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Global investment in developing COVID-19 vaccines has been substantial, but vaccine hesitancy has emerged due to misinformation. Concerns about adverse events, vaccine shortages, dosing confusion, mixing vaccines, and access issues contribute to hesitancy. Initially, the WHO recommended homologous vaccination (same vaccine for both doses), but evolving factors led to consideration of heterologous vaccination (different vaccines). The study compared reactogenicity and antibody response for both viral protein spike (S) and nucleocapsid (N) in 205 participants who received three vaccination regimens: same vaccine for all doses (Pfizer), two initial doses of the same vaccine (CoronaVac or AstraZeneca), and a Pfizer booster. ChAdOx1 and BNT162b2 vaccines were the most reactogenic vaccines, while CoronaVac vaccine was the least. ChAdOx1 and BNT162b2 achieved 100% of S-IgG seropositivity with one dose, while CoronaVac required two doses, emphasizing the importance of the second dose in achieving complete immunization across the population with different vaccine regimes. Pfizer recipients showed the highest S-IgG antibody titers, followed by AstraZeneca recipients, both after the first and second doses. A third vaccine dose was essential to boost the S-IgG antibodies and equalize the antibody levels among the different vaccine schedules. CoronaVac induced N-IgG antibodies, while in the Pfizer and AstraZeneca groups, they were induced by a natural infection, reinforcing the role of N protein as a biomarker of infection.

Cancer remains a significant global health concern, with mortality rates steadily rising and prompting an urgent search for effective treatments. This study focuses on the medicinal properties of plants from the Phyllanthus genus, specifically Phyllanthus amarus and Phyllanthus niruri, which have shown promise in traditional medicine. Through bioguided fractionation using preparative high-performance liquid chromatography (HPLC), bioactive compounds were isolated and identified using ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-QTOF-MS E ) and nuclear magnetic resonance (NMR) spectroscopy. Chemometric analyses such as principal component analysis (PCA) aided in understanding metabolite distribution. Biological assays demonstrated cytotoxic activities of specific fractions against cancer cell lines, notably the PhyN 4n fraction from P. niruri, which induced S-phase cell cycle arrest and apoptosis in HL60 cells. These findings underscore the anticancer potential of Phyllanthus species and lay the groundwork for future drug development efforts. The study's integration of advanced analytical techniques, chemometrics, and biological assays provides valuable insights for harnessing natural products in the fight against cancer., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Understanding COVID-19 exposure differences among Healthcare Workers (HCWs) across various healthcare units is crucial for their protection and effective management of future outbreaks. However, comparative data on COVID-19 among HCWs in different healthcare units are scarce in Brazil. This study evaluated the relationship between SARS-CoV-2 infection and workplaces in HCWs from three distinct healthcare settings in Brazil. It also examined COVID-19 symptom dynamics reported by them. The cohort comprised 464 HCWs vaccinated with two doses of CoronaVac and a BNT162b2 booster from different institutions: Primary Health Care Units (PHCUs), Emergency Care Units (ECUs), and Hospitals. Participants answered a questionnaire and underwent blood collection at various time points after vaccinations. RT-PCR data and post-vaccination antibody responses were utilized as indicators of SARS-CoV-2 infection. We found that most infected HCWs worked in ECUs, where positive RT-PCR percentages were higher compared to PHCUs and Hospitals. ECUs also showed the highest seropositivity and antibody levels, especially after the first CoronaVac dose. The second dose of CoronaVac diminished the differences in the antibody levels among HCWs from ECUS, PHCUs, and Hospitals, indicating the benefit of the second dose to equalize the antibody levels between previously exposed and unexposed persons. Moreover, COVID-19 symptoms appeared to evolve over time., Competing Interests: Competing interests The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We investigated the impact of the fourth dose with ChAdOx1 nCoV-19 (AstraZeneca) in the humoral immune response to SARS-CoV-2 during a 9-month follow-up period in which Omicron was the predominant variant in Brazil. IgG for the SARS-CoV-2 spike protein (S) and nucleocapsid (N) proteins were analyzed in samples collected before and after the fourth dose. All participants were tested monthly for SARS-CoV-2 infection by RT-qPCR. The antibody response induced by the fourth dose of the coronavirus disease 2019 vaccine was evaluated and compared with the response induced by the second and third doses. The additional antibody response to the viral S protein after the fourth dose was smaller than those after the third vaccine dose. In contrast, an increase in the N IgG levels could be observed after the fourth dose compared to other vaccine doses. In the comparison of the antibody response before and after the fourth dose, an increase in both S-and-N IgG was noted, mainly in the positive qPCR group. We did not observe a significant decline in IgG levels after the fourth dose, as observed after the second and third doses, therefore, a sustained humoral response to both S and N proteins seems to be achieved., (© 2023 Wiley Periodicals LLC.)

