Publications by authors named "Pedro Soares"

206 Publications

Improvement of Genome Annotation: Towards the Exploitation of Genomic Features of a Biotechnologically Relevant Yeast.

J Fungi (Basel) 2021 Apr 10;7(4). Epub 2021 Apr 10.

CBMA (Centre of Molecular and Environmental Biology), Department of Biology, University of Minho, 4710-057 Braga, Portugal.

is the most commonly used yeast in wine, beer, and bread fermentations. However, has attracted interest in recent years due to its properties, ranging from its ability to produce flavor- and aroma-enhanced wine to its ability to survive longer in frozen dough. In this work, publicly available genomes of were explored and their annotation was improved. A total of 32 proteins were additionally annotated for the first time in the type strain CBS1146, in comparison with the previous annotation available. In addition, the annotation of the remaining three strains was performed for the first time. eggNOG-mapper was used to perform the functional annotation of the deduced coding genes, offering insights into its biological significance, and revealing 24 clusters of orthologous groups (COGs), which were gathered in three main functional categories: information storage and processing (28% of the proteins), cellular processing and signaling (27%), and metabolism (23%). Small intraspecies variability was found when considering the functional annotation of the four available genomes. A comparative study was also conducted between the genome and those from 386 fungal species, revealing a high number of homologous genes with species from the and genera, but also with and . Lastly, the phylogenetic placement of was clarified using the core homologs that were found across 204 common protein sequences of 386 fungal species and strains.
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http://dx.doi.org/10.3390/jof7040287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070057PMC
April 2021

Cardiovascular and Autonomic Responses after a Single Bout of Resistance Exercise in Men with Untreated Stage 2 Hypertension.

Int J Hypertens 2021 29;2021:6687948. Epub 2021 Mar 29.

Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niteroi, State of Rio de Janeiro, Brazil.

The aim of this paper is to assess the integrated responses of ambulatory blood pressure (BP), cardiac autonomic modulation, spontaneous baroreflex sensitivity (BRS), and vascular reactivity after a single bout of resistance exercise (RE) in men with stage 2 hypertension who have never been treated before. Ten hypertensive men were subjected to a RE session of three sets of 20 repetitions and an intensity of 40% of the 1-repetition maximum (RM) test in seven different exercises. For the control (CTR) session, the volunteers were positioned on the exercise machines but did not perform any exercise. Forearm blood flow was measured by venous occlusion plethysmography. We also analyzed the heart rate variability (HRV), ambulatory BP, blood pressure variability (BPV), and BRS. All measurements were performed at different timepoints: baseline, 20 min, 80 min, and 24 h after both RE and CTR sessions. There were no differences in ambulatory BP over the 24 h between the RE and CTR sessions. However, the area under the curve of diastolic BP decreased after the RE session. Heart rate (HR) and cardiac output increased for up to 80 and 20 min after RE, respectively. Similarly, forearm blood flow, conductance, and vascular reactivity increased 20 min after RE ( < 0.05). In contrast, HRV and BRS decreased immediately after exercise and remained lower for 20 min after RE. We conclude that a single bout of RE induced an increase in vascular reactivity and reduced the pressure load by attenuating AUC of DBP in hypertensive individuals who had never been treated with antihypertensive medications.
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http://dx.doi.org/10.1155/2021/6687948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024104PMC
March 2021

Phosphatidylinositol 3-kinase gamma participates in nimesulide-induced hepatic damage.

J Pharm Pharmacol 2021 Mar;73(4):496-504

Laboratory of Experimental Physiopharmacology (LAFFEX), Department of Physioterapy, Federal University of the Parnaíba Delta, Parnaíba, Piauí, Brazil.

Objective: To evaluate the participation of the phosphatidylinositol 3-kinase pathway in the liver damage caused by nimesulide.

Methods: Liver damage been induced by nimesulide. Mice were treated with either 2% dimethyl sulfoxide or AS605240, a phosphatidylinositol 3-kinase gamma pathway antagonist. Blood samples were collected for function assays of liver. The liver was removed for analysis of liver weight/animal weight ratio, histopathological parameters, oxidative and nitrous stress, cytokine levels, and the immunostaining for cyclooxygenase 2 and nuclear factor kappa B.

Key Findings: Liver injured by nimesulide and treated with phosphatidylinositol 3-kinase gamma inhibitor significantly reversed (P < 0.05) the damage; it decreased the liver weight/animal weight ratio, histopathological scores, and neutrophil infiltration, consequently reducing oxidative stress. In addition, we show that phosphatidylinositol 3-kinase gamma is associated with hepatic damage induced by nimesulide, because it altered liver function and increased the protein immunostaining of cyclooxygenase 2 and nuclear factor kappa B in the liver tissue of nimesulide-treated animals.

Conclusions: The findings from the present study allows us to infer that nimesulide causes liver damage through the phosphatidylinositol 3-kinase gamma pathway.
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http://dx.doi.org/10.1093/jpp/rgaa049DOI Listing
March 2021

Screen time and working memory in adolescents: A longitudinal study.

J Psychiatr Res 2021 May 6;137:266-272. Epub 2021 Mar 6.

Postgraduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Brazil.

Little is known about the effects of excessive screen time on Working Memory (WM) in adolescents. The aim of this study was to investigate the association between measures of screen time in adolescence and Working Memory. Data from the 1993 Pelotas (Brazil) Birth Cohort Study were analyzed (N = 3625). Self-reported screen time was collected at ages 11, 15 and 18. Working Memory performance (Digit Span backward score) was examined at age 22. Multiple linear regression was used to assess the associations between three screen time measures (television, video game and computer time) for each age and WM at age 22. We also evaluated the direct and indirect effect by mediation analysis, using the intelligence quotient (IQ) at 18 years as mediator. In men, television and video game time at 11 years and computer at ages 11 and 15 years had a positive effect on WM. Also, these effects were mediated through IQ. In women there was no significant association between screen time measures at ages 11, 15, and 18 and WM. This study provides new insights about the relationship between television, videogame, and computer time with WM in adolescents, by exploring the paths of these associations and considering the important mediating role of IQ.
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http://dx.doi.org/10.1016/j.jpsychires.2021.02.066DOI Listing
May 2021

Fine-Tuning the Biological Profile of Multitarget Mitochondriotropic Antioxidants for Neurodegenerative Diseases.

