Antioxidant, antimicrobial and healing properties of an extract from coffee pulp for the development of a phytocosmetic.

Consumer demand for natural, chemical-free products has grown. Food industry residues, like coffee pulp, rich in caffeine, chlorogenic acid and phenolic compounds, offer potential for pharmaceutical and cosmetic applications due to their antioxidant, anti-inflammatory, and antibacterial properties. Therefore, the objective of this work was to develop a phytocosmetic only with natural products containing coffee pulp extract as active pharmaceutical ingredient with antioxidant, antimicrobial and healing activity. Eight samples from Coffea arabica and Coffea canephora Pierre were analyzed for caffeine, chlorogenic acid, phenolic compounds, tannins, flavonoids, cytotoxicity, antibacterial activity, and healing potential. The Robusta IAC-extract had the greatest prominence with 192.92 µg/mL of chlorogenic acid, 58.98 ± 2.88 mg GAE/g sample in the FRAP test, 79.53 ± 5.61 mg GAE/g sample in the test of total phenolics, was not cytotoxic, and MIC 3 mg/mL against Staphylococcus aureus. This extract was incorporated into a stable formulation and preferred by 88% of volunteers. At last, a scratch assay exhibited the formulation promoted cell migration after 24 h, therefore, increased scratch retraction. In this way, it was possible to develop a phytocosmetic with the coffee pulp that showed desirable antioxidant, antimicrobial and healing properties.

Functionalization of breast implants by cyclodextrin in-situ polymerization: a local drug delivery system for augmentation mammaplasty.

Mammaplasty is a widely performed surgical procedure worldwide, utilized for breast reconstruction, in the context of breast cancer treatment, and aesthetic purposes. To enhance post-operative outcomes and reduce risks (hematoma with required evacuation, capsular contracture, implant-associated infection and others), the controlled release of medicaments can be achieved using drug delivery systems based on cyclodextrins (CDs). In this study, our objective was to functionalize commercially available silicone breast implants with smooth and textured surfaces through in-situ polymerization of two CDs: ß-CD/citric acid and 2-hydroxypropyl-ß-CD/citric acid. This functionalization serves as a local drug delivery system for the controlled release of therapeutic molecules that potentially can be a preventive treatment for post-operative complications in mammaplasty interventions. Initially, we evaluated the pre-treatment of sample surfaces with O2 plasma, followed by chitosan grafting. Subsequently, in-situ polymerization using both types of CDs was performed on implants. The results demonstrated that the proposed pre-treatment significantly increased the polymerization yield. The functionalized samples were characterized using microscopic and physicochemical techniques. To evaluate the efficacy of the proposed system for controlled drug delivery in augmentation mammaplasty, three different molecules were utilized: pirfenidone (PFD) for capsular contracture prevention, Rose Bengal (RB) as anticancer agent, and KR-12 peptide (KR-12) to prevent bacterial infection. The release kinetics of PFD, RB, and KR-12 were analyzed using the Korsmeyer-Peppas and monolithic solution mathematical models to identify the respective delivery mechanisms. The antibacterial effect of KR-12 was assessed against Staphylococcus epidermidis and Pseudomonas aeruginosa, revealing that the antibacterial rate of functionalized samples loaded with KR-12 was dependent on the diffusion coefficients. Finally, due to the immunomodulatory properties of KR-12 peptide on epithelial cells, this type of cells was employed to investigate the cytotoxicity of the functionalized samples. These assays confirmed the superior properties of functionalized samples compared to unprotected implants.

Genome mining reveals secondary metabolites of Antarctic bacterium Streptomyces albidoflavus related to antimicrobial and antiproliferative activities.

The urgent need for new antimicrobials arises from antimicrobial resistance. Actinobacteria, especially Streptomyces genus, are responsible for production of numerous clinical antibiotics and anticancer agents. Genome mining reveals the biosynthetic gene clusters (BGCs) related to secondary metabolites and the genetic potential of a strain to produce natural products. However, this potential may not be expressed under laboratory conditions. In the present study, the Antarctic bacterium was taxonomically affiliated as Streptomyces albidoflavus ANT_B131 (CBMAI 1855). The crude extracts showed antimicrobial activity against both fungi, Gram-positive and Gram-negative bacteria and antiproliferative activity against five human tumor cell lines. Whole-genome sequencing reveals a genome size of 6.96 Mb, and the genome mining identified 24 BGCs, representing 13.3% of the genome. The use of three culture media and three extraction methods reveals the expression and recovery of 20.8% of the BGCs. The natural products identified included compounds, such as surugamide A, surugamide D, desferrioxamine B + Al, desferrioxamine E, and ectoine. This study reveals the potential of S. albidoflavus ANT_B131 as a natural product producer. Yet, the diversity of culture media and extraction methods could enhance the BGCs expression and recovery of natural products, and could be a strategy to intensify the BGC expression of natural products.

