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Background: Gross motor function impairments and manual dexterity deficits are frequently observed in children and adolescents with Cerebral Palsy (CP), having a major impact on their activity level and autonomy. Improving manual dexterity and activity level of patients with CP is often the focus of rehabilitation. Novel and adjuvant treatment methods that could support the standard training also in chronic conditions are a research priority. The transcutaneous Vagus Nerve Stimulation (tVNS) is a non-invasive brain stimulation technique, which provides a bottom-up stimulation of subcortical and cortical brain structures, enhancing brain GABA and Noradrenaline levels. This technique may play a pivotal role in brain plasticity, which has not been tested in CP patients before. Methods: 44 children and adolescents with CP will be involved, treated in pairs in a randomized, double-blind, pre-post test study. The two groups will undergo the Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) for 2 consecutive weeks, with 3 h daily sessions for 5 days per week, for an overall time interval of 30 h; the training will be combined with the application for 75 min/day of active or sham tVNS, in separate, randomly allocated groups. The primary outcome measure will include the scores at the Assisting Hand Assessment and Box and Block Test, and at an ad-hoc visuomotor task evaluating manual visuomotor control. Secondary outcomes will include the scores at the Children's Hand Experience Questionnaire, Canadian Occupational Performance Measure, Melbourne Assessment of Unilateral Upper Limb Function, Gross Motor Function Measure, Vineland, Pediatric quality of life inventory. The evaluation points will include pre (T0), post (T1) and 3-month follow up (T2) assessments. Safety and tolerability will also be assessed. Results: The results of this trial will assess whether tVNS can effectively boost the effects of an intensive two-week bimanual training, in improving manual dexterity in children and adolescents with cerebral palsy, ensuring safety and tolerability throughout the intervention period.Clinical trial registration: ClinicalTrials.gov, NCT06372028.
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BACKGROUND: Vascular endothelial injury, a key factor in diabetic foot ulcers (DFUs) pathogenesis, is linked to the impaired proliferation and migration of vascular endothelial cells, modulated by hypoxia-inducible factor, growth factors, and inflammatory elements. OBJECTIVE: The present study assesses the role of SIKVAV (Ser-Ile-Lys-Val-Ala-Val), a peptide shown to enhance cell proliferation and migration, on mouse aortic endothelial cell (MAEC) and the corresponding molecular mechanisms. METHODS: MAEC were treated with SIKVAV at 0, 100, 200, 400, and 600 µg/mL for 0, 24, 48, and 72 h. Cell viability was tested using the CCK-8 assay. Proliferating cell nuclear antigen (PCNA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein kinase B (Akt) levels were measured by qRT-PCR and western blot. RESULTS: SIKVAV augmented PCNA mRNA expression and stimulated vascular endothelial cell proliferation in a concentration and time-dependent fashion. Furthermore, it amplified the expression of p-ERK1/2 and p-Akt, pivotal components of the mitogen-activated protein kinase (MAPK)/ERK1/2 and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. The inhibition of these pathways suppressed PCNA mRNA expression, cell proliferation rate, and decreased p-ERK1/2 and p-Akt levels, highlighting SIKVAV's role in promoting vascular endothelial cell proliferation via these pathways. CONCLUSION: The results of this study confirmed that SIKVAV grafted onto scaffolds can accelerate the proliferation of vascular endothelial cells for the therapy of skin wounds, and provide a theoretical basis for its application in ischemic disease as synthesized biomaterials scaffolds of tissue engineering.
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Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators. Herein, we explore the role of Roseburia intestinalis (R)-derived EVs (R-EVs) as potent anti-inflammatory mediators in treating dextran sulfate sodium-induced colitis. R was selected as an optimal BEV producer for IBD treatment through ANCOM analysis. R-EVs with a 76 nm diameter were isolated from R using a tangential flow filtration system. Orally administered R-EVs effectively accumulated in inflamed colonic tissues and increased the abundance of Bifidobacterium on microbial changes, inhibiting colonic inflammation and prompting intestinal recovery. Due to the presence of Ile-Pro-Ile in the vesicular structure, R-EVs reduced the DPP4 activity in inflamed colonic tissue and increased the active GLP-1, thereby downregulating the NFκB and STAT3 via the PI3K pathway. Our results shed light on the impact of BEVs on intestinal recovery and gut microbiome alteration in treating IBD.
