling system may fail, developing IL-1 related inflammation.

Combined Experimental and Molecular Simulation Study of Insulin-Chitosan Complexation Driven by Electrostatic Interactions.

Protein-polysaccharide complexes constructed via self-assembly methods are often used to develop novel biomaterials for a wide range of applications in biomedicine, food, and biotechnology. The objective of this work was to investigate theoretically and to demonstrate via constant-pH Monte Carlo simulations that the complexation phenomenon between insulin (INS) and the cationic polyelectrolyte chitosan (CS) is mainly driven by an electrostatic mechanism. Experimental results obtained from FTIR spectra and ζ-potential determinations allowed us to complement the conclusions. The characteristic absorption bands for the complexes could be assigned to a combination of signals from CS amide I and INS amide II. The second peak corresponds to the interaction between the polymer and the protein at the level of amide II. INS-CS complexation processes not expected when INS is in its monomeric form, but for both tetrameric and hexameric forms, incipient complexation due to charge regulation mechanism took place at pH 5. The complexation range was observed to be 5.5 < pH < 6.5. In general, when the number of INS units increases in the simulation process, the solution pH at which the complexation can occur shifts toward acidic conditions. CS's chain interacts more efficiently, i.e. in a wider pH range, with INS aggregates formed by the highest monomer number. The charge regulation mechanism can be considered as a previous phase toward complexation (incipient complexation) caused by weak interactions of a Coulombic nature.

Blocking IL-2 Signal In Vivo with an IL-2 Antagonist Reduces Tumor Growth through the Control of Regulatory T Cells.

IL-2 is critical for peripheral tolerance mediated by regulatory T (Treg) cells, which represent an obstacle for effective cancer immunotherapy. Although IL-2 is important for effector (E) T cell function, it has been hypothesized that therapies blocking IL-2 signals weaken Treg cell activity, promoting immune responses. This hypothesis has been partially tested using anti-IL-2 or anti-IL-2R Abs with antitumor effects that cannot be exclusively attributed to lack of IL-2 signaling in vivo. In this work, we pursued an alternative strategy to block IL-2 signaling in vivo, taking advantage of the trimeric structure of the IL-2R. We designed an IL-2 mutant that conserves the capacity to bind to the αß-chains of the IL-2R but not to the γc-chain, thus having a reduced signaling capacity. We show our IL-2 mutein inhibits IL-2 Treg cell-dependent differentiation and expansion. Moreover, treatment with IL-2 mutein reduces Treg cell numbers and impairs tumor growth in mice. A mathematical model was used to better understand the effect of the mutein on Treg and E T cells, suggesting suitable strategies to improve its design. Our results show that it is enough to transiently inhibit IL-2 signaling to bias E and Treg cell balance in vivo toward immunity.

Dose-response study for the highly aggressive and metastatic primary F3II mammary carcinoma under direct current.

Electrochemical treatment has been suggested as an effective alternative to local cancer therapy. Nevertheless, its effectiveness decreases when highly aggressive primary tumors are treated. The aim of this research was to understand the growth kinetics of the highly aggressive and metastatic primary F3II tumor growing in male and female BALB/c/Cenp mice under electrochemical treatment. Different amounts of electric charge (6, 9, and 18 C) were used. Two electrodes were inserted into the base, perpendicular to the tumor's long axis, keeping about 1 cm distance between them. Results have shown that the F3II tumor is highly sensitive to direct current. The overall effectiveness (complete response + partial response) of this physical agent was ≥75.0% and observed in 59.3% (16/27) of treated F3II tumors. Complete remission of treated tumors was observed in 22.2% (6/27). An unexpected result was the death of 11 direct current-treated animals (eight females and three males). It is concluded that direct current may be addressed to significantly affect highly aggressive and metastatic primary tumor growth kinetics, including the tumor complete response. Bioelectromagnetics. 39:460-475, 2018. © 2018 Wiley Periodicals, Inc.

Human IL-2 mutein with higher antitumor efficacy than wild type IL-2.