The Senna genus has a wide diversity of species, with an interesting chemical composition of secondary metabolites and applications as medicine. The folk medicine, mainly in developing countries, uses species of Senna to treat seizures, epilepsy and constipation. Though the recognized bioactivity, some Brazilian native species of Senna remain unexplored, such as Senna cearensis , a native species of Caatinga. This is the first report about the bioactivity of the flowers of S. cearensis Afr. Fern., a native species of northeast Brazil. In this communication, flavonoids and catechins are identified in S. cearensis flowers and the chemical composition is linked with its antioxidant, anticholinesterase, and cytotoxic activities. By UPLC-QTOF, some compounds that belong to the class of flavonoids were identified. They are: catechin, epigallocatechin, guibourtinidol-(4α-8)-catechin, and cassiaflavan-(Cat)-epicatechin. The cytotoxic activity is more noticeable for the HL60 (leukemia) cell line with a cell growth inhibition (GI%) of 81.65 ± 5.65.

Lemon gum (LG) obtained from Citrus × latifolia in Brazil was isolated and characterized. In addition, gum biocompatibility was evaluated in vitro and in vivo by Galleria mellonella and mice model. The cytotoxicity against tumor cells was also evaluated. The ratio of arabinose:galactose: rhamnose:4-OMe-glucuronic acid was 1:0.65:0.06:0.15. Small traces of protein were detected, emphasizing the isolate purity. Molar mass was 8.08 × 10 5  g/mol, with three different degradation events. LG showed antiproliferative activity against human prostate adenocarcinoma cancer cells, with percentage superior to 50 %. In vivo toxicity models demonstrated that LG is biocompatible polymer, with little difference in the parameters compared to control group. These results demonstrate advance in the study of LG composition and toxicity, indicating a potential for several biomedical and biotechnological future applications., 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 © 2023 Elsevier B.V. All rights reserved.)

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.

The most widely used vaccines were messenger RNA (mRNA), viral vector, and inactivated virus with two-dose schedules. In Brazil, the CoronaVac (Sinovac) was the first vaccine approved for emergency use, and the third dose was administered, preferably, with the BNT162b2 vaccine. We evaluated antibody levels after 6 months of the booster dose with BNT162B2 in previous recipients of CoronaVac and whether a subsequent severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection enhances the antibody response. We analyze the humoral response (spike [S] IgM for the SARS-CoV-2 and IgG for the S and nucleocapsid [N] proteins) in samples collected before the third dose and 6 months after the third dose. The presence of antibodies was measured by using Abbott Architect i2000SR. The IgM and IgG antispikes were stimulated mainly 30 days after the third dose (30d/3D), with a decline over time. The IgG anti-N was stimulated predominantly in 90d/3D and 180d/3D. The N IgG levels were 50 and 35 times higher in the positive polymerase chain reaction (PCR) group in 90d/3D and 180d/3D, respectively. The S IgG titers were 1.5 times elevated in the positive PCR group, in 180d/3D. The BNT162b2 boosted the S IgG levels, decreasing after 60 days. The booster shot induced IgM and IgG antibodies against spike protein. Infection after vaccination increased antibodies against protein N., (© 2022 Wiley Periodicals LLC.)

In this study, we investigated the phenolic and antioxidant content, cytotoxic, and anticholinesterase activities of flower extracts of Senna spectabilis var. excelsa and Senna macranthera . The antioxidant activities performed by the DPPH and ABTS methods showed that the extracts possess good antioxidant activity, with emphasis on the S. macranthera extract, which obtained results very similar to the rutin pattern. In the evaluation of the cytotoxic activity, the species S. spectabilis var. excelsa presented expressive cytotoxicity against the cellular lines PC3 and HL60 with IC 50 values 21.08 and 31.37 μg mL -1 , respectively. The results of anticholinesterase activity showed that both the plants induced enzyme inhibition, reaching 14 mm of inhibition in the case of S. spectabilis var. excelsa . The good results obtained in this work may be related to the presence of compounds such as apigenin-7-apioglucoside, quercetin 3,4'-diglucoside, cassine and spectaline identified in the extracts in our previous work.