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Colitis , Vesículas Extracelulares , Microbioma Gastrointestinal , Vesículas Extracelulares/metabolismo , Animales , Colitis/metabolismo , Colitis/microbiología , Colitis/terapia , Ratones , Inflamación/metabolismo , Sulfato de Dextran , Humanos , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/terapia , Enfermedades Inflamatorias del Intestino/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Ratones Endogámicos C57BL , Masculino , Dipeptidil Peptidasa 4/metabolismo , FN-kappa B/metabolismo , Clostridiales/metabolismoRESUMEN
OBJECTIVES: To describe the knowledge, barriers and acceptability factors of parents and general practitioners about HPV vaccination amongst boys in Reunion Island, in order to adapt primary prevention locally. METHODS: This was a quantitative, descriptive, cross-sectional, observational study involving 88 parents of boys aged 11 to 19 and 81 general practitioners based in Reunion Island. Both populations volunteered to answer a questionnaire available online or on paper. RESULTS: Parents' knowledge about HPV was insufficient. In Reunion Island, social media and the precarious status of parents play a particularly negative role in the vaccine intention. The number of doctors who have started HPV vaccination on boys is low despite awareness of the recommendation, particularly older doctors who practice alone, in certain sectors of the island. CONCLUSIONS: The young and precarious population of Reunion Island is particularly at risk of pathologies related to HPV and requires adapted prevention to the territory's specificities. It seems necessary to continue to inform general practitioners, in order to promote vaccination and to fight against the misinformation of media about the HPV vaccine.
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Objectives: Evidence on the activity of patisiran therapy in specific subgroups of patients with hereditary transthyretin amyloidosis variant (ATTRv) is still scarce. This prospective real-world study was designed to provide the first in-depth clinical data on the effectiveness of patisiran in patients with ATTRv reporting the p.Ile88Leu variant, the most widespread variant in the Emilia-Romagna regional area, which has been less represented in previous clinical trials. Patients and methods: This prospective study evaluated all the patients with genetically proven ATTRv (p.Ile88Leu) and polyneuropathy treated with patisiran in the Emilia-Romagna referral centers for ATTRv (Institute of Neurological Sciences in Bologna and Division of Neurology in Rimini) from March 2021 to April 2023. All subjects underwent clinical and neurological evaluations at baseline and after 9-12 months of treatment. Results: A total of 22 patients were included in the study; the median age was 73 years (IQR: 9), the age at diagnosis was 72 years (IQR: 10), and the disease duration was 1.6 years (IQR: 2.3). We observed stability of all considered neurological and cardiological parameters at 9-12 months after the beginning of patisiran treatment. Conclusion: Our findings support the clinical data regarding the effectiveness of patisiran in stabilizing the disease course and extend this activity to the subset of patients with the p.Ile88Leu variant.
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Plant jasmonoyl-L-isoleucine (JA-Ile) is a major defense signal against insect feeding, but whether or how insect salivary effectors suppress JA-Ile synthesis and thus facilitate viral transmission in the plant phloem remains elusive. Insect carboxylesterases (CarEs) are the third major family of detoxification enzymes. Here, we identify a new leafhopper CarE, CarE10, that is specifically expressed in salivary glands and is secreted into the rice phloem as a saliva component. Leafhopper CarE10 directly binds to rice jasmonate resistant 1 (JAR1) and promotes its degradation by the proteasome system. Moreover, the direct association of CarE10 with JAR1 clearly impairs JAR1 enzyme activity for conversion of JA to JA-Ile in an in vitro JA-Ile synthesis system. A devastating rice reovirus activates and promotes the co-secretion of virions and CarE10 via virus-induced vesicles into the saliva-storing salivary cavities of the leafhopper vector and ultimately into the rice phloem to establish initial infection. Furthermore, a virus-mediated increase in CarE10 secretion or overexpression of CarE10 in transgenic rice plants causes reduced levels of JAR1 and thus suppresses JA-Ile synthesis, promoting host attractiveness to insect vectors and facilitating initial viral transmission. Our findings provide insight into how the insect salivary protein CarE10 suppresses host JA-Ile synthesis to promote initial virus transmission in the rice phloem.
