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Extracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients’ plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck.

Natural triterpenes exhibit a wide range of biological activities. Since this group of secondary metabolites is structurally diverse, effects may vary due to distinct biochemical interactions within biological systems. In this work, we investigated the anticancer-related activities of the quinone-methide triterpene maytenin and its derivative compound 22-β-hydroxymaytenin, obtained from Maytenus ilicifolia roots cultivated in vitro. Their antiproliferative and pro-apoptotic activities were evaluated in monolayer and three-dimensional cultures of immortalized cell lines. Additionally, we investigated the toxicity of maytenin in SCID mice harboring tumors derived from a squamous cell carcinoma cell line. Both isolated molecules presented pronounced pro-apoptotic activities in four cell lines derived from head and neck squamous cell carcinomas, including a metastasis-derived cell line. The molecules also induced reactive oxygen species (ROS) and down-regulated microRNA-27a and microRNA-20a/miR-17-5p, corroborating with the literature data for triterpenoids. Intraperitoneal administration of maytenin to tumor-bearing mice did not lead to pronounced histopathological changes in kidney tissue, suggesting low nephrotoxicity. The wide-ranging activity of maytenin and 22-β-hydroxymaytenin in head and neck cancer cells indicates that these molecules should be further explored in plant biochemistry and biotechnology for therapeutic applications.

Antimicrobial peptides possess a myriad of molecular properties including bacterial killing and the regulation of many aspects of innate immunity. Cathelicidins are a group of antimicrobial peptides widely investigated by the scientific community. Many studies have focused on the bactericidal and pro-inflammatory roles of cathelicidins. Because the role of endogenous cathelicidin expression remains obscure in deep-seated systemic infections, we induced sepsis in cathelicidin knockout and wild-type (WT) mice by cecal ligation and puncture, performing transcriptome screening by DNA microarray in conjunction with other immunologic assays. Cathelicidin-deficient mice showed increased survival compared to WT mice in this established experimental model of polymicrobial sepsis, in association with upregulation of certain key inflammatory response genes. Therefore, cathelicidins can exert both pro- and anti-inflammatory activities depending on the disease and cellular context. Key messages The role of cathelicidin in a CLP model is investigated using cathelicidin-KO mice. Cathelicidin-KO mice show an enhanced immune response and improved survival rates. An anti-inflammatory effect of cathelicidin is likely to be detrimental for CLP. Cathelicidin-KO mice show upregulation of genes associated with increased plasma levels of pro-inflammatory Ils. Cathelicidins appear to have both pro- and anti-inflammatory properties.

Psychobiotics correspond to a class of probiotics, mainly of the genus Lactobacillus and Bifidobacterium, capable of producing neuroactive substances, such as [gamma]-aminobutyric acid (GABA) and serotonin, which exert effects on the brain-gut axis. Evidence suggests that psychobiotics can have a beneficial effect on mood, anxiety and cognition. The present study evaluated the effects of chronic administration of two new strains of Lactobacillus plantarum, L. plantarum 286 (Lp 286) and L. plantarum 81 (Lp 81) isolated from the fermentation of cocoa (Theobroma cacao L.) and cupuaçu (Theobroma grandiflorum), respectively, on cognitive, anxiety- and depressive-like behaviors in male Swiss mice. Different groups of animals were administered (oral gavage) solutions of vehicle (0.85% saline plus 15% skim milk), Lp 286 (10.sup.9 /0.1 ml CFU) or Lp 81 (10.sup.9 /0.1 ml CFU) for 30 days, and animals were tested for general locomotor activity, depressive-like behavior in the forced swim test, and learning/memory and anxiety-like behavior in the plus-maze discriminative avoidance task. Treatment with the strains Lp 286 and Lp 81 did not interfere with locomotor activity or learning and memory. The Lp 286 strain exerted anti-depressant- and anxiolytic-like effects under our experimental conditions. Our findings add to the current body of evidence suggesting that probiotics from the genus Lactobacillus may exert psychobiotic potential and introduce a new strain, Lp 286, as a potential candidate in the prevention or as therapeutic adjuvant in the treatment of mental disorders.

Diabetes mellitus type 2 (DM2) patients have higher risk to be infected with parenterally transmitted viruses, like hepatitis B or C virus. This study aims to determine HBV and HCV infection prevalence in DM2 patients from Northeast and Southeast Brazil. A total of 537 DM2 patients were included, 194 (36.12%) males and 343 (63.87%) females, with mean age of 57.13±11.49 years. HBV and HCV markers were determined using serological and molecular analysis, and risk factors were evaluated in a subgroup from Southeast (n = 84). Two HBV acute (HBsAg+/anti-HBc -) and one HBV chronic case (HBsAg+/anti-HBc+) were found. Six individuals (1.1%) were isolated anti-HBc, 37 (6.9%) had HBV infection resolved (anti-HBc+/anti-HBs+), 40 (7.4%) were considered HBV vaccinated (anti-HBc-/anti-HBs+). Thirteen patients (2.42%) had anti-HCV and 7 of them were HCV RNA+. In the subgroup, anti-HBc positivity was associated to age and anti-HCV positivity was associated to age, time of diabetes diagnosis, total bilirubin, indirect bilirubin, alkaline phosphatase at bivariate analysis, but none of them was statistically significant at multivariate analysis. As conclusion, low prevalence of HBV and high prevalence HCV was found in DM2 patients.

