Gelatin/chitosan/polyvinyl alcohol hydrogels were fabricated at different polymer ratios using the freeze‐drying and sterilized by steam sterilization. The thermal stability, chemical structure, ...morphology, surface area, mechanical properties, and biocompatibility of hydrogels were evaluated by simultaneous thermal analysis, Fourier transform infrared spectroscopy, X‐ray diffraction, confocal microscopy, adsorption/desorption of nitrogen, rheometry, and 3‐4,5‐dimethylthiazol‐2‐yl‐2,5‐diphenyl tetrazolium bromide cell viability assay (MTT assay), respectively. The samples showed a decomposition onset temperature below 253.3 ± 4.8°C, a semicrystalline nature, and a highly porous structure. Hydrogels reached the maximum water uptake in phosphate‐buffered saline after 80 min, showing values from nine to twelve times their dry mass. Also, hydrogels exhibiting a solid‐like behavior ranging from 2,567 ± 467 to 48,705 ± 2,453 Pa at 0.1 rad/s (low frequency). The sterilized hydrogels showed low cytotoxicity (cell viability > 70%) to the HT29‐MTX‐E12 cell line. Sterilized hydrogels by steam sterilization can be good candidates as scaffolds for tissue engineering applications.
The rapid availability of effective antiviral treatments would be beneficial during the early phases of a pandemic, as they could reduce viral loads and control serious infections until antigenic ...vaccines become widely available. One promising alternative therapy to combat pandemics is nanotechnology, which has the potential to inhibit a wide variety of viruses, including the influenza virus. This review summarizes the recent progress using gold, copper, silver, silicone, zinc and selenium nanoparticles, since these materials have shown remarkable antiviral capacity against influenza A virus.
Abstract
A single intradermal vaccination with an antibiotic-less version of BCGΔBCG1419c given to guinea pigs conferred a significant improvement in outcome following a low dose aerosol exposure to
...M. tuberculosis
compared to that provided by a single dose of BCG Pasteur. BCGΔBCG1419c was more attenuated than BCG in murine macrophages, athymic, BALB/c, and C57BL/6 mice. In guinea pigs, BCGΔBCG1419c was at least as attenuated as BCG and induced similar dermal reactivity to that of BCG. Vaccination of guinea pigs with BCGΔBCG1419c resulted in increased anti-PPD IgG compared with those receiving BCG. Guinea pigs vaccinated with BCGΔBCG1419c showed a significant reduction of
M. tuberculosis
replication in lungs and spleens compared with BCG, as well as a significant reduction of pulmonary and extrapulmonary tuberculosis (TB) pathology measured using pathology scores recorded at necropsy. Evaluation of cytokines produced in lungs of infected guinea pigs showed that BCGΔBCG1419c significantly reduced TNF-α and IL-17 compared with BCG-vaccinated animals, with no changes in IL-10. This work demonstrates a significantly improved protection against pulmonary and extrapulmonary TB provided by BCGΔBCG1419c in susceptible guinea pigs together with an increased safety compared with BCG in several models. These results support the continued development of BCGΔBCG1419c as an effective vaccine for TB.
Mycobacterium tuberculosis and M. smegmatis form drug-tolerant biofilms through dedicated genetic programs. In support of a stepwise process regulating biofilm production in mycobacteria, it was ...shown elsewhere that lsr2 participates in intercellular aggregation, while groEL1 was required for biofilm maturation in M. smegmatis. Here, by means of RNA-Seq, we monitored the early steps of biofilm production in M. bovis BCG, to distinguish intercellular aggregation from attachment to a surface. Genes encoding for the transcriptional regulators dosR and BCG0114 (Rv0081) were significantly regulated and responded differently to intercellular aggregation and surface attachment. Moreover, a M. tuberculosis H37Rv deletion mutant in the Rv3134c-dosS-dosR regulon, formed less biofilm than wild type M. tuberculosis, a phenotype reverted upon reintroduction of this operon into the mutant. Combining RT-qPCR with microbiological assays (colony and surface pellicle morphologies, biofilm quantification, Ziehl-Neelsen staining, growth curve and replication of planktonic cells), we found that BCG0642c affected biofilm production and replication of planktonic BCG, whereas ethR affected only phenotypes linked to planktonic cells despite its downregulation at the intercellular aggregation step. Our results provide evidence for a stage-dependent expression of genes that contribute to biofilm production in slow-growing mycobacteria.
Metal-based nanoparticles are widely used to deliver bioactive molecules and drugs to improve cancer therapy. Several research works have highlighted the synthesis of gold and silver nanoparticles by ...green chemistry, using biological entities to minimize the use of solvents and control their physicochemical and biological properties. Recent advances in evaluating the anticancer effect of green biogenic Au and Ag nanoparticles are mainly focused on the use of conventional 2D cell culture and in vivo murine models that allow determination of the half-maximal inhibitory concentration, a critical parameter to move forward clinical trials. However, the interaction between nanoparticles and the tumor microenvironment is not yet fully understood. Therefore, it is necessary to develop more human-like evaluation models or to improve the existing ones for a better understanding of the molecular bases of cancer. This review provides recent advances in biosynthesized Au and Ag nanoparticles for seven of the most common and relevant cancers and their biological assessment. In addition, it provides a general idea of the in silico, in vitro, ex vivo, and in vivo models used for the anticancer evaluation of green biogenic metal-based nanoparticles.
