Enhancing Colorectal Cancer Screening with Droplet Digital PCR (ddPCR) Analysis of Fusobacterium nucleatum in Fecal Immunochemical Test (FIT) Samples.

Fecal immunochemical test (FIT) followed by colonoscopy in positive cases is commonly used for population-based colorectal cancer (CRC) screening. However, specificity of FIT for CRC is not ideal, and has poor performance for advanced adenoma detection. Fecal Fusobacterium nucleatum (Fn) detection has been proposed as a potential non-invasive biomarker for CRC and advanced adenoma detection. We aimed to evaluate the diagnostic performance of Fn detection using droplet digital PCR (ddPCR) in FIT samples from individuals enrolled in a CRC screening program with colorectal adenoma or cancer. We evaluated Fn presence in DNA isolated from FIT leftover material of 300 participants in a CRC Screening Program using ddPCR. The Fn DNA amount was classified as Fn-low/negative and Fn-high, and the association with patients clinicopathological features and accuracy measurements was calculated. Fn high levels were more prevalent in FIT-positive (47.2%n=34 of72) than FIT-negative samples (28.9%, n=66 of 228) (p<0.04). Among FIT-positive samples, high Fn levels were significantly more frequent in cancer patients (CA, n=8) when compared to normal (NT, n=16) (p=0.02), non-advanced adenomas (NAA, n=36) (p=0.01), and advanced adenomas (AA, n=12) (p=0.01). Performance analysis of Fn in FIT-positive samples for colorectal cancer detection yielded an AUC of 0.8203 (CI: 0.6464-0.9942), with high sensitivity (100%) and specificity of 50%%. Concluding, we showed the feasibility of detecting Fn in FIT leftovers using the ultrasensitive ddPCR technique. Furthermore, we highlighted the potential use of Fn levels in fecal samples to ameliorate CRC detection.

Antidepressant effect of PT-31, an α2-adrenoceptor agonist, on lipopolysaccharide-induced depressive-like behavior in mice.

Increasing evidence indicates that neuroinflammation, oxidative stress, and neurotrophic factors play a key role in the pathophysiology of major depressive disorder (MDD). In addition, the attenuation of inflammatory response has been considered a putative mechanism for MDD treatment. PT-31 is an imidazolidine derivative and a putative α2-adrenoceptor agonist that has previously demonstrated antinociceptive activity. The present study aimed to investigate the effect of PT-31 on depressive-like behavior and lipopolysaccharide-induced neurochemical changes. To this end, mice received intraperitoneally saline or lipopolysaccharide (600 µg/kg), and 5 h postinjection animals were orally treated with saline, PT-31 (3, 10, and 30 mg/kg), or fluoxetine (30 mg/kg). Mice were subjected to the open field test (OFT) 6 and 24 h after lipopolysaccharide administration and to the tail suspension test (TST) 24 h postlipopolysaccharide. Subsequently, animals were euthanized, and brains were dissected for neurochemical analyses. The administration of lipopolysaccharide-induced sickness- and depressive-like behaviors, besides promoting an increase in myeloperoxidase activity and a reduction in brain-derived neurotrophic factor (BDNF) levels. Noteworthy, PT-31 3 mg/kg attenuated lipopolysaccharide-induced decreased locomotor activity 6 h after lipopolysaccharide in the OFT. All tested doses of PT-31 significantly reduced the immobility time of animals in the TST and attenuated lipopolysaccharide-induced increased myeloperoxidase activity in the cortex of mice. Our results demonstrate that PT-31 ameliorates behavioral changes promoted by lipopolysaccharide in OFT and TST, which is possibly mediated by attenuation of the inflammatory response.

Protective effects of mesenchymal stromal cell-derived secretome on dermonecrosis induced in rabbits by Loxosceles intermedia spider venom.

