Magnesium, selenium and zinc deficiency compromises antioxidant defense in women with obesity.

Studies have shown that deficiencies in magnesium, selenium, and zinc in individuals with obesity compromise the endogenous antioxidant defense system. This study aimed to evaluate the impact of mineral deficiency on enzymatic antioxidant defense in women with obesity. The study involved 63 women with obesity (BMI ≥ 35 kg/m2) and 77 eutrophic women (BMI between 18.5 and 24.9 kg/m2). Variables such as fasting glucose, glycated hemoglobin, fasting insulin, and serum lipids were analyzed. Insulin resistance was measured using the homeostasis assessment model (HOMA-IR) and beta cell function using the homeostasis assessment model (HOMA-ß). Dietary intake of energy, macronutrients (including magnesium, zinc, and selenium), and plasma, erythrocyte, and urinary concentrations of these minerals were measured and analyzed. Serum cortisol, plasma leptin, plasma thiobarbituric acid reactive substances, and the activity of erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPX), and erythrocyte catalase were also analyzed. Women with obesity had reduced plasma and erythrocyte concentrations and greater urinary excretion of all minerals compared to normal weight women (p < 0.05). There was a positive association between erythrocyte concentrations of zinc and selenium and the activity of the GPX and SOD enzymes in erythrocytes in women with obesity (p < 0.05), in addition to a positive association between serum insulin and the enzyme GPX, which is dependent on dietary selenium (p < 0.05). Individuals with obesity are deficient in magnesium, selenium, and zinc, which appears to impair the antioxidant defense system and contribute to important metabolic disorders such as oxidative stress in these patients.

Effect of photobiomodulation in an experimental in vitro model of asthma-Copd overlap.

The objective of the study was to evaluate the effect of photobiomodulation (PBM) with laser on the inflammatory process in an experimental in vitro model of ACO. The groups were: (1) human bronchial epithelial cells (BEAS-2B); (2) BEAS-2B cells treated with dexamethasone; (3) BEAS-2B cells irradiated with laser; (4) BEAS-2B cells stimulated with cigarette smoke extract (CSE) + House Dust Mite (HDM); (5) BEAS-2B cells stimulated with CSE + HDM and treated with dexamethasone; (6) BEAS-2B cells incubated with CSE + HDM and irradiated with laser. After 24 h, cytokines were quantified. There was a reduction in TNF-α, IL-1ß, IL-6, IL-4, IL-5, IL-13, IL-17, IL-21, IL-23, and an increase in IL-10 and IFN-γ in cells from the laser-irradiated ACO group compared to only ACO group. With these results, we can suggest that photobiomodulation acts in the modulation of inflammation observed in ACO, and may be a treatment option.

Mixed Reality in the Operating Room: A Systematic Review.

Mixed Reality is a technology that has gained attention due to its unique capabilities for accessing and visualizing information. When integrated with voice control mechanisms, gestures and even iris movement, it becomes a valuable tool for medicine. These features are particularly appealing for the operating room and surgical learning, where access to information and freedom of hand operation are fundamental. This study examines the most significant research on mixed reality in the operating room over the past five years, to identify the trends, use cases, its applications and limitations. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to answer the research questions established using the PICO (Population, Intervention, Comparator and Outcome) framework. Although implementation of Mixed Reality applications in the operations room presents some challenges, when used appropriately, it can yield remarkable results. It can make learning easier, flatten the learning curve for several procedures, and facilitate various aspects of the surgical processes. The articles' conclusions highlight the potential benefits of these innovations in surgical practice while acknowledging the challenges that must be addressed. Technical complexity, equipment costs, and steep learning curves present significant obstacles to the widespread adoption of Mixed Reality and computer-assisted evaluation. The need for more flexible approaches and comprehensive studies is underscored by the specificity of procedures and limited samples sizes. The integration of imaging modalities and innovative functionalities holds promise for clinical applications. However, it is important to consider issues related to usability, bias, and statistical analyses. Mixed Reality offers significant benefits, but there are still open challenges such as ergonomic issues, limited field of view, and battery autonomy that must be addressed to ensure widespread acceptance.

Photoprotective potential of Passiflora cincinnata Mast. (Passifloraceae) hydro-alcoholic extracts.