produces mycolic acids which are relevant for persistence, recalcitrance to antibiotics and defiance to host immunity. c-di-GMP is a second messenger involved in transition from planktonic cells to ...biofilms, whose levels are controlled by diguanylate cyclases (DGC) and phosphodiesterases (PDE). The transcriptional regulator dosR, is involved in response to low oxygen, a condition likely happening to a subset of cells within biofilms. Here, we found that in
BCG, expression of both
and
genes, which code for a DGC and a PDE, respectively, decreased in both stationary phase and during biofilm production. The
,
, and fas genes, which are involved in mycolic acid biosynthesis, were induced in biofilm cultures, as was
, therefore suggesting an inverse correlation in their expression compared with that of genes involved in c-di-GMP metabolism. The relative abundance within trehalose dimycolate (TDM) of α-mycolates decreased during biofilm maturation, with methoxy mycolates increasing over time, and keto species remaining practically stable. Moreover, addition of synthetic c-di-GMP to mid-log phase BCG cultures reduced methoxy mycolates, increased keto species and practically did not affect α-mycolates, showing a differential effect of c-di-GMP on keto- and methoxy-mycolic acid metabolism.
Retaining the hemocompatibility, supporting cell growth, and exhibiting anti-inflammatory and antioxidant properties, while having antimicrobial activity, particularly against multidrug-resistant ...bacteria (MDR), remain a challenge when designing aerogels for biomedical applications. Here, we report that our synthesized alginate-based aerogels containing either 7.5 or 11.25 μg of lipoic acid-capped silver nanoparticles (AgNPs) showed improved hemocompatibility properties while retaining their antimicrobial effect against MDR Acinetobacter baumannii and the reference strain Escherichia coli, relative to a commercial dressing and polymyxin B, used as a reference. The differences in terms of the microstructure and nature of the silver, used as the bioactive agent, between our synthesized aerogels and the commercial dressing used as a reference allowed us to improve several biological properties in our aerogels with respect to the reference commercial material. Our aerogels showed significantly higher antioxidant capacity, in terms of nmol of Trolox equivalent antioxidant capacity per mg of aerogel, than the commercial dressing. All our synthesized aerogels showed anti-inflammatory activity, expressed as nmol of indomethacin equivalent anti-inflammatory activity per mg of aerogel, while this property was not found in the commercial dressing material. Finally, our aerogels were highly hemocompatible (less than 1% hemolysis ratio); however, the commercial material showed a 20% hemolysis rate. Therefore, our alginate-based aerogels with lipoic acid-capped AgNPs hold promise for biomedical applications.
Mycobacterium tuberculosis produces mycolic acids which are relevant for persistence, recalcitrance to antibiotics and defiance to host immunity. c-di-GMP is a second messenger involved in transition ...from planktonic cells to biofilms, whose levels are controlled by diguanylate cyclases (DGC) and phosphodiesterases (PDE). The transcriptional regulator dosR, is involved in response to low oxygen, a condition likely happening to a subset of cells within biofilms. Here, we found that in M. bovis BCG, expression of both BCG1416c and BCG1419c genes, which code for a DGC and a PDE, respectively, decreased in both stationary phase and during biofilm production. The kasA, kasB, and fas genes, which are involved in mycolic acid biosynthesis, were induced in biofilm cultures, as was dosR, therefore suggesting an inverse correlation in their expression compared with that of genes involved in c-di-GMP metabolism. The relative abundance within trehalose dimycolate (TDM) of α- mycolates decreased during biofilm maturation, with methoxy mycolates increasing over time, and keto species remaining practically stable. Moreover, addition of synthetic c-di-GMP to mid-log phase BCG cultures reduced methoxy mycolates, increased keto species and practically did not affect α-mycolates, showing a differential effect of c-di-GMP on keto- and methoxy-mycolic acid metabolism.
The prebiotic effect of fructans is well known, including their beneficial influence on health. This study shows agave fructans impact as potential prebiotics, depending on their structure and ...polymerization degree (PD). The growth of seven probiotics and three pathogens was estimated by turbidimetric analysis and the latter (Salmonella typhimurium, Staphylococcus aureus and Listeria monocytogenes) were submitted to growth inhibition tests in the presence of metabolites produced by probiotics. Lactobacillus casei and L. paracasei growth was optimal when supplemented with agave fructans. L. casei was grown in the presence of the extracted fractions obtained from Agave salmiana spp. crassipina (optical density (O.D.) 1.09 ± 0.02, 0.98 ± 0.03, 0.98 ± 0.07, low, medium and high PD, respectively), A. salmiana var. liso (0.85 ± 0.13), A. atrovirens (0.79 ± 0.03) and A. tequilana spp. (0.89 ± 0.03). The growth of L. paracasei was optimal when supplemented with those fractions obtained from the A. salmiana (O.D. 1.12 ± 0.02, 1.18 ± 0.02, 1.13 ± 0.007, low, medium and high PD, respectively) and A. tequilana var. cenizo (1.18 ± 0.01 and 1.15 ± 0.02, medium and high PD, respectively) species. Both bacteria were tested in order to assess enzyme activity using API ZYM galleries after they were grown on agave fructans. The results show an increase of five enzymes (cysteine-arylamidase, α-chymotrypsin, β-galactosidase, N-acetyl-β-glucosaminidase and α-fucosidase).
•Effect of fructans fractions from different agave species as prebiotics.•Changes in the enzymatic metabolism of probiotics in the presence of agave fructans.•Growth inhibition of pathogens when probiotics metabolize agave fructans.
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