Background: Loxoscelism refers to a set of clinical manifestations caused by the bite of spiders from the Loxosceles genus. The classic clinical symptoms are characterized by an intense inflammatory reaction at the bite site followed by local necrosis and can be classified as cutaneous loxoscelism. This cutaneous form presents difficult healing, and the proposed treatments are not specific or effective. This study aimed to evaluate the protective effect of mesenchymal stromal cells-derived secretome on dermonecrosis induced by Loxosceles intermedia spider venom in rabbits. Methods: Sixteen rabbits were distributed into four groups (n = 4). Except for group 1 (G1), which received only PBS, the other three groups (G2, G3, and G4) were initially challenged with 10 µg of L. intermedia venom, diluted in 100 µL of NaCl 0.9%, by intradermic injection in the interscapular region. Thirty minutes after the challenge all groups were treated with secretome, except for group 2. Group 1 (G1-control group) received intradermal injection (ID) of 60 µg of secretome in 0.15 M PBS; Group 2 (G2) received 0.9% NaCl via ID; Group 3 (G3) received 60 µg of secretome, via ID and Group 4 (G4), received 60 µg of secretome by intravenous route. Rabbits were evaluated daily and after 15 days were euthanized, necropsied and skin samples around the necrotic lesions were collected for histological analysis. Results: Rabbits of G1 did not present edema, erythema, hemorrhagic halo, or necrosis. In animals from G2, G3, and G4, edema appeared after 6h. However, minor edema was observed in the animals of G2 and G3. Hemorrhagic halo was observed in animals, six hours and three days after, on G2, G3, and G4. Macroscopically, in G4, only one animal out of four had a lesion that evolved into a dermonecrotic wound. No changes were observed in the skin of the animals of G1, by microscopic evaluation. All animals challenged with L. intermedia venom showed similar alterations, such as necrosis and heterophilic infiltration. However, animals from G4 showed fibroblast activation, early development of connective tissue, neovascularization, and tissue re-epithelialization, indicating a more prominent healing process. Conclusion: These results suggest that secretome from mesenchymal stromal cells cultured in a xeno-free and human component-free culture media can be promising to treat dermonecrosis caused after Loxosceles spiders bite envenoming.

Molecular modelling and anticholinesterase activity of the essential oil from three chemotypes of Lippia alba (Mill.) N.E.Br. ex Britton & P. Wilson (Verbenaceae).

Lippia alba (Mill.) N.E. Brown (Verbenaceae), popularly known as "erva cidreira", is one of the most used plants in Brazilian folk medicine. The species has several chemotypes and its volatile constituents have already been characterized, and present different chemical markers with known pharmacological properties, such as analgesic, sedative and antifungal properties. The objective of this study was to evaluate the anticholinesterase activity (AChE) of the essential oil of three chemotypes of Lippia alba and, by using molecular anchoring, determine the best receptor-ligand interaction energies of the main constituents present in the samples of oil. The essential oils were obtained via hydrodistillation (LA1 and LA2) and steam drag (LA3), and their volatile constituents determined using GC-MS. For the determination of anticholinesterase activity, direct bioautography and colorimetry assays based on Ellman's method were used. Molecular docking was performed using a multiple solution genetic algorithm and Merck molecular force field 94 (MMFF94) as the scoring function. In the main constituents of the oil samples, three chemotypes were identified for L. alba: LA1 is rich in citral, LA2 is rich in carvone and LA3 is rich in linalool. All L. alba chemotypes showed AChE enzyme inhibition with an IC50 of 3.57 µg/mL (LA1), 0.1 µg/mL (LA2) and 4.34 µg/mL (LA3). The molecular docking study complemented the results of the experiment and demonstrated significant interactions between the main constituents of the oils and the amino acid residues of the AChE enzyme. Irrespective of the chemotype, Lippia alba presents biotechnological potential for the discovery of anticholinesterase substances, with the chemotype LA2 (rich in carvone) being the most active.

[Eating Habits of People with Type 2 Diabetes Mellitus in Portugal: A Cross-Sectional Study]. / Hábitos Alimentares das Pessoas com Diabetes Mellitus Tipo 2 em Portugal: Um Estudo Transversal.