IL-2 has been used for the treatment of melanoma and renal cell carcinoma, but this therapy has limited efficacy and severe toxicity. Currently, it is assumed that part of the limited efficacy is due to the IL-2-driven preferential expansion of regulatory T cells, which dampen the antitumor immunity. In this study, we characterize a human IL-2 mutant with higher antitumor efficacy and lower toxicity than wild type human IL-2 (wtIL-2). The mutant differs from wtIL-2 by four mutations at the interface with the α subunit of IL-2R. The IL-2 mutant induces in vitro proliferation of CD8(+)CD44(hi) and NK1.1 cells as efficiently as does wtIL-2, but it shows a reduced capacity to induce proliferation of CD4(+)Foxp3(+) regulatory T cells. The IL-2 mutant shows a higher antimetastatic effect than does wtIL-2 in several transplantable tumor models: the experimental metastasis model of MB16F0 melanoma and the experimental and spontaneous metastasis models for the mouse pulmonary carcinoma 3LL-D1222. Relevantly, the IL-2 mutant also exhibits lower lung and liver toxicity than does wtIL-2 when used at high doses in mice. In silico simulations, using a calibrated mathematical model, predict that the properties of IL-2 mutein are a consequence of the reduction, of at least two orders of magnitude, in its affinity for the α subunit of IL-2R (CD25). The human IL-2 mutant described in the present work could be a good candidate for improving cancer therapy based on IL-2.

Mapping mental health care services for children and youth population in Colombia's Pacific: potential for boundary spanning between community and formal services.

BACKGROUND: Conflict and violence can impact on the mental health of children and young people, who are in a crucial stage of their personal growth. Not much is known about the provision of mental health care to young people in conflict-affected areas. Community-based care can be essential, as state-led services are often scarce in conflict contexts, like Colombia's Pacific region where this research was conducted. According to the WHO, such care is ideally provided in the form of a network of interconnected services, offered by different actors beyond the formal health sector. This article describes the relationship between the formal and community mental health systems in Colombia's Pacific region, and identifies ways of improving their interaction. METHODS: Qualitative data were collected through 98 semi-structured interviews with community organisations, schools, international organisations and state institutions. These interviews aimed to identify the strategies used to promote young people's mental health and the interactions between the different providers. Boundary spanning theory was used to analyse how different actors and forms of mental health care provision could coordinate better. RESULTS: Community organisations and schools use a wide array of strategies to attend to the mental health of children and young people, often of a collective and psychosocial nature. State institutions offer more clinically focused strategies, which are however limited in terms of accessibility and continuity. International organisations aim to strengthen state capacity, but often struggle due to high staff turnover. Although mental health care pathways exist, their effectiveness is limited due to ineffective coordination between actors. CONCLUSIONS: To make sure that the variety of strategies to improve young people's mental health effectively reach their beneficiaries, better coordination is needed between the different actors. Mental health care pathways should therefore integrate community organisations, while community connectors can help to manage the coordination between different actors and forms of clinical and psychosocial support.

Modeling the role of IL2 in the interplay between CD4+ helper and regulatory T cells: studying the impact of IL2 modulation therapies.

Several reports in the literature have drawn a complex picture of the effect of treatments aiming to modulate IL2 activity in vivo. They seem to promote indistinctly immunity or tolerance, probably depending on the specific context, dose and timing of their application. Such complexity might derives from the dual role of IL2 on T-cell dynamics. To theoretically address the latter possibility, we develop a mathematical model for helper, regulatory and memory T-cells dynamics, which account for most well-known facts relative to their relationship with IL2. We simulate the effect of three types of therapies: IL2 injections, IL2 depletion using anti-IL2 antibodies and IL2/anti-IL2 immune complexes injection. We focus in the qualitative and quantitative conditions of dose and timing for these treatments which allow them to potentate either immunity or tolerance. Our results provide reasonable explanations for the existent pre-clinical and clinical data and further provide interesting practical guidelines to optimize the future application of these types of treatments. Particularly, our results predict that: (i) Immune complexes IL2/anti-IL2 mAbs, using mAbs which block the interaction of IL2 and CD25 (the alpha chain of IL2 receptor), is the best option to potentate immunity alone or in combination with vaccines. These complexes are optimal when a 1:2 molar ratio of mAb:IL2 is used and the mAbs have the largest possible affinity; (ii) Immune complexes IL2/anti-IL2 mAbs, using mAbs which block the interaction of IL2 and CD122 (the beta chain of IL2 receptor), are the best option to reinforce preexistent natural tolerance, for instance to prevent allograft rejection. These complexes are optimal when a 1:2 molar ratio of mAb:IL2 is used and the mAbs have intermediate affinities; (iii) mAbs anti-IL2 can be successfully used alone to treat an ongoing autoimmune disorder, promoting the re-induction of tolerance. The best strategy in this therapy is to start treatment with an initially high dose of the mAbs (one capable to induce some immune suppression) and then scales down slowly the dose of mAb in subsequent applications.

Carbapenem-Resistant Gram-Negative Bacilli Characterization in a Tertiary Care Center from El Bajio, Mexico.

Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a major public health concern. We aimed to evaluate the prevalence of CR-GNB and the frequency of carbapenemase-encoding genes in a tertiary referral center from El Bajio, Mexico. A cross-sectional study was conducted between January and October 2022; Gram-negative bacilli (GNB) were screened for in vitro resistance to at least one carbapenem. CR-GNB were further analyzed for carbapenemase-production through phenotypical methods and by real-time PCR for the following genes: blaKPC, blaGES, blaNDM, blaVIM, blaIMP, and blaOXA-48. In total, 37 out of 508 GNB were carbapenem-resistant (7.3%, 95% CI 5.2-9.9). Non-fermenters had higher rates of carbapenem resistance than Enterobacterales (32.5% vs. 2.6%; OR 18.3, 95% CI 8.5-39, p < 0.0001), and Enterobacter cloacae showed higher carbapenem resistance than other Enterobacterales (27% vs. 1.4%; OR 25.9, 95% CI 6.9-95, p < 0.0001). Only 15 (40.5%) CR-GNB had a carbapenemase-encoding gene; Enterobacterales were more likely to have a carbapenemase-encoding gene than non-fermenters (63.6% vs. 30.8%, p = 0.08); blaNDM-1 and blaNDM-5 were the main genes found in Enterobacterales; and blaIMP-75 was the most common for Pseudomonas aeruginosa. The mcr-2 gene was harbored in one polymyxin-resistant E. cloacae. In our setting, NDM was the most common carbapenemase; however, less than half of the CR-GNB showed a carbapenemase-encoding gene.

Carbohydrate-Derived Polytriazole Nanoparticles Enhance the Anti-Inflammatory Activity of Cilostazol.

Poly(amide-triazole) and poly(ester-triazole) synthesized from d-galactose as a renewable resource were applied for the synthesis of nanoparticles (NPs) by the emulsification/solvent evaporation method. The NPs were characterized as stable, spherical particles, and none of their components, including the stabilizer poly(vinyl alcohol), were cytotoxic for normal rat kidney cells. These NPs proved to be useful for the efficient encapsulation of cilostazol (CLZ), an antiplatelet and vasodilator drug currently used for the treatment of intermittent claudication, which is associated with undesired side-effects. In this context, the nanoencapsulation of CLZ was expected to improve its therapeutic administration. The carbohydrate-derived polymeric NPs were designed taking into account that the triazole rings of the polymer backbone could have attractive interactions with the tetrazole ring of CLZ. The activity of the nanoencapsulated CLZ was measured using a matrix metalloproteinase model in a lipopolysaccharide-induced inflammation system. Interestingly, the encapsulated drug exhibited enhanced anti-inflammatory activity in comparison with the free drug. The results are very promising since the stable, noncytotoxic NP systems efficiently reduced the inflammation response at low CLZ doses. In summary, the NPs were obtained through an innovative methodology that combines a carbohydrate-derived synthetic polymer, designed to interact with the drug, ease of preparation, adequate biological performance, and environmentally friendly production.

Hypertensive Stimuli Indirectly Stimulate Lymphangiogenesis through Immune Cell Secreted Factors.

(1) Background: Renal immune cells and lymphatic vessel (LV) density have been reported previously to be increased in multiple mouse models of hypertension (HTN). However, whether interstitial levels of HTN stimuli such as angiotensin II, salt, or asymmetric dimethylarginine have a direct or indirect effect on lymphangiogenesis is unknown. We hypothesized that these 3 HTN stimuli directly increase lymphatic endothelial cell (LEC) proliferation, LEC 3-D matrix invasion and vessel formation, and sprouting of mouse mesometrial LVs. (2) Methods: Human LECs (hLECs) and mouse LECs (mLECs) were treated with HTN stimuli while explanted mouse mesometrial LVs were treated with either the same HTN stimuli or with HTN stimuli-conditioned media. Conditioned media was prepared by treating murine splenocytes with HTN stimuli. (3) Results: HTN stimuli had no direct effect on hLEC or mLEC proliferation. Treatment of hLECs with HTN stimuli increased the number of lumen-forming structures and invasion distance (both p < 0.05) in the 3-D matrix but decreased the average lumen diameter and the number of cells per invading structure (both p < 0.05). Conditioned media from HTN-stimuli-treated splenocytes significantly attenuated the decrease in sprout number (aside from salt) and sprout length of mouse mesometrial LVs that is found in the HTN stimuli alone. (4) Conclusions: These data indicate that HTN stimuli indirectly prevent a decrease in lymphangiogenesis through secreted factors from HTN-stimuli-treated immune cells.