Antioxidants (Basel) 2021 Feb 23;10(2). Epub 2021 Feb 23.

CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.

Neurotransmitter depletion and mitochondrial dysfunction are among the multiple pathological events that lead to neurodegeneration. Following our previous studies related with the development of multitarget mitochondriotropic antioxidants, this study aims to evaluate whether the π-system extension on the chemical scaffolds of AntiOXCIN2 and AntiOXCIN3 affects their bioactivity and safety profiles. After the synthesis of four triphenylphosphonium (TPP) conjugates (compounds -), we evaluated their antioxidant properties and their effect on neurotransmitter-metabolizing enzymes. All compounds were potent equine butyrylcholinesterase (BChE) and moderate electric eel acetylcholinesterase (AChE) inhibitors, with catechols 4 and 5 presenting lower IC values than AntiOXCIN2 and AntiOXCIN3, respectively. However, differences in the inhibition potency and selectivity of compounds - towards non-human and human cholinesterases (ChEs) were observed. Co-crystallization studies with compounds - in complex with human ChEs (ChEs) showed that these compounds exhibit different binging modes to AChE and BChE. Unlike AntiOXCINs, compounds - displayed moderate human monoamine oxidase (MAO) inhibitory activity. Moreover, compounds and presented higher ORAC-FL indexes and lower oxidation potential values than the corresponding AntiOXCINs. Catechols 4 and 5 exhibited broader safety windows in differentiated neuroblastoma cells than benzodioxole derivatives 2 and 3. Compound 4 is highlighted as a safe mitochondria-targeted antioxidant with dual ChE/MAO inhibitory activity. Overall, this work is a contribution for the development of dual therapeutic agents addressing both mitochondrial oxidative stress and neurotransmitter depletion.
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http://dx.doi.org/10.3390/antiox10020329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926627PMC
February 2021

Is Screen Time Throughout Adolescence Related to ADHD? Findings from 1993 Pelotas (Brazil) Birth Cohort Study.

J Atten Disord 2021 Mar 5:1087054721997555. Epub 2021 Mar 5.

Universidade Federal de Pelotas, Brazil.

Objective: This study investigated the association between screen time in adolescence and Attention Deficit Disorder (ADHD) at 22 years old.

Method: A sample of 2333 participants aged 11 years old without ADHD from the 1993 Pelotas Birth Cohort Study (Brazil) was followed up until the age of 22. Screen time variables included time spent in television, video game and computer at 11, 15, and 18 years old. ADHD was assessed at 22 years.

Results: ADHD symptoms at 22 years was positively associated with television time at 11 years, computer time at 18 years and total screen time at ages 11, 15, and 18 years. Television time at 11 years and total screen time at 18 years were associated with diagnosis of ADHD at 22 years of age.

Conclusions: Our findings may contribute to future investigations of possible explanatory avenues for these associations.
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http://dx.doi.org/10.1177/1087054721997555DOI Listing
March 2021

McN-A-343, a muscarinic agonist, reduces inflammation and oxidative stress in an experimental model of ulcerative colitis.

Life Sci 2021 May 18;272:119194. Epub 2021 Feb 18.

Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil; The Northeast Biotechnology Network, Federal University of Piauí, Teresina, Brazil. Electronic address:

Aim: The aim of the present study was to investigate the anti-inflammatory response mediated of the M1 muscarinic acetylcholine receptor (mAChR) during experimental colitis.

Material And Methods: After the induction of 6% acetic acid colitis, mice were treated with McN-A-343 0.5, 1.0, and 1.5 mg/kg or dexamethasone (DEXA, 2.0 mg/kg) or pirenzepine (PIR, 10 mg/kg; M1 mAChR antagonist). Colonic inflammation was assessed by macroscopic and microscopic lesion scores, colonic wet weight, myeloperoxidase (MPO) activity, interleukin-1 beta (IL1-β) levels and tumor necrosis factor alpha (TNF-α), glutathione (GSH), malondialdehyde (MDA) and nitrate and nitrite (NO/NO), mRNA expression of IKKα, nuclear factor kappa beta (NF-kB) and cyclooxygenase-2 (COX-2), as well protein expression of NF-kB and COX-2.

Results: Treatment with McN-A-343 at a concentration of 1.5 mg/kg showed a significant reduction in intestinal damage as well as a decrease in wet weight, MPO activity, pro-inflammatory cytokine concentration, markers of oxidative stress and expression of inflammatory mediators. The action of the M1 agonist by the administration of pirenzepine, which promoted the blocking of the mAChR M1-mediated anti-inflammatory response, has also been proven.

Conclusion: The results suggest that peripheral colonic M1 mAChR is involved in reversing the pro-inflammatory effect of experimentally induced colitis, which may represent a promising therapeutic alternative for patients with ulcerative colitis.
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http://dx.doi.org/10.1016/j.lfs.2021.119194DOI Listing
May 2021

Metabolic engineering of Saccharomyces cerevisiae for the production of top value chemicals from biorefinery carbohydrates.

Biotechnol Adv 2021 Mar-Apr;47:107697. Epub 2021 Jan 26.

CEB - Centre of Biological Engineering, University of Minho, Campus Gualtar, Braga, Portugal. Electronic address:

The implementation of biorefineries for a cost-effective and sustainable production of energy and chemicals from renewable carbon sources plays a fundamental role in the transition to a circular economy. The US Department of Energy identified a group of key target compounds that can be produced from biorefinery carbohydrates. In 2010, this list was revised and included organic acids (lactic, succinic, levulinic and 3-hydroxypropionic acids), sugar alcohols (xylitol and sorbitol), furans and derivatives (hydroxymethylfurfural, furfural and furandicarboxylic acid), biohydrocarbons (isoprene), and glycerol and its derivatives. The use of substrates like lignocellulosic biomass that impose harsh culture conditions drives the quest for the selection of suitable robust microorganisms. The yeast Saccharomyces cerevisiae, widely utilized in industrial processes, has been extensively engineered to produce high-value chemicals. For its robustness, ease of handling, genetic toolbox and fitness in an industrial context, S. cerevisiae is an ideal platform for the founding of sustainable bioprocesses. Taking these into account, this review focuses on metabolic engineering strategies that have been applied to S. cerevisiae for converting renewable resources into the previously identified chemical targets. The heterogeneity of each chemical and its manufacturing process leads to inevitable differences between the development stages of each process. Currently, 8 of 11 of these top value chemicals have been already reported to be produced by recombinant S. cerevisiae. While some of them are still in an early proof-of-concept stage, others, like xylitol or lactic acid, are already being produced from lignocellulosic biomass. Furthermore, the constant advances in genome-editing tools, e.g. CRISPR/Cas9, coupled with the application of innovative process concepts such as consolidated bioprocessing, will contribute for the establishment of S. cerevisiae-based biorefineries.
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http://dx.doi.org/10.1016/j.biotechadv.2021.107697DOI Listing
April 2021

Expanding the Knowledge on the Skillful Yeast .

