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Four new species [Ln(dipicNH2)3]3− (Ln = LaIII, EuIII, GdIII, TbIII), with the ligand dipicNH22− (dipic = dipicolinato), were synthesized. Incubation of the EuIII complex with glioma NG97 and pancreatic cancer PANC1 cells showed that it penetrates the cell membrane and can be used to image the cells, while also being moderately cytotoxic. [ABSTRACT FROM AUTHOR]

Nanostructured materials have been widely studied concerning their potential biomedical applications, primarily to selectively carry specific drugs or molecules within a tissue or organ. In this context, boron nitride nanotubes (BNNTs) have generated considerable interest in the scientific community because of their unique properties, presenting good chemical inertness and high thermal stability. Among the many applications proposed for BNNTs in the biomedical field in recent years, the most important include their use as biosensors, nanovectors for the delivery of proteins, drugs, and genes. In the present study, BNNTs were synthesized, purified, and functionalized with glycol chitosan through a chemical process, yielding the BNNT-GC. The size of BNNT-GC was reduced using an ultrasound probe. Two samples with different sizes were selected for in vitro assays. The nanostructures were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermal analysis (TGA), and dynamic light scattering (DLS). The in vitro assays MTT and neutral red (NR) were performed with NIH-3T3 and A549 cell lines and demonstrated that this material is not cytotoxic. Furthermore, the BNNT-GC was applied in gene transfection of plasmid pIRES containing a gene region that express a green fluorescent protein (GFP) in NIH-3T3 and A549 cell lines. The gene transfection was characterized by fluorescent protein produced in the cells and pictured by fluorescent microscopy. Our results suggest that BNNT-GC has moderate stability and presents great potential as a gene carrier agent in nonviral-based therapy, with low cytotoxicity and good transfection efficiency. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2176-2185, 2015. [ABSTRACT FROM AUTHOR]

Abstract Background This study aimed at verifying the action of multi-walled carbon nanotubes (MWCNT) under the naturally transformable Neisseria meningitidis against two different DNA obtained from isogenic mutants of this microorganism, an important pathogen implicated in the genetic horizontal transfer of DNA, causing the escape of the principal vaccination measured worldwide by the capsular switching process. Materials and methods The bacterium receptor strain C2135 was cultivated and had its mutant DNA donor M2 and M6, which received a receptor strain and MWCNT at three different concentrations. The inhibition effect of DNAse on the DNA in contact with nanoparticles was evaluated. Results The results indicated an in increase in the transformation capacity of N. meninigtidis in different concentrations of MWCNT when compared with negative control without nanotubes. A final analysis of the interaction between DNA and MWCNT was carried out using Raman Spectroscopy. Conclusion These increases in the transformation capacity mediated by MWCNT, in meningococci, indicate the interaction of these particles with the virulence acquisition of these bacteria, as well as with the increase in the vaccination escape process.

Abstract Background This study aimed the use of mesoporous silica under the naturally transformable Neisseria meningitidis, an important pathogen implicated in the genetic horizontal transfer of DNA causing a escape of the principal vaccination measures worldwide by the capsular switching process. This study verified the effects of mesoporous silica under N. meningitidis transformation specifically under the capsular replacement. Methods we used three different mesoporous silica particles to verify their action in N. meningitis transformation frequency. Results we verified the increase in the capsular gene replacement of this bacterium with the three mesoporous silica nanoparticles. Conclusion the mesouporous silica particles were capable of increasing the capsule replacement frequency in N. meningitidis.

The global impact of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic in 2019-2020 has led to significant changes in worldwide vaccination and immune prophylactic approaches. In this study, our research delves into a new immunization strategy that does not involve the use of additional adjuvants or preservatives, focusing on the effects of virus fusion with a bacterial nanostructure. The experimental procedures outlined in this paper involved the cultivation of SARS-CoV-2, the production, extraction, and nanocharacterization of outer membrane vesicles (OMV) from Neisseria meningitidis, immunization of mice with two doses of OMV combined with SARS-CoV-2, and the use of mesoporous silica SBa15 and SBa16 adsorbed to the same virus. The immune response was assessed through an indirect elisa method, analysis of cytokine expression profiles, and seroneutralization of the SARS-CoV-2 strain. The characterizations of associated OMV - SARS-CoV-2 and adsorption SBa15 and SBa16 were performed using Nanosight Tracking Analysis (NTA), which showed a high density of particles in the formulation. mice were then immunized, resulting in an immune response that produced high levels of neutralizing antibodies in IgG and IgG1 mouse immunoglobulins. In addition, expressions of IL-2, IL-4, and IL-23 in spleen cells were reinforced after the vaccination process. The comparative study of these three vaccine formulations has shown that the development of new vaccines for SARS-CoV-2 should take into consideration the production of neutralizing antibodies and the maintenance of immunological memory., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

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., (© 2024. The Author(s).)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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: β-CD/citric acid and 2-hydroxypropyl-β-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 O 2 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Escobar, Carrera, Naveas, Pulido, Manso, Guarnieri, Lancellotti, Cotta, Corrales-Ureña, Rischka and Hernandez-Montelongo.)

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.

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 (N 2 ) incidence in the encapsulation of CUR. The best outcome was at pH 3.0, 15 °C, without light incidence, and without N 2 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 N 2 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.

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.

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., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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., Competing Interests: The authors declare no conflict of interest.

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.

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/β-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/β-catenin, NF-κβ, 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., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

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., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

The membrane-active nature of phospholipase A 2 -derived peptides makes them potential candidates for antineoplastic and antibacterial therapies. Two short 13-mer C-terminal fragments taken from snake venom Lys49-PLA 2 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 A 2 isoforms, is again demonstrated as a valuable source of therapeutic peptides.