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1.
Int J Mol Sci ; 25(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38892087

RESUMO

Utilizing bioinformatics tools, this study expands our understanding of secondary metabolism in Botrytis cinerea, identifying novel genes within polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), sesquiterpene cyclase (STC), diterpene cyclase (DTC), and dimethylallyltryptophan synthase (DMATS) families. These findings enrich the genetic framework associated with B. cinerea's pathogenicity and ecological adaptation, offering insights into uncharted metabolic pathways. Significantly, the discovery of previously unannotated genes provides new molecular targets for developing targeted antifungal strategies, promising to enhance crop protection and advance our understanding of fungal biochemistry. This research not only broadens the scope of known secondary metabolites but also opens avenues for future exploration into B. cinerea's biosynthetic capabilities, potentially leading to novel antifungal compounds. Our work underscores the importance of integrating bioinformatics and genomics for fungal research, paving the way for sustainable agricultural practices by pinpointing precise molecular interventions against B. cinerea. This study sets a foundation for further investigations into the fungus's secondary metabolism, with implications for biotechnology and crop disease management.


Assuntos
Botrytis , Peptídeo Sintases , Policetídeo Sintases , Metabolismo Secundário , Botrytis/genética , Botrytis/patogenicidade , Metabolismo Secundário/genética , Peptídeo Sintases/genética , Peptídeo Sintases/metabolismo , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Biologia Computacional/métodos , Família Multigênica , Genes Fúngicos
2.
Int J Mol Sci ; 25(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38791163

RESUMO

The genome sequencing of Botrytis cinerea supplies a general overview of the map of genes involved in secondary metabolite synthesis. B. cinerea genomic data reveals that this phytopathogenic fungus has seven sesquiterpene cyclase (Bcstc) genes that encode proteins involved in the farnesyl diphosphate cyclization. Three sesquiterpene cyclases (BcStc1, BcStc5 and BcStc7) are characterized, related to the biosynthesis of botrydial, abscisic acid and (+)-4-epi-eremophilenol, respectively. However, the role of the other four sesquiterpene cyclases (BcStc2, BcStc3, BcStc4 and BcStc6) remains unknown. BcStc3 is a well-conserved protein with homologues in many fungal species, and here, we undertake its functional characterization in the lifecycle of the fungus. A null mutant ΔBcstc3 and an overexpressed-Bcstc3 transformant (OvBcstc3) are generated, and both strains show the deregulation of those other sesquiterpene cyclase-encoding genes (Bcstc1, Bcstc5 and Bcstc7). These results suggest a co-regulation of the expression of the sesquiterpene cyclase gene family in B. cinerea. The phenotypic characterization of both transformants reveals that BcStc3 is involved in oxidative stress tolerance, the production of reactive oxygen species and virulence. The metabolomic analysis allows the isolation of characteristic polyketides and eremophilenols from the secondary metabolism of B. cinerea, although no sesquiterpenes different from those already described are identified.


Assuntos
Botrytis , Sesquiterpenos , Botrytis/genética , Botrytis/metabolismo , Sesquiterpenos/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Estresse Oxidativo , Carbono-Carbono Liases
3.
JBJS Case Connect ; 14(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306443

RESUMO

CASE: We present the case of a 46-year-old patient with asymmetric deformity in the posterior tibial slope after previous high tibial osteotomy surgeries with the presence of a medial osteotomy plate. A customized cutting guide was designed to fit on the plate to perform a single surgery and avoid possible soft-tissue complications after multiple surgeries. CONCLUSIONS: The presence of a previous internal fixation device may affect the manufacture of 3-dimensional cutting guides. However, in this case, the previously placed osteosynthesis plate was used as an aid for creating the guide.


