Antibody response following the fourth SARS-CoV-2 vaccine dose during the Omicron wave in Brazil.

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.

Assessment of metabolic, mineral, and cytotoxic profile in pineapple leaves of different commercial varieties: A new eco-friendly and inexpensive source of bioactive compounds.

Pineapple is among the most produced and consumed fruits worldwide, and consequently, its agroindustrial production/processing generates high amounts of agricultural waste, which are routinely discarded. Thus, it is crucial to seek alternatives to reuse this agricultural waste that are in high availability. Therefore, this work aims to evaluate the chemical composition of a specific residue (leaves) of seven commercial varieties of pineapples, to attribute high added value uses, and to evaluate its potential as a source of secondary metabolites and minerals. Thereby, twenty-eight metabolites were annotated by UPLC-QTOF-MSE, including amino acids, organic acids, and phenolic compounds. The following minerals were quantitatively assessed by ICP-OES: Zn (5.30-19.77 mg kg-1), Cr, Cd, Mn (50.80-113.98 mg kg-1), Cu (1.05-4.01 mg kg-1), P (1030.77-6163.63 mg kg-1) and Fe (9.06-70.17 mg kg-1). In addition, Cr and Cd (toxic materials) present concentration levels below the limit of quantification of the analytical method (LOQCr and LOQCd = 0.02 mg kg-1) for all samples. The multivariate analysis was conceived from the chemical profile, through the tools of PCA (principal component analysis) and HCA (hierarchical cluster analysis). The results show that pineapple leaves have similarities and differences concerning their chemical composition. In addition, the cytotoxicity assays of the extracts against tumor and non-tumor strains shows that the extracts were non-toxic. This fact can corroborate and enhance the prospection of new uses and applications of agroindustrial co-products from pineapple, enabling the evaluation and use in different types of industries, such as pharmacological, cosmetic, and food, in addition to the possibility of being a potential source of bioactive compounds.

Antibody response 6 months after the booster dose of Pfizer in previous recipients of CoronaVac.

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.

Dynamics of SARS-CoV-2 Antibody Response to CoronaVac followed by Booster Dose of BNT162b2 Vaccine.

We evaluated the longitudinal dynamics of antibody response to the SARS-CoV-2 vaccine CoronaVac and the effect of a booster dose of BNT162b2 vaccine. We found a robust antibody response after the second dose of CoronaVac that wanes over time. The response was recovered by BNT162b2, which boosted anti-spike antibody titers.

Naphthoquinone-based Hydrazone Hybrids: Synthesis and Potent Activity Against Cancer Cell Lines.

BACKGROUND: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, and the modification at their redox center is an interesting strategy to overcome such harmful activity. OBJECTIVE: In this study, four novel semisynthetic hydrazones, derived from the isomers α- and ß- lapachones (α and ß, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. METHODS: The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. RESULTS: The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, compounds 3 and 4 being the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than ß-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90-12.40 µM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. CONCLUSION: These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.

Poly(N-isopropylacrylamide)/galactomannan from Delonix regia seed thermal responsive graft copolymer via Schiff base reaction.

Aminated poly(N-isopropylacrylamide) (PNIPAm-NH2) was grafted onto oxidized galactomannan polysaccharide extracted from Delonix regia (OXGM) via Schiff base reaction by a simple, rapid synthetic route, deprived of the use of organic solvents. Grafting was confirmed by FTIR and 1H NMR and the self-organizing ability of the obtained nanoparticle copolymers was investigated by dynamic light scattering (DLS). The minimum concentration required for self-organization (CAC) at 25 °C was higher than at 50 °C. Lower critical solution temperature (LCST) was in the range 34-40 °C, depending on both inserted PNIPAm-NH2 molar mass and on the presence of reduced imine bond. Synthesized copolymers are promising candidates for drug delivery as they show good cell viability, particle size around 250 nm and transition temperature closer to that of human body. Reaction success points out to the possibility of use free aldehyde groups of oxidized polysaccharide, not used in the copolymerization, to form a pro-drug with substances that possess NH2 groups in their structure, such as doxorubicin.

Anti-proliferative profile of Anacardium occidentale polysaccharide and characterization by AFM.

This paper explores the application of cashew gum (CG) as an in vitro antiproliferative, firstly by isolating and characterizing the gum using elemental analysis, gel-permeation chromatography, nuclear magnetic resonance (NMR) and atomic force microscopy (AFM). The molar mass of isolated CG was in the order of 103-104 g/mol, with small protein traces present. Polymer characterization by NMR identified key signals correlating to galactose, glucose, rhamnose and acid-related groups. Three distinct conformational stages were observed by AFM. The impact of CG on cell morphology and viability with both tumor and non-tumor cell lines was studied by AFM and 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay respectively. Antiproliferative activity was confirmed for HCT116 (colorectal carcinoma), B16F10 (melanoma) and HL60 (promyelocytic leukemia) cancer cell lines. A change in cell morphology was demonstrated as an increased surface roughness for HL60. Considering that a CG does not exhibit cytotoxicity to non-tumor lines, it can be seen that the CG shows selectivity for tumor cells and can be a promising biomaterial for future studies.

UPLC-HRMS and NMR applied in the evaluation of solid-phase extraction methods as a rational strategy of dereplication of Phyllanthus spp. aiming at the discovery of cytotoxic metabolites.

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:H2O 70:30 with C18 cartridges) samples showed greater in vitro cytotoxicity than the crude extracts, with IC50 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.