J Fungi (Basel) 2021 Jan 9;7(1). Epub 2021 Jan 9.

Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.

is widely used as a source of single-cell protein and is known for its ability to synthesize a great variety of valuable compounds for the food and pharmaceutical industries. Its capacity to produce compounds such as food additives, supplements, and organic acids, among other fine chemicals, has turned it into an attractive microorganism in the biotechnology field. In this review, we performed a robust phylogenetic analysis using the core proteome of and other fungal species, from Asco- to Basidiomycota, to elucidate the evolutionary roots of this species. In addition, we report the evolution of this species nomenclature over-time and the existence of a teleomorph () and anamorph state () and summarize the current nomenclature of most common strains. Finally, we highlight relevant traits of its physiology, the solute membrane transporters so far characterized, as well as the molecular tools currently available for its genomic manipulation. The emerging applications of this yeast reinforce its potential in the white biotechnology sector. Nonetheless, it is necessary to expand the knowledge on its metabolism, regulatory networks, and transport mechanisms, as well as to develop more robust genetic manipulation systems and synthetic biology tools to promote the full exploitation of .
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http://dx.doi.org/10.3390/jof7010036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827542PMC
January 2021

First Report of Root-Knot Nematode Infecting Sweetpotato in the State of Rio Grande do Norte, Brazil.

Plant Dis 2021 Jan 12. Epub 2021 Jan 12.

Sao Paulo State University Julio de Mesquita Filho - Jaboticabal Campus, 207340, Department of Agricultural Production Sciences, Jaboticabal, SP, Brazil;

The sweetpotato ( L., Convolvulaceae family) originated in Latin America and is currently cultivated worldwide. The storage roots, rich in calories, have made this crop one of the main caloric sources for low-income populations, especially in developing countries. Brazil annually produces about 805,000 tons, with the Northeast region responsible for 34% of this production (Albuquerque et al. 2020). In October 2019, sweetpotato plants cv. Campina, from a field in the region of Touros, state of Rio Grande do Norte (RN), Brazil (5°12'31"S 35°34'42"W), presented deformed storage roots, with galls, typical of root-knot nematodes. The roots were sent to the Nematology Laboratory (LabNema) where 14,032 eggs and 3,312 second-stage juveniles (J2s) of sp., in 10 g of roots, were recovered. The species of adults was identified through morphological, biochemical, and phylogenetic analysis. The perineal region of females (n = 10) presented an oval shape, with a high and semi-trapezoidal dorsal arch and streak-free perivulval region. The labial region of males (n=10) presented high and rounded head cap, labial region slightly set off from the body, without annulations. The morphological characters were compatible with the original description of (Yang and Eisenback 1983). The phenotype of esterase isoenzymes showed two major bands (VS1-S1) also characteristic of (Esbenshade and Triantaphyllou 1985). Sequences of 18S rDNA (~1200bp) of individual females (Holterman et al. 2006) obtained from sweetpotatoes before (SPme1 and 2) and after inoculation (SPme3 and 6), and from guava, used as species control, were submitted to Bayesian analysis. The sequences presented genetic diversity among them resulting from seven SNPs (Single Nucleotide Polymorphism) and 99.4 to 99.9% identity with sequences deposited in the NCBI GenBank (accession numbers MW209034-MW209039). The pathogenicity test was carried out under greenhouse conditions, in which 3,000 eggs and J2s from the original population isolated of were inoculated in sweetpotato seedlings cv. Campina (n = 6). After three months, the roots presented galls and deformations typical of root-knot nematodes, while non-inoculated plants did not present any symptoms. An average of 15,900 eggs and J2s of (RF = 5.3) were recovered from the roots, proving that sweetpotatoes were a host of this species. is known to cause great damage to sweetpotato (Ye et al. 2020). In Brazil, nematode had been reported once, isolated from a sweetpotato field in the Ceara state and the species suggested by the authors according to esterase electrophoresis was . Nonetheless, the authors did not present taxonomic, isoenzyme phenotypes and molecular species identification integratively, nor included pathogenicity tests (Silva et al. 2016). Therefore, it is the first time that , with reliable identification by different methods, including sequencing, was detected in commercial sweetpotato fields in the RN state and in Brazil. The local farmers reported that this nematode deforms the storage roots which make them useless for commercialization, resulting in minimal losses of 50% of production in the infested areas. Furthermore, as sweetpotatoes are vegetatively propagated, the spread of this nematode through planting material is favored. Considering the importance of this crop in Brazil, this report is essential for control measures of this pathogen to be taken in order to avoid its spread to other regions.
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http://dx.doi.org/10.1094/PDIS-11-20-2472-PDNDOI Listing
January 2021

The Alpha-Lipoic Acid Improves Survival and Prevents Irinotecan-Induced Inflammation and Intestinal Dysmotility in Mice.

Pharmaceuticals (Basel) 2020 Nov 3;13(11). Epub 2020 Nov 3.

Department of Morphology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE 60430-170, Brazil.

