Inflammation is a complex reaction involving cellular and molecular components and an unspecific response to a specific aggression. The use of scientific and technological innovations as a research ...tool combining multidisciplinary knowledge in informatics, biotechnology, chemistry and biology are essential for optimizing time and reducing costs in the drug design. Thus, the integration of these in silico techniques makes it possible to search for new anti-inflammatory drugs with better pharmacokinetic and toxicological profiles compared to commercially used drugs. This in silico study evaluated the anti-inflammatory potential of two benzoylpropionic acid derivatives (MBPA and DHBPA) using molecular docking and their thermodynamic profiles by molecular dynamics, in addition to predicting oral bioavailability, bioactivity and toxicity. In accordance to our predictions the derivatives proposed here had the potential capacity for COX-2 inhibition in the human and mice enzyme, due to containing similar interactions with the control compound (ibuprofen). Ibuprofen showed toxic predictions of hepatotoxicity (in human, mouse and rat; toxicophoric group 2-arylacetic or 3-arylpropionic acid) and irritation of the gastrointestinal tract (in human, mouse and rat; toxicophoric group alpha-substituted propionic acid or ester) confirming the literature data, as well as the efficiency of the DEREK 10.0.2 program. Moreover, the proposed compounds are predicted to have a good oral bioavailability profile and low toxicity (LD
< 700 mg/kg) and safety when compared to the commercial compound. Therefore, future studies are necessary to confirm the anti-inflammatory potential of these compounds.
Magnetic nanoparticles (Fe3O4) were used for physical adsorption of lipase from Yarrowia lipolytica IMUFRJ 50682. The optimal adsorption conditions were obtained as follows: enzyme/support 19.3 mg/g ...and temperature of 20 °C for standard protein. High immobilization efficiency of 99% was obtained for 4 mL of crude lipase extract (containing 0.315 mg protein/mL) and 0.02 g of magnetic nanoparticles and this biocatalyst was recycled 30 times with 70% of lipase activity in the end. Purified lipase extracts were also efficiently immobilized and ultrafiltered lipase extract (ULE) and aqueous two-phase system lipase extract (ATPS_LE) when immobilized revealed higher hydrolytic activity in relation to CLE (2.8 and 4.0 times higher, respectively). Broad pH tolerance and high thermostability could be achieved by immobilization on magnetic nanoparticles, with 40% improvement in thermodynamic parameters at 60 °C. Kinetic parameters Vmax and Km were also better for ULE (Vmax: 2.3 times higher; Km 43% reduction) and ATPS_LE (Vmax: 3.0 times higher; Km: 38% reduction) immobilized on magnetic nanoparticles in relation to CLE. These results showed that the immobilization of lipase onto magnetic nanoparticles by physical adsorption is an efficient and simple way to obtain a great catalyst.
•High Immob. Yield (99%) for lipase from Y. lipolytica on magnetic nanoparticles (MNP)•Lipase immobilized by simple physical adsorption on MNP could be reused for 30 cycles•Broad pH tolerance/high thermostability was achieved by adsorption of lipase in MNP•Thermodynamic parameters show better performance when lipase is previously purified
This study aimed to identify lactic acid bacteria (LAB) in byproducts of fruit (Malpighia glabra L., Mangifera indica L., Annona muricata L., and Fragaria vesca L.) pulp processing. Fifty strains of ...LAB were identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequence (16S rRNA) analysis. Species belonging to Lactobacillus genus were the predominant LAB in all fruit pulp processing byproducts. The average congruency between the MALDI-TOF MS and 16S rRNA in LAB species identification reached 86%. Isolates of L. plantarum, L. brevis, L. pentosus, L. lactis and L. mesenteroides were identified with 100% congruency. MALDI-TOF MS and 16S rRNA analysis presented 86 and 100% efficiency of LAB species identification, respectively. Further, five selected Lactobacillus strains (L. brevis 59, L. pentosus 129, L. paracasei 108, L. plantarum 49, and L. fermentum 111) were evaluated for desirable probiotic-related properties and growth behavior on two different cultivation media. The exposure to pH 2.0 sharply decreased the counts of the different Lactobacillus strains after a 1 or 2 h incubation, while varied decreases were noted after 3 h of exposure to pH 3.0. Overall, the exposure to pH 5.0 and to bile salts (0.15, 0.30, and 1.00%) did not decrease the counts of the Lactobacillus strains. All tested Lactobacillus strains presented inhibitory activity against Staphylococcus aureus, Salmonella Typhimurium, Salmonella Enteritidis, Listeria monocytogenes and Escherichia coli, and presented variable susceptibility to different antibiotics. The selected Lactobacillus strains presented satisfactory and reproducible growth behavior. In conclusion, MALDI-TOF MS and 16S rRNA analysis revealed high efficiency and congruency for LAB species identification, and the selected Lactobacillus strains may be candidates for further investigation of novel probiotic strains.