INTRODUCTION: Nutrition is a cornerstone of diabetes mellitus prevention and management; therefore, it is essential to enable patients to adopt healthy eating habits. Previous studies have not yet documented the main errors in the eating habits of Portuguese people with type 2 diabetes mellitus. This study aims to identify the main errors in the eating habits of people living with type 2 diabetes mellitus in Portugal and to evaluate its associations with sociodemographic variables. METHODS: Cross-sectional multicentric study in a convenience sample of people with type 2 diabetes mellitus in Primary Health Care Units. The UK Diabetes and Diet Questionnaire (UKDDQ) - translated and adapted, was applied from July to October 2022. Descriptive and inferential statistical analyses were conducted. RESULTS: Of the 550 participants, 52.2% were female, 68.3% were 65 years or over, 55.8 % had an education level up to the fourth grade, 24.7% had economic deprivation, and the mean time since diagnosis was 10.60 ± 8.13 years. Only 36.2% of the sample had a healthy UKDDQ score. Less than 50% of the sample had healthy scores for the items "high-fiber rice or pasta", "high-fiber bread", "butter, margarine and vegetable oils" and "vegetables and pulses". Only 8.9% of the sample had a healthy consumption of fiber. About 70.4% reported healthy scores for the consumption of "high-added-sugar foods" and 54.7% for "high-saturated fat". A statistically significant weak positive correlation was found between the UKDDQ score and age (ρ = 0.201, p < 0.001) with a more frequent choice of healthy foods with increasing age. Female respondents reported healthier habits, particularly in the consumption of "high-saturated fat" and "high-fiber foods". CONCLUSION: The majority of our sample did not take advantage of the potential benefits of healthy eating habits. The main food groups whose consumption should be emphasized or discouraged were individualized, particularly the need to encourage the consumption of high-fiber foods. Targeted educational actions must focus especially on younger and/or male patients.

Introdução: A nutrição é uma área de intervenção na prevenção e gestão da diabetes mellitus; por isso, é fulcral promover a capacitação da população para a adoção de hábitos alimentares saudáveis. Ainda que existam alguns estudos nesta área, não se conhecem os principais erros nos hábitos alimentares das pessoas com diabetes em Portugal. Os objetivos deste estudo foram identificar os principais erros nos hábitos alimentares das pessoas com diabetes mellitus tipo 2 em Portugal e avaliar a sua relação com variáveis sociodemográficas. Métodos: Estudo transversal multicêntrico, em amostra de conveniência de pessoas com diabetes mellitus tipo 2 seguidas em Unidades de Cuidados de Saúde Primários. Aplicação do UK Diabetes and Diet Questionnaire (UKDDQ) ­ traduzido e adaptado, de julho a outubro de 2022. Análise estatística descritiva e inferencial. Resultados: Amostra de 550 participantes, 52,2% do sexo feminino, 68,3% com 65 anos ou mais, 55,8% com nível de escolaridade igual ou inferior ao 1.º ciclo do ensino básico, 24,7% com insuficiência económica e tempo desde o diagnóstico médio de 10,60 ± 8,13 anos. Apenas 36,2% da amostra obteve um score UKDDQ considerado saudável. Menos de 50% obteve scores saudáveis para os itens "arroz ou massa ricos em fibras", "pão integral", "manteiga, margarina e óleos vegetais" e "vegetais e leguminosas". Somente 8,9% da amostra obteve score saudável para o consumo de fibras. Cerca de 70,4% obteve score saudável para o consumo de açúcares livres e 54,7% para o consumo de ácidos gordos saturados. Verificou-se a existência de uma correlação com significado estatístico positiva fraca entre o score UKDDQ e a idade (ρ = 0,201, p < 0,001), com escolha mais frequente de alimentos saudáveis com o aumentar da idade. As pessoas do sexo feminino reportaram hábitos alimentares mais saudáveis, particularmente no consumo de fibras e ácidos gordos saturados. Conclusão: A maior parte da nossa amostra não usufruiu do potencial efeito positivo de uma alimentação saudável. Individualizam-se grupos de alimentos cujos consumos devem ser enfatizados ou desencorajados, particularmente, a necessidade de incentivar o consumo de alimentos ricos em fibra. Ações educacionais dirigidas devem ter especial foco em pessoas mais jovens e/ou do sexo masculino.

A meta-analytic review of the relations between anxiety and empathy.

