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In our study, using chromatographic techniques, we isolated three bioactive compounds, which were structurally elucidated as (E)-2-(3-(3,4-dimethoxyphenyl)acrylamido)-N-methylbenzamide (1), 4-Hydroxyquinoline-2-carboxylic acid (2), and (E)-2-Cyano-3-(4-hydroxyphenyl)acrylic acid (3), using spectroscopic methods. The anti-melanogenic, anti-inflammatory, antioxidant, and anti-aging properties were evaluated in vitro by measuring the activity of pharmacological targets including tyrosinase, melanin, NF-κB, hyaluronidase, elastase, collagenase, and Nrf2. Our results show that compound 1 is the most active with IC50 values of 14.19 µM (tyrosinase inhibition), 22.24 µM (melanin inhibition), 9.82-12.72 µM (NF-κB inhibition), 79.71 µM (hyaluronidase inhibition), 80.13 µM (elastase inhibition), 76.59 µM (collagenase inhibition), and 116-385 nM (Nrf2 activation) in the THP-1, HEK001, WS1, and HMCB cells. These findings underscore the promising profiles of the aqueous extract of R. urticifolius at safe cytotoxic concentrations. Additionally, we report, for the first time, the isolation and characterisation of these nitrogenous compounds in the R. urticifolius species. Finally, compound 1, isolated from R. urticifolius, is a promising candidate for the development of more effective and safer compounds for diseases related to skin pigmentation, protection against inflammation, and oxidative stress.
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BACKGROUND: Incomplete treatment of congestion often leads to worsening heart failure (HF). The remote dielectric sensing (ReDS) system is an electromagnetic energy-based technology that accurately quantifies changes in lung fluid concentration noninvasively. OBJECTIVES: This study sought to assess whether an ReDS-guided strategy during acutely decompensated HF hospitalization is superior to routine care for improving outcomes at 1 month postdischarge. METHODS: ReDS-SAFE HF (Use of ReDS for a SAFE discharge in patients with acute Heart Failure) was an investigator-initiated, multicenter, single-blind, randomized, proof-of-concept trial in which 100 patients were randomized to a routine care strategy, with discharge criteria based on current clinical practice, or an ReDS-guided decongestion strategy, with discharge criteria requiring an ReDS value of ≤35%. ReDS measurements were performed daily and at a 7-day follow-up visit, with patients and treating physicians in the routine care arm blinded to the results. The primary outcome was a composite of unplanned visits for HF, HF rehospitalization, or death at 1 month after discharge. RESULTS: The mean age was 67 ± 14 years, and 74% were male. On admission, left ventricular ejection fraction was 37% ± 16%, and B-type natriuretic peptide was 940 pg/L (Q1-Q3: 529-1,665 pg/L). The primary endpoint occurred in 10 (20%) patients in the routine care group and 1 (2%) in the ReDS-guided strategy group (log-rank P = 0.005). The ReDS-guided strategy group experienced a lower event rate, with an HR of 0.094 (95% CI: 0.012-0.731; P = 0.003), and a number of patients needed to treat of 6 to avoid an event (95% CI: 3-17), mainly resulting from a decrease in HF readmissions. The median length of stay was 2 days longer in the ReDS-guided group vs the routine care group (8 vs 6; P = 0.203). CONCLUSIONS: A ReDS-guided strategy to treat congestion improved 1-month prognosis postdischarge in this proof-of-concept study, mainly because of a decrease of the number of HF readmissions. (Use of ReDS for a SAFE discharge in patients with acute Heart Failure [ReDS-SAFE HF]; NCT04305717).
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Insuficiência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Alta do Paciente , Volume Sistólico , Método Simples-Cego , Assistência ao Convalescente , Função Ventricular EsquerdaRESUMO
Our molecular understanding of the early stages of human inner ear development has been limited by the difficulty in accessing fetal samples at early gestational stages. As an alternative, previous studies have shown that inner ear morphogenesis can be partially recapitulated using induced pluripotent stem cells directed to differentiate into inner ear organoids (IEOs). Once validated and benchmarked, these systems could represent unique tools to complement and refine our understanding of human otic differentiation and model developmental defects. Here, we provide the first direct comparisons of the early human embryonic otocyst and fetal sensory organs with human IEOs. We use multiplexed immunostaining and single-cell RNA-sequencing to characterize IEOs at three key developmental steps, providing a new and unique signature of in vitro-derived otic placode, epithelium, neuroblasts and sensory epithelia. In parallel, we evaluate the expression and localization of crucial markers at these equivalent stages in human embryos. Together, our data indicate that the current state-of-the-art protocol enables the specification of bona fide otic tissue, supporting the further application of IEOs to inform inner ear biology and disease.
