Nimesulide inhibits pathogenic fungi: PGE2-dependent mechanisms

Certain non-steroidal anti-inflammatory drugs can inhibit fungal growth, fungal prostaglandin E2 production, and enzyme activation. This study aims to investigate the antifungal effect of nimesulide against pathogenic filamentous fungi and yeast. The experiments detailed below were also designed to investigate whether the action is dependent on E2 fungal prostaglandins. Our data showed that nimesulide exhibited potent antifungal activity, mainly against Trichophyton mentagrophytes (ATCC 9533) and Cryptococcus neoformans with MIC values of 2 and 62 μg/mL, respectively. This drug was also able to inhibit the growth of clinic isolates of filamentous fungi, such as Aspergillus fumigatus, and dermatophytes, such as T. rubrum, T. mentagrophytes, Epidermophyton floccosum, Microsporum canis, and M. gypseum, with MIC values ranging from 112 to 770 μg/mL. Our data also showed that the inhibition of fungal growth by nimesulide was mediated by a mechanism dependent on PGE2, which led to the inhibition of essential fungal enzymes. Thus, we concluded that nimesulide exerts a fungicidal effect against pathogenic filamentous fungi and yeast, involving the inhibition of fungal prostaglandins and fungal enzymes important to the fungal growth and colonization.     

Early Devonian (~410 mya) microfossils resembling Characiopsis (Tribophyceae) and Characium (Chlorophyceae)

Unusual microfossils that occurred associated with fungal spores in the Lower Devonian (~410 mya) Windyfield chert from Scotland were composed of a narrow stipe (2.5–9 μm long) to which was attached an obovoid or elongate drop‐shaped cell up to 14 μm long; a basal attachment pad was present in several specimens. The fossils were strikingly similar morphologically to certain present‐day unicellular freshwater Tribophyceae and Chlorophyceae, but affinities to the fungal phylum Chytridiomycota also cannot be ruled out. This discovery adds to the inventory of distinctive microbial morphologies in the early non‐marine paleoecosystems.     

Environmental and spatial processes influencing phytoplankton biomass along a reservoirs‐river‐floodplain lakes gradient: A metacommunity approach

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Increased expression of damage-associated molecular patterns (DAMPs) in osteoarthritis of human knee joint compared to hip joint

The aryl hydrocarbon receptor (AhR) mediates a variety of biological responses to ubiquitous environmental pollutants. In this study, the effects of administration of β-naphthoflavone (BNF), a potent AhR ligand, on the expression of AhR-dependent genes were examined by microarray and qPCR analysis in both, differentiated and undifferentiated HepaRG cell lines. To prove that BNF-induced changes of investigated genes were indeed AhR-dependent, we knock down the expression of AhR by stable transfection of HepaRG cells with shRNA. Regardless of genetical identity, our results clearly demonstrate different expression profiles of AhR-dependent genes between differentiated and undifferentiated HepaRG cells. Genes involved in metabolism of xenobiotics constitute only minute fraction of all genes regulated by AhR in HepaRG cells. Participation of AhR in induction of expression of genes associated with regulation of apoptosis or involved in cell proliferation as well as AhR-dependent inhibition of genes connected to cell adhesion could support suggestion of involvement of AhR not only in initiation but also in progression of carcinogenesis. Among the AhR-dependent genes known to be involved in metabolism of xenobiotics, cytochromes P4501A1 and 1B1 belong to the most inducible by BNF. On the contrary, expression of GSTA1 and GSTA2 was significantly inhibited after BNF treatment of HepaRG cells. Among the AhR-dependent genes that are not involved in metabolism of xenobiotics SERPINB2, STC2, ARL4C, and TIPARP belong to the most inducible by BNF. Our results imply involvement of Ah receptor in regulation of CYP19A1, the gene-encoding aromatase, and an enzyme responsible for a key step in the biosynthesis of estrogens.     