Purpose
Chiari II malformation (CM-II) is a congenital malformation of the posterior fossa associated with myelomeningocele. Of the symptomatic patients, 10–33% require surgical treatment. To this ...date, there is not a consensus about the best surgical technique, and whether to do duroplasty.
Methods
A literature search of the PubMed database and crossed references was performed, per PRISMA guidelines. Data regarding demographic features, extent of cervicomedullary deformity, clinical presentation, surgical techniques, and clinical outcomes were extracted. Pearson’s chi-squared test was applied. The
p
-values under 0.05 were considered statistically significant.
Results
Twenty studies (
N
= 330) were analyzed. C3 and C4 levels represented 56.4% of the lowest tonsil displacement. The most reported symptom was dysphagia/swallowing dysfunction (53.8%). Suboccipital craniectomy (SOC) and cervical spine expansion (CSE) with duroplasty were the most reported technique. Dural augmentation was performed in 57.4% of the patients. After surgery, 59.6% observed an improvement in symptoms and quality of life, 12.5% were unchanged, and 27.8% had a worsened clinical status. The mortality rate was 2.5% during the first month after surgery, and 17.4% at the last follow-up evaluation. Patients who underwent CSE presented a better clinical outcome (
p
= 0.002). The SOC procedure could not be correlated with symptom improvement (
p
= 0.06).
Conclusion
CM-II is associated with high morbidity and mortality. An early onset symptomatic CM-II demands intervention, which provided an improvement of outcome in most patients included in this review. The best surgical technique and the exact effect of the surgical management of CM-II on mortality are not yet clear.
Composting operations are a rich source for prospection of biomass degradation enzymes. We have analyzed the microbiomes of two composting samples collected in a facility inside the São Paulo Zoo ...Park, in Brazil. All organic waste produced in the park is processed in this facility, at a rate of four tons/day. Total DNA was extracted and sequenced with Roche/454 technology, generating about 3 million reads per sample. To our knowledge this work is the first report of a composting whole-microbial community using high-throughput sequencing and analysis. The phylogenetic profiles of the two microbiomes analyzed are quite different, with a clear dominance of members of the Lactobacillus genus in one of them. We found a general agreement of the distribution of functional categories in the Zoo compost metagenomes compared with seven selected public metagenomes of biomass deconstruction environments, indicating the potential for different bacterial communities to provide alternative mechanisms for the same functional purposes. Our results indicate that biomass degradation in this composting process, including deconstruction of recalcitrant lignocellulose, is fully performed by bacterial enzymes, most likely by members of the Clostridiales and Actinomycetales orders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients with mucopolysaccharidosis type VI (MPS VI) present with a wide range of disease severity and clinical manifestations, with significant functional impairment and shortened lifespan. Enzyme ...replacement therapy (ERT) with galsulfase has been shown to improve clinical and biochemical parameters including patient survival, quality of life and growth. The present study is a resurvey of 34 Brazilian MPS VI patients with rapidly progressive disease (classical phenotype) who initiated ERT with galsulfase under five years of age and had been on ERT until data collection in 2019, with few exceptions (n = 4 patients who died before 2019).
Anthropometric measures, urinary glycosaminoglycans, and data regarding cardiac, orthopedic, neurologic, sleep apnea, hearing and ophthalmologic outcomes were filled in by specialists. Pubertal development, clinical complications, hospitalizations, and surgeries were also assessed.
In this resurvey study, treatment with galsulfase has shown to be safe and well tolerated in MPS VI patients who initiated ERT under the age of 5 years and who have been undergoing ERT for approximately 10 years. Mortality rate suggests that early initiation of ERT may have a positive impact on patients' survival, improving but not preventing disease progression and death. MPS VI patients on ERT also showed improved growth velocity and the pubertal development was normal in all surviving patients.
Follow-up data on pneumonia and hospitalization suggest that early ERT may have a protective effect against major respiratory complications. Cardiac valve disease progressed since their prior evaluation and spinal cord compression was observed in a large number of patients, suggesting that these disease complications were not modified by ERT.
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•Lipase from Y. lipolytica was successfully purified with aqueous two-phase system.•Lipase from Y. lipolytica was concentrated in the salty phase, easier to extract.•Aqueous two-phase ...system (ATPS) method was superior to traditional methods.•Lipase purified with ATPS showed good thermostability until 50°C.•Purified lipase extract showed good stability at a wide pH range.
In this study an aqueous two-phase system (ATPS) composed of polyethylene glycol (PEG) and potassium phosphate was tested for the purification of lipase from Yarrowia lipolytica IMUFRJ 50682. Ultrafiltration and precipitation with acetone and kaolin were also used as traditional comparison methods Ultrafiltration was a good method with a purification factor of 6.55, but protease was also purified in this extract. For the precipitation with acetone and kaolin lower values of lipase and protease activity were found in relation to the original crude enzyme extract. Under the best conditions of ATPS (pH 6 and 4°C), the purification fold was greater than 40 and selectivity was almost 500. Lipase was recovered in the salty phase which makes it easier to purify it. The optimum pH and temperature ranges for purified lipase with this system was 6–7 and 35–40°C, respectively. Lipase thermostability was increased in relation to crude extract after the purification with the PEG/phosphate buffer system for temperatures lower than 50°C. All enzyme extracts showed good stability to a wide pH range. Y. lipolytca lipase was successfully purified by using ATPS in a single downstream processing step and presented good process characteristics after this treatment.