We synthesized ten enamine naphthoquinones with yields ranging from 43 to 76%. These compounds were screened for their in vitro antiproliferative activities by MTT assay against four types of human cancer cell lines: HCT116, PC3, HL60 and SNB19. The naphthoquinones bearing the picolylamine (7) and quinoline (12) moieties were the most actives (IC 50  < 24 μM for all the cell lines), which were comparable or better to the values obtained for the control drugs. In silico evaluations allowed us to develop a qualitative Structure-Activity Relationship which suggest that electrostatic features, particularly the C 2 -C 3 internuclear repulsion and the molecular dipole moment, relate to the biological response. Furthermore, Molecular Docking simulations indicate that the synthetic compounds have the potential to act as anticancer molecules by inhibiting topoisomerase-II and thymidylate synthase., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A simple and fast methodology under microwave irradiation for the synthesis of 2-aminopyrimidine and pyrazole derivatives using Atwal reaction is reported. After the optimization of the reaction conditions, eight 2-aminolpyrimidines containing ferrocene and heterocycles and three ferrocene pyrazoles were synthesized from the respective chalcones in good yields. Eight compounds had their structure determined by X-ray diffraction. The molecular hybrid 6a-h and 9a-c were tested on four cancer cell lines - HCT116, PC3, HL60 and SNB19 - where four pyrimidine 6a, 6f-h and one pyrazole 9c derivatives show promising antiproliferative activity. In addition, docking simulation and machine learning methods were carried out to explain the biological activity achieved by the synthetized compounds., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The pentacyclic triterpene 3β,6β,16β-tri-hydroxilup-20(29)-ene is a natural product produced by the Brazilian medicinal plant Combretum leprosum. Its cytotoxicity has been previously reported against breast cancer cell lines. The low water solubility of this natural product, that hampers its bioavailability, motivated the investigation of a new nanoparticle formulation containing the triterpene in order to improve its bioactivity. The triterpene was encapsulated in polycaprolactone (PCL) polymer by nanoprecipitation, producing homogenic nanoparticles with nanometer sizes (122.7 ± 2.06 nm), which were characterized by FT-IR, SEM imaging and DSC. The cytotoxicity (MTT method) of the nanoparticle containing the triterpene 1, besides the free natural product and the nanoparticle control (without 1), was assayed against three human tumor cell lines [human colon carcinoma line (HCT116), prostate (PC3) and glioblastoma (SNB19)] and the normal epithelial embryo kidney human cell line (Hek293T). The nanocarrier produced a significative effect in the cytotoxicity of the natural product in the nanoformulation (IC 50 0.11-0.26 µg mL -1 ) when compared with its free form (IC 50 1.07-1.44 µg mL -1 ). Additionally, higher selectivity of the triterpene to the tumor cells was found when it was encapsulated (SI 1.92-4.54) than in its free form (SI 0.42-0.56). In this case, the nanoencapsulated triterpene was more selective to PC3 (SI 3.33) and SNB19 (SI 4.54) tumor 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 © 2020 Elsevier Ltd. All rights reserved.)