Assuntos
Fixação Interna de Fraturas , Tíbia , Humanos , Pessoa de Meia-Idade , Tíbia/cirurgia , Fixação Interna de Fraturas/métodos , Placas Ósseas , Osteotomia/métodos
4.
Int J Mol Sci ; 25(2)2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38256097

RESUMO

Plant pathogenic infections causing substantial global food losses are a persistent challenge. This study investigates a potential biocontrol strategy against the necrotrophic fungus Botrytis cinerea using the endophytic fungus Sordaria tomento-alba isolated from Gliricidia sepium in Colombia. Today, synthetic fungicides dominate B. cinerea control, raising environmental and health concerns. S. tomento-alba exhibits notable in vitro effects, inhibiting B. cinerea growth by approximately 60% during co-culture and 50% in double disc co-culture. Additionally, it suppresses botryanes production and produces the compound heptacyclosordariolone, which has proven effective in inhibiting B. cinerea mycelial growth and spore germination in vitro. This biocontrol agent could be a potential eco-friendly alternative to replace synthetic fungicides. Our study provides insights into the chemical and biological mechanisms underpinning the antagonistic activity of S. tomento-alba, emphasizing the need for further research to understand its biosynthesis pathways and optimize its biocontrol potential. It also contributes molecular evidence of fungal interactions with implications for advanced forums in molecular studies in biology and chemistry, particularly in addressing plant pathogenic infections and promoting sustainable agriculture.


Assuntos
Fungicidas Industriais , Sordariales , Endófitos , Fungicidas Industriais/farmacologia , Agricultura , Botrytis
5.
Plants (Basel) ; 12(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38068667

RESUMO

Agriculture currently confronts a multitude of challenges arising from the excessive utilization of chemical pesticides and the proliferation of phytopathogenic fungi strains that exhibit resistance to commonly employed active compounds in the field. Botrytis cinerea and Colletotrichum acutatum are phytopathogenic fungi that inflict substantial economic losses within agriculture and food due to their high impacts on crops both pre- and post-harvest. Furthermore, the emergence of fungal strains that are resistant to commercial fungicides has exacerbated this problem. To explore more environmentally sustainable alternatives for the control of these pathogens, an investigation into the endophytic bacteria associated with ginger (Zingiber officinale Rosc.) was conducted. The primary focus of this study involved evaluating their inhibitory efficacy against the fungi and assessing their potential for promoting plant growth. The endophytic bacteria genera Lelliottia, Lysinibacillus, Kocuria, Agrococcus, Acinetobacter, Agrobacterium, Zymobacter, and Mycolicibacterium were identified. All isolates showed remarkable in vitro antagonistic ability against B. cinerea (>94%) and C. acutatum (>74%). Notably, the Lelliottia amnigena J29 strain exhibited a notable proficiency in producing extracellular enzymes and indole compounds (IAA), solubilizing phosphate and potassium, and forming biofilm. Furthermore, the Lysinibacillus capsici J26, Agrococcus citreus J28, and Mycolicibacterium sp. J5 strains displayed the capacity for atmospheric nitrogen fixation and siderophore production. These findings underscore the agricultural and biotechnological potential of endophytic bacteria derived from ginger plants and suggest the feasibility of developing alternative approaches to manage these two phytopathogenic fungi.

6.
Transplant Proc ; 55(10): 2301-2303, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38030424

RESUMO

The term monoclonal gammopathy of renal significance has been used to classify the presence of a monoclonal gammopathy or lymphoproliferative disorders that do not meet hematological criteria for myeloma but instead cause kidney damage. Mostly, post-transplant monoclonal gammopathy of renal significance occurs due to recurrent disease. In contrast, the incidence of de novo post-transplant monoclonal gammopathy of renal significance has not been established, as it is considered a rare disease, presenting a unique challenge in terms of diagnosis, management, and potential impact on graft survival. Here, we report a case of de novo monoclonal gammopathy of renal significance diagnosed after kidney transplantation and its complexity due to a concomitant chronic active antibody-mediated rejection.


Assuntos
Nefropatias , Transplante de Rim , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Humanos , Paraproteinemias/complicações , Paraproteinemias/diagnóstico , Rim , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Transplante de Rim/efeitos adversos , Nefropatias/etiologia
7.
Int J Mol Sci ; 24(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37685926