Although theory suggests that empathy may signal a risk for anxiety (Tone & Tully, 2014), the relation between these constructs remains unclear due to the lack of a quantitative synthesis of empirical findings. We addressed this question by conducting three meta-analyses assessing anxiety and general, cognitive, and affective empathy (k's = 70-102 samples; N's = 19,410-25,102 participants). Results suggest that anxiety has a small and significant association with general empathy (r = .08). The relation of clinical anxiety with cognitive empathy was significant but very weak (r = -.03), and small for affective empathy (r = .16). Geographic region and the type of cognitive (e.g., perspective taking, fantasy) and affective empathy (e.g., affective resonance, empathic concern) emerged as moderators. Results suggest that anxiety has a weaker association with general empathy but a stronger association with affective empathy in participants from predominantly collectivistic geographic regions. Further, greater anxiety was weakly associated with less perspective-taking and greater fantasy, and anxiety had a more modest association with empathic concern than other types of affective empathy. Targeting affective empathy (e.g., promoting coping strategies when faced with others' distress) in interventions for anxiety may be beneficial.

Comparative toxicity of coal and coal ash: Assessing biological impacts and potential mechanisms through in vitro and in vivo testing.

BACKGROUND: Coal and coal ash present inorganic elements associated with negative impacts on environment and human health. The objective of this study was to compare the toxicity of coal and coal ash from a power plant, assess their inorganic components, and investigate the biological impacts and potential mechanisms through in vitro and in vivo testing. METHODS: Particle-Induced X-ray Emission method was used to quantify inorganic elements and the toxicity was evaluated in Caenorhabditis elegans and Daphnia magna in acute and chronic procedures. The genotoxic potential was assessed using alkaline and FPG-modified Comet assay in HepG2 cells and mutagenicity was evaluated using Salmonella/microsome assay in TA97a, TA100, and TA102 strains. RESULTS: Inorganic elements such as aluminum (Al) and chromium (Cr) were detected at higher concentrations in coal ash compared to coal. These elements were found to be associated with increased toxicity of coal ash in both Caenorhabditis elegans and Daphnia magna. Coal and coal ash did not induce gene mutations, but showed genotoxic effects in HepG2 cells, which were increased using the FPG enzyme, indicating DNA oxidative damage. CONCLUSIONS: The combined findings from bioassays using C. elegans and D. magna support the higher toxicity of coal ash, which can be attributed to its elevated levels of inorganic elements. The genotoxicity observed in HepG2 cells confirms these results. This study highlights the need for continuous monitoring in areas affected by environmental degradation caused by coal power plants. Additionally, the analysis reveals significantly higher concentrations of various inorganic elements in coal ash compared to coal, providing insight into the specific elemental composition contributing to its increased toxicity.

Psychosocial correlates of risk for suicidal ideation: the COVID-19 pandemic as a magnifying glass / Correlatos psicossociais de risco para ideação suicida: a pandemia de COVID-19 como uma lupa

Abstract Objective The effects of the COVID-19 pandemic on suicidal behavior are still the subject of studies. It is hypothesized that the pandemic may have contributed to the development of suicidal ideation by intensifying psychosocial risk factors. Our objective was to investigate such correlated factors in Brazil. Method The study used an online and cross-sectional survey encompassing 448 adult participants. Sociodemographic questionnaires and the Self-Reporting Questionnaire were used, and binary logistic regression was employed to identify predictors. Results The prevalence of suicidal ideation was 22.3%. The results indicate that people who self-identified as black and brown (OR = 2.42), who were part of the risk group for COVID-19 (OR = 2.41), and who reported more psychological symptoms (OR = 1.50) were more likely to have suicidal ideation. Conclusion Public policies to prevent suicidal behavior and promote mental health in the most vulnerable groups might be needed beyond the pandemic context, especially among the black population.

Resumo Objetivos Os efeitos da pandemia de COVID-19 no comportamento suicida continuam sendo tema de estudos. Hipotetiza-se que a pandemia pode ter contribuído para a ideação suicida ao intensificar fatores de risco psicossociais. Nosso objetivo foi investigar tais fatores correlatos no Brasil. Método Este estudo realizou uma coleta de dados online e transversal, englobando 448 participantes adultos. Utilizaram-se questionários sociodemográficos e o Self-Reporting Questionnaire, empregando-se regressão logística binária para identificação de preditores. Resultados A prevalência de ideação suicida foi de 22,3%. Os resultados apontam que pessoas autoidentificadas como negros e pardos (OR = 2,42), que faziam parte do grupo de risco para COVID-19 (OR = 2,41), e que reportaram mais sintomas psicológicos (OR = 1,50) tiveram maior chance de apresentar ideação suicida. Conclusão Políticas públicas de prevenção do comportamento suicida e promoção de saúde mental nos grupos mais vulneráveis podem ser necessárias para além do contexto pandêmico, sobretudo entre a população negra.

