Atorvastatin attenuates intestinal mucositis induced by 5-fluorouracil in mice by modulating the epithelial barrier and inflammatory response.

Chemotherapy-induced intestinal mucositis is a major side effect of cancer treatment. Statins are 3-hydroxy-3-methyl glutaryl coenzyme reductase inhibitors used to treat hypercholesterolemia and atherosclerotic diseases. Recent studies have demonstrated that atorvastatin (ATV) has antioxidant, anti-inflammatory, and resulting from the regulation of different molecular pathways. In the present study, we investigated the effects of ATV on intestinal homeostasis in 5-fluorouracil (5-FU)-induced mucositis. Our results showed that ATV protected the intestinal mucosa from epithelial damage caused by 5-FU mainly due to inflammatory infiltrate and intestinal permeability reduction, downregulation of inflammatory markers, such as Tlr4, MyD88, NF-κB, Tnf-a, Il1ß, and Il6 dose-dependent. ATV also improved epithelial barrier function by upregulating the mRNA transcript levels of mucin 2 (MUC2), and ZO-1 and occludin tight junction proteins. The results suggest that the ATV anti-inflammatory and protective effects on 5-FU-induced mice mucositis involve the inhibition of the TLR4/MYD88/NPRL3/NF-κB, iNos, and caspase 3.

Comparative genetic and pathogenic approaches of Escherichia coli isolated simultaneously from pyometra and urine of bitches.

Escherichia coli (E. coli) are widely related to pyometra and cystitis in dogs, and these infections can occur simultaneously. The goal of this study was to determine genetic and pathogenic insights of 14 E. coli isolated simultaneously from pyometra content and bladder urine of seven bitches. To achieve this, in silico and in vitro comparative analyses were conducted. Whole-genome comparisons demonstrated that E. coli isolated from pyometra and urine of the same animal were predominantly genetic extraintestinal E. coli clones belonging to the same Sequence Type and phylogroup. The E. coli clones identified in this study included ST372, ST457, ST12, ST127, ST646, and ST961. Five isolates (35.7%) belonged to the ST12 complex. Except for two E. coli, all other isolates belonged to the B2 Clermont phylogroup. Interestingly, some genomes of E. coli from urine carried more virulence genes than those E. coli from pyometra. Both pyometra and urine E. coli isolates demonstrated a strong affinity for adhering to HeLa and T24 cells, with a low affinity for invading them. However, certain isolates from urine exhibited a greater tendency to adhere to T24 cells in qualitative and quantitative assays compared to isolates from pyometra. In conclusion, this study revealed the high genomic similarity between pyometra and urine E. coli isolates, as well as the virulent capacity of both to colonize endometrial and urothelial cells. The findings of this study underscore the importance of concurrently managing both infections clinically and could potentially contribute to future resources for the prevention of cystitis and pyometra.

Association of Fructo-oligosaccharides and Arginine Improves Severity of Mucositis and Modulate the Intestinal Microbiota.

Mucositis is defined as inflammatory and ulcerative lesions along of the gastrointestinal tract that leads to the imbalance of the intestinal microbiota. The use of compounds with action on the integrity of the intestinal epithelium and their microbiota may be a beneficial alternative for the prevention and/or treatment of mucositis. So, the aim of this study was to evaluate the effectiveness of the association of fructo-oligosaccharides (FOS) and arginine on intestinal damage in experimental mucositis. BALB/c mice were randomized into five groups: CTL (without mucositis + saline), MUC (mucositis + saline), MUC + FOS (mucositis + supplementation with FOS-1st until 10th day), MUC + ARG (mucositis + supplementation with arginine-1st until 10th day), and MUC + FOS + ARG (mucositis + supplementation with FOS and arginine-1st until 10th day). On the 7th day, mucositis was induced with an intraperitoneal injection of 300 mg/kg 5-fluorouracil (5-FU), and after 72 h, the animals were euthanized. The results showed that association of FOS and arginine reduced weight loss and oxidative stress (P < 0.05) and maintained intestinal permeability and histological score at physiological levels. The supplementation with FOS and arginine also increased the number of goblet cells, collagen area, and GPR41 and GPR43 gene expression (P < 0.05). Besides these, the association of FOS and arginine modulated intestinal microbiota, leading to an increase in the abundance of the genera Bacteroides, Anaerostipes, and Lactobacillus (P < 0.05) in relation to increased concentration of propionate and acetate. In conclusion, the present results show that the association of FOS and arginine could be important adjuvants in the prevention of intestinal mucositis probably due to modulated intestinal microbiota.