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Ciclopentanos , Hemípteros , Isoleucina , Oryza , Floema , Oryza/virología , Oryza/genética , Oryza/metabolismo , Animales , Hemípteros/virología , Hemípteros/genética , Ciclopentanos/metabolismo , Floema/metabolismo , Floema/virología , Isoleucina/análogos & derivados , Isoleucina/metabolismo , Reoviridae/fisiología , Carboxilesterasa/metabolismo , Carboxilesterasa/genética , Enfermedades de las Plantas/virología , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Insectos Vectores/virología , Insectos Vectores/metabolismo , Insectos Vectores/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Oxilipinas/metabolismoRESUMEN
(3R,7S)-Jasmonoyl-L-isoleucine (JA-Ile) is a plant hormone that regulates plant defense responses and other physiological functions. The mechanism of attenuation of JA-Ile signaling in the plant body is essential because prolonged JA-Ile signaling can be detrimental to plant survival. In Arabidopsis thaliana, the cytochrome P450 monooxygenases, CYP94B1/B3/C1, inactivate JA-Ile by converting it into 12-hydroxy-jasmonoyl-L-isoleucine (12-OH-JA-Ile), and CYP94C1 converts 12-OH-JA-Ile into 12-carboxy-jasmonoyl-L-isoleucine (12-COOH-JA-Ile). In the present study, we aimed to identify the cytochrome P450 monooxygenases involved in the catabolic pathway of JA-Ile in tomato leaves. Based on a gene expression screening of SlCYP94 subfamily monooxygenases using qPCR and the time-course of JA-Ile catabolism, we identified SlCYP94B18 and SlCYP94B19 expressed in tomato leaves as candidate monooxygenases catalyzing the two-step catabolism of JA-Ile. An in vitro enzymatic assay using a yeast expression system revealed that these enzymes efficiently converted JA-Ile to 12-OH-JA-Ile, and then to 12-COOH-JA-Ile. SlCYP94B18 and SlCYP94B19 also catalyzed the oxidative catabolism of several JA-amino acid conjugates (JA-AAs), JA-Leu and JA-Val, in tomatoes. These results suggest that SlCYP94B18 and SlCYP94B19 plays a role in the two-step oxidation of JA-AAs, suggesting their broad involvement in regulating jasmonate signaling in tomatoes. Our results contribute to a deeper understanding of jasmonate signaling in tomatoes and may help to improve tomato cultivation and quality.
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Ciclopentanos , Sistema Enzimático del Citocromo P-450 , Oxilipinas , Hojas de la Planta , Solanum lycopersicum , Solanum lycopersicum/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Hojas de la Planta/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Isoleucina/metabolismo , Isoleucina/análogos & derivados , Oxigenasas de Función Mixta/metabolismo , Arabidopsis/metabolismoRESUMEN
Background: Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric dysfunction caused by a mutant huntingtin protein. Compromised metabolic activity resulting from systemic administration of the mitochondrial toxin, 3-nitropropionic acid (3-NP), is known to mimic the pathology of HD and induce HD-like symptoms in rats. N-hexanoic-Tyr-Ile-(6)-amino hexanoic amide (PNB-0408), also known as Dihexa, has been shown to have neuroprotective and procognitive properties in animal models of Alzheimer's and Parkinson's diseases. Given the mechanism of action and success in other neurodegenerative diseases, we felt it an appropriate compound to investigate further for HD. Objective: The present study was designed to test if PNB-0408, an angiotensin IV analog, could attenuate 3-NP-induced HD-like symptoms in rats and serve as a potential therapeutic agent. Methods: Forty male Wistar rats were randomized into three groups consisting of a "vehicle" group, a "3-NP" group, and a "3-NPâ+âPNB-0408" group. PNB-0408 was administered along with chronic exposure to 3-NP. Animal body weight, motor function, and cognitive abilities were measured for five weeks, before euthanasia and histopathological analysis. Results: Exposure to 3-NP decreased the amount of weight rats gained, impaired spatial learning and memory consolidation, and led to marked motor dysfunction. From our observations and analysis, PNB-0408 did not protect rats from the deficits induced by 3-NP neurotoxicity. Conclusions: Our findings suggest that PNB-0408 may not be an efficacious treatment strategy for preventing 3-NP-induced HD-like symptoms in a preclinical model. These data highlight the need for further research of this compound in alternate models and/or alternative approaches to managing this disorder.
