Representação social da Covid-19 para a população de uma cidade de pequeno porte / Social representation of Covid-19 for the population of a small-sized city / Representación social del Covid-19 para la población de un pequeño pueblo

Objetivo: analisar a representação social da Covid-19 para a população geral de uma cidade de pequeno porte do Estado do Rio de Janeiro. Método: estudo qualitativo, apoiado na abordagem estrutural das representações sociais. Participaram 100 usuários de serviços de saúde. Os dados foram coletados por questionário sociodemográfico de evocações livres de palavras e roteiro de entrevista semiestruturada. Os dados foram analisados com o auxílio dos softwares Excel, EVOC 2005 e análise de conteúdo temático-categorial para contextualização das evocações respectivamente. Resultados: os termos do possível núcleo central foram: morte, sofrimento, cuidados, ansiedade-angústia e vacina. Na primeira periferia: medo e prevenção. À segunda periferia: informação-desinformação; desgoverno; ter-fé e proteção. A zona de contrate: doença; isolamento-social; dificuldades; catástrofe-mundial; desemprego e pandemia. Considerações finais: marcaram essa representação os impactos psicossociais negativos resultantes da desestruturação da vida e das mortes ocasionadas pela nova doença, no entanto o grupo aderiu as medidas de cuidados de proteção.

Objective: to analyze the social representation of Covid-19 among the general population of a small-sized city in the State of Rio de Janeiro. Method: Qualitative study, based on the structural approach of social representations. One hundred healthcare service users participated. Data were collected through a sociodemographic questionnaire, free word evocation, and a semi-structured interview guide. The data were analyzed using Excel software, EVOC 2005, and thematic-categorical content analysis for contextualization of the evocations, respectively. Results: the terms of the possible central core were: death, suffering, care, anxiety-distress, and vaccine. In the first periphery: fear and prevention. In the second periphery: information-misinformation; mismanagement; having faith and protection. The contrast zone: disease; social isolation; difficulties; global catastrophe; unemployment; and pandemic. Final considerations: this representation was marked by the negative psychosocial impacts resulting from the disruption of life and the deaths caused by the new disease; however, the group adhered to protective care measures.

Objetivo: analizar la representación social del Covid-19 para la población general de una pequeña ciudad del Estado de Río de Janeiro. Método: estudio cualitativo, basado en el enfoque estructural de las representaciones sociales. Participaron 100 usuarios de servicios de salud. Los datos se recolectaron mediante un cuestionario sociodemográfico con evocación libre de palabras y una guía de entrevista semiestructurada. Los datos fueron analizados utilizando lo software Excel y EVOC 2005 y análisis de contenido temático-categórico para contextualizar las evocaciones respectivamente. Resultados: los términos del posible núcleo central eran: muerte, sufrimiento, cuidados, ansiedad-angustia y vacuna. En la primera periferia: miedo y prevención. En la segunda periferia: información-desinformación; desgobierno; tener fe y protección. La zona de contraste: enfermedad; aislamiento-social; dificultades; catástrofe-mundial; desempleo y pandemia. Consideraciones finales: esta representación se caracterizó por los impactos psicosociales negativos derivados de la desestructuración de la vida y de las muertes causada por la nueva enfermedad, sin embargo, el grupo adhirió a las medidas de protección.

The impact of periodontitis and periodontal treatment on rheumatoid arthritis outcomes: an exploratory clinical trial.

OBJECTIVE: Studies suggest rheumatoid arthritis (RA) patients could benefit from periodontal treatment. However, published data are inconsistent, and there is a need for better-controlled research. Our study aims to address these limitations. METHODS: In this exploratory randomised delayed-start study, 22 RA patients with moderate/severe periodontitis were subjected to full-mouth debridement. Periodontal and rheumatological assessments, including measuring anti-cyclic citrullinated peptide 2 (CCP2) IgG levels, were performed at baseline (V1), 2 months (V2) and 6 months (V3) after step 1 and 2 of periodontal therapy. Primary outcome was changes in disease activity score for 28 joints (DAS28) between V2 and V1. Secondary outcomes were changes in other rheumatological or periodontal clinical parameters (V2 or V3-V1). RESULTS: RA disease activity was significantly higher in RA patients with severe periodontitis compared to moderate periodontitis at baseline, with significant positive correlations between several rheumatological and periodontal parameters. After periodontal treatment, RA patients with severe, but not moderate, periodontitis demonstrated significant improvements in DAS28 (ΔV2-V1, p = 0.042; ΔV3-V1, p = 0.001) and significant reduction in anti-CCP2 IgG levels at V3 (p = 0.032). CONCLUSION: Periodontal treatment is locally effective in patients with RA and impacts RA disease activity and anti-CCP2 antibody levels in patients with severe periodontitis. Hence, our data suggest that periodontal assessment and treatment should be integrated in the management of RA patients within a treat-to-target strategy. CLINICAL TRIAL REGISTRATION: www.isrctn.com, ISRCTN 17950307.