Irinotecan, an anticancer drug, induces diarrhea and intestinal inflammation, resulting in an increase in the cost of care and in treatment delays. In this study, we investigated whether alpha-lipoic acid (α-LA) could improve irinotecan-mediated intestinal inflammation, diarrhea and dysmotility. Intestinal mucositis was induced by irinotecan injection (75 mg/kg, i.p., for 4 days) in Swiss mice. α-LA (50, 100 or 200 mg/kg, gavage) was administered daily 1 h before the injection of irinotecan. Duodenum tissues were obtained for inflammation and proliferation analysis. The outcomes: diarrhea, intestinal dysmotility, weight body loss and survival were evaluated. Compared with the control condition, irinotecan diminished ( < 0.05) intestinal villus height, caused a loss of crypt integrity and intense inflammatory cell infiltration, increased myeloperoxidase (MPO), IL-6 and IL-1β levels and decreased reduced glutathione (GSH) levels in duodenum segments and increased gastric retention and decreased liquid retention in the medial intestinal segment, resulting in increased intestinal transit, severe diarrhea and reduced survival (approximately 72%). Furthermore, α-LA (200 mg/kg) pretreatment ameliorated ( < 0.05) these irinotecan-induced effects. Our findings show that α-LA reduced irinotecan-induced inflammation, intestinal dysmotility and diarrhea, resulting in improved survival. α-LA may be a useful therapeutic agent for the treatment of gut dysmotility in patients with intestinal mucositis associated with irinotecan treatment.
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http://dx.doi.org/10.3390/ph13110361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692584PMC
November 2020

Phylogeography of 27,000 SARS-CoV-2 Genomes: Europe as the Major Source of the COVID-19 Pandemic.

Microorganisms 2020 Oct 29;8(11). Epub 2020 Oct 29.

Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal.

The novel coronavirus SARS-CoV-2 emerged from a zoonotic transmission in China towards the end of 2019, rapidly leading to a global pandemic on a scale not seen for a century. In order to cast fresh light on the spread of the virus and on the effectiveness of the containment measures adopted globally, we used 26,869 SARS-CoV-2 genomes to build a phylogeny with 20,247 mutation events and adopted a phylogeographic approach. We confirmed that the phylogeny pinpoints China as the origin of the pandemic with major founders worldwide, mainly during January 2020. However, a single specific East Asian founder underwent massive radiation in Europe and became the main actor of the subsequent spread worldwide during March 2020. This lineage accounts for the great majority of cases detected globally and even spread back to the source in East Asia. Despite an East Asian source, therefore, the global pandemic was mainly fueled by its expansion across and out of Europe. It seems likely that travel bans established throughout the world in the second half of March helped to decrease the number of intercontinental exchanges, particularly from mainland China, but were less effective between Europe and North America where exchanges in both directions are visible up to April, long after bans were imposed.
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http://dx.doi.org/10.3390/microorganisms8111678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693378PMC
October 2020

BAGS: An automated Barcode, Audit & Grade System for DNA barcode reference libraries.

Mol Ecol Resour 2021 Feb 28;21(2):573-583. Epub 2020 Oct 28.

Department of Biology, CBMA - Centre of Molecular and Environmental Biology, University of Minho, Braga, Portugal.

Biodiversity studies greatly benefit from molecular tools, such as DNA metabarcoding, which provides an effective identification tool in biomonitoring and conservation programmes. The accuracy of species-level assignment, and consequent taxonomic coverage, relies on comprehensive DNA barcode reference libraries. The role of these libraries is to support species identification, but accidental errors in the generation of the barcodes may compromise their accuracy. Here, we present an R-based application, Barcode, Audit & Grade System (BAGS) (https://github.com/tadeu95/BAGS), that performs automated auditing and annotation of cytochrome c oxidase subunit I (COI) sequences libraries, for a given taxonomic group of animals, available in the Barcode of Life Data System (BOLD). This is followed by implementing a qualitative ranking system that assigns one of five grades (A to E) to each species in the reference library, according to the attributes of the data and congruency of species names with sequences clustered in barcode index numbers (BINs). Our goal is to allow researchers to obtain the most useful and reliable data, highlighting and segregating records according to their congruency. Different tests were performed to perceive its usefulness and limitations. BAGS fulfils a significant gap in the current landscape of DNA barcoding research tools by quickly screening reference libraries to gauge the congruence status of data and facilitate the triage of ambiguous data for posterior review. Thereby, BAGS has the potential to become a valuable addition in forthcoming DNA metabarcoding studies, in the long term contributing to globally improve the quality and reliability of the public reference libraries.
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http://dx.doi.org/10.1111/1755-0998.13262DOI Listing
February 2021

Euterpe oleracea Mart. (Açaí) attenuates experimental colitis in rats: involvement of TLR4/COX-2/NF-ĸB.

Inflammopharmacology 2021 Feb 29;29(1):193-204. Epub 2020 Sep 29.

LAFFEX-Laboratory of Experimental Physiopharmacology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Av. São Sebastião 2819, Parnaíba, PI, 64202-020, Brazil.

Euterpe oleracea Mart., commonly known as açaí, has been demonstrated to exhibit significantly antioxidant and inflammatory activities in experimental models. These effects of the hydroalcoholic extract from the açaí seed (ASE) were investigated in TNBS-induced (2,4,6-trinitrobenzenesulfonic acid) acute colitis model in rats. Wistar rats (180-220 g) were orally pretreated with saline (0.3 mL), ASE (10, 30 and 100 mg/kg) and dexamethasone (control group, 1 mg/kg) once daily for 3 days starting before TNBS instillation. On day 3 after TNBS, the animals were euthanized, the portion of distal colon was collected and washed with 0.9% saline for macroscopy and histological evaluation, glutathione (GSH) and malonyldialdehyde (MDA) levels, myeloperoxidase (MPO) and catalase (CAT) activity, nitrate and nitrite (NO/NO) concentration, pro-inflammatory cytokines levels and intestinal barrier integrity. We also evaluated Toll-like Receptor 4/cyclooxygenase-2/nuclear factor kappa B expression as a possible mechanism related to the ASE effects. Treatment with ASE 100 mg/kg decreased significantly macroscopic and microscopic damage induced by TNBS. In addition, MPO activity, TNF-α (tumor necrosis factor-alpha) and IL-1β (interleukin 1) levels were reduced in rats with colitis. ASE 100 mg/kg restored GSH and MDA levels, CAT activity, NO/NO concentration and improved the intestinal barrier integrity in the TNBS group. ASE 100 mg/kg significantly reduced TNBS-induced expression of the TLR4, COX-2 and NF-κB p65. ASE 100 mg/kg improved macroscopy and histological parameters, inflammation, intestinal barrier integrity and nitric and oxidative stress through the TLR-4/COX-2/NF-κB pathway.
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http://dx.doi.org/10.1007/s10787-020-00763-xDOI Listing
February 2021

First Report of Infecting in Brazil.