Passiflora cincinnata is a Passifloraceae typical of the Caatinga, a biome unique to Brazil. It has various pharmacological properties associated with its high flavonoid content. Vitexin, isovitexin, orientin, isoorientin and derivatives are the main chemical and pharmacological markers for this plant. Although flavonoids enriched-extracts have been widely applied in phytocosmetics, especially in sunscreen formulations, the use of P. cincinnata as a photoprotective ingredient remains unexplored. Different hydro-alcoholic extracts were prepared and their antioxidant and photoprotective activities were evaluated by in vitro assays. The most promising extract (Pc-1) was analyzed by HPLC-DAD-ESI-MS/MS. Nine flavonoids were identified as major compounds: isovitexin-7-O-glucoside, isoorientin-2"O-hexoside, orientin, isoorientin, isovitexin-2"-O-glucoside, isovitexin-6"-O-glucoside, isoscoparin and isoquercitrin. Finally, Pc-1 (5 and 10%, v/v) was incorporated into gel formulations, alone or combined to commercial chemical filters (benzophenone-3 and octyl methoxycinnamate). Formulations containing Pc-1 showed high SPFspectrophotometric values. When combined to commercial filters, Pc-1 (5%) potentiated their photoprotective efficacy (p<0.05). A physicochemical characterization indicated no incompatibility or signs of instability after extract incorporation. Altogether, these findings encourage the use of Pc-1 as a photoprotective ingredient or co-adjuvant in sunscreens formulations.

Alloreactive memory CD4 T cells promote transplant rejection by engaging DCs to induce innate inflammation and CD8 T cell priming.

Alloreactive memory T cells have been implicated as central drivers of transplant rejection. Perplexingly, innate cytokines, such as IL-6, IL-1ß, and IL-12, are also associated with rejection of organ transplants. However, the pathways of innate immune activation in allogeneic transplantation are unclear. While the role of microbial and cell death products has been previously described, we identified alloreactive memory CD4 T cells as the primary triggers of innate inflammation. Memory CD4 T cells engaged MHC II-mismatched dendritic cells (DCs), leading to the production of innate inflammatory cytokines. This innate inflammation was independent of several pattern recognition receptors and was primarily driven by TNF superfamily ligands expressed by alloreactive memory CD4 T cells. Blocking of CD40L and TNFα resulted in dampened inflammation, and mice genetically deficient in these molecules exhibited prolonged survival of cardiac allografts. Furthermore, myeloid cell and CD8 T cell infiltration into cardiac transplants was compromised in both CD40L- and TNFα-deficient recipients. Strikingly, we found that priming of naive alloreactive CD8 T cells was dependent on licensing of DCs by memory CD4 T cells. This study unravels the key mechanisms by which alloreactive memory CD4 T cells contribute to destructive pathology and transplant rejection.

Fish Fillet Analogue Using Formulation Based on Mushroom (Pleurotus ostreatus) and Enzymatic Treatment: Texture, Sensory, Aromatic Profile and Physicochemical Characterization.

The growing demand for alternative sources of non-animal proteins has stimulated research in this area. Mushrooms show potential in the innovation of plant-based food products. In this study, the aim was to develop prototype fish fillets analogues from Pleurotus ostreatus mushrooms applying enzymatic treatment (ß-glucanase and transglutaminase-TG). A Plackett-Burman 20 experimental design was used to optimize forty variables. Oat flour (OF) exerted a positive effect on the hardness and gumminess texture parameters but a negative effect on cohesiveness and resilience. Soy protein isolate (SPI) exhibited a positive effect on elasticity, gumminess and chewiness, while acacia gum had a negative effect on elasticity, cohesiveness and resilience. After sensory analysis the assay with 1% cassava starch, 5% OF, 5% SPI, 0.1% transglutaminase (240 min/5 °C), 1% coconut oil, 1% soybean oil, 0.2% sodium tripolyphosphate, 0.6% ß-glucanase (80 °C/10 min) and without ß-glucanase inactivation was found to exhibit greater similarity to fish fillet. The classes hydrocarbons, alcohols and aldehydes are the predominant ones in aromatic profile analysis by chromatography and electronic nose. It is concluded that a mushroom-based analogue of fish fillet can be prepared using enzymatic treatment with TG.