Platinum-based chemotherapy: trends in organic nanodelivery systems.

Despite the investment in platinum drugs research, cisplatin, carboplatin and oxaliplatin are still the only Pt-based compounds used as first line treatments for several cancers, with a few other compounds being approved for administration in some Asian countries. However, due to the severe and worldwide impact of oncological diseases, there is an urge for improved chemotherapeutic approaches. Furthermore, the pharmaceutical application of platinum complexes is hindered by their inherent toxicity and acquired resistance. Nanodelivery systems rose as a key strategy to overcome these challenges, with recognized versatility and ability towards improving the safety, bioavailability and efficacy of the available drugs. Among the known nanocarriers, organic systems have been widely applied, taking advantage of their potential as drug vehicles. Researchers have mainly focused on the development of lipidic and polymeric carriers, including supramolecular structures, with an overall improvement of encapsulated platinum complexes. Herein, an overview of recent trends and strategies is presented, with the main focus on the encapsulation of platinum compounds into organic nanocarriers, showcasing the evolution in the design and development of these promising systems. This comprehensive review highlights formulation methods as well as characterization procedures, providing insights that may be helpful for the development of novel platinum nanocarriers aiming at future pharmaceutical applications.

Antimicrobial photodynamic therapy with methylene blue and its derivatives in animal studies: Systematic review.

BACKGROUND: Infections are complications in the wound healing process, and their treatment can lead to antibiotic overuse and bacterial resistance. Antimicrobial photodynamic therapy (aPDT) is used to treat infectious diseases caused by fungi, viruses, or bacteria. Methylene blue (MB) and its derivatives are commonly used dyes in antimicrobial photodynamic therapy (aPDT-MB). METHODS: This study is a PRISMA systematic review of animal models used to discuss the usefulness and therapeutic parameters of aPDT-MB or its derivatives for treating infected skin wounds. RESULTS: After an extensive literature review, 13 controlled trials totaling 261 animals were selected to evaluate skin infection by leishmaniasis and cutaneous bacterial and fungal infections. All studies found results favoring the use of aPDT-MB. Great variability in parameters was found for radiant exposure from 12 to 360 J/cm2, MB diluted in saline solution or distilled water, irradiation time from 40 to 3600 s, irradiance most commonly at a maximum of 100 mW/cm2, and wavelength used mainly in the 630-670 nm range. CONCLUSION: MB is a safe and promising agent used as a photosensitizer in aPDT for skin-infected lesions. There is great variability in the parameters found. Comparisons concerning concentration, irradiation time, and light intensity need to be performed.

Tumor-Infiltrating T Cells in Skin Basal Cell Carcinomas and Squamous Cell Carcinomas: Global Th1 Preponderance with Th17 Enrichment-A Cross-Sectional Study.

Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are high-incidence, non-melanoma skin cancers (NMSCs). The success of immune-targeted therapies in advanced NMSCs led us to anticipate that NMSCs harbored significant populations of tumor-infiltrating lymphocytes with potential anti-tumor activity. The main aim of this study was to characterize T cells infiltrating NMSCs. Flow cytometry and immunohistochemistry were used to assess, respectively, the proportions and densities of T cell subpopulations in BCCs (n = 118), SCCs (n = 33), and normal skin (NS, n = 30). CD8+ T cells, CD4+ T cell subsets, namely, Th1, Th2, Th17, Th9, and regulatory T cells (Tregs), CD8+ and CD4+ memory T cells, and γδ T cells were compared between NMSCs and NS samples. Remarkably, both BCCs and SCCs featured a significantly higher Th1/Th2 ratio (~four-fold) and an enrichment for Th17 cells. NMSCs also showed a significant enrichment for IFN-γ-producing CD8+T cells, and a depletion of γδ T cells. Using immunohistochemistry, NMSCs featured denser T cell infiltrates (CD4+, CD8+, and Tregs) than NS. Overall, these data favor a Th1-predominant response in BCCs and SCCs, providing support for immune-based treatments in NMSCs. Th17-mediated inflammation may play a role in the progression of NMSCs and thus become a potential therapeutic target in NMSCs.

