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Abstract The alkaloid extract and five alkaloids isolated from subterranean stem bark of Duguetia furfuracea (Annonaceae) were investigated for the following activities: antitumoral, trypanocidal and leishmanicidal. Dicentrinone showed weak cytotoxicity, [...]

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Mathias V Melega,1 Rodrigo Pessoa Cavalcanti Lira,2 Iuri Cardoso da Silva,1 Bruna Gil Ferreira,1 Hermano LG Assis Filho,1 Alexandre AF Martini,1 Roberto dos Reis,1 Carlos Eduardo Leite Arieta,1 Monica Alves1 1School of Medical Sciences, Ophthalmology Department of University of Campinas (UNICAMP), Campinas, São Paulo, Brazil; 2School of Medical Sciences, Ophthalmology Department of Federal University of Pernambuco (UFPE), Recife, Pernambuco, BrazilCorrespondence: Mathias V MelegaSchool of Medical Sciences, University of Campinas (UNICAMP), Rua Dona Josefina Sarmento 120, Ap 71, Cambuí, Campinas, SP CEP 13025-260, BrazilTel +55 19 997513150Email mvmelega@hotmail.comPurpose: To evaluate outcomes of resident-performed cataract surgeries in different training levels in a retrospective case series.Patients and Methods: A total of 730 surgeries performed by residents were evaluated into three groups: surgeries performed during residents’ first semester of training in phacoemulsification (Level 1 – L1), surgeries performed during the second semester (Level 2 – L2), and surgeries performed during the third semester (Level 3 – L3). The primary outcome was the incidence of intraoperative complications in each group. Secondary outcomes were the comparisons between initial and final corrected distance visual acuity (CDVA), intraocular pressure (IOP), endothelial cell density (ECD), and central corneal thickness (CCT) in each group. Descriptive statistical analyses were employed in the presentation of the results using central tendency and variance measurements.Results: The rate of complications within six weeks of follow-up was 24 out of 102 eyes (23.53%) in the L1 group, 63 out of 301 eyes (20.93%) in the L2 group, and 37 out of 327 (11.31%) in the L3 group (p=0.001). Posterior capsule rupture (PCR) was the most frequent intercurrence observed in all three semesters: it occurred in 12.7% of the surgeries in the first semester (13/102), 16.9% of surgeries in the second semester (51/301), and 9.5% of surgeries in the third semester (31/327). There was no significant difference in CDVA (p=0.298), ECD (p=0.067), IOP (p=0.217), or CCT (p=0.807) between the groups.Conclusion: When measured by rates of complications and by the aforementioned parameters, surgical competency was found to improve as surgical experience and frequency increased. Therefore, this study identified some patterns of skill development that can be applied to teaching strategies and better assist surgeons in training.Keywords: cataract, phacoemulsification, complications, practicing surgeons, surgical education, ophthalmology residency

The literature has identified complex aspects of intracellular host-parasite relationships, which require systematic, nonreductionist approaches and spatial/temporal information. Increasing and integrating temporal and spatial dimensions in host cell imaging have contributed to elucidating several conceptual gaps in the biology of intracellular parasites. To access and investigate complex and emergent dynamic events, it is mandatory to follow them in the context of living cells and organs, constructing scientific images with integrated high quality spatiotemporal data. This review discusses examples of how advances in microscopy have challenged established conceptual models of the intracellular life cycles of Leishmania spp. and Trypanosoma cruzi protozoan parasites. [ABSTRACT FROM AUTHOR]

BackgroundWith the evolution of digital media, areas such as public health are adding new platforms to complement traditional systems of epidemiological surveillance. Participatory surveillance and digital epidemiology have become innovative tools for the construction of epidemiological landscapes with citizens’ participation, improving traditional sources of information. Strategies such as these promote the timely detection of warning signs for outbreaks and epidemics in the region. ObjectiveThis study aims to describe the participatory surveillance platform Guardians of Health, which was used in a project conducted during the 2016 Olympic and Paralympic Games in Rio de Janeiro, Brazil, and officially used by the Brazilian Ministry of Health for the monitoring of outbreaks and epidemics. MethodsThis is a descriptive study carried out using secondary data from Guardians of Health available in a public digital repository. Based on syndromic signals, the information subsidy for decision making by policy makers and health managers becomes more dynamic and assertive. This type of information source can be used as an early route to understand the epidemiological scenario. ResultsThe main result of this research was demonstrating the use of the participatory surveillance platform as an additional source of information for the epidemiological surveillance performed in Brazil during a mass gathering. The platform Guardians of Health had 7848 users who generated 12,746 reports about their health status. Among these reports, the following were identified: 161 users with diarrheal syndrome, 68 users with respiratory syndrome, and 145 users with rash syndrome. ConclusionsIt is hoped that epidemiological surveillance professionals, researchers, managers, and workers become aware of, and allow themselves to use, new tools that improve information management for decision making and knowledge production. This way, we may follow the path for a more intelligent, efficient, and pragmatic disease control system.