Effect of photobiomodulation with different wavelengths on periodontal repair in non-hyperglycemic and hyperglycemic rats.

BACKGROUND: Hyperglycemic conditions is associated with more severe periodontitis and poorer outcomes after nonsurgical periodontal treatment (NPT). Then, these patients are candidates for adjunctive therapy associated with NPT. This study evaluates the effect of photobiomodulation (PBMT) at different wavelengths on periodontal repair in non-hyperglycemic/hyperglycemic animals. MATERIALS AND METHODS: Sixty-four rats were submitted to induction of periodontitis by ligatures. Hyperglycemia was induced in half of these animals, whereas the other half remained non-hyperglycemic. The animals were subdivided into 4 groups according to the PBMT protocol applied at the time of ligature removal (n = 8): CTR: Without PBMT; IRL: PBMT with infrared laser (808 nm); RL: PBMT with red laser (660 nm); and RL-IRL: PBMT with red (660 nm) and infrared laser (808 nm). After a period of 7 days, the animals were euthanized. The parameters assessed by microtomography were the bone volume relative to total tissue volume (BV/TV%), distance from the cemento-enamel junction to the top of the bone crest (CEJ-CB), trabecular thickness, space between trabeculae, and number of trabeculae. Additionally, the percentage of inflammatory cells, blood vessels, and connective tissue matrix were assessed by histomorphometric analysis. RESULTS: PBMT reduced bone loss and increased trabecular density in hyperglycemic animals (p < .05), with RL being more effective in reducing linear bone loss (CEJ-CB), whereas RL-IRL was more effective in maintaining BV/TV%. PBMT reduced blood vessels and increased the connective tissue component in hyperglycemic animals (p < .05). RL-IRL reduced inflammatory cells regardless of the systemic condition of the animal (p < .05). CONCLUSION: PBMT (RL, RL-IRL) improves the repair of periodontal tissues in hyperglycemic animals.

Cellular senescence and sleep in childhood and adolescence: A scoping review focusing on sleep-disordered breathing.

BACKGROUND: Sleep is a fundamental and complex physiological process whose duration decreases and characteristics change with age. Around 50 % of children will experience sleep disturbances at some point in their early life. Sleep disturbances can result in a number of deleterious consequences, including alterations in the levels of cellular senescence (CS) markers. CS is a complex process essential for homeostasis characterized by the irreversible loss of cell proliferation capacity; however, the accumulation of senescent cells can lead to age-related diseases. OBJECTIVE: In this review, our objective was to gather information about the relationship between sleep duration, sleep-disordered breathing (SDB) and cellular senescence markers, namely: oxidative stress, inflammation, insulin-like growth factor 1 (IGF-1), and growth hormone (GH) in newborns, children, and teenagers. METHODS: To achieve this, we searched six databases: MEDLINE, Scopus, LILACS, Web of Science, Embase, and SciELO, and identified 20 articles that met our inclusion criteria. RESULTS: Our results show that better sleep quality and duration and, both the surgical and non-surgical treatment of sleep disorders are associated with a reduction in oxidative stress, inflammation, and telomeric attrition levels. Furthermore, our results also show that surgical treatment for SDB significantly reduced the levels of cellular senescence markers. Further studies need to be conducted in this area, particularly longitudinal studies, for a greater understanding of the mechanisms involved in the relationship between sleep and senescence. CONCLUSION: Better sleep quality and duration were associated with less oxidative stress, inflammation, and telomeric attrition and a higher level of IGF-1 in children and teenagers.

Anticancer, anti-inflammatory and analgesic activities of aminoalcohol-based quinoxaline small molecules.