Review of Piezoelectrical Materials Potentially Useful for Peripheral Nerve Repair.

It has increasingly been recognized that electrical currents play a pivotal role in cell migration and tissue repair, in a process named "galvanotaxis". In this review, we summarize the current evidence supporting the potential benefits of electric stimulation (ES) in the physiology of peripheral nerve repair (PNR). Moreover, we discuss the potential of piezoelectric materials in this context. The use of these materials has deserved great attention, as the movement of the body or of the external environment can be used to power internally the electrical properties of devices used for providing ES or acting as sensory receptors in artificial skin (e-skin). The fact that organic materials sustain spontaneous degradation inside the body means their piezoelectric effect is limited in duration. In the case of PNR, this is not necessarily problematic, as ES is only required during the regeneration period. Arguably, piezoelectric materials have the potential to revolutionize PNR with new biomedical devices that range from scaffolds and nerve-guiding conduits to sensory or efferent components of e-skin. However, much remains to be learned regarding piezoelectric materials, their use in manufacturing of biomedical devices, and their sterilization process, to fine-tune their safe, effective, and predictable in vivo application.

Sistema Único de Saúde: acessibilidade das pessoas surdas no interior da Bahia / Unified Health System: accessibility of deaf people in the countryside of Bahia state / Sistema Único de Salud: accesibilidad de las personas sordas en el interior de Bahia

A acessibilidade das pessoas surdasno Sistema Único de Saúde ainda é precária devido às barreiras de comunicação. O objetivo do estudo foi analisar o acesso e o atendimento ofertado à comunidade surda nos serviços de saúde públicos, no município de Vitória da Conquista, Bahia, por meio de uma pesquisa qualitativa. Participaram oito profissionais de saúde e treze usuários surdos, cujos dados foram coletados com aplicação de um questionário e um roteiro de entrevista semiestruturada. Os resultados, com base na análise do conteúdo, apontaram que não há capacitação, as Unidades Básicas de Saúde não apresentam estratégias de acessibilidade nos atendimentos, têm rara comunicação em Libras e um número reduzido de intérpretes ­ o que dificulta a comunicação entre o profissional de saúde e o usuário surdo. A formação em Libras e a presença de um intérprete são apontadas como estratégias para um atendimento de qualidade às pessoas surdas

The accessibility of deaf people in the Unified Health System is still precarious due to communication barriers. The objective of the study was to analyze the access and care offered to the deaf community in public health services, in the city of Vitória da Conquista, Bahia, through qualitative research. Eight health professionals and thirteen deaf users took part in the research, whose data were collected using a questionnaire and a semi-structured interview script. Based on the content analysis, the results showed that there is no training, the Basic Health Units do not have accessibility strategies in care, rarely communicate in Libras and a have a small number of interpreters in their ranks ­ hindering the communication between health professional and deaf user. Training in Libras and the presence of an interpreter are identified as strategies for quality care for deaf people

La accesibilidad para los sordos en el Sistema Único de Salud todavía es precaria debido a las barreras de comunicación. El objetivo del estudio fue analizar el acceso y la atención ofrecida a este público en los servicios de salud públicos, en el municipio de Vitória da Conquista, Bahia, con una investigación cualitativa. Participaron ocho profesionales de la salud y trece usuarios sordos, cuyos datos fueron recolectados a través de cuestionario y guión de entrevista semiestructurada. Los resultados, basados en el análisis de contenido, mostraron que no hay capacitación, las Unidades Básicas de Salud no tienen estrategias de accesibilidad, y tienen poca comunicación en Libras y reducido número de intérpretes ­ lo que dificulta la comunicación entre el profesional de la salud y el usuario sordo. La formación en Libras y la presencia de un intérprete se identifican como estrategias para la atención de calidad a los sordos

Differences in MCF-7 response to endocrine disruptors in waste, superficial, and treated water from Southern Brazil.