Production of Recombinant Zika Virus Envelope Protein by Airlift Bioreactor as a New Subunit Vaccine Platform.

The Zika Virus (ZIKV) is an emerging arbovirus of great public health concern, particularly in the Americas after its last outbreak in 2015. There are still major challenges regarding disease control, and there is no ZIKV vaccine currently approved for human use. Among many different vaccine platforms currently under study, the recombinant envelope protein from Zika Virus (rEZIKV) constitutes an alternative option for vaccine development and has great potential for monitoring ZIKV infection and antibody response. This study describes a method to obtain a bioactive and functional rEZIKV using an E. coli expression system, with the aid of a 5-L airlift bioreactor and following an automated fast protein liquid chromatography (FPLC) protocol, capable of obtaining high yields of approximately 20 mg of recombinant protein per liter of bacterium cultures. The purified rEZIKV presented preserved antigenicity and immunogenicity. Our results show that the use of an airlift bioreactor for the production of rEZIKV is ideal for establishing protocols and further research on ZIKV vaccines bioprocess, representing a promising system for the production of a ZIKV envelope recombinant protein-based vaccine candidate.

Selection and Control of Process Conditions Enable the Preparation of Curcumin-Loaded Poly(lactic-co-glycolic acid) Nanoparticles of Superior Performance.

Curcumin (CUR) is one natural bioactive compound acknowledged for diverse therapeutic activities, but its use is hindered by its poor bioavailability, fast metabolism, and susceptibility to pH variations and light exposure. Thus, the encapsulation in poly(lactic-co-glycolic acid), or PLGA, has been successfully used to protect and enhance CUR absorption in the organism, making CUR-loaded PLGA nanoparticles (NPs) promising drug delivery systems. However, few studies have focused beyond CUR bioavailability, on the environmental variables involved in the encapsulation process, and whether they could help obtain NPs of superior performance. Our study evaluated pH (3.0 or 7.0), temperature (15 or 35 °C), light exposure, and inert atmosphere (N2) incidence in the encapsulation of CUR. The best outcome was at pH 3.0, 15 °C, without light incidence, and without N2 usage. This best nanoformulation showed NP size, zeta potential, and encapsulation efficiency (EE) of 297 nm, -21 mV, and 72%, respectively. Moreover, the CUR in vitro release at pH values 5.5 and 7.4 suggested different potential applications for these NPs, one of which was demonstrated by the effective inhibition of multiple bacteria (i.e., Gram-negative, Gram-positive, and multi-resistant) in the minimal inhibition concentration assay. Besides, statistical analyses confirmed a significant impact of temperature on the NP size; in addition, temperature, light, and N2 affected the EE of CUR. Thus, the selection and control of process variables resulted in higher CUR encapsulation and customizable outcomes, ultimately enabling more economical processes and providing future scale-up guidelines.

Terbinafine Nanohybrid: Proposing a Hydrogel Carrying Nanoparticles for Topical Release.

A poloxamer 407 (P407)-Casein hydrogel was chosen to carry polycaprolactone nanoparticles carrying terbinafine (PCL-TBH-NP). In this study, terbinafine hydrochloride (TBH) was encapsulated into polycaprolactone (PCL) nanoparticles, which were further incorporated into a poloxamer-casein hydrogel in a different addition order to evaluate the effect of gel formation. Nanoparticles were prepared by the nanoprecipitation technique and characterized by evaluating their physicochemical characteristics and morphology. The nanoparticles had a mean diameter of 196.7 ± 0.7 nm, PDI of 0.07, negative ζ potential (-0.713 mV), high encapsulation efficiency (>98%), and did not show cytotoxic effects in primary human keratinocytes. PCL-NP modulated terbinafine was released in artificial sweat. Rheological properties were analyzed by temperature sweep tests at different addition orders of nanoparticles into hydrogel formation. The rheological behavior of nanohybrid hydrogels showed the influence of TBH-PCL nanoparticles addition in the mechanical properties of the hydrogel and a long-term release of the nanoparticles from it.

Biomimetic Nanovesicles-Sources, Design, Production Methods, and Applications.