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Angiotensina II/análogos & derivados , Enfermedad de Huntington , Fármacos Neuroprotectores , Ratas , Masculino , Animales , Ratas Wistar , Enfermedad de Huntington/inducido químicamente , Enfermedad de Huntington/tratamiento farmacológico , Enfermedad de Huntington/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Nitrocompuestos/toxicidad , Nitrocompuestos/uso terapéutico , Propionatos/toxicidad , Propionatos/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
BACKGROUND AND OBJECTIVE: Several genetic variations are associated with acute myeloid leukemia (AML) susceptibility, including the GSTP1 Ile105Val polymorphism. Even with the existing meta-analysis conducted on the topic, no consensus has been reached since none of the studies available performed in-depth data analysis. Hence, we performed an updated systematic review and meta-analysis in this paper to obtain more precise estimates. MATERIALS AND METHODS: We searched various databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to examine whether the GSTP1 Ile105Val polymorphism is associated with AML susceptibility. Further statistical analysis was also done to obtain more accurate and reliable findings. RESULTS: A total of 15 studies are included in the systematic review, but only 9 were included in the meta-analysis due to the studies deviating from the Hardy-Weinberg equilibrium. The analysis showed significantly increased susceptibility to AML in the allelic, co-dominant, and recessive models. Furthermore, subgroup analysis noted increased AML susceptibility in the non-Asian population. Comparing the proportions of the genotypes and alleles showed a significantly higher proportion of the Val/Val genotype and Val allele in the non-Asian cohort. CONCLUSION: The GSTP1 Ile105Val polymorphism is significantly associated with AML susceptibility, especially among non-Asians. Further investigation should be performed to strengthen the current results.
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Predisposición Genética a la Enfermedad , Gutatión-S-Transferasa pi , Leucemia Mieloide Aguda , Humanos , Estudios de Casos y Controles , Genotipo , Gutatión-S-Transferasa pi/genética , Leucemia Mieloide Aguda/genética , Polimorfismo Genético , Polimorfismo de Nucleótido SimpleRESUMEN
Background and objectives: The study aimed to analyze the prevalence, trends, and outcomes of twin pregnancies in Ile-Ife, Nigeria, over two distinct periods. Materials and methods: This research, based on a 14-year retrospective cohort study, scrutinized twin births occurring in two-time frames: recent years (2012-2018; Period II) and the recent past (2005-2011; Period I) at a University Teaching Hospital in Ile-Ife, Nigeria. The inclusion criteria were limited to twin births, excluding singleton and higher-order gestations. Outcomes were evaluated based on several parameters, including mode of delivery, birth weights, fetal gender combinations, APGAR scores, perinatal mortality, and maternal complications. Data analysis was conducted using the 26th version of Statistical Package for the Social Science, with a significance threshold of p < 0.05. Results: The study documented a stable prevalence of twin gestations, registering at 20.7 per 1,000 births without a significant discrepancy between the two time periods (21.7 versus 19.7; p = 0.699). Individuals from the Yoruba tribe predominantly featured in both cohorts, showing no considerable variation between the two time periods [83 (95.4) vs. 120 (99.2); p-value = 0.116]). The data exhibited recurrent instances of caesarean delivery (65.6% vs. 50.2%, p = 0.119), vertex-vertex presentation (38.0% vs. 44.7%, p = 0.352), and differing sex combinations (33.3% vs. 38.0%, p = 0.722) across both time frames. Twin II neonates born through Caesarean section were more frequently admitted to neonatal intensive care units than Twin I (5.1% versus 4.6%; p = 0.001). The recent years witnessed a surge in preterm labor complications, notably higher than the earlier period (17.1% versus 7.8%; p = 0.008). Conclusion: The prevalence of twin births in Ile-Ife, Nigeria, demonstrates a fluctuating decline. To comprehensively understand the dynamics of twin births in the region, there is a pressing need for expansive, community-centric research in southwest Nigeria.