PURPOSE: Bioactive molecules are relevant to fight cancer and associated conditions. Quinoxaline is a privileged N-heterocycle, notably as anticancer agents. Herein, we report the evaluation of the quinoxaline derivatives DEQX and OAQX as anticancer agents, as well as in function of their anti-inflammatory and analgesic activities. METHODS: Quinoxalines were synthesized and tested as anticancer agents based on cell viability and Annexin V-FITC apoptosis. Anti-inflammatory activity was evaluated from mouse carrageenan peritonitis and levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-alfa for enzyme-linked immunosorbent assay. Hot-plate and acetic acid-induced writing test were employed to investigate analgesia. RESULTS: Both reduced the Ht-29 cell viability in a dependent-concentration manner (p < 0.001). Total apoptosis was detected for cells treated with 12.5 and 25 µg/mL of both the compounds for 24 and 48 h (all doses, p < 0.0001). DEQX (all doses, p < 0.01) and OAQX (all doses, p < 0.001) acted in leukocyte migration and decreased the IL-1ß and TNF-ß levels (p < 0.05). DEQX (all doses, p < 0.05) and OAQX (5mg/kg, p < 0.001) showed peripheral analgesic effect. CONCLUSIONS: In-vitro and in-vivo results suggest that these quinoxalines are promising for application in pharmacological area due to their anticancer, anti-inflammatory, and peripheric analgesia.

Exploring antiviral and antiparasitic activity of gold N-heterocyclic carbenes with thiolate ligands.

Gold(I) N-heterocyclic carbenes have been explored for their therapeutic potential against several diseases. Neglected tropical diseases, including leishmaniasis, Chagas disease, and viral infections, such as zika, mayaro, and chikungunya, urgently require new treatment options. The emergent SARS-CoV-2 also demands significant attention. Gold complexes have shown promise as alternative treatments for these conditions. Previously, gold(I)(1,3-bis(mesityl)imidazole-2-ylidene)Cl (AuIMesCl) demonstrated significant leishmanicidal and anti-Chikungunya virus activities. In this study, we synthesized and fully characterized a series of gold(I)(1,3-bis(mesityl)imidazole-2-ylidene)(SR) complexes, where SR includes thiolate donor species such as 1,3-thiazolidine-2-thione, 1,3-benzothiazole-2-thione, 2-mercaptopyrimidine, and 2-thiouracil. These compounds were stable in solution, and ligand exchange reactions with N-acetyl-L-cysteine indicated that complexes with SR ligands are more labile than those with chloride. Although the reactions are rapid, they reach equilibrium at varying molar ratios depending on the SR ligand. The increased lability of these compounds results in higher cytotoxicity to host cells, such as Vero E6 and bone marrow-differentiated macrophages, compared to AuIMesCl. Despite this, the compounds effectively inhibited viral replication, achieving 95.5% inhibition of Zika virus replication at 2 µM with 96% host cell viability. Although active at low concentrations (∼2 µM) against Leishmania (L.) amazonensis and Trypanosoma cruzi, their high cytotoxicity for macrophages confirmed AuIMesCl as a better candidate with a higher selectivity index. This work correlates the coordination chemistry of pyrimidines and thiazolidines with their in vitro biological activities against significant diseases.

Enhancing stress resilience in soybeans (Glycine max): assessing the efficacy of priming and cross-priming for mitigating water deficit and waterlogging effects.

Priming enables plants to respond more promptly, minimise damage, and survive subsequent stress events. Here, we aimed to assess the efficacy of priming and cross-priming in mitigating the stress caused by waterlogging and/or dehydration in soybeans (Glycine max ). Soybean plants were cultivated in a greenhouse in plastic pots in which soil moisture was maintained at pot capacity through irrigation. The first stress was applied in plants at the vegetative stage for 5days and involved either dehydration or waterlogging, depending on the treatment. Subsequently, the plants were irrigated or drained and maintained at pot capacity until the second stress. For the second stress, the conditions were repeated in plants at the reproductive stage. We then evaluated the levels of hydrogen peroxide (H2 O2 ), lipid peroxidation, total soluble sugars (TSS), amino acids, proline, and starch, and the activity of antioxidant, fermentative, and aminotransferase enzymes. Under waterlogging and dehydration, priming and cross-priming significantly increased the activity of antioxidant enzymes and the levels of TSS, amino acids, and proline while reducing H2 O2 concentration and lipid peroxidation. Under waterlogging, priming suppressed fermentative activity and increased carbohydrate content. This demonstrates that soybean plants activate their defence systems more promptly when subjected to priming.

Repeated saline injections reduce the pulmonary allergic inflammatory response in rats by inducing short-term stress.