Genetic Mutations and Mitochondrial Redox Signaling as Modulating Factors in Hypertrophic Cardiomyopathy: A Scoping Review.

Hypertrophic cardiomyopathy (HCM) is a heart condition characterized by cellular and metabolic dysfunction, with mitochondrial dysfunction playing a crucial role. Although the direct relationship between genetic mutations and mitochondrial dysfunction remains unclear, targeting mitochondrial dysfunction presents promising opportunities for treatment, as there are currently no effective treatments available for HCM. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews guidelines. Searches were conducted in databases such as PubMed, Embase, and Scopus up to September 2023 using "MESH terms". Bibliographic references from pertinent articles were also included. Hypertrophic cardiomyopathy (HCM) is influenced by ionic homeostasis, cardiac tissue remodeling, metabolic balance, genetic mutations, reactive oxygen species regulation, and mitochondrial dysfunction. The latter is a common factor regardless of the cause and is linked to intracellular calcium handling, energetic and oxidative stress, and HCM-induced hypertrophy. Hypertrophic cardiomyopathy treatments focus on symptom management and complication prevention. Targeted therapeutic approaches, such as improving mitochondrial bioenergetics, are being explored. This includes coenzyme Q and elamipretide therapies and metabolic strategies like therapeutic ketosis. Understanding the biomolecular, genetic, and mitochondrial mechanisms underlying HCM is crucial for developing new therapeutic modalities.

Ecotoxicological Consequences of Urbanization: A Multi-Biomarker Approach to Assessing Sewage Treatment Plant Effects on Free-Living Birds.

Birds are good bioindicators of disturbance in the environment. They are present in different habitats and trophic levels. In addition, rapid urbanization has led birds to use cities as shelter and for seeking food resources. Sewage treatment plants (STPs) are suitable locations for free-living birds within cities. However, few studies address the impacts of emerging pollutants from sewage treatment plants on wild birds. In this sense, the aim of this study was to analyze the genotoxic, mutagenic, and immunological impacts from metal and pollutant exposure on free-living birds collected at a STP. For comparison, birds were collected in a preserved environment, the Silvania National Forest (FLONA). To achieve this, we used non-destructive biomarkers sensitive to environmental changes. Birds were collected in both environments using mist nets. After collection, birds were weighed, measured, species-identified, and released. Blood was collected for comet assay, micronucleus test, and leukocyte profile, while feathers were collected for metal concentration analysis. Water physicochemical parameters were measured at both sites, and water samples were collected for metal analysis. Our results demonstrated that birds collected at the STP exhibit a higher frequency of genotoxic damage and erythrocyte abnormalities, and increased immune response compared to FLONA birds. Traces of potentially toxic metals, such as Hg and As, were found in the birds feathers from both environments, raising concerns about metal contamination in both environments. Trophic guilds appear to respond similarly to exposure. The parameters and metals found in the water reflect environmental characteristics and may be influencing pollutant availability. Finally, despite the advancement of our findings, studies linking these damages to detrimental effects on behavior and reproduction are encouraged.

Can Salvinia auriculata bioremediate the toxic effects of Fipronil 800wg on the tadpoles of Dendropsophus minutus?