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BACKGROUND: Thrombin is a critical protease modulating thrombosis as well as inflammation, which are one of the main pathophysiological mechanisms in sickle vasculopathy, and its levels were reported to be high in sickle cell disease (SCD). The thrombin-thrombomodulin complex activates the TAFI inhibitor of fibrinolysis, which acts by reducing plasmin affinity for its substrate thus hindering fibrinolysis. OBJECTIVE: We aimed to determine the influence of the Thr325Ile single nucleotide polymorphism (SNP) on TAFI antigen levels and potential effects on the severity of SCD in a cohort of Egyptian patients. METHODS: Genotyping of Thr325lle polymorphism using Taq-Man SNP genotyping assay and TAFI level measurement using an enzyme-linked immunosorbent assay were performed for 80 SCD patients (45 homozygous HbSS, 16 S/ß0 and 19 Sß+) as well as 80 age- and gender-matched healthy control subjects. RESULTS: Plasma TAFI levels were higher in SCD patients with Thr325Ile polymorphism, yet the difference was not statistically significant (p = .204). SCD patients with polymorphic genotypes had a greater number of hospital admissions (p = .03). Ten patients with acute chest syndrome had the homozygous polymorphic genotype (GG), and all patients with pulmonary hypertension had the polymorphic genotype (six were homozygous [GG] and five were heterozygous [GA]). Patients with SCD complicated with pulmonary hypertension showed significantly higher plasma TAFI levels (p = .044). CONCLUSION: The analysis of Thr325Ile polymorphisms combined with plasma TAFI levels suggests that the analyzed SNP could influence plasma TAFL levels and SCD disease severity and hospitalization rates, which could be predictors for complex disease.
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Anemia de Células Falciformes , Carboxipeptidasa B2 , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Adulto Joven , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/sangre , Carboxipeptidasa B2/genética , Carboxipeptidasa B2/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Egipto , Genotipo , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
Rural households all over the world rear backyard chicken mainly for their own consumption and, to a lesser extent, for barter trade. These chickens represent a staple dish with numerous culinary variations and a cheap source of protein. Although some Campylobacter species, and particularly Campylobacter jejuni and Campylobacter coli, have been associated with industrial poultry carcasses, studies concerning the ecology of this genus in rural households do not exist. To assess the prevalence of Campylobacter species in the tissues of backyard chickens, samples were collected from birds Gallus domesticus bred in households in the rural area of Epirus (Greece), and Campylobacter strains were isolated by quantitative methods at 37 °C and 42 °C. In total, 256 strains were identified, belonging to 17 Campylobacter species, with C. jejuni and C. coli being the most prevalent. From the four ecological parameters studied (size of the flock, presence of small ruminants in the same household, presence of other poultry species in the same household, and feeding leftovers of the household), the size of the flock and the presence of small ruminants and/or pigs in the same household mostly affected the distribution of these strains. To study the phenotypical resistance against 14 antibiotics, 215 strains were selected. The results showed a high prevalence of multidrug-resistance (MDR) strains extending to all classes of antibiotics. Further genome analysis revealed the presence of genes coding resistance (blaOxA-61, tet(O), tet(A) cmeA, cmeB, cmeC, and gyrA (Thr-86-Ile mutation)), with the efflux pump CmeABC being the most prevalent. All antimicrobial resistance-encoded genes co-circulated, except for blaOXA-61, which moved independently. The minimum inhibitory concentration (MIC) values of two out of three antibiotics (representing different classes) were reduced when the strains tested were exposed to carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a known efflux pump inhibitor. The same result was obtained with the addition of CCCP to the MIC values of bile salts. These results lead to the conclusion that Campylobacter species are present in an impressive diversity in backyard chicken tissues and that they exert a significant resistance to antibiotics, raising a potential danger for public health.