Purpose: Asthma is characterized by pulmonary cell infiltration and hyper-responsiveness of the airways. Short-term stress reduces airway inflammation. Thus, in the present study, we examined the effects of short-term stress induced by repeated treatment with saline injections on the pulmonary allergic inflammatory response in rats. Methods: Adult male rats were divided into three groups: Naïve group (non-sensitized, challenged, or treated rats), Control group (rats sensitized with ovalbumin (OVA) to induce lung inflammation), and Saline group (rats treated for five days with saline before OVA sensitization). Inhalation challenges were performed one week after the booster with aerosolized OVA. On day 18, the effect of saline injections on total and differential leukocytes in bronchoalveolar lavage (BAL), femoral marrow lavage (FML), and blood was evaluated. The percentage of mucus, serum corticosterone, collagen, cytokines in lung explants, and norepinephrine levels were also measured. Results: OVA sensitization increased the circulating leukocytes and their migration to the lung, decreasing the bone marrow leukocytes. The repeated saline injections prevented this migration by decreasing the number of leukocytes in BAL and blood in the control group. Cytokine Interleukin-4 (IL-4) was higher in the control group than in the naive and saline groups; cytokines Interleukin-6 (IL-6), Interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNFα) were higher in the control and saline groups than in the naïve group; Interferon gamma (IFNγ) was higher in the saline group than in the naive and control groups; norepinephrine increased in animals sensitized with OVA and was higher only in the saline group relative to the naïve group. Conclusions: These results suggest that short-term stress could contribute to the anti-allergic airway inflammation effects of a given treatment.

An engineered POSS drug delivery system for copper(II) anticancer metallodrugs in a selective application toward melanoma cells.

In this work, a polyhedral silsesquioxane (POSS) was used as an engineered drug delivery system for two oxindolimine-copper(II) anticancer complexes, [Cu(isaepy)]+ and [Cu(isapn)]+. The interest in hybrid POSS comes from the necessity of developing materials that can act as adjuvants to improve the cytotoxicity of non-soluble metallodrugs. Functionalization of POSS with a triazole ligand (POSS-atzac) permitted the anchorage of such copper complexes, producing hybrid materials with efficient cytotoxic effects. Structural and morphological characterizations of these copper-POSS systems were performed by using different techniques (IR, NMR, thermogravimetric analysis). A combination of continuous-wave (CW) and pulsed EPR (HYSCORE) spectroscopies conducted at the X-band have enabled the complete characterization of the coordination environment of the copper ion in the POSS-atzac matrix. Additionally, the cytotoxic effects of the loaded materials, [Cu(isapn)]@POSS-atzac and [Cu(isaepy)]@POSS-atzac, were assessed toward melanomas (SK-MEL), in comparison to non-tumorigenic cells (fibroblast P4). Evaluation of their nuclease activity or ability to facilitate cleavage of DNA indicated concentrations as low as 0.6 µg mL-1, while complete DNA fragmentation was observed at 25 µg mL-1. By using adequate scavengers, investigations on active intermediates responsible for their cytotoxicity were performed, both in the absence and in the presence of ascorbate as a reducing agent. Based on the observed selective cytotoxicity of these materials toward melanomas, investigations on the reactivity of these complexes and corresponding POSS-materials with melanin, a molecule that contributes to melanoma resistance to chemotherapy, were carried out. Results indicated the main role of the binuclear copper species, formed at the surface of the silica matrix, in the observed reactivity and selectivity of these copper-POSS systems.

Development and validation of Mayaro virus with luciferase reporter genes as a tool for antiviral assays.

Arboviruses are etiological agents in an extensive group of emerging diseases with great clinical relevance in Brazil, due to the wide distribution of their vectors and the favorable environmental conditions. Among them, the Mayaro virus (MAYV) has drawn attention since its emergence as the etiologic agent of Mayaro fever, a highly debilitating disease. To study viral replication and identify new drug candidates, traditional antiviral assays based on viral antigens and/or plaque assays have been demonstrating low throughput, making it difficult to carry out larger-scale assays. Therefore, we developed and characterized two DNA-launched infectious clones reporter viruses based on the MAYV strain BeAr 20290 containing the reporter genes of firefly luciferase (FLuc) and nanoluciferase (NLuc), designated as MAYV-firefly and MAYV-nanoluc, respectively. The viruses replicated efficiently with similar properties to the parental wild-type MAYV, and luminescence expression levels reflected viral replication. Reporter genes were also preserved during passage in cell culture, remaining stably expressed for one round of passage for MAYV-firefly and three rounds for MAYV-nanoluc. Employing the infectious clone, we described the effect of Rimantadine, an FDA-approved Alzheimer's drug, as a repurposing agent for MAYV but with a broad-spectrum activity against Zika virus infection. Additionally, we validated MAYV-nanoluc as a tool for antiviral drug screening using the compound EIDD-2749 (4'-Fluorouridine), which acts as an inhibitor of alphavirus RNA-dependent RNA polymerase.

