Prednisone and prednisolone are steroids widely used as anti-inflammatory drugs. Development of the pharmaceutical industry is currently aimed at introducing biotechnological processes and replacing ...multiple-stage chemical syntheses. In this work we evaluated the ability of bacteria belonging to the
genus to biotransform substrates, such as cortisone and hydrocortisone, to obtain prednisone and prednisolone, respectively. These products are of great interest from a pharmaceutical point of view as they have higher anti-inflammatory activity than the starting substrates. After an initial lab-scale screening of 13
strains, to select the highest producers of prednisone and prednisolone, we reported the 200 ml-batch scale-up to test the process efficiency and productivity of the most promising
strains.
,
and
gave the Δ1-dehydrogenation products of cortisone and hydrocortisone (prednisone and prednisolone) in variable amounts. In these biotransformations, the formation of products with the reduced carbonyl group in position C
of the lateral chain of the steroid nucleus was also observed (i.e., 20β-hydroxy-prednisone and 20β-hydroxy-prednisolone). The yields, the absence of collateral products, and in some cases the absence of starting products allow us to say that cortisone and hydrocortisone are partly degraded.
This systematic review aims to highlight the differences between different clear aligner therapies that differ in the presence of attachments or in attachment configuration. Eight electronic ...databases were searched up to March 2020. Two authors independently proceeded to study selection, data extraction, and risk of bias assessment. The analysis of the results was carried out examining six groups of movements (mesio-distal tipping/bodily movement; anterior bucco-lingual tipping/root torque; posterior bucco-lingual tipping/expansion; intrusion; extrusion; rotation). Five clinical trials were selected and all of them showed a medium risk of bias. Literature showed that attachments mostly increase the effectiveness of orthodontic treatment with clear aligners, improving anterior root torque, rotation, and mesio-distal (M-D) movement; they are also important to increase posterior anchorage. However, some articles showed contradictory or not statistically significant results. Attachments also seem to improve intrusion, but the evidence about this movement, as well as extrusion, is lacking. No studies evaluated posterior bucco-lingual tipping/expansion. Further clinical trials are strongly suggested to clarify the influence of attachments and their number, size, shape, and position on each orthodontic movement.
Phytopathogenic fungi are among the main causes of productivity losses in agriculture. To date, synthetic chemical pesticides, such as hydroxyanilides, anilinopyrimidines and azole derivatives, ...represent the main treatment tools for crop plant defence. However, the large and uncontrolled use of these substances has evidenced several side effects, namely the resistance to treatments, environmental damage and human health risks. The general trend is to replace chemicals with natural molecules in order to reduce these side effects. Moreover, the valorisation of agri-food industry by-products through biotransformation processes represents a sustainable alternative to chemical synthesis in several sectors. This research is aimed at comparing the anti-phytopathogenic activity of waste bovine and porcine bile with secosteroids obtained by biotransformation of bile acids with
strains. The ultimate goal is to apply these natural products on food crops affected by phytopathogenic fungi.
Bile acids (BAs) are a family of steroids synthesized from cholesterol in the liver. Among bile acids, ursodeoxycholic acid (UDCA) is the drug of choice for treating primary biliary cirrhosis and ...dissolving cholesterol gallstones. The clinical effectiveness of UDCA includes its choleretic activity, the capability to inhibit hydrophobic bile acid absorption by the intestine under cholestatic conditions, reducing cholangiocyte injury, stimulation of impaired biliary output, and inhibition of hepatocyte apoptosis. Despite its clinical effectiveness, UDCA is poorly soluble in the gastro-duodeno-jejunal contents, and pharmacological doses of UDCA are not readily soluble in the stomach and intestine, resulting in incomplete absorption. Indeed, the solubility of 20 mg/L greatly limits the bioavailability of UDCA. Since the bioavailability of drug products plays a critical role in the design of oral administration dosages, we investigated the enzymatic esterification of UDCA as a strategy of hydrophilization. Therefore, we decided to enzymatically synthesize a glyceric ester of UDCA bile acid to produce a more water-soluble molecule. The esterification reactions between UDCA and glycerol were performed with an immobilized lipase B from Candida antarctica (Novozym 435) in solvent-free and solvent-assisted systems. The characterization of the UDCA-monoglyceride, enzymatically synthesized, has been performed by 1H-NMR, 13C-NMR, COSY, HSQC, HMBC, IR, and MS spectroscopy.