RESUMO

Familial partial lipodystrophies (FPLD) are rare diseases characterized by selective loss of subcutaneous adipose tissue at different sites. This cross-sectional observational study aimed to estimate adipose tissue in the bone marrow (BMAT), intra (IMCL) and extra-myocyte lipids (EMCL), and define the bone phenotype in the context of FPLD2/Dunnigan syndrome (DS). The subjects comprised 23 controls (C) and 18 DS patients, matched by age, weight and height. Blood samples, dual-energy X-ray absorptiometry for bone mineral density (BMD) and trabecular bone score (TBS) and 1H-spectroscopy using magnetic resonance to estimate BMAT in the lumbar spine, IMCL, EMCL and osteoclastogenesis were assessed. The prevalence of diabetes mellitus was 78% in DS patients. Glucose, HbA1c, triglycerides, insulin and HOMA-IR levels were elevated in DS, whereas HDLc, 25(OH)D, PTH and osteocalcin levels were reduced. BMD was similar between groups at all sites, except 1/3 radius, which was lower in DS group. TBS was reduced in DS. DS presented increased osteoclastogenesis and elevated BMAT, with greater saturation levels and higher IMCL than the C group. HOMA-IR and EMCL were negatively associated with TBS; osteocalcin and EMCL were correlated negatively with BMD. This study contributes to refining the estimation of adipose tissue in DS by showing increased adiposity in the lumbar spine and muscle tissue. DXA detected lower TBS and BMD in the 1/3 radius, suggesting impairment in bone quality and that bone mass is mainly affected in the cortical bone.


Assuntos
Adiposidade , Lipodistrofia Parcial Familiar , Humanos , Densidade Óssea , Estudos Transversais , Obesidade , Osteocalcina
8.
Int J Mol Sci ; 24(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37446093

RESUMO

The endocannabinoid system (ECS) constitutes a broad-spectrum modulator of homeostasis in mammals, providing therapeutic opportunities for several pathologies. Its two main receptors, cannabinoid type 1 (CB1) and type 2 (CB2) receptors, mediate anti-inflammatory responses; however, their differing patterns of expression make the development of CB2-selective ligands therapeutically more attractive. The benzo[d]imidazole ring is considered to be a privileged scaffold in drug discovery and has demonstrated its versatility in the development of molecules with varied pharmacologic properties. On the other hand, the main psychoactive component of Cannabis sativa, delta-9-tetrahydrocannabinol (THC), can be structurally described as an aliphatic terpenoid motif fused to an aromatic polyphenolic (resorcinol) structure. Inspired by the structure of this phytocannabinoid, we combined different natural product motifs with a benzo[d]imidazole scaffold to obtain a new library of compounds targeting the CB2 receptor. Here, we synthesized 26 new compounds, out of which 15 presented CB2 binding and 3 showed potent agonist activity. SAR analysis indicated that the presence of bulky aliphatic or aromatic natural product motifs at position 2 of the benzo[d]imidazoles ring linked by an electronegative atom is essential for receptor recognition, while substituents with moderate bulkiness at position 1 of the heterocyclic core also participate in receptor recognition. Compounds 5, 6, and 16 were further characterized through in vitro cAMP functional assay, showing potent EC50 values between 20 and 3 nM, and compound 6 presented a significant difference between the EC50 of pharmacologic activity (3.36 nM) and IC50 of toxicity (30-38 µM).


Assuntos
Produtos Biológicos , Canabinoides , Animais , Agonistas de Receptores de Canabinoides/farmacologia , Produtos Biológicos/farmacologia , Canabinoides/farmacologia , Canabinoides/química , Imidazóis , Receptor CB2 de Canabinoide , Receptor CB1 de Canabinoide , Relação Estrutura-Atividade , Mamíferos
9.
PLoS One ; 18(4): e0281837, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37186111

RESUMO

A method is proposed to study the temporal variability of legislative roll-call votes in a parliament from the perspective of complex dynamical systems. We studied the Chilean Chamber of Deputies' by analyzing the agreement ratio and the voting outcome of each vote over the last 19 years with a Recurrence Quantification Analysis and an entropy analysis (Sample Entropy). Two significant changes in the temporal variability were found: one in 2014, where the voting outcome became more recurrent and with less entropy, and another in 2018, where the agreement ratio became less recurrent and with higher entropy. These changes may be directly related to major changes in the Chilean electoral system and the composition of the Chamber of Deputies, given that these changes occurred just after the first parliamentary elections with non-compulsory voting (2013 elections) and the first elections with a proportional system in conjunction with an increase in the number of deputies (2017 elections) were held.