Despite all the progress in the field of liposomes and nanoparticles for applications as drug and gene delivery systems, the specific targeting and immune system escape capabilities of these systems are still limited. Biomimetic nanovesicles emerged as a strategy to overcome these and other limitations associated with synthetic carriers, such as short circulation time, cytotoxicity, and difficulty in crossing biological barriers, since many of the desirable abilities of drug delivery systems are innate characteristics of biological vesicles. Thus, the question arises: would biomimetic nanovesicles be responsible for addressing these advances? It is currently known that biomimetic nanovesicles (BNV) can combine the intrinsic advantages of natural materials with the well-known production methods and controllability of synthetic systems. Besides, the development of the biotechnology and nanotechnology fields has provided a better understanding of the functionalities of biological vesicles and the means for the design and production of biomimetic nanovesicles (BNV). Based on this, this work will focus on tracking the main research on biomimetic nanovesicles (BNV) applied as drug and gene delivery systems, and for vaccines applications. In addition, it will describe the different sources of natural vesicles, the technical perspectives on obtaining them, and the possibility of their hybridization with synthetic liposomes.

Development and Evaluation of an Antimicrobial Formulation Containing Rosmarinus officinalis.

Rosmarinus officinalis belongs to the Lamiaceae family, and its constituents show antioxidant, anti-inflammatory, antidepressant, antinociceptive, and antibacterial properties. The aim of this study was to develop a topical formulation with R. officinalis extract that had antimicrobial and antioxidant activity. Maceration, infusion, Soxhlet, and ultrasound were used to produce rosemary extracts, which were submitted to antioxidant, compound quantification, cell viability, and antimicrobial assays. Infusion and Soxhlet showed better results in the DPPH assay. During compound quantification, infusion showed promising metabolite extraction in phenolic compounds and tannins, although maceration was able to extract more flavonoids. The infusion and ultrasound extracts affected more strains of skin bacteria in the disk diffusion assays. In the minimum inhibitory concentration assay, the infusion extract showed results against S. aureus, S. oralis, and P. aeruginosa, while ultrasound showed effects against those three bacteria and E. coli. The infusion extract was chosen to be incorporated into a green emulsion. The infusion extract promoted lower spreadability and appropriated the texture, and the blank formulation showed high levels of acceptance among the volunteers. According to the results, the rosemary extract showed promising antioxidant and antimicrobial activity, and the developed formulations containing this extract were stable for over 90 days and had acceptable characteristics, suggesting its potential use as a phytocosmetic. This paper reports the first attempt to produce an oil-in-water emulsion using only natural excipients and rosemary extract, which is a promising novelty, as similar products cannot be found on the market or in the scientific literature.

Differentially expressed plasmatic microRNAs in Brazilian patients with Coronavirus disease 2019 (COVID-19): preliminary results.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is known that host microRNAs (miRNAs) can be modulated to favor viral infection or to protect the host. Herein, we report preliminary results of a study aiming at identifying differentially expressed plasmatic miRNAs in Brazilian patients with COVID-19. METHODS AND RESULTS: miRNAs were extracted from the plasma of eight patients with COVID-19 (four patients with mild COVID-19 and four patients with severe/critical COVID-19) and four healthy controls. Patients and controls were matched for sex and age. miRNA expression levels were detected using high-throughput sequencing. Differential miRNA expression and enrichment analyses were further evaluated. A total of 18 miRNAs were differentially expressed between patients with COVID-19 and controls. miR-4433b-5p, miR-6780b-3p, miR-6883-3p, miR-320b, miR-7111-3p, miR-4755-3p, miR-320c, and miR-6511a-3p were the most important miRNAs significantly involved in the PI3K/AKT, Wnt/ß-catenin, and STAT3 signaling pathways. Moreover, 42 miRNAs were differentially expressed between severe/critical and mild patients with COVID-19. miR-451a, miR-101-3p, miR-185-5p, miR-30d-5p, miR-25-3p, miR-342-3p, miR-30e-5p, miR-150-5p, miR-15b-5p, and miR-29c-3p were the most important miRNAs significantly involved in the Wnt/ß-catenin, NF-κß, and STAT3 signaling pathways. CONCLUSIONS: If validated by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in a larger number of participants, the miRNAs identified in this study might be used as possible biomarkers for the diagnosis and severity of COVID-19.

In silico design and in vitro assessment of anti-Helicobacter pylori compounds as potential small-molecule arginase inhibitors.