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) introduced in the 1960s and widely used as an analgesic, anti-inflammatory, and antipyretic. In its acid form, the solubility of 21 mg/L ...greatly limits its bioavailability. Since the bioavailability of a drug product plays a critical role in the design of oral administration dosage, this study investigated the enzymatic esterification of ibuprofen as a strategy for hydrophilization. This work proposes an enzymatic strategy for the covalent attack of highly hydrophilic molecules using acidic functions of commercially available bioactive compounds. The poorly water-soluble drug ibuprofen was esterified in a hexane/water biphasic system by direct esterification with sorbitol using the cheap biocatalyst porcine pancreas lipase (PPL), which demonstrated itself to be a suitable enzyme for the effective production of the IBU-sorbitol ester. This work reports the optimization of the esterification reaction.
Leuconostoc
is a genus of saccharolytic heterofermentative lactic acid bacteria that inhabit plant-derived matrices and a variety of fermented foods (dairy products, dough, milk, vegetables, and ...meats), contributing to desired fermentation processes or playing a role in food spoilage. At present, the genus encompasses 17 recognized species. In total, 216 deposited genome sequences of
Leuconostoc
were analyzed, to check the delineation of species and to infer their evolutive genealogy utilizing a minimum evolution tree of Average Nucleotide Identity (ANI) and the core genome alignment. Phylogenomic relationships were compared to those obtained from the analysis of 16S rRNA,
pheS
, and
rpoA
genes. All the phylograms were subjected to split decomposition analysis and their topologies were compared to check the ambiguities in the inferred phylogenesis. The minimum evolution ANI tree exhibited the most similar topology with the core genome tree, while single gene trees were less adherent and provided a weaker phylogenetic signal. In particular, the 16S rRNA gene failed to resolve several bifurcations and
Leuconostoc
species. Based on an ANI threshold of 95%, the organization of the genus
Leuconostoc
could be amended, redefining the boundaries of the species
L. inhae, L. falkenbergense, L. gelidum, L. lactis, L. mesenteroides
, and
L. pseudomesenteroides
. Two strains currently recognized as
L. mesenteroides
were split into a separate lineage representing a putative species (G16), phylogenetically related to both
L. mesenteroides
(G18) and
L. suionicum
(G17). Differences among the four subspecies of
L. mesenteroides
were not pinpointed by ANI or by the conserved genes. The strains of
L. pseudomesenteroides
were ascribed to two putative species, G13 and G14, the former including also all the strains presently belonging to
L. falkenbergense. L. lactis
was split into two phylogenetically related lineages, G9 and G10, putatively corresponding to separate species and both including subgroups that may correspond to subspecies. The species
L. gelidum
and
L. gasicomitatum
were closely related but separated into different species, the latter including also
L. inhae
strains. These results, integrating information of ANI, core genome, and housekeeping genes, complemented the taxonomic delineation with solid information on the phylogenetic lineages evolved within the genus
Leuconostoc
.