O ácido salicílico (AS) pode ser usado como atenuador de estresses causados por herbicidas em plantas e, assim, viabilizar a utilização de flumioxazin na cultura do trigo. Diante disso, objetivou-se avaliar o efeito do AS como atenuador de fitotoxicidade causada por flumioxazin na cultura do trigo. Realizou-se um experimento em campo, de maio a setembro de 2015, no delineamento em blocos casualizados com quatro repetições. Os tratamentos aplicados foram: controle (sem herbicida, sem AS e capinado); flumioxazin (40 g.ha-1); flumioxazin + AS em mistura de calda (40 g.ha-1 + 0,5 mM); flumioxazin + AS em mistura de calda + AS 7 dias após a aplicação (DAA) do herbicida (40 g.ha-1 + 0,5 mM + 0,5 mM); AS (0,5 mM). Foram realizadas avaliações de índice SPAD, fitotoxicidade, massa de mil grãos, peso hectolitro e produtividade. A mistura de AS com flumioxazin aumentou em 7% o índice SPAD aos 21 DAA, reduziu em 30% a fitotoxicidade aos 28 DAA e elevou em 3,43% a produtividade em relação à aplicação isolada de flumioxazin. A aplicação adicional de AS aos 7 DAA reduziu a fitotoxicidade em até 50%, aumentou em até 8,72% o índice SPAD e possibilitou ganhos de 1,49% na produtividade e de 5,46% no peso hectolitro, quando comparado ao herbicida aplicado isoladamente. A aplicação de AS atenuou o estresse causado por flumioxazin no trigo.

The article offers information on behavior of Gymnodactylus geckoides (Phyllodactylidae); and mnentions post-copulation licking of the hemipenis in G. geckoides.

Information on gymnodactylus darwinii from Atlantic rainforest including information related to topics like its diet, the habitat in which it is found, and its physical traits is presented.

The most promising approach for the development of electrochemical biosensors is to establish a direct electrical communication between the biomolecules and the electrode surface. This review focuses on advances, directions and strategies in the development of third generation electrochemical biosensors. Subjects covered include a brief description of the fundamentals of the electron transfer phenomenon and amperometric biosensor development (different types and new oriented enzyme immobilization techniques). Special attention is given to different redox enzymes and proteins capable of electrocatalyzing reactions via direct electron transfer. The analytical applications and future trends for third generation biosensors are also presented and discussed.

Penile squamous cell carcinoma (SCC) is a rare and aggressive tumour mainly related to lifestyle behaviour and human papillomavirus (HPV) infection. Environmentally induced loss of imprinting (LOI) at the H19 differentially methylated region (H19DMR) is associated with many cancers in the early events of tumorigenesis and may be involved in the pathogenesis of penile SCC. We sought to evaluate the DNA methylation pattern at H19DMR and its association with HPV infection in men with penile SCC by bisulfite sequencing (bis-seq). We observed an average methylation of 32.2% ± 11.6% at the H19DMR of penile SCC and did not observe an association between the p16 INK4a + ( p  = 0.59) and high-risk HPV+ ( p  = 0.338) markers with methylation level. The average methylation did not change according to HPV positive for p16 INK4a + or hrHPV+ (35.4% ± 10%) and negative for both markers (32.4% ± 10.1%) groups. As the region analysed has a binding site for the CTCF protein, the hypomethylation at the surrounding CpG sites might alter its insulator function. In addition, there was a positive correlation between intense polymorphonuclear cell infiltration and hypomethylation at H19DMR ( p  = 0.035). Here, we report that hypomethylation at H19DMR in penile SCC might contribute to tumour progression and aggressiveness regardless of HPV infection.