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Orelha Interna , Células-Tronco Pluripotentes , Humanos , Gravidez , Feminino , Epitélio/metabolismo , Diferenciação Celular , OrganoidesRESUMO
Time-specific modulation of gene expression during differentiation by transcription factors promotes cell diversity. However, estimating their dynamic regulatory activity at the single-cell level and in a high-throughput manner remains challenging. We present FateCompass, an integrative approach that utilizes single-cell transcriptomics data to identify lineage-specific transcription factors throughout differentiation. By combining a probabilistic framework with RNA velocities or differentiation potential, we estimate transition probabilities, while a linear model of gene regulation is employed to compute transcription factor activities. Considering dynamic changes and correlations of expression and activities, FateCompass identifies lineage-specific regulators. Our validation using in silico data and application to pancreatic endocrine cell differentiation datasets highlight both known and potentially novel lineage-specific regulators. Notably, we uncovered undescribed transcription factors of an enterochromaffin-like population during in vitro differentiation toward ß-like cells. FateCompass provides a valuable framework for hypothesis generation, advancing our understanding of the gene regulatory networks driving cell-fate decisions.
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Regulação da Expressão Gênica , Fatores de Transcrição , Fatores de Transcrição/genética , Diferenciação Celular/genética , Redes Reguladoras de Genes , Perfilação da Expressão GênicaRESUMO
A hallmark of many malignant tumors is dedifferentiated (immature) cells bearing slight or no resemblance to the normal cells from which the cancer originated. Tumor dedifferentiated cells exhibit a higher capacity to survive to chemo and radiotherapies and have the ability to incite tumor relapse. Inducing cancer cell differentiation would abolish their self-renewal and invasive capacity and could be combined with the current standard of care, especially in poorly differentiated and aggressive tumors (with worst prognosis). However, differentiation therapy is still in its early stages and the intrinsic complexity of solid tumor heterogeneity demands innovative approaches in order to be efficiently translated into the clinic. We demonstrate here that microRNA 203, a potent driver of differentiation in pluripotent stem cells (ESCs and iPSCs), promotes the differentiation of mammary gland tumor cells. Combining mouse in vivo approaches and both mouse and human-derived tridimensional organoid cultures, we report that miR-203 influences the self-renewal capacity, plasticity and differentiation potential of breast cancer cells and prevents tumor cell growth in vivo. Our work sheds light on differentiation-based antitumor therapies and offers miR-203 as a promising tool for directly confronting the tumor-maintaining and regeneration capability of cancer cells.
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Neoplasias da Mama , MicroRNAs , Humanos , Camundongos , Animais , Feminino , MicroRNAs/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/patologia , Diferenciação Celular/genética , Proliferação de Células/genética , Células-Tronco Neoplásicas/patologiaRESUMO
Below and aboveground vegetation dynamics are crucial in understanding how climate warming may affect terrestrial ecosystem carbon cycling. In contrast to aboveground biomass, the response of belowground biomass to long-term warming has been poorly studied. Here, we characterized the impacts of decadal geothermal warming at two levels (on average +3.3°C and +7.9°C) on below and aboveground plant biomass stocks and production in a subarctic grassland. Soil warming did not change standing root biomass and even decreased fine root production and reduced aboveground biomass and production. Decadal soil warming also did not significantly alter the root-shoot ratio. The linear stepwise regression model suggested that following 10 yr of soil warming, temperature was no longer the direct driver of these responses, but losses of soil N were. Soil N losses, due to warming-induced decreases in organic matter and water retention capacity, were identified as key driver of the decreased above and belowground production. The reduction in fine root production was accompanied by thinner roots with increased specific root area. These results indicate that after a decade of soil warming, plant productivity in the studied subarctic grassland was affected by soil warming mainly by the reduction in soil N.