Near-Infrared Spectroscopy is a cost-effective and environmentally friendly technique that could represent an alternative to conventional soil analysis methods, including total organic carbon (TOC). ...Soil fertility and quality are usually measured by traditional methods that involve the use of hazardous and strong chemicals. The effects of physical soil characteristics, such as moisture content and particle size, on spectral signals could be of great interest in order to understand and optimize prediction capability and set up a robust and reliable calibration model, with the future perspective of being applied in the field. Spectra of 46 soil samples were collected. Soil samples were divided into three data sets: unprocessed, only dried and dried, ground and sieved, in order to evaluate the effects of moisture and particle size on spectral signals. Both separate and combined normalization methods including standard normal variate (SNV), multiplicative scatter correction (MSC) and normalization by closure (NCL), as well as smoothing using first and second derivatives (DV1 and DV2), were applied to a total of seven cases. Pretreatments for model optimization were designed and compared for each data set. The best combination of pretreatments was achieved by applying SNV and DV2 on partial least squares (PLS) modelling. There were no significant differences between the predictions using the three different data sets (
< 0.05). Finally, a unique database including all three data sets was built to include all the sources of sample variability that were tested and used for final prediction. External validation of TOC was carried out on 16 unknown soil samples to evaluate the predictive ability of the final combined calibration model. Hence, we demonstrate that sample preprocessing has minor influence on the quality of near infrared spectroscopy (NIR) predictions, laying the ground for a direct and fast in situ application of the method. Data can be acquired outside the laboratory since the method is simple and does not need more than a simple band ratio of the spectra.
Biocatalyzed synthesis can be exploited to produce high-value products, such as prodrugs. The replacement of chemical approaches with biocatalytic processes is advantageous in terms of environmental ...prevention, embracing the principles of green chemistry. In this work, we propose the covalent attachment of xylitol to ibuprofen to produce an IBU-xylitol ester prodrug. Xylitol was chosen as a hydrophilizer for the final prodrug, enhancing the water solubility of ibuprofen. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) extensively used as an analgesic, anti-inflammatory, and antipyretic. Despite being the third-most-prescribed medicine in the world, the aqueous solubility of ibuprofen is just 21 mg/L. This poor water solubility greatly limits the bioavailability of ibuprofen. We aimed to functionalize ibuprofen with xylitol using the reusable immobilized N435 biocatalyst. Instead of a biphasic media, we proposed a monophasic reaction environment. The characterization of the IBU-xylitol ester was performed by
H,
C-NMR, DEPT, COSY, HMQC, HMBC, FTIR, and MS spectroscopy. Preliminary in vitro tests showed that this enzymatically synthesized prodrug of ibuprofen reduced the expression of the interleukin 8 genes in human bronchial epithelial cells (IB3-1) from cystic fibrosis (CF) patients.
Cortisone is a metabolite belonging to the corticosteroid class that is used pharmaceutically directly as a drug or prodrug. In addition to its large consumption, its use is linked to several side ...effects, so pharmaceutical research aims to develop effective drugs with low or no side effects, alternative compounds to cortisone are part of an active investment in ongoing research on drug discovery. Since biotransformation can be considered a source of new molecules with potential therapeutic use, the present work focuses on a preliminary in vitro study aimed at evaluating the mutagenic, anti-inflammatory, antioxidant and neuroprotective activity of SCA and SCB molecules obtained from the biotransformation of cortisone using Rh. Rhodnii strain DSM 43960. The results obtained are very encouraging due to the safety of biotransformed compounds with reference to genotoxicity checked by Ames test, to the very high antioxidant capacity and to the anti-inflammatory activity. In fact, thecompounds inhibited both the TNFα-stimulated expression and secretion of NFkB target cytokines, and COX activity, and can activate the glucocorticoid receptor. Finally SCA and SCB exhibited neuroprotective properties.
Cortisone is a steroid widely used as an anti-inflammatory drug able to suppress the immune system, thus reducing inflammation and attendant pain and swelling at the site of an injury. Due to its ...numerous side effects, especially in prolonged and high-dose therapies, the development of the pharmaceutical industry is currently aimed at finding new compounds with similar activities but with minor or no side effects. Biotransformations are an important methodology towards more sustainable industrial processes, according to the principles of "green chemistry". In this work, the biotransformation of cortisone with
DSM 43960 to give two new steroids, i.e., 1,9β,17,21-tetrahydoxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11,20-dione and 1,9β,17,20β,21-pentahydoxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11-one, is reported. These new steroids have been fully characterized.
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