Juvenile Nasopharyngeal Angiofibroma: A Series of 96 Surgical Cases.

Introduction Juvenile nasopharyngeal angiofibroma (JNA) is a benign vascularized tumor that affects almost exclusively male adolescents. Surgery is the treatment of choice for JNA. Objectives The present study is a 42-year retrospective review of a series of JNA cases treated surgically without previous embolization. Methods The present is a retrospective, descriptive study based on medical records of 96 patients with JNA who underwent microscopic or endoscopic excision without previous embolization from 1978 to 2020 in a single institution. The patients were categorized according to the Andrews et al. stage, and data were collected on age, gender, tumor staging, surgical approach, affected side, and outcome. Results All patients were male, with an average age of 17 years. The predominant tumor stage consisted of type II, with 52.1%. A total of 33.3% of the patients were submitted to the microscopic technique and 66.7%, to the endonasal technique. The rate of intraoperative blood transfusion was of 17.7%. Conclusion The present study reinforces that resection of JNA in various stages is viable without previous artery embolization.

UV light and adaptive divergence of leaf physiology, anatomy, and ultrastructure drive heat stress tolerance in genetically distant grapevines.

The genetic basis of plant response to light and heat stresses had been unveiled, and different molecular mechanisms of leaf cell homeostasis to keep high physiological performances were recognized in grapevine varieties. However, the ability to develop heat stress tolerance strategies must be further elucidated since the morpho-anatomical and physiological traits involved may vary with genotype × environment combination, stress intensity, and duration. A 3-year experiment was conducted on potted plants of Sardinian red grapevine cultivars Cannonau (syn. Grenache) and Carignano (syn. Carignan), exposed to prolonged heat stress inside a UV-blocking greenhouse, either submitted to low daily UV-B doses of 4.63 kJ m-2 d-1 (+UV) or to 0 kJ m-2 d-1 (-UV), and compared to a control (C) exposed to solar radiation (4.05 kJ m-2 d-1 average UV-B dose). Irrigation was supplied to avoid water stress, and canopy light and thermal microclimate were monitored continuously. Heat stress exceeded one-third of the duration inside the greenhouse and 6% in C. In vivo spectroscopy, including leaf reflectance and fluorescence, allowed for characterizing different patterns of leaf traits and metabolites involved in oxidative stress protection. Cannonau showed lower stomatal conductance under C (200 mmol m-2 s-1) but more than twice the values inside the greenhouse (400 to 900 mmol m-2 s-1), where water use efficiency was reduced similarly in both varieties. Under severe heat stress and -UV, Cannonau showed a sharper decrease in primary photochemical activity and higher leaf pigment reflectance indexes and leaf mass area. UV-B increased the leaf pigments, especially in Carignano, and different leaf cell regulatory traits to prevent oxidative damage were observed in leaf cross-sections. Heat stress induced chloroplast swelling, plastoglobule diffusion, and the accumulation of secretion deposits in both varieties, aggravated in Cannonau -UV by cell vacuolation, membrane dilation, and diffused leaf blade spot swelling. Conversely, in Carignano UV-B, cell wall barriers and calcium oxalate crystals proliferated in mesophyll cells. These responses suggest an adaptive divergence among cultivars to prolonged heat stress and UV-B light. Further research on grapevine biodiversity, heat, and UV-B light interactions may give new insights on the extent of stress tolerance to improve viticulture adaptive strategies in climate change hotspots.

Imiquimod-Loaded Nanosystem for Treatment Human Papillomavirus-Induced Lesions.