Prevalence of molar incisor hypomineralization in the city of Buenos Aires.

The prevalence of Molar Incisor Hypomineralization (MIH) still remains unknown in Argentina. The objectives of this work were to: estimate prevalence of MIH in a group of children seeking dental care in the city of Buenos Aires, analyze distribution according to year of birth and compare prevalence and severity of MIH in children with different access to health care services. A prospective, observational, transversal, descriptive study was designed, to be conducted on children seeking attention at Department of Comprehensive Children's Dentistry at the School of Dentistry of Buenos Aires University and at 3 pediatric dentistry offices attended by members of the team, located in Buenos Aires city (Kappa 0.933 0.911-0.952), from April to August 2010. The study included all children born between 1993 and 2003, whose 4 first molars and 8 permanent incisors had erupted. After prophylaxis and drying, the teeth were clinically evaluated and specially designed charts were used to record sex, year of birth, type of access to dental care, presence of MIH, number of affected incisors and molars, and maximum degree of severity for each tooth. The data obtained were analyzed using percentages, Fisher's Exact Test and Linear regression. 1098 children, mean age 11.3 years (11.08-11.39) were evaluated. Prevalence of MIH in this study was 15.9% (13.8-18.2). A highly significant positive correlation was obtained between MIH and year of birth (p<0.0001). Group A (private sector: prepaid medical insurance) was made up of 586 children (age: 10.92 6.22-15.62) while group B (public sector: university hospital) was made up of 512 children (age: 11.59 5.31-16.90). In Group A, MIH prevalence was 24.40% (20.9-27.9) while in Group B it was 6.44% (4.31-8.56) (p<0.0001). Of the affected molars, 37% (32.2-42) in A and 13.7% (6.7-23.8) in B had grade 3 lesions, with loss of enamel (p<0.0001). In this study, MIH was a frequent pathology (15.9%) and a significant increase was found according to year of birth during the study period. Patients with better access to health care had greater prevalence and degree of severity of MIH.

Modeling the role of IL-2 in the interplay between CD4+ helper and regulatory T cells: assessing general dynamical properties.

Mathematical models accounting for well-known evidences relating to the dynamics of interleukin 2, helper and regulatory T cells are presented. These models extend an existent model (the so-called cross-regulation model of immunity), by assuming IL-2 as the growth factor produced by helper cells, but used by both helper and regulatory cells to proliferate and survive. Two model variants, motivated by current literature, are explored. The first variant assumes that regulatory cells suppress helper cells by limiting IL-2 production and consuming the available IL-2; i.e. they just trigger competition for IL-2. The second model variant adds to the latter competitive mechanism the direct inhibition of helper cells activation by regulatory cells. The extended models retain key dynamical features of the cross-regulation model. But such reasonable behavior depends on parameter constraints, which happen to be realistic and lead to interesting biological discussions. Furthermore, the introduction of IL-2 in these models breaks the local/specific character of interactions, providing new properties to them. In the extended models, but not in the cross-regulation model, the response triggered by an antigen affects the response to other antigens in the same lymph node. The first model variant predicts an unrealistic coupling of the immune reactions to all the antigens in the lymph node. In contrast, the second model variant allows the coexistent of concomitant tolerant and immune responses to different antigens. The IL-2 derived from an ongoing immune reaction reinforces tolerance to other antigens in the same lymph node. Overall the models introduced here are useful extensions of the cross-regulation formalism. In particular, they might allow future studies of the effect of different IL-2 modulation therapies on CD4+ T cell dynamics.

Structural characterization of nanoemulsions stabilized with sodium caseinate and of the hydrogels prepared from them by acid-induced gelation.

Hydrogels obtained by acidification with glucono-δ-lactone (GDL), starting from nanoemulsions formulated with different concentrations of sodium caseinate (1-4 wt%) or 4 wt% sodium caseinate and sucrose (2-8 wt%), were prepared with the aim of quantifying structural parameters of both, initial nanoemulsions and hydrogels after 2.5 h of GDL addition, using the Guinier-Porod (GP) or the generalized GP models. Gelation process was followed by performing in situ temperature-controlled X-ray small angle scattering experiments (SAXS) using synchrotron radiation. In nanoemulsions, the calculated radius of gyration for oil nanodroplets (Rg oil ) decreased with increasing protein concentration and for the 4 wt% protein nanoemulsion, with increasing sucrose content. Calculated values of Rg oil were validated correlating them with experimental Z-average values as measured by dynamic light scattering (DLS). For hydrogels, radii of gyration for the sphere equivalent to the hydrogel scattering object (R gsph ) were close to 3 nm while correlation distances among building blocks (R g2 ) were dependent on formulation. They increased with increasing contents of sodium caseinate and sucrose. R g2 parameter linearly correlated with hydrogel strength (G' ∞ ): a more connected nanostructure led to a stronger hydrogel.