Arylacetamides are widely used as synthetic intermediates to obtain medicinal substances. This work evaluated in vitro antiproliferative activity of ten 2-Chloro-N-arylacetamides on human normal and cancer cells and detailed in vivo toxicological and anticancer investigations. Initially, cytotoxic colorimetric assays were performed using tumor lines, peripheral blood mononuclear cells (PBMC) and erythrocytes. Compounds 2, 3 and 4 were tested for acute toxicity (50, 150 and 300 mg/kg) and for subacute antitumoral capacity in HCT-116 colon carcinoma-bearing xenograft mice for 15 days at 25 mg/kg/day. Most compounds revealed cytotoxic action on tumor lines and PBMC, but activity on human erythrocytes were not detected. Molecular dipole moment, lipophilicity and electronic constant of aryl substituents had effects upon in vitro antiproliferative capacity. More common in vivo acute behavioral signals with compounds 2, 3 and 4 were muscle relaxation, reduction of spontaneous locomotor activity and number of entries in closed arms and increased number of falls andtime spent in open arms, suggesting diazepam-like anxiolytic properties. Decrease of grabbing strength and overall activity were common, but palpebral ptosis and deaths occurred at 300 mg/kg only. Compounds 2 and 3 reduced colon carcinoma growth (21.2 and 27.5%, respectively, p < 0.05) without causing apparent signals of organ-specific toxicity after subacute exposure. The structural chemical simplicity of arylacetamides make them cost-effective alternatives and justifies further improvements to enhance activity, selectivity and the development of pharmaceutical formulations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The classical approach to drug discovery from natural products (NP's) requires strenuous and complex purification steps for the isolation and structural elucidation. Modern strategies as dereplication aim to accelerate the identification of known compounds present in a crude or partially purified extract. In this work, we investigated the influence of the solid-phase extraction (Oasis, Plexa, and Agilent C18 cartridges with and without organic modifiers) chemical profile obtained by UPLC-QTOF-MS and NMR and cytotoxicities of aqueous extracts from Phyllanthus niruri and P. amarus. Our results showed differences between the SPE cartridges and the mass recovered. P. niruri showed higher mass recovery than P. amarus indicating a higher amount of secondary metabolites. The UPLC-QTOF-MS analysis revealed that P. niruri crude extract presents higher contents of phenolic compounds than P. amarus. According to NMR analysis, P. niruri contained more tyrosine, corilagin, and glycosidic residues while P. amarus, presented higher content of ellagic acid. The different stationary phases, as well as mobile phases for exploratory SPE, enabled the exploitation of the different chemical functionalities within the Phyllanthus species. The SPE (MeOH:H 2 O 70:30 with C18 cartridges) samples showed greater in vitro cytotoxicity than the crude extracts, with IC 50 ranging from 8.01 to 94.92 μg mL -1 against the tumor lines tested. The solid phase extraction allowed the concentration of molecules with desirable physicochemical characteristics, which might increase the hit of therapeutically useful substances., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The physicochemical and sensorial characterization of beef burgers with added sorghum flours as replacer for the isolated soy protein (ISP) usually used in the conventional formulations was performed. Three formulations were prepared: one conventional (CN) with 3% ISP and two with 3% tannin (BRS 305) and tannin-free (BR 501) whole sorghum flour (WSF) of BRS 305 and BR 501 genotypes. There was no difference among the formulations for most of the physicochemical characteristics. The moisture retention was higher in BRS 305 (P < .05). The added WSF influenced the color of the raw beef burger; and the proximate composition and the antioxidant characteristics of the raw and cooked formulations (P < .05). The purchase intention and flavor, texture and overall acceptability scores were higher for the sorghum products than CN (P < .05). Therefore, the replacing of ISP by WSF in beef burger, especially by the BRS 305 genotype, might be a technologically, nutritionally and sensorially viable option., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We investigated if pumpkin and flaxseeds could improve postprandial glycemic, food intake, and appetitive responses. Herein, we hypothesize based on the literature that pumpkin seed has potential to lower postprandial glycemic effects. Therefore, we conducted a randomized, single-blind, placebo-controlled, crossover design study involving normoglycemic adults (food intake: n = 25; glycemia: n = 15). Three high-carbohydrate mixed meals presenting no seed (control [C]) or 65 g of the tested seeds (pumpkin seed [P] or flaxseed [F]) were consumed in 3 nonconsecutive days. Test meals had similar nutritional composition. Blood glucose was measured by capillary finger blood at 0 (immediately before), 15, 30, 45, 60, 90, and 120 minutes after the ingestion of each meal, and the incremental area under glycemic response curves (iAUC) were calculated. Appetitive responses were assessed, and dietary records were used to evaluate food intake on testing days. Glucose iAUC was significantly lower in P compared with C (reduction of ~35%, P = .025). There was no significant differences in glucose iAUC between F and C (P = .257). Glycemic response at each time point did not differ between C, P, and F (P group × time = .238). Fiber consumption was higher in F (P = .009) than in C, but there were no differences in appetitive responses, energy, or macronutrient consumptions between dietary interventions. Acute consumption of 65 g of pumpkin seed markedly reduced postprandial glycemia. Pumpkin seed has potential as a hypoglycemic food, which now deserves to be confirmed in long-term studies., (Copyright © 2018. Published by Elsevier Inc.)