Plant Dis 2020 Sep 23. Epub 2020 Sep 23.

Sao Paulo State University Julio de Mesquita Filho - Jaboticabal Campus, 207340, Department of Agricultural Production Sciences, Jaboticabal, SP, Brazil;

C. Koch (Lamiaceae alt. Labiatae), commonly known as lamb's ear, is an important medicinal plant with anti-inflammatory, antitumor, anticancer, antispasmodic, sedative and diuretic properties (Asnaashari et al. 2010). This plant is widely consumed in Europe and Asia as aromatic teas. In Brazil, it is an unconventional food plant, nonetheless, its medicinal properties have been recognized as well as its production. In May 2019, in a Sao Paulo State municipality, Jaboticabal, (21°14'38.7"S 48°17'10.6"W), plants presented reduced growth and chlorotic leaves associated with root galls. In the phytopathological clinic, 7,983 eggs and juveniles of sp. were counted in 10 g of the plant roots. In 100 cm³ of soil surrounding the plant, 532 second-stage sp. juveniles (J2) were found. Morphological, enzymatic and molecular identification of the nematode species found were performed (Fig. S1). For morphological analysis, perineal pattern of females (n = 10) and labial region of males (n = 10) were analyzed. In the perineal region of females, a high and trapezoidal dorsal arch with thick striations was observed, whereas the males presented the trapezoidal labial region with the prominent labial disc in relation to the sub-median lips and transverse streaks in the head region, typical characteristics of (Kofoid and White, 1919) Chitwood 1949. (Netscher and Taylor 1974; Eisenback and Hirschmann 1981). The esterase enzyme profile, obtained individually from 8 females, was compatible with phenotype I1 [Rm (x100) = 46.25], also associated with (Esbenshade and Triantaphyllou 1985). Molecular analysis was realized (n = 3) by applying the primers Finc/Rinc (Zijlstra et al. 2000) in the DNA of individual females, which resulted in the amplification of an amplicon of 1200 bp specific for . Pathogenicity testing was conducted in a greenhouse by inoculation of 5,000 eggs and juveniles from the original population into seedlings (n = 4). After 90 days, the inoculated plants, unlike the non-inoculated ones, exhibited symptoms similar to those initially observed in the field. The nematodes were extracted from the roots of the inoculated plants, quantified, and the identity of was confirmed. The average reproductive factor obtained was 136.6, confirming the pathogenicity of to . Thus, this is the first report of associated with in Brazil and in the world. Lamb's ear is a horticultural plant, and its high reproductive factor to can also result in damage to the subsequent crops. In addition, Lamb's ear is propagated vegetatively and this favors the spread of nematodes to other areas. This new report is important in order to alert producers to realize the proper management of this nematode in .
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http://dx.doi.org/10.1094/PDIS-07-20-1628-PDNDOI Listing
September 2020

Engineered for lignocellulosic valorization: a review and perspectives on bioethanol production.

Bioengineered 2020 12;11(1):883-903

CEB - Centre of Biological Engineering, University of Minho, Campus Gualtar , Braga, Portugal.

The biorefinery concept, consisting in using renewable biomass with economical and energy goals, appeared in response to the ongoing exhaustion of fossil reserves. Bioethanol is the most prominent biofuel and has been considered one of the top chemicals to be obtained from biomass. , the preferred microorganism for ethanol production, has been the target of extensive genetic modifications to improve the production of this alcohol from renewable biomasses. Additionally, strains from harsh industrial environments have been exploited due to their robust traits and improved fermentative capacity. Nevertheless, there is still not an optimized strain capable of turning second generation bioprocesses economically viable. Considering this, and aiming to facilitate and guide the future development of effective strains, this work reviews genetic engineering strategies envisioning improvements in generation bioethanol production, with special focus in process-related traits, xylose consumption, and consolidated bioprocessing. Altogether, the genetic toolbox described proves to be a key microorganism for the establishment of a bioeconomy, not only for the production of lignocellulosic bioethanol, but also having potential as a cell factory platform for overall valorization of renewable biomasses.
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http://dx.doi.org/10.1080/21655979.2020.1801178DOI Listing
December 2020

[Epidemiology of Common Mental Disorders among women in the rural zones of Rio Grande, RS, Brazil].

Cien Saude Colet 2020 Aug;25(8):3087-3095

Faculdade de Medicina, Universidade Federal do Rio Grande. R. Gen. Osório s/n, Centro. 96200-400 Rio Grande RS Brasil.

The scope of this study is to describe the prevalence and the factors associated with common mental disorders in women aged 18 to 49, residents in the rural zone of the municipality of Rio Grande-RS. A cross-sectional study was carried out with data collection conducted in 2017. A systematic sampling process of the residences of the rural area of the municipality was utilized. The General Health Questionnaire-12 (GHQ-12) was used to track common mental disorders. Crude and adjusted Poisson regression was used to estimate the prevalence ratios (PR) and respective 95% confidence intervals. The overall prevalence of Common Mental Disorders was 36.4%, being more common among women with lower levels of education, who had had an abortion and were smokers. In quantifying the occurrence and factors associated with common mental disorders in a population of women in a rural area, this study provides an original scientific contribution on the burden of this important outcome in a population that has not been studied in epidemiological surveys. The results can contribute to the health services by identifying the women most susceptible to this outcome, thus, improving the adequacy of the services offered to the health needs of rural residents.
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http://dx.doi.org/10.1590/1413-81232020258.31582018DOI Listing
August 2020

Inspiratory muscles contributions to postural control in healthy older women.

Respir Physiol Neurobiol 2020 10 22;281:103505. Epub 2020 Jul 22.

Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Brazil; National Institute for Science & Technology - INCT (In)activity & Exercise, CNPq - Niterói (RJ), Rio de Janeiro, Brazil. Electronic address:

It was hypothesized that induced inspiratory muscles effort, by an acute inspiratory resistance load (IRL) use, increases the postural sway and the neuromuscular activity of postural muscles in older adults. Fifteen older women breathed spontaneously, controlled (15 cycles/minute), and with acute IRL (15 cycles/minute and target load of 30 % of maximal inspiratory pressure) in random order. The breathing tasks were performed in an orthostatic position (eyes closed) during one minute on a baropodometer plate to acquire center-of-pressure (COP) oscillations and with electromyography (EMG) recording. The root mean square (RMS) of EMG was calculated. COP oscillations were higher with IRL use than spontaneous and controlled breathing tasks, but not between spontaneous and controlled conditions. EMG activity of Tibialis anterior and Soleus muscles were higher with IRL use in comparison to spontaneous and controlled breathing conditions. In conclusion, IRL use influenced the postural control through increased postural sway and neuromuscular compensation of the lower limbs in older women.
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http://dx.doi.org/10.1016/j.resp.2020.103505DOI Listing
October 2020

Inspiratory muscle training improves cerebrovascular and postural control responses during orthostatic stress in older women.

Eur J Appl Physiol 2020 Oct 23;120(10):2171-2181. Epub 2020 Jul 23.

Department of Physiology and Pharmacology, Fluminense Federal University, Rua Professor Hernani Pires de Melo, 101, São Domingos, Niteroi, RJ, CEP 24210-130, Brazil.

Purpose: We aimed to investigate the effect of inspiratory muscle training (IMT) on, hemodynamic, cerebrovascular and postural balance responses during orthostatic stress, in older women.

Methods: Fourteen elderly women were assigned to perform IMT at 50% of maximal inspiratory pressure (MIP) (IMT group, n = 8) or placebo training at 5% MIP (Sham group, n = 6), in a counter-balanced order, using an inspiratory threshold device for 4 weeks. During the protocol, MIP was tested weekly once. In a second visit, blood pressure, heart rate, stroke volume, cardiac output, middle cerebral artery blood flow velocity (MCAv), and ventilation parameters were recorded continuously at rest and during orthostatic stress testing, which was conducted on a force plate to measure center-of-pressure (COP) oscillations (postural balance) and the electromyographic activity of the right medial gastrocnemius and tibialis anterior.

Results: IMT increased MIP from second to 4th week. The drops in MCAv, stroke volume, and cardiac output, as well as COP displacements during initial orthostasis decreased post-IMT.

Conclusion: IMT improves the interplay of the respiratory pump, hemodynamic, cerebrovascular and postural balance responses during orthostatic stress in older women.
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http://dx.doi.org/10.1007/s00421-020-04441-2DOI Listing
October 2020

Population Analysis and Evolution of Mitogenomes.

Microorganisms 2020 Jul 4;8(7). Epub 2020 Jul 4.

Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal.

The study of mitogenomes allows the unraveling of some paths of yeast evolution that are often not exposed when analyzing the nuclear genome. Although both nuclear and mitochondrial genomes are known to determine phenotypic diversity and fitness, no concordance has yet established between the two, mainly regarding strains' technological uses and/or geographical distribution. In the current work, we proposed a new method to align and analyze yeast mitogenomes, overcoming current difficulties that make it impossible to obtain comparable mitogenomes for a large number of isolates. To this end, 12,016 mitogenomes were considered, and we developed a novel approach consisting of the design of a reference sequence intended to be comparable between all mitogenomes. Subsequently, the population structure of 6646 mitogenomes was assessed. Results revealed the existence of particular clusters associated with the technological use of the strains, in particular regarding clinical isolates, laboratory strains, and yeasts used for wine-associated activities. As far as we know, this is the first time that a positive concordance between nuclear and mitogenomes has been reported for , in terms of strains' technological applications. The results obtained highlighted the importance of including the mtDNA genome in evolutionary analysis, in order to clarify the origin and history of yeast species.
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http://dx.doi.org/10.3390/microorganisms8071001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409325PMC
July 2020

Abdominal Actinomycosis After Bariatric Surgery.

Obes Surg 2021 Jan 17;31(1):405-408. Epub 2020 Jun 17.

Department of Surgery - Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.

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http://dx.doi.org/10.1007/s11695-020-04784-xDOI Listing
January 2021

Sulfated polysaccharide from Gracilaria caudata reduces hypernociception and inflammatory response during arthritis in rodents.

Int J Biol Macromol 2020 Oct 10;161:1061-1069. Epub 2020 Jun 10.

Departamento de Fisiologia e Farmacologia, Universidade Federal de Pernambuco, 50670-600 Recife, PE, Brazil. Electronic address:

Polysaccharide from marine alga Gracilaria caudata has potential health benefits, such as anti-inflammatory, gastroprotective and antidiarrheal effects. Here, we investigated the effect of a sulfated polysaccharide from G. caudata (SP-GC) on hypernociception and inflammatory response in arthritis models. The animals received SP-GC (3, 10 or 30 mg/kg) 1 h before tibio-tarsal injection of zymosan. Hypernociception, histopathology, edema, vascular permeability, myeloperoxidase (MPO) activity, cell influx, interleukin (IL)-1β and nitric oxide (NO) levels were evaluated in acute phase. In another protocol, animals received SP-GC (30 mg/kg) 2 h post-complete Freund's adjuvant (CFA). Hypernociception, edema and arthritis index were determined in acute, sub-chronic and chronic phases. Rota-rod test measured the motor performance. SP-GC significantly reduced, in a dose-dependent manner, the zymosan-induced hypernociception with maximal effect at 30 mg/kg. The microscopic inflammation, joint edema, MPO activity, cell influx, IL-1β and NO levels were also reduced by SP-GC. In the CFA-induced arthritis, SP-GC inhibits the hypernociception, edema and arthritic index in acute, sub-chronic and chronic phases. SP-GC did not alter the motor performance of animals. In conclusion, SP-GC exerts protective effect in models of arthritis due to the modulation of cell influx, IL-1β and NO levels, culminating in the reduction of hypernociception and edema.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.060DOI Listing
October 2020

Aqueous solutions of deep eutectic systems as reaction media for the saccharification and fermentation of hardwood xylan into xylitol.

Bioresour Technol 2020 Sep 12;311:123524. Epub 2020 May 12.