The aim of this study was to evaluate the effect of possible endocrine disruptors in surface and wastewater using a cell proliferation assay in an estrogen-responsive cell line (MCF-7). This study was conducted in the Sinos River (Brazil). The residual water was collected from a Pilot Treatment Plant (using Typha domingensis) and surface waters of the Luis Rau stream, the Sinos River, and the Water Treatment Station (WTS). After exposures (24-120 h), a Sulforhodamine B assay was performed to determine the proliferation rate. The higher increase in proliferation rate was observed with the Luiz Rau stream and the sewage treated by macrophytes in a flotation filter. The results from WTS water remained with a proliferation rate similar to the negative control at all times, suggesting that the conventional treatment is partially effective for the withdrawal of endocrine-disrupting agents. The study demonstrated the efficiency of the MCF-7 line in assessing endocrine disruption caused by wastewater and surface water samples. Our results indicate that conventional water treatment can partially remove the polluting load of endocrine disruptors, minimizing their environmental and public health impacts. Besides, it demonstrates the need to expand sanitary services to improve the population's quality of life.

Hierarchical Virtual Screening of Potential New Antibiotics from Polyoxygenated Dibenzofurans against Staphylococcus aureus Strains.

Staphylococcus aureus is a microorganism with high morbidity and mortality due to antibiotic-resistant strains, making the search for new therapeutic options urgent. In this context, computational drug design can facilitate the drug discovery process, optimizing time and resources. In this work, computational methods involving ligand- and structure-based virtual screening were employed to identify potential antibacterial agents against the S. aureus MRSA and VRSA strains. To achieve this goal, tetrahydroxybenzofuran, a promising antibacterial agent according to in vitro tests described in the literature, was adopted as the pivotal molecule and derivative molecules were considered to generate a pharmacophore model, which was used to perform virtual screening on the Pharmit platform. Through this result, twenty-four molecules were selected from the MolPort® database. Using the Tanimoto Index on the BindingDB web server, it was possible to select eighteen molecules with greater structural similarity in relation to commercial antibiotics (methicillin and oxacillin). Predictions of toxicological and pharmacokinetic properties (ADME/Tox) using the eighteen most similar molecules, showed that only three exhibited desired properties (LB255, LB320 and LB415). In the molecular docking study, the promising molecules LB255, LB320 and LB415 showed significant values in both molecular targets. LB320 presented better binding affinity to MRSA (-8.18 kcal/mol) and VRSA (-8.01 kcal/mol) targets. Through PASS web server, the three molecules, specially LB320, showed potential for antibacterial activity. Synthetic accessibility (SA) analysis performed on AMBIT and SwissADME web servers showed that LB255 and LB415 can be considered difficult to synthesize and LB320 is considered easy. In conclusion, the results suggest that these ligands, particularly LB320, may bind strongly to the studied targets and may have appropriate ADME/Tox properties in experimental studies.

New method of video-assisted vaginoscopy in Nellore heifers.

Vaginoscopy allows an intravaginal endoscopic evaluation and can help in the diagnosis of female bovine genital tract disorders. The aim of this study is to validate a new method of gynaecological examination using a Scope VOR&GDI videovaginoscope. Twenty-six heifers were used, divided into 2 groups with 13 animals, control group (GC) and videovaginoscopic group (GV). In the CG, vaginoscopy was performed with a vaginal speculum and in the GV with a Scope VOR&GDI videovaginoscope. All heifers underwent vaginoscopy on day 0 (D0), and 9 days later, on day 9 (D9). Vaginoscopy provided adequate intravaginal inspection. In the CG, 23% (3/13) of the heifers showed discomfort during the test. In GV, vaginal inspection was better due to better image quality. The videovaginoscope is the most effective equipment for carrying out the vaginoscopy procedure in Nellore heifers, as it produces sharper and clearer images and can help in the diagnostic and therapeutic routine of veterinarians.

A New Truncated Lindley-Generated Family of Distributions: Properties, Regression Analysis, and Applications.