Human papillomavirus (HPV)-associated cervical cancer is the most common cancer among women worldwide. The treatment options are strongly related to increased infertility in women. Imiquimod (IQ) is an imidazoquinoline, which has proven antiviral effects against persistent HPV infection by activating immune cells via Toll-like receptors 7/8 when formulated in carriers, like nanogels, for topical use. An effective alternative to conventional therapies is the nanoparticle drug delivery system. We studied lipidic nanoparticles with IQ (Lipo IQ) and functionalized them with a DNA aptamer, AT11 (Lipo IQ AT11), to improve the selectivity for cervical cancer cells combined with the efficacy of essential oils. The formulations showed that the physicochemical properties are adequate for vaginal drug delivery and have antimicrobial activity at higher concentrations (with MIC50 starting from 0.625%). The final formulations exhibited cytotoxicity in cancer cells, enhanced by essential oils without affecting healthy cells, resulting in less than 10% cell viability in HeLa cells and over 60% in NHDF cells. Essential oils potentiate Lipo IQ's effectiveness, while AT11 increases the selectivity for cervical cancer cells. As suggested by the results of the permeation assay, the formulations were internalized by the cancer cells. Overall, the obtained results suggested that the synergistic effect of the essential oils and the nanosystem potentiate the cytotoxic effect of Lipo IQ and that Lipo IQ AT11 promotes selectivity towards cancer cells.

Streamlining Skin Regeneration: A Ready-To-Use Silk Bilayer Wound Dressing.

Silk proteins have been highlighted in the past decade for tissue engineering (TE) and skin regeneration due to their biocompatibility, biodegradability, and exceptional mechanical properties. While silk fibroin (SF) has high structural and mechanical stability with high potential as an external protective layer, traditionally discarded sericin (SS) has shown great potential as a natural-based hydrogel, promoting cell-cell interactions, making it an ideal material for direct wound contact. In this context, the present study proposes a new wound dressing approach by developing an SS/SF bilayer construct for full-thickness exudative wounds. The processing methodology implemented included an innovation element and the cryopreservation of the SS intrinsic secondary structure, followed by rehydration to produce a hydrogel layer, which was integrated with a salt-leached SF scaffold to produce a bilayer structure. In addition, a sterilization protocol was developed using supercritical technology (sCO2) to allow an industrial scale-up. The resulting bilayer material presented high porosity (>85%) and interconnectivity while promoting cell adhesion, proliferation, and infiltration of human dermal fibroblasts (HDFs). SS and SF exhibit distinct secondary structures, pore sizes, and swelling properties, opening new possibilities for dual-phased systems that accommodate the different needs of a wound during the healing process. The innovative SS hydrogel layer highlights the transformative potential of the proposed bilayer system for biomedical therapeutics and TE, offering insights into novel wound dressing fabrication.

Knowledge in Inflammatory Bowel Disease: Translation to Portuguese, Validation, and Clinical Application of the IBD-KNOW Questionnaire.

Background/Aims: Inflammatory bowel disease (IBD)-related knowledge empowers patients, providing the development of adaptative coping strategies. Recently, a more comprehensive questionnaire for evaluating IBD-related knowledge was developed, the IBD-KNOW. The main aim of our study was to translate to Portuguese and validate the IBD-KNOW questionnaire. We also explored the predictors of high scores of disease-related knowledge and the effect of knowledge on health-related quality of life (HRQoL) and therapeutic adherence. Methods: This is an observational, unicentric, and cross-sectional study. We translated and adapted the original English version of the IBD-KNOW questionnaire into Portuguese. Afterwards, IBD patients in the outpatient clinics were invited to fill out a multimodal form including the Portuguese version of IBD-KNOW, a visual analogue scale (VAS) of self-perceived knowledge, the Portuguese version of Short IBD Questionnaire (SIBDQ) and the Portuguese version of Morisky Adherence Scale 8-item (MMAS-8). Demographic and disease characteristics were collected. We assessed validity (through discriminate validity among non-IBD volunteers and correlation between IBD-KNOW and VAS) and reliability (through internal consistency, test-retest, and intraclass correlation). Statistical analysis was performed using SPSS version 25.0. Results: The mean IBD-KNOW score was significantly different among non-IBD validation group (doctors: 23, nurses: 18, and non-medical volunteers: 12, p < 0.001). IBD-KNOW showed a high internal consistency (Cronbach's α 0.78) and intraclass correlation (0.90). As expected, the IBD-KNOW score was positively correlated with VAS for self-perceived knowledge (r = 0.45, p < 0.001). One hundred and one patients with IBD (54 with ulcerative colitis and 47 with Crohn's disease) completed the questionnaire at baseline. Multivariate analyses showed that a high IBD-KNOW score was associated with longer disease duration (OR: 2.59 [CI 1.11-5.74]; p = 0.04), previous hospitalization (OR: 3.63 [CI 1.301-9.96]; p = 0.01), current biologic treatment (OR: 3.37 [CI 1.31-8.65]; p = 0.02), and higher educational level (OR: 4.66 [CI 1.74-10.21]; p = 0.02). Moreover, there was no significant correlation between overall IBD-KNOW and SIBDQ, nor between IBD treatment adherence (MMAS-8 = 8) and a higher mean IBD-KNOW score (p = 0.552). Conclusion: The Portuguese version of IBD-KNOW is a simple, valid, and reliable tool for assessing IBD-related knowledge. Longer disease duration, hospitalization, use of biologics, and higher educational level are associated with higher levels of knowledge. Higher patient knowledge was not associated with higher HRQoL and adherence to therapy.