Background Arboviruses are a group of viruses transmitted to vertebrate hosts by certain blood-feeding arthropods. Among urban vectors of arboviruses, mosquitoes of the genus Aedes are the most common. However, other mosquitoes may be susceptible to infection and involved in the transmission, such as Mansonia spp. Therefore, this study aimed to investigate whether Mansonia humeralis can be infected with the Mayaro virus (MAYV). Methods These insects were collected from 2018 to 2020 in chicken coops of rural communities in Jaci Paraná in Porto Velho, Rondônia, Brazil, while performing blood-feeding on roosters. The mosquitoes were randomly grouped in pools from which the head and thorax were macerated and checked for the presence of MAYV by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The positive pools were used to infect the C6/36 cell line, and on different days post-infection, the supernatant of the infected cells was subjected to viral detection by RT-qPCR. Results A total of 183 pools of female mosquitoes were tested, of which 18% were positive for MAYV; some samples from insect pools inoculated into C6/36 cells showed in vitro multiplication capacity between 3 and 7 days post-infection. Conclusions This is the first report of Ma. humeralis mosquitoes that are naturally infected by MAYV, indicating that these vectors may be potential transmitting agents of this arbovirus. Graphical Abstract

AbstractMetal complexes based on ruthenium have established excellent activity with less toxicity and great selectivity for tumor cells. This study aims to assess the anticancer potential of ruthenium(II)/allopurinol complexes called [RuCl2(allo)2(PPh3)2] (1) and [RuCl2(allo)2(dppb)] (2), where allo means allopurinol, PPh3 is triphenylphosphine and dppb, 1,4-bis(diphenylphosphino)butane. The complexes were synthesized and characterized by elemental analysis, IR, UV–Vis and NMR spectroscopies, cyclic voltammetry, molar conductance measurements, as well as the X-ray crystallographic analysis of complex 2. The antitumor effects of compounds were determined by cytotoxic activity and cellular and molecular responses to cell death mechanisms. Complex 2 showed good antitumor profile prospects because in addition to its cytotoxicity, it causes cell cycle arrest, induction of DNA damage, morphological and biochemical alterations in the cells. Moreover, complex 2 induces cell death by p53-mediated apoptosis, caspase activation, increased Beclin-1 levels and decreased ROS levels. Therefore, complex 2 can be considered a suitable compound in antitumor treatment due to its cytotoxic mechanism.Graphic abstract

Introduction: The COVID-19 pandemic influenced the behaviour of numerous diseases, overloading health systems and weakening public health infrastructure and access. Methodology: This study aimed to analyse the repercussions of the COVID-19 pandemic on tuberculosis diagnosis indicators. A systematic review was conducted, examining studies published between 2020 and 2024 in Portuguese, English, or Spanish across five databases and Google Scholar. The search, performed in March 2024, led to the identification of 6,378 studies, of which 23 were included after an independent review of titles, abstracts, and full texts. Data were extracted and narratively synthesized following a methodological quality assessment. Results: The review revealed significant declines in TB incidence, detection, notification, and diagnosis during the pandemic, alongside reduced etiological confirmation of cases. Conclusions: The findings highlight a need to reorganize and enhance health service responses to address the disruptions caused by the pandemic. Strengthening these services is crucial to recover missed TB cases and improve indicators, supporting the goal of eliminating TB by 2030.

Background. The PPARG2 Pro12Ala (rs1801282) and IL6 -174G >C (rs1800795) have important function in body weight regulation and a potential role in obesity risk. We aimed to investigate the association between PPARG2 Pro12Ala and IL6 -174G >C variants and the genotypes interaction with body composition, metabolic markers, food consumption, and physical activity in severely obese patients. Methods. 150 severely obese patients (body mass index (BMI) ≥ 35 kg/m2) from Central Brazil were recruited. Body composition, metabolic parameters, physical activity, and dietary intake were measured. The genotype was determined by the qPCR TaqMan Assays System. Multiple linear regression and multiple logistic regression models were fitted adjusting for confounders. Results. Ala carriers of the Pro12Ala polymorphism had higher adiposity measures (BMI: p=0.031, and fat mass: p=0.049) and systolic blood pressure (p=0.026) compared to Pro homozygotes. We found no important associations between the -174G >C polymorphism and obesity phenotypes. When genotypes were combined, individuals with genotypes ProAla + AlaAla and GC + CC presented higher BMI (p=0.029) and higher polyunsaturated fatty acids (PUFAs) consumption (p=0.045) compared to the ones with genotypes ProPro and GG, and individuals carriers of the PPARG2 Ala allele only (genotype ProAla + AlaAla and GG) had higher fat mass and systolic and diastolic blood pressure compared to the ones with genotypes ProPro and GG. Conclusions. Severely obese individuals carrying the Ala allele of the PPARG2 Pro12Ala polymorphism had higher measures of adiposity and blood pressure, while no important associations were found for the IL6 -174G >C polymorphism.

Chitosan comprises polymeric macromolecules with technical and biological properties that have been used in biomedical healing applications requiring anti-microbial and anti-inflammatory capacities worldwide. In the tropical regions, green banana peel extract and andiroba oil are considered natural products with wound healing properties. The present study, for the first time, synthesized chitosan/green banana peel extract/andiroba oil (CGA) membranes and analyzed them using scanning electron microscopy (SEM) and the swelling and moisture tests. The CGA membranes together with control membranes of plain chitosan and chitosan plus green banana peel extract, were characterized by contact angle measurement, X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Macroscopic analysis showed significant differences in color and transparency caused by the number of decoction days used for extract preparation and the oil content. SEM observations disclosed the formation of two phases, lipid and polymer, in the CGA. The number of decoction days and the andiroba oil content were inversely related to the swelling moisture uptake. All membranes were found to be hydrophilic with contact angles less than 90°. The incorporation of plant extract and oil promoted the appearance of related XRD peaks. DSC curves revealed a reduction in the enthalpy of the CGA membranes compared with plain chitosan, which might be attributed to the evaporation of the natural extract and oil. Based on these findings, the studied newly synthesized membranes demonstrated a potential for healing epithelial lesions.