Chronic Stress Causes Sex-Specific and Structure-Specific Alterations in Mitochondrial Respiratory Chain Activity in Rat Brain

Chronic restraint stress (CRS) induces a variety of changes in brain function, some of which are mediated by glucocorticoids. The response to stress occurs in a sex-specific way, and may include mitochondrial and synaptic alterations. The synapse is highly dependent on mitochondrial energy supply, and when mitochondria become dysfunctional, they orchestrate cell death. This study aimed to investigate the CRS effects on mitochondrial respiratory chain activity, as well as mitochondrial potential and mass in cell body and synapses using hippocampus, cortex and striatum of male and female rats. Rats were divided into non-stressed (control) and stressed group (CRS during 40 days). Results showed that CRS increased complex I–III activity in hippocampus. We also observed an interaction between CRS and sex in the striatal complex II activity, since CRS induced a reduction in complex II activity in males, while in females this activity was increased. Also an interaction was observed between stress and sex in cortical complex IV activity, since CRS induced increased activity in females, while it was reduced in males. Glucocorticoid receptor (GR) content in cortex and hippocampus was sexually dimorphic, with female rats presenting higher levels compared to males. No changes were observed in GR content, mitochondrial potential or mass of animals submitted to CRS. It was concluded that CRS induced changes in respiratory chain complex activities, and some of these changes are sex-dependent: these activities are increased in the striatal mitochondria by CRS protocol mainly in females, while in males it is decreased.

     

Effect of culture container and carbohydrate content on in vitro slow growth storage of the cherry rootstock ‘Gisela<Superscript>®</Superscript>5’

The present study investigated the effects of gas-tight and gas-permeable culture containers and different sucrose concentrations, as well as sucrose and mannitol combinations on the development of an effective in vitro slow growth storage protocol (at 4 °C, in darkness) for ‘Gisela^®5’ shoot cultures. ‘Gisela^®5’ is the most widely used cherry rootstock in Europe. This dwarf triploid hybrid has many advantages over the conventional cherry rootstocks. Optimizations for the cold storage of ‘Gisela^®5’ in vitro shoot cultures included use of storage medium supplemented with 10, 20, 30, 45, and 60 g L^?1 sucrose and sucrose (15, 30 g L^?1) and mannitol (15 g L^?1) combinations, contained in gas-tight glass jars and gas-permeable ‘Star Pac?’ bags. Cold storage was prolonged to 12 months, during which in every 3 months, cultures were evaluated. Possibility of 16 month-cold storage in gas-tight glass jars was also explored, during which gas chromatographic analysis was performed for the detection of CO₂ and ethylene accumulation for the first 5 months of cold storage. Our results showed that both the 12- and 16-month conservations were possible, especially when 45 or 60 g L^?1 sucrose was supplemented to storage medium, contained in glass jars. Mannitol inclusion to the storage medium was also effective to reduce the metabolic activity of the shoot cultures during storage; however, it did not have a significant positive influence on shoot quality in post-conservation.     

Selenium Status in Patients with Turner Syndrome: a Biochemical Assessment Related with Body Composition

Studies about selenium status in patients with Turner syndrome (TS) are non-existent in the literature. The aim of this study was to evaluate selenium status in patients with TS, while considering the different ages of the studied population and the relation with body composition. In total, 33 patients with TS were evaluated and grouped according to their developmental stages (children, adolescents, and adults). Selenium concentrations in their plasma, erythrocytes, urine, and nails were determined by using hydride generation atomic absorption spectrometry and erythrocyte glutathione peroxidase activity were measured by using Randox commercial kits. Additionally, height, weight, body fat percentage, waist circumference, and waist-height ratio were measured to characterize the patients. No differences in the selenium concentrations in the plasma, erythrocyte, urine, and nails or in the glutathione peroxidase activity were observed among the age groups (p > 0.05). The evaluated selenium levels were less than the established normal ones. The patients with larger waist circumference, body fat percentage, body mass index, and waist-height ratio showed lower glutathione peroxidase enzyme activity (p = 0.023). The present study shows that most patients with TS are deficient in selenium and that those with a greater accumulation of body fat have a lower GPx activity.     