Potential in vitro action of an adenosine analog and synergism with penicillin against Corynebacterium pseudotuberculosis.

Caseous lymphadenitis is a well-known disease caused by Corynebacterium pseudotuberculosis affecting small ruminants with small significance to human health because of its minor zoonotic potential. In both cases, few treatment options are available and conventional antimicrobial therapy is commonly refractory due to development of pyogranulomatous reactions, bringing great interest in discovering novel therapeutics for more suitable approaches. Dideoxynucleotides presented antibacterial action against various bacteria but were never described for C. pseudotuberculosis. Hypothesizing the antimicrobial action of 2',3'-dideoxiadenosine (ddATP) against C. pseudotuberculosis, we performed for the first time an investigation of its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in the ATCC® 19,410 strain and a well-characterized clinical isolate of C. pseudotuberculosis. We also assessed potential synergism with penicillin. ddATP showed a growth delay effect for C. pseudotuberculosis at 2 µmol/mL and a MIC and MBC of 4 µmol/mL against the ATCC® 19,410 strain, but not for the clinical strain. An antimicrobial effect was observed when using concentrations lower than the MIC of ddATP associated with penicillin for both strains tested. Our data suggest the potential of nucleotide analogs, especially adenosine, and its combination with penicillin, as a possible novel treatment for C. pseudotuberculosis-induced infections, and contributes with knowledge regarding alternative drugs to treat C. pseudotuberculosis infections.

Paraprobiotic Lacticaseibacillus rhamnosus Protects Intestinal Damage in an Experimental Murine Model of Mucositis.

Intestinal mucositis (IM) is a common side effect resulting from cancer treatment. However, the management so far has not been very effective. In the last years, the role of the gut microbiota in the development and severity of mucositis has been studied. Therefore, the use of probiotics and paraprobiotics could have a potential therapeutic effect on IM. The aim of our study was to investigate the impact of the administration of Lacticaseibacillus rhamnosus (L. rhamnosus) CGMCC1.3724 and the paraprobiotic on IM in mice. For 13 days, male Balb/c mice were divided into six groups: control (CTL) and mucositis (MUC)/0.1 mL of saline; CTL LrV and MUC LrV/0.1 mL of 108 CFU of viable Lr; CTL LrI and MUC LrI/0.1 mL of 108 CFU of inactivated Lr. On the 10th day, mice from the MUC, MUC LrV, and MUC LrI groups received an intraperitoneal injection (300 mg/kg) of 5-fluorouracil to induce mucositis. The results showed that the administration of the chemotherapeutic agent increased the weight loss and intestinal permeability of the animals in the MUC and MUC LrV groups. However, administration of paraprobiotic reduced weight loss and maintained PI at physiological levels. The paraprobiotic also preserved the villi and intestinal crypts, reduced the inflammatory infiltrate, and increased the mucus secretion, Muc2 gene expression, and Treg cells frequency.

Proteomic fingerprinting for the fast and accurate identification of species in the Polyporoid and Hymenochaetoid fungi clades.

Basidiomycotan fungi play significant roles in the biogeochemical cycle of carbon as wood decomposers and are used in the food industry for mushroom production and in biotechnology for the production of diverse bioactive compounds and bioremediation. The correct identification of basidiomycotan isolates is crucial for understanding their biology and being able to expand their applications. Currently, the identification of these organisms is performed by analyzing morphological and genomic characteristics, primarily those based on DNA biomarkers. Despite their efficiency, such methods require considerable expertise and are both time-consuming and error-prone (multistep workflow). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has emerged in the last decade as an accurate, fast, and powerful alternative for the identification of microorganisms. MALDI-TOF MS has been widely applied for the identification and taxonomical characterization of both bacteria and ascomycotan fungi from clinical origins. However, species of Basidiomycota have been poorly evaluated using this method. In the present study, we assessed the performance of MALDI-TOF MS using basidiomycotan isolates of two distinct taxonomical families: Polyporaceae and Hymenochaetaceae. Using a simple protocol, which eliminates the protein extraction step, we obtained high-quality mass spectra data and demonstrated that this method is efficient for the discrimination of isolates at the species level. SIGNIFICANCE: In this study, the MALDI-TOF mass spectrometry was employed to test its accuracy on the recognition of fungal species with high biotechnological and environmental interest. Using a simple and fast protocol, we obtained high-quality mass-spectra (protein fingerprinting) and proved that MALDI-TOF MS is sufficiently robust to the identification at species level and to evaluate the relationships among the isolates of the polyporoid and hymenochaetoid clades (Basidiomycota).