The cytotoxic activity of the pimarane diterpene annonalide (1) and nine of its semisynthetic derivatives (2-10) was investigated against the human tumor cell lines HL-60 (leukemia), PC-3 (prostate adenocarcinoma), HepG2 (hepatocellular carcinoma), SF-295 (glioblastoma) and HCT-116 (colon cancer), and normal mouse fibroblast (L929) cells. The preparation of 2-10 involved derivatization of the side chain of 1 at C-13. Except for 2, all derivatives are being reported for the first time. Most of the tested compounds presented IC 50 s below 4.0 μM, being considered potential antitumor agents. The structures of all new compounds were elucidated by spectroscopic analyses including 2D NMR and HRMS. Additionally, the interaction of annonalide (1) with ctDNA was evaluated using spectroscopic techniques, and the formation of a supramolecular complex with the macromolecule was confirmed. Competition assays with fluorescent probes (Hoechst and ethidium bromide) and theoretical studies confirmed that 1 interacts preferentially via DNA intercalation with stoichiometric ratio of 1:1 (1:ctDNA). The ΔG value was calculated as -28.24 kJ mol -1 , and indicated that the interaction process occurs spontaneously. Docking studies revealed that van der Walls is the most important interaction in 1-DNA and EB-DNA complexes, and that both ligands (1 and EB) interact with the same DNA residues (DA6, DA17 and DT19)., (Copyright © 2018. Published by Elsevier B.V.)

In this work, we characterize nor-β-lapachone-loaded (NβL-loaded) microcapsules prepared using an emulsification/solvent extraction technique. Features such as surface morphology, particle size distribution, zeta potential, optical absorption, Raman and Fourier transform infrared spectra, thermal analysis data, drug encapsulation efficiency, drug release kinetics and in vitro cytotoxicity were studied. Spherical microcapsules with a size of 1.03 ± 0.46 μm were produced with an encapsulation efficiency of approximately 19%. Quantum DFT calculations were also performed to estimate typical interaction energies between a single nor-β-lapachone molecule and the surface of the microparticles. The NβL-loaded PLGA microcapsules exhibited a pronounced initial burst release. After the in vitro treatment with NβL-loaded microcapsules, a clear phagocytosis of the spheres was observed in a few minutes. The cytotoxic activity against a set of cancer cell lines was investigated.

Predictive equations and methods tend to overestimate or underestimate resting energy expenditure (REE) compared with indirect calorimetry (IC). This cross-sectional study aimed to evaluate the agreement between methods and equations for REE estimation of overweight and obese Brazilian men. Data from 48 healthy volunteers, ages 20 to 43 years and with body mass index ranging from 26.4 to 35.2, were collected between October 2008 and October 2009. REE was measured by IC, using Deltatrac (IC1) and KORR-MetaCheck (IC2) devices. It was estimated by bioelectrical impedance analysis (BIA) using tetrapolar (BIA1) and bipolar (BIA2) devices, and by the equations of Mifflin, World Health Organization/Food and Agriculture Organization/United Nations University, Fleisch, Horie-Waitzberg and Gonzalez, and Ireton-Jones. The association and agreement among the methods and equations were assessed by the interclass correlation coefficient, Bland-Altman analysis, and by the percentage of the difference between values obtained from the standard method and alternative methods and equations. Most methods showed high agreement with IC1. The highest agreements were found for Mifflin (-2.14%), Fleisch (-3.05%), Horie-Waitzberg and Gonzalez (4.41%), and BIA2 (5.25%). Similar results were shown by the Bland-Altman analyses. BIA2, followed by BIA1, Ireton-Jones, Mifflin, and Fleisch, showed the highest association with IC1. Thus, the Mifflin, Fleisch, Horie-Waitzberg and Gonzalez equations, and BIA2, were the most accurate methods for REE estimation in this study. However, because those equations have shown considerable variability, they should be used cautiously. In addition, the IC2 was not found to be an accurate method for REE estimation in overweight and obese men included in this study., (Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)