Introdução/objetivos: O conhecimento relacionado com a Doença Inflamatória Intestinal (DII) visa capacitar os doentes, proporcionando o desenvolvimento de estratégias adaptativas de coping. Recentemente, foi desenvolvido um questionário mais abrangente para avaliar os conhecimentos relacionados com a DII, o IBD-KNOW. O principal objetivo do nosso estudo foi traduzir para português e validar o questionário IBD-KNOW. Também explorámos os preditores de um elevado nível de conhecimento relacionado com a DII e avaliámos o impacto do conhecimento na qualidade de vida associada a cuidados de saúde (QVACS) e na adesão terapêutica. Métodos: Este é um estudo observacional, unicêntrico e transversal. Traduzimos e adaptámos para português a versão original inglesa do questionário IBD-KNOW. Posteriormente, os doentes com DII de ambulatório foram convidados a preencher um questionário multimodal que incluía, a versão portuguesa do IBD-KNOW, uma escala visual analógica (EVA) de autoperceção do conhecimento, a versão portuguesa do Short IBD Questionnaire (SIBDQ) e a versão portuguesa do Morisky Adherence Scale 8-item (MMAS-8). Foram colhidos dados referentes a aspetos demográficos e da doença. Avaliámos a validade (através da validade discriminatória entre voluntários sem DII e da correlação entre IBD-KNOW e a EVA) e a fiabilidade (através da consistência interna, do teste-reteste e da correlação intraclasse). A análise estatística foi realizada utilizando a versão 25.0 do SPSS. Resultados: A pontuação média do IBD-KNOW foi significativamente diferente entre os voluntários não-DII (médicos: 23, enfermeiros: 18 e voluntários não-médicos: 12, p < 0,001). O IBD-KNOW mostrou uma elevada consistência interna (Cronbach's α 0,78) e uma correlação intraclasse (0,90). Como esperado, a pontuação IBD-KNOW correlacionou-se positivamente com a EVA de autoperceção do conhecimento (r=0,45, p < 0,001). Cento e um doentes com DII (54 com colite ulcerosa e 47 com doença de Crohn) preencheram o questionário. A análise multivariada mostrou valores médios de IBD-KNOW superiores em indivíduos com doença de longa duração (OR: 2,59; [IC 1,11-5,74] p=0,04), hospitalização prévia (OR 3,63 [IC 1,301-9,96]; p=0,01), sob tratamento biológico atual (OR 3,37 [1,31-8,65]; p=0,02) e com nível educacional superior (OR 4,66 [IC 1,74-10,21]; p=0,02). Além disso, não houve correlação significativa entre IBD-KNOW e SIBDQ, nem entre a adesão ao tratamento IBD (MMAS-8=8) e um IBD-KNOW acima da média (p=0,552). Conclusão: A versão portuguesa do IBD-KNOW é uma ferramenta simples, válida e fiável para avaliar os conhecimentos relacionados com a DII. Uma maior duração da doença, hospitalização, utilização de biológicos e um nível de educação mais elevado estão associados a níveis de conhecimento mais elevados. Na nossa coorte, níveis superiores de conhecimento não se associaram a melhor qualidade de vida nem a maior adesão à terapêutica.