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Ecossistema , Traqueófitas , Solo , Pradaria , Nitrogênio/análise , Mudança Climática , Biomassa , Plantas , CarbonoRESUMO
Neuroanatomy is always a challenging topic for veterinary students. It is widely accepted that understanding the anatomy of the central nervous system (CNS) is essential to explain many of the pathological processes that affect the brain. Although its study has varied over time to achieve this goal, in human and veterinary medicine it is difficult to find a teaching method that associates normal anatomy with pathological alterations of the brain. For the first time, we have created an educational tool that combines neuroanatomy and neuropathology, using different magnetic resonance (MR) images as a basis and EspINA software as analyzer, to obtain segmented structures and 3D reconstructions of the dog brain. We demonstrate that this combination is an optimal tool to help anatomists to understand the encephalon, and additionally to help clinicians to recognize illness including a multitude of neurological problems. In addition, we have tried to see whether photogrammetry, which is a common technique in other sciences, for example geology, could be useful to teach veterinary neuroanatomy. Although we still need further investigations, we have been able to generate 3D reconstructions of the whole brain, with very promising results to date.
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Our molecular understanding of the early stages of human inner ear development has been limited by the difficulty in accessing fetal samples at early gestational stages. As an alternative, previous studies have shown that inner ear morphogenesis can be partially recapitulated using induced pluripotent stem cells (iPSCs) directed to differentiate into Inner Ear Organoids (IEOs). Once validated and benchmarked, these systems could represent unique tools to complement and refine our understanding of human otic differentiation and model developmental defects. Here, we provide the first direct comparisons of the early human embryonic otocyst and human iPSC-derived IEOs. We use multiplexed immunostaining, and single-cell RNA sequencing to characterize IEOs at three key developmental steps, providing a new and unique signature of in vitro derived otic -placode, -epithelium, -neuroblasts, and -sensory epithelia. In parallel, we evaluate the expression and localization of critical markers at these equivalent stages in human embryos. We show that the placode derived in vitro (days 8-12) has similar marker expression to the developing otic placode of Carnegie Stage (CS) 11 embryos and subsequently (days 20-40) this gives rise to otic epithelia and neuroblasts comparable to the CS13 embryonic stage. Differentiation of sensory epithelia, including supporting cells and hair cells starts in vitro at days 50-60 of culture. The maturity of these cells is equivalent to vestibular sensory epithelia at week 10 or cochlear tissue at week 12 of development, before functional onset. Together, our data indicate that the current state-of-the-art protocol enables the specification of bona fide otic tissue, supporting the further application of IEOs to inform inner ear biology and disease.
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Environmental conditions greatly impact plant growth and development. In the current context of both global climate change and land degradation, abiotic stresses usually lead to growth restriction limiting crop production. Plants have evolved to sense and respond to maximize adaptation and survival; therefore, understanding the mechanisms involved in the different converging signaling networks becomes critical for improving plant tolerance. In the last few years, several studies have shown the plant responses against drought and salinity, high and low temperatures, mechanical wounding, heavy metals, hypoxia, UV radiation, or ozone stresses. These threats lead the plant to coordinate a crosstalk among different pathways, highlighting the role of phytohormones and reactive oxygen and nitrogen species (RONS). In particular, plants sense these reactive species through post-translational modification (PTM) of macromolecules such as nucleic acids, proteins, and fatty acids, hence triggering antioxidant responses with molecular implications in the plant welfare. Here, this review compiles the state of the art about how plant systems sense and transduce this crosstalk through PTMs of biological molecules, highlighting the S-nitrosylation of protein targets. These molecular mechanisms finally impact at a physiological level facing the abiotic stressful traits that could lead to establishing molecular patterns underlying stress responses and adaptation strategies.