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CARD14 (caspase activation and recruitment domain) mutations have been associated with psoriasis vulgaris, psoriatic arthritis, generalized and palmoplantar pustular psoriasis, pityriasis rubra pilaris, and atopic dermatitis. We present a pediatric patient with a novel CARD14: c.394A > T/- (Ile123Phe) mutation, diagnosed with CARD14-associated papulosquamous eruption (CAPE), who was successfully treated with biological treatment.
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Atypical hemolytic uremic syndrome (aHUS) is a rare kidney disease due to a dysregulation of the complement alternative pathway. Complement factor I (CFI) negatively regulates the alternative pathway and CFI gene rare variants have been associated to aHUS with a low disease penetrance. We report 10 unrelated cases of HUS associated to a rare CFI variant, p.Ile357Met (c.1071T>G). All patients with isolated p.Ile357Met CFI missense variant were retrospectively identified among patients included between January 2007 and January 2022 in the French HUS Registry. We identified 10 unrelated patients (70% women; median age at HUS diagnosis, 36.5 years) who carry the same rare variant p.Ile357Met in the CFI gene. Seven patients (cases 1-7) presented with aHUS in the native kidney associated with malignant hypertension in 5 patients. None received a C5 inhibitor. Two of these cases occurred in the peripartum period with complete recovery of kidney function, while 5 of these patients reached kidney failure requiring replacement therapy (KFRT). Four patients with KFRT subsequently underwent kidney transplantation. Three later developed C3 glomerulopathy in their kidney graft, but none had aHUS recurrence. Three other patients (cases 8-10) experienced de novo thrombotic microangiopathy after kidney transplantation, precipitated by various triggers. The rare CFI variant p.Ile357Met appears to be a facilitating genetic factor for HUS and for some forms of secondary HUS.
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Síndrome Hemolítico Urémico Atípico , Factor I de Complemento , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Síndrome Hemolítico Urémico Atípico/genética , Factor I de Complemento/genética , Mutación Missense , Estudios RetrospectivosRESUMEN
Jasmonic acid-isoleucine (JA-Ile) is a plant defence hormone whose cellular levels are elevated upon herbivory and regulate defence signalling. Despite their pivotal role, our understanding of the rapid cellular perception of bioactive JA-Ile is limited. This study identifies cell type-specific JA-Ile-induced Ca2+ signal and its role in self-amplification and plant elicitor peptide receptor (PEPR)-mediated signalling. Using the Ca2+ reporter, R-GECO1 in Arabidopsis, we have characterized a monophasic and sustained JA-Ile-dependent Ca2+ signature in leaf epidermal cells. The rapid Ca2+ signal is independent of positive feedback by the JA-Ile receptor, COI1 and the transporter, JAT1. Microarray analysis identified up-regulation of receptors, PEPR1 and PEPR2 upon JA-Ile treatment. The pepr1 pepr2 double mutant in R-GECO1 background exhibits impaired external JA-Ile induced Ca2+ cyt elevation and impacts the canonical JA-Ile responsive genes. JA responsive transcription factor, MYC2 binds to the G-Box motif of PEPR1 and PEPR2 promoter and activates their expression upon JA-Ile treatment and in myc2 mutant, this is reduced. External JA-Ile amplifies AtPep-PEPR pathway by increasing the AtPep precursor, PROPEP expression. Our work shows a previously unknown non-canonical PEPR-JA-Ile-Ca2+ -MYC2 signalling module through which plants sense JA-Ile rapidly to amplify both AtPep-PEPR and jasmonate signalling in undamaged cells.