Assuntos
Política , Chile
10.
Rev. Soc. Andal. Traumatol. Ortop. (Ed. impr.) ; 40(1): 33-42, ene.-mar. 2023. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-EMG-498

RESUMO

Objetivo Comparar los resultados radiológicos en el plano coronal y axial y los resultados funcionales en los pacientes intervenidos de Hallux Valgus mediante la artrodesis de Lapidus modificada y la osteotomía de Austin-Chevron. Material y método Estudio de cohortes retrospectivo entre enero de 2018 y enero de 2020 en el que se incluyeron pacientes intervenidos de Hallux Valgus mediante artrodesis de Lapidus modificada y la osteotomía de Austin-Chevron con al menos 1 año de seguimiento. Se analizaron variables radiológicas: Ángulo Intermetatarsiano, Ángulo de Hallux Valgus, Posición de sesamoideo medial pre y postquirúrgico. Los resultados funcionales fueron evaluados según la escala AOFAS. Resultados 78 pacientes fueron incluidos. No se encontraron diferencias estadísticamente significativas en el valor del ángulo intermetatarsiano y la técnica quirúrgica utilizada (p=0,367). Se encontraron diferencias estadísticamente significativas en el valor de ángulo de Hallux Valgus y la posición del sesamoideo medial según la técnica quirúrgica utilizada ( p=0,010 y p=0,000). Se encontraron diferencias estadísticamente significativas en cuanto al valor de la escala AOFAS y la técnica quirúrgica utilizada (p=0,032) y el valor de la escala AOFAS y la posición del sesamoideo medial (p=0,035; R=-0,245). Conclusión La técnica de Lapidus modificada corrige la deformidad presente en el plano axial y coronal en la patología del Hallux Valgus, encontrando mejores resultados funcionales y radiológicos que en la técnica de Austin-Chevron convencional. (AU)


Objetive To compare radiographic outcomes in the cor-onal and axial planes and functional results in pa-tients who underwent hallux valgus surgery using modified Lapidus arthrodesis and Austin-Chevron osteotomy. Methods Retrospective cohort study conducted from 2018 to January 2020 with patients who underwent hallux valgus surgery using modified Lapidus arthrodesis and Austin-Chevron osteotomy with a minimum 1-year follow-up. The analysed radiographic variables were pre- and postoper-ative intermetatarsal angle, hallux valgus angle, and tibial sesamoid position. Functional outcomes were assessed using the AOFAS score. Results 78 patients were included. No statistically sig-nificant differences were found in the measurement of the intermetatarsal angle by surgical procedure (p=0.367). Statistically significant differences were found in the measurement of the hallux val-gus angle and tibial sesamoid position according to the surgical procedure (p=0.010 and p=0.000). Statistically significant differences were found for the AOFAS score by surgical procedure (p=0.032) and for the AOFAS score by tibial sesamoid position (p=0.035); R=-0.245). Conclusion The modified Lapidus procedure corrects the coronal and axial plane deformity in hallux valgus, resulting in better functional and radiographic outcomes than the conventional Austin-Chevron procedure. (AU)


Assuntos
Humanos , Hallux Valgus/cirurgia , Artrodese , Osteotomia , Estudos Retrospectivos , Estudos de Coortes
11.
Rev. Soc. Andal. Traumatol. Ortop. (Ed. impr.) ; 40(1): 33-42, ene.-mar. 2023. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-229880

RESUMO

Objetivo Comparar los resultados radiológicos en el plano coronal y axial y los resultados funcionales en los pacientes intervenidos de Hallux Valgus mediante la artrodesis de Lapidus modificada y la osteotomía de Austin-Chevron. Material y método Estudio de cohortes retrospectivo entre enero de 2018 y enero de 2020 en el que se incluyeron pacientes intervenidos de Hallux Valgus mediante artrodesis de Lapidus modificada y la osteotomía de Austin-Chevron con al menos 1 año de seguimiento. Se analizaron variables radiológicas: Ángulo Intermetatarsiano, Ángulo de Hallux Valgus, Posición de sesamoideo medial pre y postquirúrgico. Los resultados funcionales fueron evaluados según la escala AOFAS. Resultados 78 pacientes fueron incluidos. No se encontraron diferencias estadísticamente significativas en el valor del ángulo intermetatarsiano y la técnica quirúrgica utilizada (p=0,367). Se encontraron diferencias estadísticamente significativas en el valor de ángulo de Hallux Valgus y la posición del sesamoideo medial según la técnica quirúrgica utilizada ( p=0,010 y p=0,000). Se encontraron diferencias estadísticamente significativas en cuanto al valor de la escala AOFAS y la técnica quirúrgica utilizada (p=0,032) y el valor de la escala AOFAS y la posición del sesamoideo medial (p=0,035; R=-0,245). Conclusión La técnica de Lapidus modificada corrige la deformidad presente en el plano axial y coronal en la patología del Hallux Valgus, encontrando mejores resultados funcionales y radiológicos que en la técnica de Austin-Chevron convencional. (AU)