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Islet-1 (Isl1) is one of the most conserved transcription factors in the evolution of vertebrates, due to its continuing involvement in such important functions as the differentiation of motoneurons, among other essential roles in cell fate in the forebrain. Although its functions are thought to be similar in all vertebrates, the knowledge about the conservation of its expression pattern in the central nervous system goes as far as teleosts, leaving the basal groups of actinopterygian fishes overlooked, despite their important phylogenetic position. In order to assess the extent of its conservation among vertebrates, we studied its expression pattern in the central nervous system of selected nonteleost actinopterygian fishes. By means of immunohistochemical techniques, we analyzed the Isl1 expression in the brain, spinal cord, and sensory ganglia of the cranial nerves of young adult specimens of the cladistian species Polypterus senegalus and Erpetoichthys calabaricus, the chondrostean Acipenser ruthenus, and the holostean Lepisosteus oculatus. We also detected the presence of the transcription factor Orthopedia and the enzymes tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) to better locate all the immunoreactive structures in the different brain areas and to reveal the possible coexpression with Isl1. Numerous conserved features in the expression pattern of Isl1 were observed in these groups of fishes, such as populations of cells in the subpallial nuclei, preoptic area, subparaventricular and tuberal hypothalamic regions, prethalamus, epiphysis, cranial motor nuclei and sensory ganglia of the cranial nerves, and the ventral horn of the spinal cord. Double labeling of TH and Isl1 was observed in cells of the preoptic area, the subparaventricular and tuberal hypothalamic regions, and the prethalamus, while virtually all motoneurons in the hindbrain and the spinal cord coexpressed ChAT and Isl1. Altogether, these results show the high degree of conservation of the expression pattern of the transcription factor Isl1, not only among fish, but in the subsequent evolution of vertebrates.
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Encéfalo , Sistema Nervoso Central , Animais , Filogenia , Sistema Nervoso Central/metabolismo , Encéfalo/metabolismo , Peixes/metabolismo , Colina O-Acetiltransferase/metabolismo , Prosencéfalo/metabolismo , Colinérgicos/metabolismo , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND & AIMS: Enteroendocrine cells (EECs) and their hormones are essential regulators of whole-body energy homeostasis. EECs sense luminal nutrients and microbial metabolites and subsequently secrete various hormones acting locally or at a distance. Impaired development of EECs during embryogenesis is life-threatening in newborn mice and humans due to compromised nutrient absorption. However, the physiological importance of the EEC system in adult mice has yet to be directedly studied. Herein, we aimed to determine the long-term consequences of a total loss of EECs in healthy adults on energy metabolism, intestinal transcriptome, and microbiota. METHODS: We depleted intestinal EECs by tamoxifen treatment of adult Neurog3fl/fl; Villin-CreERT2 male mice. We studied intestinal cell differentiation, food efficiency, lipid absorption, microbiota composition, fecal metabolites, and transcriptomic responses in the proximal and distal small intestines of mice lacking EECs. We also determined the high-fat diet-induced transcriptomic changes in sorted Neurog3eYFP/+ EECs. RESULTS: Induction of EEC deficiency in adults is not life-threatening unless fed with a high-fat diet. Under a standard chow diet, mice lose 10% of weight due to impaired food efficiency. Blood concentrations of cholesterol, triglycerides, and free fatty acids are reduced, and lipid absorption is impaired and delayed in the distal small intestine. Genes controlling lipogenesis, carbohydrate metabolism, and neoglucogenesis are upregulated. Microbiota composition is rapidly altered after EECs depletion and is characterized by decreased α-diversity. Bacteroides and Lactobacillus were progressively enriched, whereas Lachnospiraceae declined without impacting fecal short-chain fatty acid concentrations. CONCLUSIONS: EECs are dispensable for survival in adult male mice under a standard chow diet. The absence of EECs impairs intestinal lipid absorption, leading to transcriptomic and metabolic adaptations and remodeling of the gut microbiota.