CEB - Centre of Biological Engineering, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.

The aim of this study was to evaluate the effect of aqueous solutions of deep eutectic solvent, Cholinium Chloride:Urea ([Ch]Cl:U) at 50 wt% and 20 wt%, using different molar ratios (1:1, 2:1 and 1:2) on the enzymatic hydrolysis of xylan for xylose production and its subsequent bioconversion into xylitol using a recombinant yeast strain. The lowest xylan conversion into xylose (45%) was obtained using 1:2 [Ch]Cl:U molar ratio. On the other hand, the 1:1 [Ch]Cl:U molar ratio, at 20 wt% in water, improved this conversion, achieving the highest xylose yield (81.4%). The xylitol production was then optimized with [Ch]Cl:U (1:1) at 20 wt% by simultaneous saccharification and fermentation process, attaining 23.67 g/L, corresponding to 66.04% of xylitol yield. This study reveals the possibility of using xylan solubilized in DES aqueous solutions directly for xylitol production, thus assembling a one-step process.
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http://dx.doi.org/10.1016/j.biortech.2020.123524DOI Listing
September 2020

Carboxylic Acid Transporters in Pathogenesis.

mBio 2020 05 12;11(3). Epub 2020 May 12.

Centre of Molecular and Environmental Biology (CBMA), University of Minho, Campus de Gualtar, Braga, Portugal

Opportunistic pathogens such as species can use carboxylic acids, like acetate and lactate, to survive and successfully thrive in different environmental niches. These nonfermentable substrates are frequently the major carbon sources present in certain human body sites, and their efficient uptake by regulated plasma membrane transporters plays a critical role in such nutrient-limited conditions. Here, we cover the physiology and regulation of these proteins and their potential role in virulence. This review also presents an evolutionary analysis of orthologues of the Jen1 lactate and Ady2 acetate transporters, including a phylogenetic analysis of 101 putative carboxylate transporters in twelve medically relevant species. These proteins are assigned to distinct clades according to their amino acid sequence homology and represent the major carboxylic acid uptake systems in yeast. While Jen transporters belong to the sialate:H symporter (SHS) family, the Ady2 homologue members are assigned to the acetate uptake transporter (AceTr) family. Here, we reclassify the later members as ATO (acetate transporter ortholog). The new nomenclature will facilitate the study of these transporters, as well as the analysis of their relevance for pathogenesis.
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http://dx.doi.org/10.1128/mBio.00156-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218280PMC
May 2020

Epidemiological profile, referral routes and diagnostic accuracy of cases of acute cholangitis among individuals with obstructive jaundice admitted to a tertiary-level university hospital: a cross-sectional study.

Sao Paulo Med J 2019 Nov-Dec;137(6):491-497

MD, PhD. Adjunct Professor, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas (SP), Brazil.

Background: Obstructive jaundice may lead to ominous complications and requires complex diagnostic evaluations and therapies that are not widely available.

Objective: To analyze the epidemiological profile, referral routes and diagnostic accuracy at admittance of cases of acute cholangitis among patients with obstructive jaundice treated at a referral unit.

Design And Setting: Cross-sectional study at a tertiary-level university hospital.

Methods: Patients with obstructive jaundice who were treated by means of endoscopic retrograde cholangiopancreatography, resection and/or surgical biliary drainage were evaluated. The main variables analyzed were epidemiological data, referral route, bilirubin levels and time elapsed between symptom onset and admittance and diagnosing of acute cholangitis at the referral unit. The accuracy of the clinical diagnosis of acute cholangitis was compared with a retrospective analysis on the medical records in accordance with the Tokyo criteria.

Results: Female patients predominated (58%), with an average age of 56 years. Acute cholangitis was detected in 9.9% of the individuals; application of the Tokyo criteria showed that the real prevalence was approximately 43%. The main referral route was direct contact (31.8%) and emergency care (29.7%); routing via official referral through the public healthcare system accounted for 17.6%, and internal referral from other specialties, 20%. The direct route with unofficial referral was the most important route for cases of neoplastic etiology (P < 0.01) and was the fastest route (P < 0.01).

Conclusions: There is a deficiency in the official referral routes for patients with obstructive jaundice. The accuracy of the clinical diagnosis of acute cholangitis was poor. Wider dissemination of the Tokyo criteria is essential.
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http://dx.doi.org/10.1590/1516-3180.2019.0109170919DOI Listing
May 2020

Evolutionary analysis of Mycobacterium bovis genotypes across Africa suggests co-evolution with livestock and humans.

PLoS Negl Trop Dis 2020 03 2;14(3):e0008081. Epub 2020 Mar 2.

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.

Mycobacterium bovis is the pathogenic agent responsible for bovine tuberculosis (bTB), a zoonotic disease affecting mostly cattle, but also transmittable to humans and wildlife. Genetic studies on M. bovis allow to detect possible routes of bTB transmission and the identification of genetic reservoirs that may provide an essential framework for public health action. We used a database with 1235 M. bovis genotypes collected from different regions in Africa with 45 new Mozambican samples. Our analyses, based on phylogeographic and population genetics' approaches, allowed to identify two clear trends. First, the genetic diversity of M. bovis is geographically clustered across the continent, with the only incidences of long-distance sharing of genotypes, between South Africa and Algeria, likely due to recent European introductions. Second, there is a broad gradient of diversity from Northern to Southern Africa with a diversity focus on the proximity to the Near East, where M. bovis likely emerged with animal domestication in the last 10,000 years. Diversity indices are higher in Eastern Africa, followed successively by Northern, Central, Southern and Western Africa, roughly correlating with the regional archaeological records of introduction of animal domesticates. Given this scenario M. bovis in Africa was probably established millennia ago following a concomitant spread with cattle, sheep and goat. Such scenario could translate into long-term locally adapted lineages across Africa. This work describes a novel scenario for the spread of M. bovis in Africa using the available genetic data, opening the field to further studies using higher resolution genomic data.
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http://dx.doi.org/10.1371/journal.pntd.0008081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077849PMC
March 2020

Isothiazolinone Biocides: Chemistry, Biological, and Toxicity Profiles.

Molecules 2020 Feb 23;25(4). Epub 2020 Feb 23.