Current antiretroviral therapy (ART) regimens efficiently limit HIV replication, thereby improving the life expectancy of people living with HIV; however, they also cause metabolic side effects. The ongoing obesity epidemic has resulted in more people with metabolic comorbidities at the time of HIV infection, yet the effect of preexisting metabolic dysregulation on infection sequelae and response to ART is unclear. Here, to investigate the impact of preexisting obesity and insulin resistance on acute infection and subsequent long-term ART, we infected a cohort of lean and obese adult male macaques with SIV and administered ART. The responses of lean and obese macaques to SIV and ART were similar with respect to plasma and cell-associated viral loads, ART drug levels in plasma and tissues, SIV-specific immune responses, adipose tissue and islet morphology, and colon inflammation, with baseline differences between lean and obese groups largely maintained. Both groups exhibited a striking depletion of CD4+ T cells from adipose tissue that did not recover with ART. However, differential responses to SIV and ART were observed for body weight, omental adipocyte size, and the adiponectin/leptin ratio, a marker of cardiometabolic risk. Thus, obesity and insulin resistance had limited effects on multiple responses to acute SIV infection and ART, while several factors that underlie long-term metabolic comorbidities were influenced by prior obesity and insulin resistance. These studies provide the foundation for future investigations into the efficacy of adjunct therapies such as metformin and glucagon-like peptide-1 receptor agonists in the prevention of metabolic comorbidities in people living with HIV.

Tumor cells may develop alterations in glycosylation patterns during the initial phase of carcinogenesis. These alterations may be important therapeutic targets for lectins with antitumor action. This work aimed to evaluate the in vitro cytotoxicity of VML on tumor and non-tumor cells (concentration of 25 μg/mL and then microdiluted) and evaluate its in vivo toxicity at different concentrations (1.8, 3.5 and 7.0 μg/mL), using Drosophila melanogaster. Toxicity in D. melanogaster evaluated mortality rate, as well as oxidative stress markers (TBARS, iron levels, nitric oxide levels, protein and non-protein thiols). The cytotoxicity assay showed that VML had cytotoxic effect on leukemic lines HL-60 (IC 50  = 3.5 μg/mL), KG1 (IC 50  = 18.6 μg/mL) and K562 (102.0 μg/mL). In the toxicity assay, VML showed no reduction in survival at concentrations of 3.5 and 7.0 μg/mL and did not alter oxidative stress markers at any concentrations tested. Cytotoxicity of VML from HL-60, KG1 and K562 cells could arise from the interaction between the lectin and specific carbohydrates of tumor cells. In contrast, effective concentrations of VML against no-tumor cells human keratinocyte - HaCat and in the D. melanogaster model did not show toxicity, suggesting that VML is a promising molecule in vivo studies involving leukemic cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In the present study, the effect of sulfonamide-chalcone 185 (SSC185) was investigated against B16-F10 metastatic melanoma cells aggressive actions, besides migration and adhesion processes, by in silico and in vitro assays. In silico studies were used to characterize the pharmacokinetic profile and possible targets of SSC185, using the pkCSM web server, and docking simulations with AutoDock Tools. Furthermore, the antimetastatic effect of SSC185 was investigated by in vitro experiments using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), colony, scratch, and cell adhesion assays, and atomic force microscopy (AFM). The molecular docking results show better affinity of SSC185 with the metalloproteinases-2 (MMP-2) and α5β1 integrin. SSC185 effectively restricts the formation of colonies, migration, and adhesion of B16-F10 metastatic melanoma cells. Through the AFM images changes in cells morphology was identified, with a decrease in the filopodia and increase in the average cellular roughness. The results obtained demonstrate the potential of this molecule in inhibit the primordial steps for metastasis, which is responsible for a worse prognosis of late stage cancer, being the main cause of morbidity among cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The impact of vaccination on the world's population is difficult to calculate. For developing different types of vaccines, adjuvants are substances added to vaccines to increase the magnitude and durability of the immune response and the effectiveness of the vaccine. This work explores the potential use of spherical gold nanoparticles (AuNPs) as adjuvants. Thus, we employed docking techniques and molecular mechanics to describe how a AuNP 7.0 nm in diameter interacts with cell signaling pathway proteins. Initially, we used X-ray crystallization data of the proteins ovalbumin, glutathione, LC3, TLR4, ASC PYCARD, PI3K, and NF-Kβ to study the adsorption with an AuNP through molecular docking. Therefore, interaction energies were obtained for the AuNP complexes and individual proteins, as well as the AuNP and OVA complex (AuNP@OVA) with each cellular protein, respectively. Results showed that AuNPs had the highest affinity for OVA individually, followed by glutathione, ASC PYCARD domain, LC3, PI3K, NF-Kβ, and TLR4. Furthermore, when evaluating the AuNP@OVA complex, glutathione showed a greater affinity with more potent interaction energy when compared to the other studied systems., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The puma population is constantly decreasing, and cloning by somatic cell nuclear transfer can be used to conserve the species. One of the factors determining the success of the development of cloned embryos is the cell cycle stage of the donor cells. We evaluated the effects of full confluency (~100%), serum starvation (0.5% serum), and roscovitine (15 µM) treatments on the cell cycle synchronization in G 0 /G 1 of puma skin-derived fibroblasts by flow cytometric analysis. Also, we assessed the effects of these synchronization methods on morphology, viability, and apoptosis levels using microscopy tools. The results showed that culturing the cells to confluence for 24 h (84.0%), 48 h (84.6%), and 72 h (84.2%) and serum starvation for 96 h (85.4%) yielded a significantly higher percentage of cells arrested in the G 0 /G 1 (P 0.05) phase than cells not subjected to any cell cycle synchronization method (73.9%). Nevertheless, while serum starvation reduced the percentage of viable cells, no difference was observed for the full confluence and roscovitine treatments (P 0.05). Moreover, roscovitine for 12 h (78.6%) and 24 h (82.1%) was unable to synchronize cells in G 0 /G 1 (P 0.05). In summary, full confluency induces puma fibroblast cell cycle synchronization at the G 0 /G 1 stage without affecting cell viability. These outcomes may be valuable for planning donor cells for somatic cell nuclear transfer in pumas., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare.