Related to a variety of gastrointestinal disorders ranging from gastric ulcer to gastric adenocarcinoma, the infection caused by the gram-negative bacteria Helicobacter pylori (H. pylori) poses as a great threat to human health; hence, the search for new treatments is a global priority. The H. pylori arginase (HPA) protein has been widely studied as one of the main virulence factors of this bacterium, being involved in the prevention of nitric oxide-mediated bacterial cell death, which is a central component of innate immunity. Given the growing need for the development of new drugs capable of combating the infection by H. pylori, the present work describes the search for new HPA inhibitors, using virtual screening techniques based on molecular docking followed by the evaluation of the proposed modes of interaction at the HPA active site. In vitro studies of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), followed by cytotoxicity activity in gastric adenocarcinoma and non-cancer cells, were performed. The results highlighted compounds 6, 11, and 13 as potential inhibitors of HPA; within these compounds, the results indicated 13 presented an improved activity toward H. pylori killing, with MIC and MBC both at 64 µg/mL. Moreover, compound 13 also presented a selectivity index of 8.3, thus being more selective for gastric adenocarcinoma cells compared to the commercial drug cisplatin. Overall, the present work demonstrates the search strategy based on in silico and in vitro techniques is able to support the rational design of new anti-H. pylori drugs.

Whole-genome analysis of haemophilus influenzae invasive strains isolated from Campinas state University hospital. An epidemiological approach 2012 - 2019 and ancestor strains.

Thirteen Haemophylus influenzae invasive strains isolated from patients at Clinical Hospital of State University of Campinas, from May 2013 through August 2019, was submitted to Illumina genome sequencing HiSeq platform. Further in silico analysis of serogroup and Multi Locus Sequence Typing (MLST) from whole DNA sequencing had demonstrated the actual clonal distribution in the Campinas Metropolitan region. Thus, results showed the existence of a new ST Haemophilus influenzae found in the Brazilian territory and an increase of strains belonging to serogroup a (three strains also belonging to ST23). In conclusion, we observed an increase of non-typable H. influenzae (NTHi) and a strain involved in invasive diseases in the Campinas - São Paulo region after frequent detection of those serotypes and genotypes in other Brazilian regions.

Whole-genome analysis of haemophilus influenzae invasive strains isolated from Campinas state University hospital. An epidemiological approach 2012 - 2019 and ancestor strains

Abstract Thirteen Haemophylus influenzae invasive strains isolated from patients at Clinical Hospital of State University of Campinas, from May 2013 through August 2019, was submitted to Illumina genome sequencing HiSeq platform. Further in silico analysis of serogroup and Multi Locus Sequence Typing (MLST) from whole DNA sequencing had demonstrated the actual clonal distribution in the Campinas Metropolitan region. Thus, results showed the existence of a new ST Haemophilus influenzae found in the Brazilian territory and an increase of strains belonging to serogroup a (three strains also belonging to ST23). In conclusion, we observed an increase of non-typable H. influenzae (NTHi) and a strain involved in invasive diseases in the Campinas - São Paulo region after frequent detection of those serotypes and genotypes in other Brazilian regions.

A pre-formulation study of tetracaine loaded in optimized nanostructured lipid carriers.

Tetracaine (TTC) is a local anesthetic broadly used for topical and spinal blockade, despite its systemic toxicity. Encapsulation in nanostructured lipid carriers (NLC) may prolong TTC delivery at the site of injection, reducing such toxicity. This work reports the development of NLC loading 4% TTC. Structural properties and encapsulation efficiency (%EE > 63%) guided the selection of three pre-formulations of different lipid composition, through a 23 factorial design of experiments (DOE). DLS and TEM analyses revealed average sizes (193-220 nm), polydispersity (< 0.2), zeta potential |- 21.8 to - 30.1 mV| and spherical shape of the nanoparticles, while FTIR-ATR, NTA, DSC, XRD and SANS provided details on their structure and physicochemical stability over time. Interestingly, one optimized pre-formulation (CP-TRANS/TTC) showed phase-separation after 4 months, as predicted by Raman imaging that detected lack of miscibility between its solid (cetyl palmitate) and liquid (Transcutol) lipids. SANS analyses identified lamellar arrangements inside such nanoparticles, the thickness of the lamellae been decreased by TTC. As a result of this combined approach (DOE and biophysical techniques) two optimized pre-formulations were rationally selected, both with great potential as drug delivery systems, extending the release of the anesthetic (> 48 h) and reducing TTC cytotoxicity against Balb/c 3T3 cells.