An in vitro evaluation of the effects of a Yucca schidigera extract and chestnut tannins on composition and metabolic profiles of canine and feline faecal microbiota

The in vitro effect of a Yucca schidigera extract (YSE) and tannins from chestnut wood on composition and metabolic activity of canine and feline faecal microbiota was evaluated. Four treatments were carried out: control diet, chestnut tannins (CT), YSE and CT + YSE. The YSE was added to canine and feline faecal cultures at 0.1 g/l, while CT were added at 0.3 g/l for a 24-h incubation. A total of 130 volatile compounds were detected by means of headspace-solid phase microextraction gas-chromatography/mass spectrometry analyses. Several changes in the metabolite profiles of fermentation fluids were found, including a decrease of alcohols (?19%) and esters (?42%) in feline and canine inoculum, respectively, which was due to the antibacterial properties of tannins. In canine inoculum, after 6 h, YSE + CT caused lower cadaverine concentrations (?37%), while ammonia (?4%) and quinolone (?27%) were reduced by addition of CT. After 24 h, the presence of CT resulted in a decrease of sulphur compounds, such as dimethyl sulphide (?69%) and dimethyl disulphide (?20%). In feline faecal cultures, after 6 h, CT lowered the amount of indole (?48%), whereas YSE tended to decrease trimethylamine levels (?16%). Both in canine and feline inoculum, addition of CT and, to a minor extent, YSE affected volatile fatty acids patterns. In canine faecal cultures, CT exerted a marginal inhibitory effect on Escherichia coli population (?0.45 log 10 numbers of DNA copies/ml), while enterococci were increased (+2.06 log 10 numbers of DNA copies/ml) by YSE. The results from the present study show that YSE and tannins from chestnut wood exert different effects on the composition and metabolism of canine and feline faecal microbiota. In particular, the supplementation of YSE and tannins to diets for dogs and cats may be beneficial due to the reduction of the presence of some potentially toxic volatile metabolites in the animals’ intestine.     

Birth delivery method affects expression of immune genes in lung and jejunum tissue of neonatal beef calves

Background

Caesarean section is a routine veterinary obstetrical procedure employed to alleviate dystocia in cattle. However, CS, particularly before the onset of labour, is known to negatively affect neonatal respiration and metabolic adaptation in humans, though there is little published information for cattle. The aim of this study was to investigate the effect of elective caesarean section (ECS) or normal trans-vaginal (TV) delivery, on lung and jejunal gene expression profiles of neonatal calves.

Results

Paternal half-sib Angus calves (gestation length 278 + 1.8 d) were delivered either transvaginally (TV; n?=?8) or by elective caesarean section (ECS; n?=?9) and immediately euthanized. Lung and jejunum epithelial tissue was isolated and snap frozen. Total RNA was extracted using Trizol reagent and reverse transcribed to generate cDNA. For lung tissue, primers were designed to target genes involved in immunity, surfactant production, cellular detoxification, membrane transport and mucin production. Primers for jejunum tissue were chosen to target mucin production, immunoglobulin uptake, cortisol reaction and membrane trafficking. Quantitative real-time PCR reactions were performed and data were statistically analysed using mixed models ANOVA. In lung tissue the expression of five genes were affected (p?<?0.05) by delivery method. Four of these genes were present at lower (LAP, CYP1A1, SCN11α and SCN11β) and one (MUC5AC) at higher abundance in ECS compared with TV calves. In jejunal tissue, expression of TNFα, Il-1β and 1 l-6 was higher in ECS compared with TV calves.

Conclusions

This novel study shows that ECS delivery affects the expression of key genes involved in the efficiency of the pulmonary liquid to air transition at birth, and may lead to an increased inflammatory response in jejunal tissue, which could compromise colostral immunoglobulin absorption. These findings are important to our understanding of the viability and management of neonatal calves born through ECS.