Objetive To compare radiographic outcomes in the cor-onal and axial planes and functional results in pa-tients who underwent hallux valgus surgery using modified Lapidus arthrodesis and Austin-Chevron osteotomy. Methods Retrospective cohort study conducted from 2018 to January 2020 with patients who underwent hallux valgus surgery using modified Lapidus arthrodesis and Austin-Chevron osteotomy with a minimum 1-year follow-up. The analysed radiographic variables were pre- and postoper-ative intermetatarsal angle, hallux valgus angle, and tibial sesamoid position. Functional outcomes were assessed using the AOFAS score. Results 78 patients were included. No statistically sig-nificant differences were found in the measurement of the intermetatarsal angle by surgical procedure (p=0.367). Statistically significant differences were found in the measurement of the hallux val-gus angle and tibial sesamoid position according to the surgical procedure (p=0.010 and p=0.000). Statistically significant differences were found for the AOFAS score by surgical procedure (p=0.032) and for the AOFAS score by tibial sesamoid position (p=0.035); R=-0.245). Conclusion The modified Lapidus procedure corrects the coronal and axial plane deformity in hallux valgus, resulting in better functional and radiographic outcomes than the conventional Austin-Chevron procedure. (AU)


Assuntos
Humanos , Hallux Valgus/cirurgia , Artrodese , Osteotomia , Estudos Retrospectivos , Estudos de Coortes
12.
Nat Commun ; 14(1): 1099, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36841809

RESUMO

Crustal recycling in the Earth's mantle is fingerprinted by trace-element and isotopic proxies in oceanic basalts. Positive Eu and Sr anomalies in primitive lavas and melt inclusions that are not otherwise enriched in Al2O3 are often interpreted as reflecting the presence of recycled, plagioclase-rich oceanic crust in their mantle source - referred to as "ghost plagioclase" signatures. Here, we report natural evidence of Eu anomalies and extreme crystal-scale heterogeneity developed kinetically in mantle peridotite clinopyroxene. Numerical modelling shows that diffusional fractionation between clinopyroxene and melts can account for this intra-crystal heterogeneity and generate Eu anomalies without requiring plagioclase. We demonstrate that kinetically induced Eu anomalies are likely to develop at temperatures, redox conditions and transport timescales compatible with the genesis of mid-ocean ridge and ocean island basalts. Our results show that, in the absence of converging lines of evidence such as radiogenic isotope data, ghost plagioclase signatures are not an unequivocal proxy for the presence of recycled crust in oceanic basalt sources.

13.
Affect Sci ; 3(1): 46-61, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36046095

RESUMO

Machine learning findings suggest Eurocentric (aka White/European) faces structurally resemble anger more than Afrocentric (aka Black/African) faces (e.g., Albohn, 2020; Zebrowitz et al., 2010); however, Afrocentric faces are typically associated with anger more so than Eurocentric faces (e.g., Hugenberg & Bodenhausen, 2003, 2004). Here, we further examine counter-stereotypic associations between Eurocentric faces and anger, and Afrocentric faces and fear. In Study 1, using a computer vision algorithm, we demonstrate that neutral European American faces structurally resemble anger more and fear less than do African American faces. In Study 2, we then found that anger- and fear-resembling facial appearance influences perceived racial prototypicality in this same counter-stereotypic manner. In Study 3, we likewise found that imagined European American versus African American faces were rated counter-stereotypically (i.e., more like anger than fear) on key emotion-related facial characteristics (i.e., size of eyes, size of mouth, overall angularity of features). Finally in Study 4, we again found counter-stereotypic differences, this time in processing fluency, such that angry Eurocentric versus Afrocentric faces and fearful Afrocentric versus Eurocentric faces were categorized more accurately and quickly. Only in Study 5, using race-ambiguous interior facial cues coupled with Afrocentric versus Eurocentric hairstyles and skin tone, did we find the stereotypical effects commonly reported in the literature. These findings are consistent with the conclusion that the "angry Black" association in face perception is socially constructed in that structural cues considered prototypical of African American appearance conflict with common race-emotion stereotypes.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35206354