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Microbioma Gastrointestinal , Humanos , Masculino , Camundongos , Animais , Intestinos , Células Enteroendócrinas/metabolismo , Hormônios/metabolismo , Colesterol/metabolismoRESUMO
Satb1 and Satb2 belong to a family of homeodomain proteins with highly conserved functional and regulatory mechanisms and posttranslational modifications in evolution. However, although their distribution in the mouse brain has been analyzed, few data exist in other non-mammalian vertebrates. In the present study, we have analyzed in detail the sequence of SATB1 and SATB2 proteins and the immunolocalization of both, in combination with additional neuronal markers of highly conserved populations, in the brain of adult specimens of different bony fish models at key evolutionary points of vertebrate diversification, in particular including representative species of sarcopterygian and actinopterygian fishes. We observed a striking absence of both proteins in the pallial region of actinopterygians, only detected in lungfish, the only sarcopterygian fish. In the subpallium, including the amygdaloid complex, or comparable structures, we identified that the detected expressions of SATB1 and SATB2 have similar topologies in the studied models. In the caudal telencephalon, all models showed significant expression of SATB1 and SATB2 in the preoptic area, including the acroterminal domain of this region, where the cells were also dopaminergic. In the alar hypothalamus, all models showed SATB2 but not SATB1 in the subparaventricular area, whereas in the basal hypothalamus the cladistian species and the lungfish presented a SATB1 immunoreactive population in the tuberal hypothalamus, also labeled with SATB2 in the latter and colocalizing with the gen Orthopedia. In the diencephalon, all models, except the teleost fish, showed SATB1 in the prethalamus, thalamus and pretectum, whereas only lungfish showed also SATB2 in prethalamus and thalamus. At the midbrain level of actinopterygian fish, the optic tectum, the torus semicircularis and the tegmentum harbored populations of SATB1 cells, whereas lungfish housed SATB2 only in the torus and tegmentum. Similarly, the SATB1 expression in the rhombencephalic central gray and reticular formation was a common feature. The presence of SATB1 in the solitary tract nucleus is a peculiar feature only observed in non-teleost actinopterygian fishes. At these levels, none of the detected populations were catecholaminergic or serotonergic. In conclusion, the protein sequence analysis revealed a high degree of conservation of both proteins, especially in the functional domains, whereas the neuroanatomical pattern of SATB1 and SATB2 revealed significant differences between sarcopterygians and actinopterygians, and these divergences may be related to the different functional involvement of both in the acquisition of various neural phenotypes.
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Encéfalo , Peixes , Animais , Camundongos , Encéfalo/metabolismo , Peixes/metabolismo , Dopamina/metabolismo , Neurônios/metabolismo , TálamoRESUMO
INTRODUCTION: Vitiligo is a chronic skin condition with no cure. Clinical assessment and treatment evaluation relies heavily on clinometry tools and expert knowledge. The Vitiligo Extent Score has been proposed as one of the most reliable and easy-to-use clinometry tools for vitiligo. METHODS AND ANALYSIS: We proposed a scoping review to identify all the available evidence on the clinical research availability around the Vitiligo Extent Score. The following databases will be searched: MEDLINE (PubMed), Embase, Open Grey, Lens and Directory of Open Access Journals. In addition, the approach proposed in the Joanna Briggs Institute Reviewer's Manual will be followed. Finally, this review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. ETHICS AND DISSEMINATION: Ethics approval for this review is not required. We intend to publish the results in a specialised peer-reviewed journal and local, national and international conference presentations. It will also be incorporated as educational material in our institution's postgraduate programme in dermatology.
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Vitiligo , Humanos , Academias e Institutos , Bases de Dados Factuais , Conhecimento , MEDLINE , Projetos de Pesquisa , Literatura de Revisão como Assunto , Vitiligo/diagnóstico , Vitiligo/terapiaRESUMO
CONTEXT: Apart from the canonical cAMP-PKA pathway, ram sperm capacitation can be achieved by the MAPK ERK1/2 signalling cascade, activated by epidermal growth factor (EGF). AIMS: This study aims to investigate the effect of melatonin and nitric oxide (NO·) on capacitation and apoptotic-like changes in EGF-capacitated ram spermatozoa. METHODS: In vitro capacitation was induced by EGF in the absence or presence of melatonin (100pM or 1µM). Also, a NO· precursor, L-arginine, or a NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), were added to capacitation media to study the interaction of NO· and melatonin during EGF-capacitation. Sperm functionality parameters (motility, viability, capacitation state), apoptotic markers (caspase activation and DNA damage), NO· levels, and phosphorylated c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (assessed by Western blot), were evaluated in swim-up and capacitated samples with EGF. KEY RESULTS: NO· levels and the apoptotic-related markers were raised after EGF incubation. Melatonin had a bimodal role on sperm EGF-capacitation, preventing it at high concentration and promoting acrosome reaction at low concentration, but neither of the two concentrations prevented the increase in apoptotic-like markers or NO· levels. However, melatonin at 1µM prevented the activation of JNK. CONCLUSIONS: NO· metabolism does not seem to modulate the apoptosis-like events in ram spermatozoa. Melatonin at 1µM prevents ram sperm capacitation induced by EGF independently from nitric oxide metabolism, and it could be exerted by limiting the JNK mitogen-activated protein kinase (MAPK) activation. IMPLICATIONS: This study improvesour understanding of the biochemical mechanisms involved in sperm capacitation, and ultimately, fertility.