We present the truncated Lindley-G (TLG) model, a novel class of probability distributions with an additional shape parameter, by composing a unit distribution called the truncated Lindley distribution with a parent distribution function G(x). The proposed model's characteristics including critical points, moments, generating function, quantile function, mean deviations, and entropy are discussed. Also, we introduce a regression model based on the truncated Lindley-Weibull distribution considering two systematic components. The model parameters are estimated using the maximum likelihood method. In order to investigate the behavior of the estimators, some simulations are run for various parameter settings, censoring percentages, and sample sizes. Four real datasets are used to demonstrate the new model's potential.

Virtual Screening of Different Subclasses of Lignans with Anticancer Potential and Based on Genetic Profile.

Cancer is a multifactorial disease that continues to increase. Lignans are known to be important anticancer agents. However, due to the structural diversity of lignans, it is difficult to associate anticancer activity with a particular subclass. Therefore, the present study sought to evaluate the association of lignan subclasses with antitumor activity, considering the genetic profile of the variants of the selected targets. To do so, predictive models were built against the targets tyrosine-protein kinase ABL (ABL), epidermal growth factor receptor erbB1 (EGFR), histone deacetylase (HDAC), serine/threonine-protein kinase mTOR (mTOR) and poly [ADP-ribose] polymerase-1 (PARP1). Then, single nucleotide polymorphisms were mapped, target mutations were designed, and molecular docking was performed with the lignans with the best predicted biological activity. The results showed more anticancer activity in the dibenzocyclooctadiene, furofuran and aryltetralin subclasses. The lignans with the best predictive values of biological activity showed varying binding energy results in the presence of certain genetic variants.

Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia.

Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by reduced visual acuity, nystagmus, photophobia, and very poor or absent color vision. Pathogenic variants in six genes encoding proteins composing the cone phototransduction cascade (CNGA3, CNGB3, PDE6C, PDE6H, GNAT2) and of the unfolded protein response (ATF6) have been related to ACHM cases, while CNGA3 and CNGB3 alone are responsible for most cases. Herein, we provide a clinical and molecular overview of 42 Brazilian patients from 38 families affected with ACHM related to biallelic pathogenic variants in the CNGA3 and CNGB3 genes. Patients' genotype and phenotype were retrospectively evaluated. The majority of CNGA3 variants were missense, and the most prevalent CNGB3 variant was c.1148delC (p.Thr383Ilefs*13), resulting in a frameshift and premature stop codon, which is compatible with previous publications in the literature. A novel variant c.1893T>A (p.Tyr631*) in the CNGB3 gene is reported for the first time in this study. A great variability in morphologic findings was observed in our patients, although no consistent correlation with age and disease stage in OCT foveal morphology was found. The better understanding of the genetic variants landscape in the Brazilian population will help in the diagnosis of this disease.

Mass Spectrometry-Based Investigation of Sugarcane Exposed to Five Different Pesticides.

The use of agrochemicals has become a standard practice worldwide to ensure the productivity and quality of sugarcane crops. This study aimed to analyze the metabolic changes in sugarcane culms treated with five different nematicides. The experimental design was randomized in blocks, and agro-industrial and biometric variables were evaluated. The samples were extracted and then analyzed using LC-MS, LC-MS/MS, and LC-HRMS. The data obtained were submitted to statistical methods (PCA and PLS). Fragmentation patterns, retention time, and UV absorptions of the main features were analyzed. The plantations treated with carbosulfan (T4) obtained higher agricultural productivity and total recoverable sugar (TRS), while the use of benfuracarb (T3) was associated with lower growth and lower TRS. Statistical analysis revealed the contribution of the features at m/z 353 and m/z 515, assigned as chlorogenic acids, which discriminated the groups. The MS profile also supported the occurrence of flavonoids (C-glycosides and O-glycosides) in the samples.

Preparation of 3D Decellularized Matrices from Fetal Mouse Skeletal Muscle for Cell Culture.