Lessons from a Single Amino Acid Substitution: Anticancer and Antibacterial Properties of Two Phospholipase A2-Derived Peptides.

The membrane-active nature of phospholipase A2-derived peptides makes them potential candidates for antineoplastic and antibacterial therapies. Two short 13-mer C-terminal fragments taken from snake venom Lys49-PLA2 toxins (p-AppK and p-Acl), differing by a leucine/phenylalanine substitution, were synthesized and their bioactivity was evaluated. Their capacity to interfere with the survival of Gram-positive and Gram-negative bacteria as well as with solid and liquid tumors was assessed in vitro. Toxicity to red blood cells was investigated via in silico and in vitro techniques. The mode of action was mainly studied by molecular dynamics simulations and membrane permeabilization assays. Briefly, both peptides have dual activity, i.e., they act against both bacteria, including multidrug-resistant strains and tumor cells. All tested bacteria were susceptible to both peptides, Pseudomonas aeruginosa being the most affected. RAMOS, K562, NB4, and CEM cells were the main leukemic targets of the peptides. In general, p-Acl showed more significant activity, suggesting that phenylalanine confers advantages to the antibacterial and antitumor mechanism, particularly for osteosarcoma lines (HOS and MG63). Peptide-based treatment increased the uptake of a DNA-intercalating dye by bacteria, suggesting membrane damage. Indeed, p-AppK and p-Acl did not disrupt erythrocyte membranes, in agreement with in silico predictions. The latter revealed that the peptides deform the membrane and increase its permeability by facilitating solvent penetration. This phenomenon is expected to catalyze the permeation of solutes that otherwise could not cross the hydrophobic membrane core. In conclusion, the present study highlights the role of a single amino acid substitution present in natural sequences towards the development of dual-action agents. In other words, dissecting and fine-tuning biomembrane remodeling proteins, such as snake venom phospholipase A2 isoforms, is again demonstrated as a valuable source of therapeutic peptides.

In vitro activity and formulation of a flavonoid-containing cashew pulp extract for the topical treatment of acne and the protection of skin against premature aging.

The cashew nut is an important product in Brazil, both for consumption and export, with the pulp of the cashew fruit being considered a by-product despite its high flavonoid content. In this study, the use of cashew pulp extract as a treatment for acne and in the prevention of early skin damage was investigated. Its flavonoid content was determined using spectrophotometric identification, and its effects on cell and bacterial viability, the migration of keratinocytes, and antioxidant activity in vitro were evaluated. Furthermore, it was incorporated into an emulsion for topical administration, and the physical-chemical stability parameters of the formulation were determined. The cashew pulp contained flavonoids with healing and antioxidant activity, and was not toxic to keratinocyte cells in a viability test. The flavonoid-rich formulation was stable, indicating that this is a promising formulation for use in the treatment of acne and protection of skin against premature damage.[Figure: see text].

Electrospun PCL-based nanofibers Arrabidaea chica Verlot - Pterodon pubescens Benth loaded: synergic effect in fibroblast formation.

The guided tissue regeneration (GTR) technique can be applied in dentistry and other medical specializations, such as orthopedics. In modern dentistry, GTR has been used in periodontics and implantology to treat periodontal defects, to reconstruct lost, damaged and atrophied bone tissue in dental implant procedures, and to preserve alveolar bases after tooth extraction. In order to create and improve new therapies and to develop new biomaterials that restore, improve and prevent aggravation of compromised tissue function, poly (ϵ-caprolactone) (PCL) polymer membranes were obtained by the electrospinning process and were associated with two plant extracts: Pterodon pubescens Benth (P. pubescens) and Arrabidaea chica Verlot (A. chica) which are characterized by their pharmacological activities of anti-inflammatory and healing actions, respectively. Fiber morphology was analyzed using scanning electron microscopy (SEM), where fiber average diameter was measured from SEM images. Contact angle measurements were performed in order to evaluate the hydrophilicity of electrospun membranes containing vegetal extract. High-performance liquid chromatography was used to evaluate the ability to release active ingredients. Cytotoxicity and cell proliferation assays were performed in vitro on NIH-3T3 cells for 1, 3 and 7 d. Electrospun PCL membranes associated with plant extracts P. pubescens and/or A. chica presented a controlled release profile of the active compounds induced fibroblast formation, suggesting that they are promising and suitable for applications in GTR.