RESUMO

This study examined racial/ethnic differences in health/life insurance denial due to cancer among cancer survivors after the passage of the Affordable Care Act (ACA). Behavioral Risk Factor Surveillance System data were obtained from 2012-2020. The dependent variable asked: "Were you ever denied health insurance or life insurance coverage because of your cancer?" Cancer survivors were included if they were diagnosed with cancer after the Affordable Care Act (N = 14,815). Unadjusted and adjusted logistic regressions for age, sex, income, and employment provided odds ratios of insurance denial due to cancer across racial/ethnic groups: Non-Hispanic White, Black, and Other/mixed race; and Hispanic. Statistically significant differences (p < 0.05) were found between those who were denied or not denied insurance across sex, age, race/ethnicity, income, and employment. Adjusted regressions found significantly higher odds ratios of insurance denial for Blacks (OR: 3.00, 95% CI: 1.77, 5.08), Other/mixed race (OR: 2.16, 95% CI: 1.16, 4.02), and Hispanics (OR: 2.13, 95% CI: 1.02, 4.42) compared to Whites. Differences were observed across sex, income, and employment. Cancer survivors report racial/ethnic disparities in health and life insurance denial due to their cancer despite policy changes. This may be harmful for those who are already financially vulnerable due to their cancer diagnosis and exacerbate racial/ethnic cancer disparities.


Assuntos
Sobreviventes de Câncer , Neoplasias , Etnicidade , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Humanos , Cobertura do Seguro , Seguro Saúde , Seguro de Vida , Neoplasias/epidemiologia , Patient Protection and Affordable Care Act , Estados Unidos/epidemiologia
15.
Vet Pathol ; 59(2): 371-384, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34841988

RESUMO

The kidneys play an important role in blood pressure regulation under normal and pathological conditions. We examined the histological changes and expression patterns of cyclooxygenase-2, renin, and (pro)renin receptor (PRR) in the renal cortex of prehypertensive spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs). Moreover, blood pressure and plasma urea, creatinine, angiotensin II, and angiotensin (1-7) levels were measured. The results showed that both strains had similar blood pressure and plasma urea and creatinine levels. The glomerular area, basement membrane thickness, collagen fiber content, and arterial wall thickness were greater in SHRs than in WKYs. By immunohistochemistry, cyclooxygenase-2 was localized in the macula densa and renal tubules of both strains. In SHRs, cyclooxygenase-2 was detected in a larger number of tubules, and the cortical expression of cyclooxygenase-2 was also increased. In both strains, PRR and renin were localized in the tubular epithelium and juxtaglomerular cells, respectively. In SHRs, PRR immunolocalization was increased in the glomerulus. The cortical expression of immature renin was markedly increased in SHRs compared to that in WKYs, while renin was significantly decreased. These changes were associated with higher plasma angiotensin II levels and lower plasma angiotensin (1-7) levels in SHRs. The results indicate that the kidneys of SHRs showed morphological changes and variations in cortical expression patterns of PRR, cyclooxygenase-2, and renin before the development of hypertension.