CIETI/School of Engineering (ISEP), Polytechnic of Porto, 4200-072 Porto, Portugal.

The importance of isothiazole and of compounds containing the isothiazole nucleus has been growing over the last few years. Isothiazolinones are used in cosmetic and as chemical additives for occupational and industrial usage due to their bacteriostatic and fungiostatic activity. Despite their effectiveness as biocides, isothiazolinones are strong sensitizers, producing skin irritations and allergies and may pose ecotoxicological hazards. Therefore, their use is restricted by EU legislation. Considering the relevance and importance of isothiazolinone biocides, the present review describes the state-of-the-art knowledge regarding their synthesis, antibacterial components, toxicity (including structure-activity-toxicity relationships) outlines, and (photo)chemical stability. Due to the increasing prevalence and impact of isothiazolinones in consumer's health, analytical methods for the identification and determination of this type of biocides were also discussed.
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http://dx.doi.org/10.3390/molecules25040991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070760PMC
February 2020

Polysaccharide from Gracilaria caudata protects the human esophageal mucosal barrier: A differential topical effect and structural dependence.

Int J Biol Macromol 2020 May 10;150:354-361. Epub 2020 Feb 10.

Department of Clinical Medicine, Federal University of Ceará, Fortaleza, Brazil; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil. Electronic address:

This study aimed to evaluate the in vitro protective effect of topical treatment with a native sulfated polysaccharide of G. caudata (SP-Gc), hydrolyzed (H-SP-Gc), or desulfated (D-SP-Gc) polysaccharide of Gracilaria caudata in esophageal biopsies obtained from GERD patients. Biopsies were obtained from nonerosive reflux disease (NERD) patients and from erosive esophagitis patients. Then, the biopsies were mounted in an Ussing chamber to measure the basal transepithelial electrical resistance (TEER). The effect of mucosal exposure to an acid solution on TEER was analyzed with or without different concentrations (1, 0.3 or 1%) of SP-Gc, H-SP-Gc, or D-SP-Gc, precoated on the mucosa. Basal esophageal mucosal electrical resistance was significantly lower in erosive esophagitis than from NERD. Mucosal samples precoated with native SP-Gc (1%) significantly prevented TEER drop induced by an acidic solution in NERD, but this effect was not observed in erosive esophagitis. Topical application of D-SP-Gc showed no difference compared to native SP-Gc. However, when treated with chemically-modified SP-Gc, the protective effect observed with native SP-Gc was lost. The present study indicated that SP-Gc protects the human esophageal mucosal barrier in NERD patients. This effect is dependent on the structure but is independent of the presence of sulfate.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.02.074DOI Listing
May 2020

Gabapentin attenuates intestinal inflammation: Role of PPAR-gamma receptor.

Eur J Pharmacol 2020 Apr 3;873:172974. Epub 2020 Feb 3.

LAFFEX - Laboratory of Experimental Physiopharmacology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, 64202-020, PI, Brazil. Electronic address:

Gabapentin is an anticonvulsant drug that is also used for post-herpetic neuralgia and neuropathic pain. Recently, gabapentin showed anti-inflammatory effect. Nuclear factor kappa B (NFκB) is a regulator of the inflammatory process, and Peroxisome Proliferator-activated Receptor gamma (PPAR-gamma) is an important receptor involved in NFκB regulation. The aim of the present work was to study the potential role of PPAR-gamma receptor in gabapentin-mediated anti-inflammatory effects in a colitis experimental model. We induced colitis in rats using trinitrobenzenosulfonic acid and treated them with gabapentin and bisphenol A dicyldidyl ether (PPAR-gamma inhibitor). Macroscopic lesion scores, wet weight, histopathological analysis, mast cell count, myeloperoxidase, malondialdehyde acid, glutathione, nitrate/nitrite, and interleukin levels in the intestinal mucosa were determined. In addition, western blots were performed to determine the expression of Cyclooxygenase-2 (COX-2) and NFκB; Nitric Oxide Inducible Synthase (iNOS) and Interleukin 1 beta (IL-1β) levels were also determined. Gabapentin was able to decrease all inflammatory parameters macroscopic and microscopic in addition to reducing markers of oxidative stress and cytokines such as IL-1β and Tumor Necrosis Factor alpha (TNF-α) as well as enzymes inducible nitric oxide synthase and cyclooxygenase 2 and inflammatory genic regulator (NFκB). These effect attributed to gabapentin was observed to be lost in the presence of the specific inhibitor of PPAR-gamma. Gabapentin inhibits bowel inflammation by regulating mast cell signaling. Furthermore, it activates the PPAR-gamma receptor, which in turn inhibits the activation of NFκB, and consequently results in reduced activation of inflammatory genes involved in inflammatory bowel diseases.
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http://dx.doi.org/10.1016/j.ejphar.2020.172974DOI Listing
April 2020

Aggressive Central Nervous System Relapse after Autologous Stem Cell Transplant in Multiple Myeloma: Case Reports and Literature Review.

Case Rep Hematol 2020 3;2020:8563098. Epub 2020 Jan 3.

Hematology Department, Centro Hospitalar São João, Porto, Portugal.

Extramedullary disease is an aggressive presentation at diagnosis and relapse for multiple myeloma (MM) patients. Central nervous system (CNS) is a very rare manifestation of the extramedullary disease, accounting for less than 1% of MM on diagnosis and relapse. Neurological symptoms are unspecific and usually attributed to other causes. We present two patients with CNS-MM at relapse after autologous stem cell transplant highlighting the importance of clinical suspicion and interdisciplinarity at diagnostic workup as well as the need for intensive therapeutic options on such rare and aggressive cases. The presence of neurological abnormalities in anamnesis and physical examination on a patient with MM should always prompt to suspect of a CNS involvement, and active investigation must be undertaken. MRI is the standard radiological method to detect CNS-MM, with histopathological corroboration by stereotactic biopsy and CSF evaluation alongside. Treatment of CNS-MM should include two essential approaches-be able to cross the BBB and treat the systemic disease. There is no standard therapy for this extramedullary relapse, and a tailored and multiple therapy should be promptly started-intrathecal therapy, radiotherapy, and systemic therapy, including an immunomodulator.
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http://dx.doi.org/10.1155/2020/8563098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964715PMC
January 2020