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Fator de Crescimento Epidérmico , Melatonina , Masculino , Animais , Ovinos , Fator de Crescimento Epidérmico/farmacologia , Fator de Crescimento Epidérmico/metabolismo , Melatonina/farmacologia , Melatonina/metabolismo , Óxido Nítrico/metabolismo , Sêmen , Espermatozoides/metabolismo , Capacitação Espermática , Reação AcrossômicaRESUMO
Sperm orientation mechanisms, such as chemotaxis, are essential for the sperm to reach the oocyte and fertilize it. Melatonin is secreted by the cumulus cells and is also present in the follicular fluid in mammals. The presence of membrane receptors for melatonin in ram spermatozoa, and its proven involvement in the sperm functionality, may suggest a possible role in the guided movement towards the oocyte. Hence, the objective of the present work is to study the in vitro potential chemotactic action of melatonin on ram spermatozoa, analysing the influence of the season (breeding and non-breeding) and the sperm capacitation state. The first experimental approach consisted in the inclusion of melatonin in the upper layer of a swim-up selection method. During the non-breeding season, the presence of melatonin at 100 pM and 1 µM concentrations significantly increased the cell recovery rate, and induced changes in the sperm location of the MT2 melatonin receptor, compared with the standard swim-up. Moreover, the selected sperm population with 100 pM melatonin presented a higher percentage of capacitated spermatozoa. The greater recovery rate obtained with melatonin could be due to the stimulation of sperm movement in random directions, i.e., a chemokinetic effect, or due to a guided movement (chemotaxis) towards the gradient of the melatonin. To elucidate this issue, together with the study of the influence of the sperm capacitation status, we performed a second experimental approach which consisted in the use of chemotaxis chambers and an open-source software (Open-CASA) that analyses the sperm trajectories towards the hormone gradient and calculates a chemotaxis index (SL index). There was a significant difference between the SL index in the presence of 1 µM melatonin and the control without hormone. This effect was only observed in capacitated spermatozoa with cAMP-elevating agents (Cap-CK samples) obtained during the non-breeding season. These results would point to an in vitro chemotactic effect of melatonin on ram spermatozoa, although chemokinesis cannot be ruled out. Nonetheless, the inclusion of this hormone in the swim-up procedure could enhance the sperm recovery rate.
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Melatonina , Feminino , Masculino , Ovinos , Animais , Melatonina/farmacologia , Sêmen , Espermatozoides/fisiologia , Fertilização , Capacitação Espermática , Motilidade dos Espermatozoides , MamíferosRESUMO
Plant root growth and developmental capacities reside in a few stem cells of the root apical meristem (RAM). Maintenance of these stem cells requires regenerative divisions of the initial stem cell niche (SCN) cells, self-maintenance, and proliferative divisions of the daughter cells. This ensures sufficient cell diversity to guarantee the development of complex root tissues in the plant. Damage in the root during growth involves the formation of a new post-embryonic root, a process known as regeneration. Post-embryonic root development and organogenesis processes include primary root development and SCN maintenance, plant regeneration, and the development of adventitious and lateral roots. These developmental processes require a fine-tuned balance between cell proliferation and maintenance. An important regulator during root development and regeneration is the gasotransmitter nitric oxide (NO). In this review we have sought to compile how NO regulates cell rate proliferation, cell differentiation, and quiescence of SCNs, usually through interaction with phytohormones, or other molecular mechanisms involved in cellular redox homeostasis. NO exerts a role on molecular components of the auxin and cytokinin signaling pathways in primary roots that affects cell proliferation and maintenance of the RAM. During root regeneration, a peak of auxin and cytokinin triggers specific molecular programs. Moreover, NO participates in adventitious root formation through its interaction with players of the brassinosteroid and cytokinin signaling cascade. Lately, NO has been implicated in root regeneration under hypoxia conditions by regulating stem cell specification through phytoglobins.