Assuntos
Hipertensão , Angiotensina II/metabolismo , Animais , Pressão Sanguínea , Creatinina , Ciclo-Oxigenase 2/metabolismo , Hipertensão/veterinária , Rim/patologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Renina/metabolismo , Ureia
16.
Int J Mol Sci ; 22(20)2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34681877

RESUMO

The activation of the human cannabinoid receptor type II (CB2R) is known to mediate analgesic and anti-inflammatory processes without the central adverse effects related to cannabinoid receptor type I (CB1R). In this work we describe the synthesis and evaluation of a novel series of N-aryl-2-pyridone-3-carboxamide derivatives tested as human cannabinoid receptor type II (CB2R) agonists. Different cycloalkanes linked to the N-aryl pyridone by an amide group displayed CB2R agonist activity as determined by intracellular [cAMP] levels. The most promising compound 8d exhibited a non-toxic profile and similar potency (EC50 = 112 nM) to endogenous agonists Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) providing new information for the development of small molecules activating CB2R. Molecular docking studies showed a binding pose consistent with two structurally different agonists WIN-55212-2 and AM12033 and suggested structural requirements on the pyridone substituents that can satisfy the orthosteric pocket and induce an agonist response. Our results provide additional evidence to support the 2-pyridone ring as a suitable scaffold for the design of CB2R agonists and represent a starting point for further optimization and development of novel compounds for the treatment of pain and inflammation.


Assuntos
Agonistas de Receptores de Canabinoides/química , Agonistas de Receptores de Canabinoides/farmacologia , Piridonas/química , Receptor CB2 de Canabinoide/agonistas , Animais , Ácidos Araquidônicos/química , Ácidos Araquidônicos/farmacologia , Benzoxazinas/química , Benzoxazinas/farmacologia , Sítios de Ligação , Células CHO , Agonistas de Receptores de Canabinoides/síntese química , Sobrevivência Celular/efeitos dos fármacos , Cricetulus , AMP Cíclico/metabolismo , Avaliação Pré-Clínica de Medicamentos , Endocanabinoides/química , Endocanabinoides/farmacologia , Glicerídeos/química , Glicerídeos/farmacologia , Células HL-60 , Células Hep G2 , Humanos , Simulação de Acoplamento Molecular , Morfolinas/química , Morfolinas/farmacologia , Naftalenos/química , Naftalenos/farmacologia , Alcamidas Poli-Insaturadas/química , Alcamidas Poli-Insaturadas/farmacologia , Piridonas/farmacologia , Receptor CB2 de Canabinoide/química , Receptor CB2 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo , Relação Estrutura-Atividade
17.
J Fungi (Basel) ; 7(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34575759

RESUMO

During the infection of grapevine (Vitis vinifera) by the fungus Botrytis cinerea, the concentration of polyamines, which are toxic substances for the phytopathogen, increases in the grape. Nine NRPS genes have been identified in the genome of B. cinerea, yet the function of five of them remains unknown. For this reason, we have studied the expression of the 9 NRPS genes by RT-qPCR in a medium supplemented with sublethal concentrations of three polyamines (1,3-diaminopropane (1,3-DAP), spermidine (SPD), and spermine (SPM)). Our results show that the presence of polyamines in the culture medium triggered the overexpression of the Bcnrps1 gene in the pathogen. Deleting Bcnrps1 did not affect mycelial growth or adaptation to osmotic stress, and we show that its expression is not essential for the cycle of infection of the B. cinerea. However, mutating the Bcnrps1 gene resulted in overexpression of the Bcnrps6 gene, which encodes for the excretion of siderophores of the coprogen family. Moreover, gene deletion has reduced the tolerance of B. cinerea B05.10 to toxic substances such as the polyamine SPD and the fungicide pyrimethanil, and its virulence has increased. Our findings provide new insights into the function of the Bcnrps1 gene and its involvement in the tolerance of B. cinerea against exogenous toxic compounds.

18.
Rev. Soc. Andal. Traumatol. Ortop. (Ed. impr.) ; 38(3): 63-69, Juli-Sep. 2021. ilus
Artigo em Espanhol | IBECS | ID: ibc-230752

RESUMO

Proponer la centralización del cúbito distal en El desgaste de los materiales tras la artroplastia total de cadera (ATC) es uno de los grandes problemas en el paciente joven. Con el avance en los diseños de las nuevas cerámicas, parece haber disminuido la tasa de desgaste. Sin embargo, existen complicaciones exclusivas del par cerámica-cerámica, como la fractura de los componentes, sien-do la fractura del liner cerámico por traumatismo directo una complicación poco frecuente. Exponemos el caso clínico de un paciente de 41 años de edad que tras ser intervenido de ATC con par de fricción cerámica-cerámica, sufrió un traumatismo de alta energía tras atropello, asociado a fractura del liner cerámico. Se realizó una revisión de la ATC y se recambió el par de fricción a cerámica-politelieno, obteniendo buenos resultados en el postoperatorio, con una puntuación en la escala visual analógica (EVA) de 1, una puntuación en la escala Harris Hip Score de 92,8, una puntuación en la escala Oxford de 44 y una dismetría de 0,5 cm. Además se hizo una comparativa de los resultados obtenidos en nuestro caso clínico con los expuestos en la literatura.(AU)