The extracellular matrix (ECM) plays a crucial role in providing structural support for cells and conveying signals that are important for various cellular processes. Two-dimensional (2D) cell culture models oversimplify the complex interactions between cells and the ECM, as the lack of a complete three-dimensional (3D) support can alter cell behavior, making them inadequate for understanding in vivo processes. Deficiencies in ECM composition and cell-ECM interactions are important contributors to a variety of different diseases. One example is LAMA2-congenital muscular dystrophy (LAMA2-CMD), where the absence or reduction of functional laminin 211 and 221 can lead to severe hypotony, detectable at or soon after birth. Previous work using a mouse model of the disease suggests that its onset occurs during fetal myogenesis. The present study aimed to develop a 3D in vitro model permitting the study of the interactions between muscle cells and the fetal muscle ECM, mimicking the native microenvironment. This protocol uses deep back muscles dissected from E18.5 mouse fetuses, treated with a hypotonic buffer, an anionic detergent, and DNase. The resultant decellularized matrices (dECMs) retained all ECM proteins tested (laminin α2, total laminins, fibronectin, collagen I, and collagen IV) compared to the native tissue. When C2C12 myoblasts were seeded on top of these dECMs, they penetrated and colonized the dECMs, which supported their proliferation and differentiation. Furthermore, the C2C12 cells produced ECM proteins, contributing to the remodeling of their niche within the dECMs. The establishment of this in vitro platform provides a new promising approach to unravel the processes involved in the onset of LAMA2-CMD, and has the potential to be adapted to other skeletal muscle diseases where deficiencies in communication between the ECM and skeletal muscle cells contribute to disease progression.

Antimicrobial Potential of Betulinic Acid and Investigation of the Mechanism of Action against Nuclear and Metabolic Enzymes with Molecular Modeling.

Natural products have important pharmacological activities. This study sought to investigate the activity of the compound betulinic acid (BA) against different strains of bacteria and fungi. The minimum inhibitory concentration (MIC) was determined and then the minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC). After performing the in vitro tests, molecular modeling studies were carried out to investigate the mechanism of action of BA against the selected microorganisms. The results showed that BA inhibited the growth of microbial species. Among the 12 species (Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Escherichia coli, Mycobacterium tuberculosis, Candida albicans, C. tropicalis, C. glabrata, Aspergillus flavus, Penicillium citrinum, Trichophyton rubrum, and Microsporum canis) investigated, 9 (75%) inhibited growth at a concentration of 561 µM and 1 at a concentration of 100 µM. In general, the MBC and MFC of the products were between 561 and 1122 µM. In silico studies showed that BA presented a mechanism of action against DNA gyrase and beta-lactamase targets for most of the bacteria investigated, while for fungi the mechanism of action was against sterol 14α-demethylase (CYP51) targets and dihydrofolate reductase (DHFR). We suggest that BA has antimicrobial activity against several species.

Epidemiological and molecular evaluation of BRAF, KRAS, NRAS genes and MSI in the development of colorectal cancer.

BACKGROUND AND OBJECTIVES: KRAS, NRAS, BRAF mutations and microsatellite instability (MSI) can be associated with Colorectal Cancer (CRC) development. MATERIAL AND METHODS: We evaluated 828 medical records of CRC patients from a school hospital from January/2016 to December/2020. Variables such as age, gender, ethnicity, literacy level, smoking, alcoholism, primary anatomical site, tumor staging, presence of BRAFV600E, KRAS, NRAS mutations and MSI , survival and metastasis were identified. The statistical analyses were performed (p < 0.05 was considered significant). RESULTS: There was a predominance of males (51.93%), whites (90.70%), low education (72.34%), smokers (73.79%), and non-alcoholics (79.10%). Rectum was the most affected site (42.14%), advanced tumor stage was most prevalent (62.07%), and metastasis occurred in (64.61%). Of the enrolled patients; 204 were investigated for BRAF mutation and detected in (2.94%); 216 for KRAS gene and detected in (26.08%); 210 for NRAS gene, and detected in (25.36%); 370 for MSI and detected in (44.68%). A significant association of CRC with NRAS mutation and alcohol habit (p = 0.043) was observed. The presence of MSI was associated with primary site proximal colon (p < 0.000), distal colon (p = 0.001) and rectum (p = 0.010). CONCLUSION: Patients with CRC are male, over 64 years old, white, with low education, smokers and non-alcoholics. The most affected primary site is rectum in advanced stage with metastasis. CRC is associated with NRAS mutation and alcohol habit, there is increased risk for primary site of proximal colon and MSI; decreased risk for distal colon and rectum in the presence of MSI.