•The sequence of the ATP-binding cassette transporter TcABCG1 gene of fourteen T. cruzi strains was determined.•Gene polymorphisms were not associated with benznidazole resistance.•TcABCG1 hybrid ...haplotypes are mosaics originated by inter-strain intragenic recombination.•Orthologues of TcABCG1 transporter were found in Leishmania spp. and African trypanosomes.
Benznidazole (BZ) is one of the two drugs for Chagas disease treatment. In a previous study we showed that the Trypanosoma cruzi ABCG-like transporter gene, named TcABCG1, is over-expressed in parasite strains naturally resistant to BZ and that the gene of TcI BZ-resistant strains exhibited several single nucleotide polymorphisms (SNPs) as compared to the gene of CL Brener BZ-susceptible strain. Here we report the sequence of TcABCG1 gene of fourteen T. cruzi strains, with diverse degrees of BZ sensitivity and belonging to different discrete typing units (DTUs) and Tcbat group. Although DTU-specific SNPs and amino acid changes were identified, no direct correlation with BZ-resistance phenotype was found. Thus, it is plausible that the transporter abundance is a determinant factor for drug resistance, as pointed out above. Sequence data were used for Bayesian phylogenies and network genealogy analysis. The network showed a high degree of reticulation suggesting genetic exchange between the parasites. TcI and TcII clades were clearly separated. Tcbat sequences were close to TcI. A fourth clade clustered TcABCG1 haplotypes of TcV, TcVI and TcIII strains, with closer proximity to TcI. Analysis of the recombination patterns indicated that hybrid strains contain haplotypes that are mosaics most likely derived by intragenic recombination of parental sequences. The data confirm that TcII and TcIII as the parentals of TcV and TcVI DTUs. Since genetic fingerprint of TcI was found in TcIII, we sustain the previously proposed “Two Hybridization model” for the origin of hybrid strains. Among the twenty best BLASTP hits in databases, orthologues of TcABCG1 transporter were found in Leishmania spp. and African trypanosomes, though their function remains undescribed.
Contents
The aim of this study was to evaluate the effect of intratesticular injection of calcium chloride (CaCl2) combined with dimethyl sulphoxide (DMSO) as a chemical sterilization in dogs. Twelve ...dogs were divided into two groups: the treated group (n = 6), in which 15 mg/kg of a 7.5% CaCl2 solution combined with 0.5% DMSO was injected into each testicle (volume range 1.0‐4.76 ml); and a control group (n = 6) that received the same volume/kg of 0.9% sodium chloride solution (NaCl). Semen characteristics pre‐ and post‐treatment were evaluated. Serum testosterone concentration was determined before the injection (D‐1) and at 15 (D15), 30 (D30) and 60 (D60) days after intratesticular injection. Testicle sizes and local pain were evaluated for 7 consecutive days (D1 to D7) and at D15, D30 and D60 after injection. At D60, testicle histological evaluation was performed after orchiectomy. No pain was observed by testicular palpation, with the exception of one dog in the treated group; this dog then received analgesic therapy. An increase in testicular volume was evident within 24 hr after treatment, followed by gradual reduction for 3 weeks. Five of 6 dogs from the treated group presented azoospermia at D15; the remaining dog presented at D30. There was no significant difference in testosterone concentrations in the treated group during the experimental period. Histological evaluation showed testicular degenerative lesions, especially at the proximal and middle portions. The results indicated that one injection of 7.5% CaCl2 combined with 0.5% DMSO into each testis is a viable alternative for canine sterilization.
This paper intends to show how to use collagen to assist in obtaining single crystals of small molecules of two one-dimensional coordination polymers built by 5-sulfoisophthalic acid and lanthanide ...ions. The crystals were grown at room temperature and crystalline forms appeared into viscous solution exhibiting well-shaped faces and large volumes with small amount of samples. The use of collagen in the system prevents the formation of precipitate, an advantage when compared to many crystals obtained in pure solution. The samples, Nd(5SIS)·(DMF)
2
·5H
2
O (
1
) and La(5sis)·8H
2
O (
2
), have been prepared and characterized by single-crystal X-ray diffraction and vibrational spectroscopic (Raman and FT-IR) analyses. The results have shown that the compounds belong to the monoclinic system and it is stabilized by a complex hydrogen bonds network. Coordination environment of metals tend to have more ionic character in their bonds. The advantages and limitations of the use of collagen in small molecule crystallization have also been discussed.
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