Worldwide, the indiscriminate and escalating application of pesticides has led to extensive impacts on both the environment and non-target organisms. Phytoremediation, which employs plants to decontaminate environments, is a potential strategy for the mitigation of this damage. The present study assessed the phytoremedial potential of Salvinia auriculata, an aquatic macrophyte known to be effective for the removal of environmental contaminants. In the laboratory, Dendropsophus minutus tadpoles were exposed to different concentrations (0.035, 0.1, 1.0, and 1.5 mg/l) of the commercial insecticide Fipronil 800wg in two treatments - (i) simple exposure for 96 h, and (ii) exposure for 168 h in aquariums containing S. auriculata. In the first experiment, a mortality rate of 33.3 % was recorded at the highest Fipronil concentration (1.5 mg/l), and genotoxic parameters increased at all concentrations except 0.035 mg/L, in comparison with the control. In the second experiment, phytoremediation occurred at all the concentrations tested, with lower frequencies of cells with micronuclei, and binucleated, anucleated, and pyknotic nuclei being observed, in comparison with the first experiment. These findings highlight the potential effectiveness of S. auriculata for the phytoremediation of environments contaminated by pesticides and contribute to the understanding of the benefits of this approach for the protection and preservation of aquatic biodiversity.

Biocompatible adipose extracellular matrix and reduced graphene oxide nanocomposite for tissue engineering applications.

Despite the immense need for effective treatment of spinal cord injury (SCI), no successful repair strategy has yet been clinically implemented. Multifunctional biomaterials, based on porcine adipose tissue-derived extracellular matrix (adECM) and reduced graphene oxide (rGO), were recently shown to stimulate in vitro neural stem cell growth and differentiation. Nevertheless, their functional performance in clinically more relevant in vivo conditions remains largely unknown. Before clinical application of these adECM-rGO nanocomposites can be considered, a rigorous assessment of the cytotoxicity and biocompatibility of these biomaterials is required. For instance, xenogeneic adECM scaffolds could still harbour potential immunogenicity following decellularization. In addition, the toxicity of rGO has been studied before, yet often in experimental settings that do not bear relevance to regenerative medicine. Therefore, the present study aimed to assess both the in vitro as well as in vivo safety of adECM and adECM-rGO scaffolds. First, pulmonary, renal and hepato-cytotoxicity as well as macrophage polarization studies showed that scaffolds were benign invitro. Then, a laminectomy was performed at the 10th thoracic vertebra, and scaffolds were implanted directly contacting the spinal cord. For a total duration of 6 weeks, animal welfare was not negatively affected. Histological analysis demonstrated the degradation of adECM scaffolds and subsequent tissue remodeling. Graphene-based scaffolds showed a very limited fibrous encapsulation, while rGO sheets were engulfed by foreign body giant cells. Furthermore, all scaffolds were infiltrated by macrophages, which were largely polarized towards a pro-regenerative phenotype. Lastly, organ-specific histopathology and biochemical analysis of blood did not reveal any adverse effects. In summary, both adECM and adECM-rGO implants were biocompatible upon laminectomy while establishing a pro-regenerative microenvironment, which justifies further research on their therapeutic potential for treatment of SCI.

Transport Properties in Multicomponent Systems Containing Cyclodextrins and Nickel Ions.

In this work, we propose a comprehensive experimental study of the diffusion of nickel ions in combination with different cyclodextrins as carrier molecules for enhanced solubility and facilitated transport. For this, ternary mutual diffusion coefficients measured by Taylor dispersion method are reported for aqueous solutions containing nickel salts and different cyclodextrins (that is, α-CD, ß-CD, and γ-CD) at 298.15 K. A combination of Taylor dispersion and other methods, such as UV-vis spectroscopy, will be used to obtain complementary information on these systems. The determination of the physicochemical properties of these salts with CDs in aqueous solution provides information that allows us to understand solute-solvent interactions, and gives a significant contribution to understanding the mechanisms underlying diffusional transport in aqueous solutions, and, consequently, to mitigating the potential toxicity associated with these metal ions. For example, using mutual diffusion data, it is possible to estimate the number of moles of each ion transported per mole of the cyclodextrin driven by its own concentration gradient.

Development of Mechanistic In Vitro-In Vivo Extrapolation to Support Bioequivalence Assessment of Long-Acting Injectables.