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Proteínas de Arabidopsis , Arabidopsis , Isoleucina/análogos & derivados , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Isoleucina/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Plantas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Although many important discoveries have been made regarding the jasmonate signaling pathway, how jasmonate biosynthesis is initiated is still a major unanswered question in the field. Previous evidences suggest that jasmonate biosynthesis is limited by the availability of fatty acid precursor, such as âº-linolenic acid (âº-LA). This indicates that the lipase responsible for releasing α-LA in the chloroplast, where early steps of jasmonate biosynthesis take place, is the key initial step in the jasmonate biosynthetic pathway. Nicotiana benthamiana glycerol lipase A1 (NbGLA1) is homologous to N. attenuata GLA1 (NaGLA1) which has been reported to be a major lipase in leaves for jasmonate biosynthesis. NbGLA1 was studied for its potential usefulness in a species that is more common in laboratories. Virus-induced gene silencing of both NbGLA1 and NbGLA2, another homolog, resulted in more than 80% reduction in jasmonic acid (JA) biosynthesis in wounded leaves. Overexpression of NbGLA1 utilizing an inducible vector system failed to increase JA, indicating that transcriptional induction of NbGLA1 is insufficient to trigger JA biosynthesis. However, co-treatment with wounding in addition to NbGLA1 induction increased JA accumulation several fold higher than the gene expression or wounding alone, indicating an enhancement of the enzyme activity by wounding. Domain-deletion of a 126-bp C-terminal region hypothesized to have regulatory roles increased NbGLA1-induced JA level. Together, the data show NbGLA1 to be a major lipase for wound-induced JA biosynthesis in N. benthamiana leaves and demonstrate the use of inducible promoter-driven construct of NbGLA1 in conjunction with its transient expression in N. benthamiana as a useful system to study its protein function.
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Lipasa , Nicotiana , Oxilipinas , Nicotiana/genética , Lipasa/genética , Cloroplastos , Ciclopentanos , GlicerolRESUMEN
Intravenous lipid emulsion (ILE) has been widely used as an effective antidote in both veterinary and human medicine for the treatment of acute intoxications caused by drugs and pesticides with high lipid solubility. This study was conducted to investigate the effect of ILE co-administration on the kinetic dispositions of ivermectin (IVM) and carprofen (CRP) following intravenous bolus administration at subtoxic doses in rabbits.Twenty-four male New Zealand rabbits weighing 2.78 ± 0.2 kg were used in this study. Rabbits were divided into four groups (Group 1: IVM and Group 2: IVM + ILE or Group 3: CRP and Group 4: CRP + ILE), each group consisting of 6 animals. In the IVM study, Group 1 received IVM (0.6 mg/kg) alone while Group 2 received IVM (0.6 mg/kg) and ILE (2.5 ml/kg). In the CRP study, Group 3 received CRP (12 mg/kg) alone while Group 4 received CRP (12 mg/kg) and ILE (2.5 ml/kg). In both drug groups, ILE was administered 3 times as an i.v. bolus at the 10th min and repeated 4th and 8th h after the drug administration. Blood samples were collected from the auricular vein at various times after drug administration. The drug concentrations in plasma samples were determined by high-pressure liquid chromatography. Kinetic parameters were calculated using a non-compartmental model for both CRP and IVM.The C0 and area under the concentration-time curve from zero up to ∞ (AUC0-∞) values were significantly greater with ILE co-administration (2136 ng/ml and 360.84 ng.d/ml) compared to the IVM alone (1340.63 ng/ml and 206 ng.d/ml), respectively. Moreover, the volume of distribution (Vdss) and clearance (Cl) of IVM were reduced by approximately 42% and 46% with ILE co-administration compared to IVM alone resulting in a reduction of the distribution and slower elimination, respectively. Similar differences in C0, and Vdss values were also observed in CRP with ILE co-administration compared to CRP alone. ILE co-administration changed significantly the kinetic profile of both IVM and CRP in rabbits, supporting the lipid sink theory in which highly lipid-soluble compounds are absorbed into the lipid phase of plasma from peripheral organs such as the heart and brain affected by the acute toxicity of the compounds.