Resveratrol encapsulation in high molecular weight chitosan-based nanogels for applications in ocular treatments: Impact on human ARPE-19 culture cells.

Oxidative stress and inflammation play a pivotal role in ocular diseases. Resveratrol (RSV) is a natural bioactive that has recently attracted attention due to it potent antioxidant and anti-inflammatory properties. However, RSV presents poor aqueous solubility and chemical instability. Besides, effective drug delivery to the posterior segment of the eye is challenge. Nanotechnology emerges as a possible solution to improve both limitations. Here, we developed and characterized nanogels (NG) based on high molecular weight chitosan (HCS) crosslinked with sodium tripolyphosphate. The distribution size of NG presented a major population around 140 nm with a ζ-potential value of 32 ± 2 mV. TEM and AFM images showed that NG exhibited a rounded morphology. RSV encapsulation efficiency was 59 ± 1%. Photodegradation experiments showed that HCS by its own protects RSV from UV light-induced degradation. Biocompatibility assays revealed that NG were not cytotoxic neither inflammatory in human retinal pigment epithelial cells (ARPE-19), which constitutes the outer blood-retinal barrier. After cellular internalization, we report an endo-lysosomal escape of NG, which is crucial for efficient nanocarriers delivery systems. In conclusion, we envision that HCS based NG could constitute novel carriers for RSV, opening the possibility of its application in ocular diseases.

Serum Kynurenines Correlate With Depressive Symptoms and Disability in Poststroke Patients: A Cross-sectional Study.

BACKGROUND: Poststroke depression (PSD) is related to adverse functional and cognitive prognosis in stroke patients. The participation of kynurenine pathway metabolites in depression has been previously proposed; however, there are few studies on its role in PSD and disability in stroke. OBJECTIVE: To investigate if there is a correlation between serum kynurenines levels with poststroke anxiety and depression symptoms and disability scales. METHODS: A cross-sectional case-control study was conducted in patients with first stroke, of >1 month and <1 year of evolution, with no history of previous psychiatric or neurological disorders; the Hospital Anxiety and Depression Scale (HADS), Montreal Cognitive Assessment (MoCA), functional evaluations (Barthel index, Functional Independence Measure [FIM]) were applied and serum kynurenines (Kyns) were determined. RESULTS: Sixty patients were included; significant depressive symptoms were found in 63% of the cases; a significant and positive correlation was obtained between levels of 3-hydroxykynurenine (3-HK) with HADS-T (r = 0.30, P = .025) and HADS-D (r = 0.28, P = .039). Depressed patients showed significantly higher levels of 3HK (P = .048) and KYNA (P = .0271) than nondepressed patients; the 3HK levels were inversely correlated with functional scales: Barthel index (r = -0.31, P = .02), FIM (r = -0.40, P = .01); in addition, serum 3HK levels were significantly higher in patients with poor sleep quality (P = .0190). CONCLUSIONS: Serum Kyns show correlation with the presence and severity of depressive symptoms and with the disability and sleep quality. Kyns may be a potential marker of depression risk and disability in stroke in future.

Hepatocellular Carcinoma of Fibrolamellar Type in an Adolescent: Case Report and Literature Review.

We present a female patient, 13 years old, with diagnosis of hepatocellular carcinoma of fibrolamellar type, which was rapidly evolving. The fibrolamellar hepatocellular carcinoma invaded more than 80% of the hepatic parenchyma without surgical possibility or liver transplantation. Measures applied corresponded to chemotherapy of 1 cycle of cisplatin 40 mg/s/5 days + vincristine 1.5 mg/m2/day, 5-fluorouracil, doxorubicin, and dexrazoxane. The case presented aggressive evolution of hepatocellular carcinoma, which led to acute liver failure, with hyperammonemia, sepsis, pulmonary focus plus septic shock, grade III-IV encephalopathy, portal hypertension, and ascites with intra-abdominal hypertension. Death occurred due to multiple organ failure, which involved respiratory failure type KDIGO 1 and 2, acute liver failure, severe pneumonia, pericardial effusion, AKIN 2 acute kidney injury, carcinoma, and pulmonary metastasis. This type of ailment is infrequent in children and adolescents, and the first symptoms are crucial to achieve treatment possibilities.