Long-acting injectable (LAI) formulations provide sustained drug release over an extended period ranging from weeks to several months to improve efficacy, safety, and compliance. Nevertheless, many challenges arise in the development and regulatory assessment of LAI drug products due to a limited understanding of the tissue response to injected particles (e.g., inflammation) impacting in vivo performance. Mechanism-based in silico methods may support the understanding of LAI-physiology interactions. The objectives of this study were as follows: (1) to use a mechanistic modeling approach to delineate the in vivo performance of DepoSubQ Provera® and formulation variants in preclinical species; (2) to predict human exposure based on the knowledge gained from the animal model. The PBPK model evaluated different elements involved in LAI administration and showed that (1) the effective in vivo particle size is potentially larger than the measured in vitro particle size, which could be due to particle aggregation at the injection site, and (2) local inflammation is a key process at the injection site that results in a transient increase in depot volume. This work highlights how a mechanistic modeling approach can identify critical physiological events and product attributes that may affect the in vivo performance of LAIs.

Naturally occurring small molecules with dual effect upon inflammatory signaling pathways and endoplasmic reticulum stress response.

The endoplasmic reticulum (ER) is determinant to maintain cellular proteostasis. Upon unresolved ER stress, this organelle activates the unfolded protein response (UPR). Sustained UPR activates is known to occur in inflammatory processes, deeming the ER a potential molecular target for the treatment of inflammation. This work characterizes the inflammatory/UPR-related molecular machinery modulated by an in-house library of natural products, aiming to pave the way for the development of new selective drugs that act upon the ER to counter inflammation-related chronic diseases. Starting from a library of 134 compounds of natural occurrence, mostly occurring in medicinal plants, nontoxic molecules were screened for their inhibitory capacity against LPS-induced nuclear factor kappa B (NF-κB) activation in a luciferase-based reporter gene assay. Since several natural products inhibited NF-κB expression in THP-1 macrophages, their effect on reactive oxygen species (ROS) production and inflammasome activation was assessed, as well as their transcriptional outcome regarding ER stress. The bioactivities of several natural products are described herein for the first time. We report the anti-inflammatory potential of guaiazulene and describe 5-deoxykaempferol as a novel inhibitor of inflammasome activation. Furthermore, we describe the dual potential of 5-deoxykaempferol, berberine, guaiazulene, luteolin-4'-O-glucoside, myricetin, quercetagetin and sennoside B to modulate inflammatory signaling ER stress. Our results show that natural products are promising molecules for the discovery and pharmaceutical development of chemical entities able to modulate the inflammatory response, as well as proteostasis and the UPR.

Pathological analysis and etiological assessment of pulmonary lesions and its association with pleurisy in slaughtered pigs.

The intensification of pig farming has posed significant challenges in managing and preventing sanitary problems, particularly diseases of the respiratory complex. Monitoring at slaughter is an important control tool and cannot be overstated. Hence, this study aimed at characterizing both macroscopical and microscopical lesions and identifying the Actinobacillus pleuropneumoniae (APP), Mycoplasma hyopneumoniae (Mhyo), and Pasteurella multocida (PM) associated with pleurisy in swine. For this, a selected slaughterhouse in São Paulo State underwent a thorough examination of carcasses on the slaughter line, followed by lung sampling. The carcasses and lungs underwent macroscopical examination and were classified according to the score of pleurisy and lung samples were allocated into five groups, being: G0: score 0 - no lesions; G1: score 1; G2: score 2; G3: score 3; and G4: score 4. In total, 217 lung fragments were collected, for the histopathological evaluation and detection of the following respiratory pathogens: APP, Mhyo, and PM by qPCR. The results demonstrated that Mhyo and APP were the most prevalent etiological agents (single and co-identification) in lung samples, in different scores of pleurisies, while bronchopneumonia and bronchus-associated lymphoid tissue (BALT) hyperplasia lesions were the most frequent histopathological findings. Positive correlations were found between the quantification of APP DNA with 1) the score of pleurisy (R=0.254); 2) with the score of lung consolidation in all lung lobes (R=0.181 to R=0.329); and 3) with the score of lung consolidation in the entire lung (R=0.389). The study brings relevant information regarding the main bacterial pathogens associated with pleurisy in pigs and helps with understanding the relationship between the abovementioned pathogens and their impact on the respiratory health of pigs.

Nature and strength of group-14 A-A' bonds.