Wear after total hip arthroplasty (THA) is one of the great problems in young patients. With the advancement in new ceramic designs, the wear rate appears to have decreased. However, there are complications exclusive to the ceramic-ceramic pair, such as component fracture, with the ceramic liner fracture due to direct trauma being a rare complication. We present the clinical case of a 41-year-old patient who, after undergoing THA with a ceramic-ceramic friction pair, suffered a high-energy trauma after being run over, associated with a fracture of the ceramic liner. A revision of the THA was carried out and the friction pair was changed to ceramicolythene, obtaining good results in the postoperative period, with a score on the visual analog scale (VAS) of 1, a score on the Harris Hip Score of 92,8, an Oxford scale score of 44, and a leg length discrepancy of 0.5 cm. In addition, a comparison was made of the results obtained in our clinical case with those reported in the literature.(AU)


Assuntos
Humanos , Masculino , Feminino , Lesões do Quadril/cirurgia , Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Prótese de Quadril , Artroplastia de Quadril
19.
Artigo em Inglês | MEDLINE | ID: mdl-34207880

RESUMO

The sorption behavior of 2,4-dichlorophenoxyacetic acid (2,4-D) in the abundant agricultural volcanic ash-derived soils (VADS) is not well understood despite being widely used throughout the world, causing effects to the environment and human health. The environmental behavior and risk assessment of groundwater pollution by pesticides can be evaluated through kinetic models. This study evaluated the sorption kinetics and 2,4-D sorption-desorption in ten VADS through batch sorption experiments. Differences in the sorption extent for the fast and slow phases was observed through the IPD model where 2,4-D sorption kinetics was controlled by external mass transfer and intra organic matter diffusion in Andisols (C1 ≠ 0). We confirmed from the spectroscopic analysis that the carboxylate group directly drives the interaction of 2,4-D on Andisol soil. The MLR model showed that IEP, FeDCB, and pH×Silt are important soil descriptors in the 2,4-D sorption in VADS. The Freundlich model accurately represented sorption equilibrium data in all cases (Kf values between 1.1 and 24.1 µg1-1/n mL1/ng-1) with comparatively higher sorption capacity on Andisols, where the highest hysteresis was observed in soils that presented the highest and lowest OC content (H close to 0).


Assuntos
Herbicidas , Poluentes do Solo , Ácido 2,4-Diclorofenoxiacético , Adsorção , Herbicidas/análise , Humanos , Cinética , Solo , Poluentes do Solo/análise
20.
Biology (Basel) ; 10(6)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205845

RESUMO

Plant diseases are one of the main factors responsible for food loss in the world, and 20-40% of such loss is caused by pathogenic infections. Botrytis cinerea is the most widely studied necrotrophic phytopathogenic fungus. It is responsible for incalculable economic losses due to the large number of host plants affected. Today, B. cinerea is controlled mainly by synthetic fungicides whose frequent application increases risk of resistance, thus making them unsustainable in terms of the environment and human health. In the search for new alternatives for the biocontrol of this pathogen, the use of endophytic microorganisms and their metabolites has gained momentum in recent years. In this work, we isolated endophytic bacteria from Zea mays cultivated in Colombia. Several strains of Bacillus subtilis, isolated and characterized in this work, exhibited growth inhibition against B. cinerea of more than 40% in in vitro cultures. These strains were characterized by studying several of their biochemical properties, such as production of lipopeptides, potassium solubilization, proteolytic and amylolytic capacity, production of siderophores, biofilm assays, and so on. We also analyzed: (i) its capacity to promote maize growth (Zea mays) in vivo, and (ii) its capacity to biocontrol B. cinerea during in vivo infection in plants (Phaseolus vulgaris).

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