Luciana Machado Bastos

Malaria remains a major global health challenge. While treatments targeting parasite replication exist, effective interventions for neurological manifestations are scarce, necessitating new strategies for cerebral malaria. In this study, we investigated the effect of a single-chain variable fragment (scFv) against glycosylphosphatidylinositol (GPI) as an intervention tool to mitigate the effects of Plasmodium in a preclinical model. We used C57BL/6J mice infected with Plasmodium berghei-ANKA (PbA) and treated them with anti-GPI scFv or phosphate-buffered saline (PBS) on days 0, 3, and 6 post-infection. Uninfected controls were treated on the same days with scFv or PBS. The animals were evaluated for morbidity and mortality, body weight, parasitemia, blood count, cytokines, and histopathology. Results show that anti-GPI scFv prevented lethality in 71.4% of infected animals and promoted recovery from weight loss. Furthermore, the intervention inhibited neurological and systemic signs, reduced parasitemia, and improved hematological and histopathological parameters in the brain, lungs, and kidneys. In conclusion, anti-GPI scFv exerts a significant systemic effect on experimental cerebral malaria (ECM) pathology, representing a promising tool for severe manifestations of the disease.

Introduction Robust evidence endorsed by the International Agency for Research on Cancer demonstrates that excess body fat represents a risk for the development of at least 13 types of cancer. Objective We investigated the serum of individuals with obesity who had no history of cancer (either personal or familial) to identify biomarkers. Methods 45 individuals were included in this study; they did not show significant differences regarding age, sex, or physical activity. A quality-of-life questionnaire was administered to all participants, revealing that the obese group self-reported difficulties in functional capacity and a greater association with comorbidities, notably hypertension. FTIR, metabolomic, and lipidomic analyses were performed to identify spectral peaks, metabolic, and lipids differentiating between the NO (non-obese) and OB (obese) groups. Results The identified peaks are predominantly associated with profiles of lipids, carbohydrates, and nitrogenous compounds. A total of six metabolites and lipids were identified at different levels in the serum of the OB group that have a direct relationship with the development or metabolism of cancer cells (three metabolites and three lipids). Among these, some suggest a reduced likelihood of cancer development, while others indicate an increased potential for cancer development. In this context, we can highlight two substances: the metabolite 4-Hydroxyphenylglyoxylate, which is reduced in the serum of individuals with obesity, and the lipid Glycidyl palmitate, which is elevated in individuals with obesity. Conclusion 4-Hydroxyphenylglyoxylate and Glycidyl palmitate can be used as biomarkers for cancer and obesity correlation. New experiments manipulating these substances may contribute to a better understanding of their interactions with cancer cells.

Glioblastoma multiforme (GBM) accounts for 70% of all primary malignancies of the central nervous system. Current treatment strategies involve surgery followed by chemotherapy with temozolomide (TMZ); however, the median survival after treatment is approximately 15 months. Many GBM cases develop resistance to TMZ, resulting in a poor prognosis for patients, which underscores the urgent need for novel therapeutic approaches. One promising avenue is the inhibition of histone deacetylase 6 (HDAC6), an enzyme that deacetylates α-tubulin and is increasingly recognized as a potential pharmacological target in cancer. In GBM specifically, HDAC6 overexpression has been linked to poor prognosis and chemoresistance. In this study, we demonstrate that HDAC6 protein levels are elevated in GBM and evaluate the effects of the novel selective HDAC6 inhibitor, WT161, on U251, U87, and T98G cells to assess its potential to revert the malignant phenotype. Our results show a significant increase in acetylated α-tubulin levels, suppression of cell growth, cell cycle arrest at the G2/M phase, and decreased clonogenicity of 2D-cultured GBM cells. Additionally, WT161 acted synergistically with TMZ, induced apoptosis and enhanced TMZ-induced apoptosis. Notably, HDAC6 inhibition resulted in reduced cell migration and invasion, associated with decreased β-catenin levels. When cultured in 3D conditions, WT161-treated T98G spheroids were sensitized to TMZ and exhibited reduced migration. Finally, HDAC6 inhibition altered the metabolome, particularly affecting metabolites associated with lipid peroxidation. In conclusion, our data reveal, for the first time, the efficacy of the selective HDAC6 inhibitor WT161 in a preclinical GBM setting.

Campylobacter is a virulent Gram-negative bacterial genus mainly found in the intestines of poultry. The indiscriminate use of traditional antibiotics has led to drug resistance in these pathogens, necessitating the development of more efficient and less toxic therapies. Despite their complex biologically active structures, the clinical applications of essential oils (EOs) remain limited. Therefore, this study aimed to increase the bioavailability, stability, and biocompatibility and decrease the photodegradation and toxicity of EO using nanotechnology. The diffusion disk test revealed the potent anti-Campylobacter activity of cinnamon, lemongrass, clove, geranium, and oregano EOs (>50 mm). These were subsequently used to prepare nanostructured lipid carriers (NLCs). Formulations containing these EOs inhibited Campylobacter spp. growth at low concentrations (0.2 mg/mL). The particle size, polydispersity index, and zeta potential of these systems were monitored, confirming its physicochemical stability for 210 days at 25 °C. FTIR-ATR and DSC analyses confirmed excellent miscibility among the excipients, and FE-SEM elucidated a spherical shape with well-delimited contours of nanoparticles. The best NLCs were tested regarding nanotoxicity in a chicken embryo model. These results indicate that the NLC-based geranium EO is the most promising and safe system for the control and treatment of multidrug-resistant strains of Campylobacter spp.

Bovine brucellosis is a disease that significantly impacts animal production and human health. Although many sensitive diagnostic tests are used, there is still no ideal fast serological test for all epidemiological situations. In this context, we developed peptides that mimic regions of antigenic proteins of Brucella abortus and can be used in serological diagnosis. Results From phage display technology, we randomly selected nine clones of phage displaying peptide binders to B. abortus. These clones were sequenced and translated. After molecular docking analysis, two peptides (Ba4 and Ba9) were selected, chemically synthesized, and verified for their potential diagnostic value. By enzyme-linked immunoassay (ELISA), Ba9 showed a sensitivity of up to 97.5% to detect antibodies circulating in animals with brucellosis. We incorporated the peptide Ba9 onto a bioelectrode (graphite modified with poly-3-hydroxyphenylacetic acid). Then, direct serum detection was demonstrated by differential pulse voltammetry, micrographs, and topographic analyses in addition to the average roughness coefficient (Ra) and the value of the mean squared deviation of the roughness (Rms). Conclusion This work shows that the mimetic epitope of B. abortus can be useful for developing new platforms for diagnosing brucellosis. In addition, we propose a fast test based on an electrochemical sensor using graphite modified with poly-3-hydroxyphenylacetic acid.

Phage display (PD) is a tool for developing new molecules to control pathogens. Peptides selected by PD are commonly synthesised and tested, but the use of phage M13 displaying the selected peptides as a direct biding in the intestinal tract has not yet been tested. This study evaluated whether phage M13 can remain viable in the chicken gastrointestinal tract and whether it causes injury or humoral immune response. We inoculated phage M13 or E. coli ER2738 (ECR) infected with M13 into birds at different ages. We found the virus in faeces at 5 or 13 days after inoculation, just when it infected the ECR. The presence of phage M13 or ECR did not result in gut injuries and had no impacts on weight gain and bird health. Furthermore, the levels of IgY were similar in all treatments, which indicates that the virus can be used in chicken until 42 days without being recognised by the immune system. This work provides a scientific basis for the use of PD as a tool in numerous applications to control different pathogens.