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Proteínas de Arabidopsis , Raízes de Plantas , Raízes de Plantas/metabolismo , Óxido Nítrico/metabolismo , Meristema , Citocininas/metabolismo , Ácidos Indolacéticos/metabolismo , Plantas/metabolismo , Hormônios/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Arabidopsis/metabolismoRESUMO
Background: The lysis of platelets during in vitro coagulation leads to increased potassium concentrations.We aimed to establish the cut-off value for platelet count interfering serum potassium and to estimate the percentage of cases of pseudohyperkalemia and pseudonormokalemia in our hospital. Materials and methods: Individuals diagnosed with essential thrombocytosis (2010-2019) based on the WHO criteria for the classification of myeloid neoplasms and acute leukemia were considered.The cut-off value for the interference of platelet count on serum potassium results was calculated using the reference change value. Sensitivity and specificity were calculated using a ROC-curve, and the size of the effect by the Cohen's d.The clinical impact of both phenomena was assessed by reviewing the medical records of individuals classified as such, and also looking for potential cases in 2019 on the laboratory information system. Results: Fifty-four individuals with essential thrombocytosis were included. Potassium concentration correlated with platelet count (P-value<0.001; Spearman's ρ =0.394) in serum. The cut-off value of platelet count interfering potassium was 598x103/µL [CI95%: 533-662x103/µL], with an associated sensitivity and specificity of 0.67 [CI95%:0.52-0.80] and 0.58 [CI95%:0.42-0.72] respectively.The medical records of patients classified as pseudohyperkalemia or pseudonormokalemia did not include any medical action for the modification of potassium levels. In 2019, up to 0.14% of the total serum potassium determinations were susceptible to be pseudohyperkalemia or pseudonormokalemia. Conclusion: This study provides a cut-off value for platelet count interfering serum potassium concentrations, and brings to light not only pseudohyperkalemia-related issues, but also the pseudonormokalemia phenomenon, which usually goes unnoticed.
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Coronavirus disease 2019 (COVID-19) in kidney transplant recipients has a high risk of complications and mortality, especially in older recipients diagnosed during the early period after transplantation. Management of immunosuppression has been challenging during the pandemic. We investigated the impact of induction immunosuppression, either basiliximab or thymoglobulin, on the clinical evolution of kidney transplant recipients developing COVID-19 during the early period after transplantation. We included kidney transplant recipients with Ë6 months with a functioning graft diagnosed with COVID-19 from the initial pandemic outbreak (March 2020) until 31 July 2021 from different Spanish centres participating in a nationwide registry. A total of 127 patients from 17 Spanish centres developed COVID-19 during the first 6 months after transplantation; 73 (57.5%) received basiliximab and 54 (42.5%) thymoglobulin. Demographics were not different between groups but patients receiving thymoglobulin were more sensitized [calculated panel reactive antibodies (cPRAs) 32.7 ± 40.8% versus 5.6 ± 18.5%] and were more frequently retransplants (30% versus 4%). Recipients Ë65 years of age treated with thymoglobulin showed the highest rate of acute respiratory distress syndrome [64.7% versus 37.1% for older recipients receiving thymoglobulin and basiliximab (P < .05), respectively, and 23.7% and 18.9% for young recipients receiving basiliximab and thymoglobulin (P > .05)], respectively, and the poorest survival [mortality rate 64.7% and 42.9% for older recipients treated with thymoglobulin and basiliximab, respectively (P < .05) and 8.1% and 10.5% for young recipients treated with thymoglobulin and basiliximab (P > .05), respectively]. Older recipients treated with thymoglobulin showed the poorest survival in the Cox regression model adjusted for comorbidities. Thus thymoglobulin should be used with caution in older recipients during the present pandemic era.