Synthesis and biological evaluation of 2'-Aminochalcone: A multi-target approach to find drug candidates to treat Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative process that compromises cognitive functions. The physiopathology of AD is multifactorial and is mainly supported by the cholinergic and amyloid hypotheses, which allows the identification the fundamental role of some markers, such as the enzymes acetylcholinesterase (AChE) and ß-secretase (BACE-1), and the ß-amyloid peptide (Aß). In this work, we prepared a series of chalcones and 2'-aminochalcones, which were tested against AChE and BACE-1 enzymes and on the aggregation of Aß. All compounds inhibited AChE activity with different potencies. We have found that the majority of chalcones having the amino group are able to inhibit BACE-1, which was not observed for chalcones without this group. The most active compound is the one derived from 2,3-dichlorobenzaldeyde, having an IC50 value of 2.71 µM. A molecular docking study supported this result, showing a good interaction of the amino group with aspartic acid residues of the catalytic diade of BACE-1. Thioflavin-T fluorescence emission is reduced in 30 - 40%, when Aß42 is incubated in the presence of some chalcones under aggregation conditions. In vitro cytotoxicity and in silico prediction of pharmacokinetic properties were also conducted in this study.

Influence of environmental dust in transformation capacity of Streptococcus pneumoniae.

S. pneumoniae, commonly known as pneumococcus, is a naturally competent Gram-positive bacterium and is the major cause of pneumonia in elderly and children in developing countries. This pathogen is associated with respiratory diseases affected by pollution. The objective of this work was determining the effect of ash and environmental dust from the burning of sugarcane on pneumococci bacterial transformation. The transformation capacity of the Pn360 pneumococci strain was performed using the assays of DNA donor of mutant for luxS gene. Thus, the transformation tests were performed in contact with dust collected in the southwestern region of Brazil (important region where burning of sugar cane is present in the agriculture). The use of degradative practices in the sugar cane agriculture in Brazil was involved in the transformation capacity of the S. pneumoniae. This phenomenon includes important consequences for public health concerning to resistance acquisition and new virulence factors of this important infection. In conclusion, we obtained important results concerning the action of environmental pollution in Streptococcus pneumoniae transformation, increasing the DNA acquisition for this pathogen.

Analysis of potential virulence genes and competence to transformation in Haemophilus influenzae biotype aegyptius associated with Brazilian Purpuric Fever.

Brazilian Purpuric Fever (BPF) is a hemorrhagic pediatric illness caused by Haemophilus influenzae biogroup aegyptius (Hae), a bacterium that was formerly associated with self-limited purulent conjunctivitis. BPF is assumed to be eradicated. However, the virulence mechanisms inherent to Hae strains associated with BPF is still a mystery and deficient in studies. Here, we aim to analyze the role of the autotransporter genes related to adherence and colonization las, tabA1, and hadA genes through RT-qPCR expression profiling and knockout mutants. Relative quantification by real-time PCR after infection in human cells and infant rat model suggests that las was initially downregulated probably duo to immune evasion, tabA1, and hadA were overexpressed in general, suggesting an active role of TabA1 and HadA1 adhesins in Hae in vitro and in vivo. Transformation attempts were unsuccessful despite the use of multiple technical approaches and in silico analysis revealed that Hae lacks genes related to competence in Haemophilus, which could be part of the elucidation of the difficulty of genetically manipulating Hae strains.

Molecular signatures associated with prostate cancer cell line (PC-3) exposure to inactivated Zika virus.

The recent outbreak of Zika virus (ZIKV) infection associated with microcephaly cases has elicited much research on the mechanisms involved in ZIKV-host cell interactions. It has been described that Zika virus impairs cell growth, raising a hypothesis about its oncolytic potential against cancer cells. ZIKV tumor cell growth inhibition was later confirmed for glioblastoma. It was also demonstrated that an inactivated ZIKV prototype (ZVp) based on bacterial outer membrane vesicles has antiproliferative activity upon other cancer cell lines, such as PC-3 prostate cancer cell. This study aims at understanding the pathways that might be involved with the antiproliferative effect of Zika virus against prostate cancer cells. A metabolomic approach based on high-resolution mass spectrometry analysis led to the identification of 21 statistically relevant markers of PC-3 cells treated with ZVp. The markers were associated with metabolic alterations that trigger lipid remodeling, endoplasmic reticulum stress, inflammatory mediators, as well as disrupted porphyrin and folate metabolism. These findings highlight molecular signatures of ZVp-induced response that may be involved on cellular pathways triggered by its antiproliferative effect. To our knowledge, this is the first reported metabolomic assessment of ZIKV effect on prostate cancer cells, a promising topic for further research.