We have quantum chemically investigated the nature and stability of C-C and Si-Si bonds in R3A-AR3 (A = C, Si; R3 = H3, Me3, Me2Ph, MePh2, Ph3, t-Bu3) using density functional theory (DFT). Systematic increase of steric bulk of the substituents R has opposite effects on C-C and Si-Si bonds: the former becomes weaker whereas the latter becomes stronger. Only upon going further, from R = Ph to the bulkiest R = t-Bu, the R3Si-SiR3 bond begins to weaken. Our bonding analyses show how different behavior upon increasing the steric bulk of the substituents stems from the interplay of (Pauli) repulsive and (dispersion) attractive steric mechanisms. Extension of our analyses to other model systems shows that C-Si bonds display behavior that is in between that of C-C and Si-Si bonds. Further increasing the size of the group-14 atoms from C-C and Si-Si to Ge-Ge, Sn-Sn and Pb-Pb leads to a further decrease in the sensitivity of the bond strength with respect to the substituents' bulkiness. Our findings can be used as design principles for tuning A-A and A-A' bond strengths.

Autologous anti-GD2 CAR T cells efficiently target primary human glioblastoma.

Glioblastoma (GBM) remains a deadly tumor. Treatment with chemo-radiotherapy and corticosteroids is known to impair the functionality of lymphocytes, potentially compromising the development of autologous CAR T cell therapies. We here generated pre-clinical investigations of autologous anti-GD2 CAR T cells tested against 2D and 3D models of GBM primary cells. We detected a robust antitumor effect, highlighting the feasibility of developing an autologous anti-GD2 CAR T cell-based therapy for GBM patients.

Proximate and fatty acid profile analysis of Tenebrio molitor and Zophobas morio using different killing methods.

The present work aimed to quantify the macronutrients and the fatty acid (FA) profile in different killing methods, blanching (BC) and freezing (FR), on edible insects of the speciesTenebrio molitor(TM) andZophobas morio(ZM). Concerning macronutrients TM-BC and TM-FR presented 51.2% and 50.6% of protein, 28% and 29.4% of lipids, and 12.4% and 11.4%. Meanwhile, ZM-BC and ZM-FR expressed 42.8% and 43.7% of protein, 39.1% and 40.1% of lipids, and 10.7% and 8.9% of carbohydrates. The FA of TM and ZM shows respectively values of Saturated Fatty Acids (∑SFA) 30% - 45%, Monounsaturated (MUFA) 47% - 32%, Polyunsaturated (∑PUFA) 23% - 22%, Atherogenicity Index (AI) 0.64 - 0.75, Thrombogenicity Index (TI) 0.77 - 1.44 and hypocholesterolemic/hypercholesterolemic index (h/H) of 2.50-1.51. Based on the results obtained, the slaughter methods showed statistically differences in relation to MUFA's in TM, and ZM larvae only in the minority fraction of FA.

Exploring structural determinants of neuroprotection bias on novel glypromate conjugates with bioactive amines.

Neurodegenerative disorders of the central nervous system (CNS) such as Alzheimer's and Parkinson's diseases, afflict millions globally, posing a significant public health challenge. Despite extensive research, a critical hurdle in effectively treating neurodegenerative diseases is the lack of neuroprotective drugs that can halt or reverse the underlying disease processes. In this work, we took advantage of the neuroprotective properties of the neuropeptide glycyl-l-prolyl-l-glutamic acid (Glypromate) for the development of new peptidomimetics using l-pipecolic acid as a proline surrogate and exploring their chemical conjugation with relevant active pharmaceutical ingredients (API) via a peptide bond. Together with prolyl-based Glypromate conjugates, a total of 36 conjugates were toxicologically and biologically evaluated. In this series, the results obtained showed that a constrained ring (l-proline) at the central position of the peptide motif accounts for enhanced toxicological profiles and biological effects using undifferentiated and differentiated human neuroblastoma SH-SY5Y cells. Additionally, it was shown that biased biological responses are API-dependent. Conjugation with (R)-1-aminoindane led to a 38-43% reduction of protein aggregation induced by Aß25-35 (10 µM), denoting a 3.2-3.6-fold improvement in comparison with the parent neuropeptide, with no significative difference between functionalization at α and γ-carboxyl ends. On the other hand, the best-performing neuroprotective conjugate against the toxicity elicited by 6-hydroxydopamine (6-OHDA, 125 µM) was obtained by conjugation with memantine at the α-carboxyl end, resulting in a 2.3-fold improvement of the neuroprotection capacity in comparison with Glypromate neuropeptide. Altogether, the chemical strategy explored in this work shows that the neuroprotective capacity of Glypromate can be modified and fine-tuned, opening a new avenue for the development of biased neurotherapeutics for CNS-related disorders.