LASSBio-1920 was synthesized due to the poor solubility of its natural precursor, combretastatin A4 (CA4). The cytotoxic potential of the compound against human colorectal cancer cells (HCT-116) and non-small cell lung cancer cells (PC-9) was evaluated, yielding IC 50 values of 0.06 and 0.07 μM, respectively. Its mechanism of action was analyzed by microscopy and flow cytometry, where LASSBio-1920 was found to induce apoptosis. Molecular docking simulations and the enzymatic inhibition study with wild-type (wt) EGFR indicated enzyme-substrate interactions similar to other tyrosine kinase inhibitors. We suggest that LASSBio-1920 is metabolized by O-demethylation and NADPH generation. LASSBio-1920 demonstrated excellent absorption in the gastrointestinal tract and high central nervous system (CNS) permeability. The pharmacokinetic parameters obtained by predictions indicated that the compound presents zero-order kinetics and, in a human module simulation, accumulates in the liver, heart, gut, and spleen. The pharmacokinetic parameters obtained will serve as the basis to initiate in vivo studies regarding LASSBio-1920's antitumor potential.

Theranostics combines therapeutic and imaging diagnostic techniques that are extremely dependent on the action of imaging agent, transporter of therapeutic molecules, and specific target ligand, in which fluorescent probes can act as diagnostic agents. In particular, naphthoimidazoles are potential bioactive heterocycle compounds to be used in several biomedical applications. With this aim, a group of seven naphth[1,2- d ]imidazole compounds were synthesized from β-lapachone. Their optical properties and their cytotoxic activity against cancer cells and their compounds were evaluated and confirmed promising values for molar absorptivity coefficients (on the order of 10 3 to 10 4 ), intense fluorescence emissions in the blue region, and large Stokes shifts (20-103 nm). Furthermore, the probes were also selective for analyzed cancer cells (leukemic cells (HL-60). The naphth[1,2- d ]imidazoles showed IC 50 between 8.71 and 29.92 μM against HL-60 cells. For HCT-116 cells, values for IC 50 between 21.12 and 62.11 μM were observed. The selective cytotoxicity towards cancer cells and the fluorescence of the synthesized naphth[1,2- d ]imidazoles are promising responses that make possible the application of these components in antitumor theranostic systems.

In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres ( ortho -quinone/ para -quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of para -naphthoquinones and subsequent conjugation with different ortho -quinoidal moieties. As anticipated, our study identified several compounds with IC 50 values below 0.5 µM in tumour cell lines. Some of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity on L929, the control cell line. The antitumour evaluation of the compounds separately and in their conjugated form proved that the activity is strongly enhanced in the derivatives containing two redox centres. Thus, our study confirms the efficiency of using A-ring functionalized para -quinones coupled with ortho -quinones to obtain a diverse range of two redox centre compounds with potential applications against cancer cell lines. Here as well, it literally takes two for an efficient tango!