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Carbazoles , Emulsiones Grasas Intravenosas , Ivermectina , Humanos , Conejos , Masculino , Animales , Ivermectina/toxicidad , Toxicocinética , LípidosRESUMEN
BACKGROUND: Congenital entropion is the most frequent ocular disorder in newborn lambs of certain sheep breeds, which, if not treated, can result in complete blindness and death due to starvation. OBJECTIVES: The aims of this study were to compare the spontaneous healing of entropion in two breeds and assess the outcome of cases with and without therapeutic intervention. METHODS: A total of 158 entropion cases (119 Ile de France and 39 Romane) were investigated, and swab samples were collected from the cornea and conjunctiva of 73 of the affected lambs for bacteriological investigation. In addition, an ocular intervention was carried out in 123 affected animals. RESULTS: The Romane breed developed entropion at an average age of 7 days compared to the Ile de France, which developed it at an average age of 1 day. Likewise, significant differences were found between bilateral and unilateral involvement in both breeds. Meanwhile, 22.1% of cases recovered spontaneously, and the highest rate of spontaneous recovery without intervention was observed in the Romane breed (66%). Bacteria isolated from ocular samples included Staphylococcus spp. (42.5%), Bacillus spp. (21.9%), Trueperella pyogenes (13.7%), Corynebacterium spp. (12.3%) and Escherichia coli (9.6%). CONCLUSIONS: The results of the study showed that the onset time of entropion, bilateral involvement, the severity of the process and the need for re-treatment were higher in the Ile de France breed than in the Romane breed. Likewise, the Romane breed showed a higher degree of spontaneous recovery of entropion.
Asunto(s)
Entropión , Enfermedades de las Ovejas , Ovinos , Animales , Entropión/cirugía , Entropión/veterinaria , Oveja Doméstica , Francia/epidemiologíaRESUMEN
Resumen El estudio tuvo como objetivo explorar la experiencia y significados de la Interrupción Legal del Embarazo (ILE) con medicamentos, en nueve mujeres jóvenes habitantes de la Ciudad de México y Zona Metropolitana. Desde una postura fenomenológica, se empleó una metodología interpretativa. Con la técnica de la entrevista en profundidad, se recuperaron las narraciones de las mujeres sobre el proceso del aborto. Los resultados indican que el método medicamentoso supone una alternativa aceptable y ventajosa para la resolución del aborto. Sin embargo, también puede generar situaciones imprácticas e incómodas, e incluso resultar en complicaciones cuando se realiza con misoprostol y sin mifepristona. El contexto de legalidad conlleva consecuencias prácticas y simbólicas en la experiencia de aborto, y el acompañamiento y apoyo de otras personas es muy relevante en cómo se vive y significa esta práctica.
Abstract The objective of the study was to explore the experience and meanings of the Legal Interruption of Pregnancy (LIP) with medication, in nine young women living in Mexico City and the Metropolitan Area. From a phenomenological position, an interpretive methodology was used. Using the in-depth interview technique, the women's narratives about the abortion process were recovered. The results indicate that the medical procedure is an acceptable and advantageous method for abortion. However, it can also lead to impractical and uncomfortable situations, and even result in complications when only misoprostol is used without mifepristone. The context of legality results in practical and symbolic consequences in the abortion experience. Accompaniment and support from other people are very relevant in both the experience and meaning of abortion.
Resumo O objetivo do estudo foi explorar a experiência e os significados da interrupção legal da gravidez (ILE) com medicação entre nove mulheres jovens que vivem na Cidade do México e em sua área metropolitana. A partir de uma perspectiva fenomenológica, foi utilizada uma metodologia interpretativa. Usando a técnica de entrevista em profundidade, foram coletadas as narrativas das mulheres sobre o processo de aborto. Os resultados indicam que o método médico é uma alternativa aceitável e vantajosa para a resolução do aborto. No entanto, ele também pode gerar situações impraticáveis e desconfortáveis, e até mesmo resultar em complicações quando realizado com misoprostol e sem mifepristona. O contexto da legalidade tem consequências práticas e simbólicas para a experiência do aborto, e o acompanhamento e o apoio de outras pessoas são muito relevantes para a forma como essa prática é vivenciada e significada.