Distinct roles of vaccine-induced SARS-CoV-2-specific neutralizing antibodies and T cells in protection and disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing antibodies (NAbs) lack cross-reactivity between SARS-CoV species and variants and fail to mediate long-term protection against infection. The maintained protection against severe disease and death by vaccination suggests a role for cross-reactive T cells. We generated vaccines containing sequences from the spike or receptor binding domain, the membrane and/or nucleoprotein that induced only T cells, or T cells and NAbs, to understand their individual roles. In three models with homologous or heterologous challenge, high levels of vaccine-induced SARS-CoV-2 NAbs protected against neither infection nor mild histological disease but conferred rapid viral control limiting the histological damage. With no or low levels of NAbs, vaccine-primed T cells, in mice mainly CD8+ T cells, partially controlled viral replication and promoted NAb recall responses. T cells failed to protect against histological damage, presumably because of viral spread and subsequent T cell-mediated killing. Neither vaccine- nor infection-induced NAbs seem to provide long-lasting protective immunity against SARS-CoV-2. Thus, a more realistic approach for universal SARS-CoV-2 vaccines should be to aim for broadly cross-reactive NAbs in combination with long-lasting highly cross-reactive T cells. Long-lived cross-reactive T cells are likely key to prevent severe disease and fatalities during current and future pandemics.

Clinical and molecular profiling of human visceral adipose tissue reveals impairment of vascular architecture and remodeling as an early hallmark of dysfunction.

Adipose tissue dysfunction is more related to insulin resistance than body mass index itself and an alteration in adipose tissue function is thought to underlie the shift from metabolically healthy to unhealthy obesity. Herein, we performed a clustering analysis that revealed distinct visceral adipose tissue gene expression patterns in patients with obesity at distinct stages of metabolic dysregulation. We have built a cross-sectional cohort that aims at reflecting the evolution of the metabolic sequelae of obesity with the main objective to map the sequential events that play a role in adipose tissue dysfunction from the metabolically healthy (insulin-sensitive) state to several incremental degrees of metabolic dysregulation, encompassing insulin resistance establishment, pre-diabetes, and type 2 diabetes. We found that insulin resistance is mainly marked by the downregulation of adipose tissue vasculature remodeling-associated gene expression, suggesting that processes like angiogenesis and adaptative expansion/retraction ability suffer early dysregulation. Prediabetes was characterized by compensatory growth factor-dependent signaling and increased response to hypoxia, while type 2 diabetes was associated with loss of cellular response to insulin and hypoxia and concomitant upregulation of inflammatory markers. Our findings suggest a putative sequence of dysregulation of biological processes that is not linear and has multiple distinct phases across the metabolic dysregulation process, ultimately culminating in the climax of adipose tissue dysfunction in type 2 diabetes. Several studies have addressed the transcriptomic changes in adipose tissue of patients with obesity. However, to the best of our knowledge, this is the first study unraveling the potential molecular mechanisms associated with the multi-step evolution of adipose tissue dysfunction along the metabolic sequelae of obesity.

Chemical, ecotoxicological, cytotoxic, and mutagenic evaluation of gelling agents used in the production of 70% alcohol gel.

With COVID-19, there has been an increase in the use of gelling agents for hand sanitizer production, and as a result, the release of this product into wastewater could induce impacts and adverse reactions in living organisms. Thus, ecotoxicological and cytotoxicological assessments of gelling agents with test organisms from different trophic levels are necessary to assess their environmental safety. For this, seven cellulose-based gelling agents and a polyacrylic acid derivative (C940) were selected for tests with Artemia salina. The most toxic agent was tested on Allium cepa to assess cytotoxicity. The volatile compounds of the gelling agents were analyzed. Cellulose-based gelling agents were not considered toxic according to their LC50, but C940 presented moderate toxicity to A. salina and cytotoxicity to Allium cepa, but without mutagenicity. In addition, C940 contained cyclohexane as a volatile compound. Thus, cellulose-based gelling agents are better environmental options than carbomer for 70% alcohol gel sanitizer.