RESUMO
Canopy shade enhances the activity of PHYTOCHROME INTERACTING FACTORs (PIFs) to boost auxin synthesis in the cotyledons. Auxin, together with local PIFs and their positive regulator CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1), promotes hypocotyl growth to facilitate access to light. Whether shade alters the cellular redox status thereby affecting growth responses, remains unexplored. Here, we show that, under shade, high auxin levels increased reactive oxygen species and nitric oxide accumulation in the hypocotyl of Arabidopsis. This nitroxidative environment favored the promotion of hypocotyl growth by COP1 under shade. We demonstrate that COP1 is S-nitrosylated, particularly under shade. Impairing this redox regulation enhanced COP1 degradation by the proteasome and diminished the capacity of COP1 to interact with target proteins and to promote hypocotyl growth. Disabling this regulation also generated transversal asymmetries in hypocotyl growth, indicating poor coordination among different cells, which resulted in random hypocotyl bending and predictably low ability to compete with neighbors. These findings highlight the significance of redox signaling in the control of diffuse growth during shade avoidance.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Hipocótilo , Espécies Reativas de Oxigênio , Ubiquitina-Proteína Ligases , Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Espécies Reativas de Oxigênio/metabolismo , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Óxido Nítrico/metabolismo , Ácidos Indolacéticos/metabolismo , Luz , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Oxirredução , Transdução de SinaisRESUMO
La púrpura fulminante adquirida postinfecciosa es una entidad aguda y grave, poco frecuente, caracterizada por necrosis cutánea asociada a coagulopatía intravascular diseminada (CID), en ausencia de infección activa o alteraciones previas de la coagulación. Afecta fundamentalmente a la población pediátrica y, en el 90 % de los casos, está precedida por un proceso infeccioso. El mecanismo fisiopatológico es un déficit transitorio de proteína S mediado por autoanticuerpos que favorece un estado de hipercoagulabilidad. Se presenta el caso de un varón de 8 años previamente sano, con lesiones cutáneas purpúricas características de púrpura fulminante asociada a CID en ausencia de sepsis. Se constató deficiencia plasmática transitoria de proteína S. Requirió tratamiento sustitutivo con plasma fresco congelado y anticoagulación; la evolución fue favorable. La actividad de la proteína S permaneció disminuida durante 2 meses.
Acquired postinfectious purpura fulminans is a rare, acute, and severe disease characterized by skin necrosis associated with disseminated intravascular coagulation (DIC) in the absence of active infection or previous coagulation disorders. It mainly affects the pediatric population and, in 90% of cases, it is preceded by an infectious process. The pathophysiological mechanism is a transient autoantibodymediated protein S deficiency that favors a hypercoagulable state. Here we describe the case of a previously healthy 8-year-old boy with purpuric skin lesions typical of purpura fulminans associated with DIC in the absence of sepsis. A transient plasma protein S deficiency was confirmed. He required replacement therapy with fresh frozen plasma and anticoagulation; he had a favorable course. Protein S activity remained decreased for 2 months.
Assuntos
Humanos , Masculino , Criança , Púrpura Fulminante/diagnóstico , Púrpura Fulminante/etiologia , Deficiência de Proteína S/complicações , Deficiência de Proteína S/diagnóstico , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/etiologiaRESUMO
ABSTRACT Purpose To evaluate the morphological and stereological parameters of the testicles in mice exposed to bisphenol S and/or high-fat diet-induced obesity. Material and Methods Forty adult male C57BL/6 mice were fed a standard diet (SC) or high-fat diet (HF) for a total of 12 weeks. The sample was randomly divided into 4 experimental groups with 10 mices as follows: a) SC - animals fed a standard diet; b) SC-B - animals fed a standard diet and administration of BPS (25 μg/kg of body mass/day) in drinking water; c) HF: animals fed a high-fat diet; d) HF-B - animals fed a high-fat diet and administration of BPS (25 μg/Kg of body mass/day) in drinking water. BPS administration lasted 12 weeks, following exposure to the SC and HF diets. BPS was diluted in absolute ethanol (0.1%) and added to drinking water (concentration of 25 μg/kg body weight/day). The animals were euthanized, and the testes were processed and stained with hematoxylin and eosin (H&E) for morphometric and stereological parameters, including density of seminiferous tubules per area, length density and total length of seminiferous tubules, height of the tunica albuginea and the diameter of the seminiferous tubules. The images were captured with an Olympus BX51 microscope and Olympus DP70 camera. The stereological analysis was done with the Image Pro and Image J programs. Means were statistically compared using ANOVA and the Holm-Sidak post-test (p<0.05). Results The seminiferous tubule density per area reduced in all groups when compared with SC samples (p<0.001): HF (40%), SC-B 3(2%), and HF-B (36%). Length density was reduced significantly (p<0.001) in all groups when compared with SC group: HF (40%), SC-B (32%), and HF-B (36%). The seminiferous tubule total length was reduced (p<0.001) when compared to f HF (28%) and SC-B (26%) groups. The tubule diameter increased significantly (p<0.001) only when we compared the SC group with SC (54%) an SC-B (25%) groups and the tunica thickness increased significantly only in HF group (117%) when compared with SC-B (20%) and HF-B 31%. Conclusion Animals exposed to bisphenol S and/or high-fat diet-induced obesity presented important structural alterations in testicular morphology.
RESUMO
INTRODUCTION: The Ad26.COV2·S (Janssen/Johnson & Johnson) COVID-19 vaccine, has been rarely associated with vaccine-induced immune thrombocytopenia and thrombosis (VITT). We investigated the prevalence of anti-PF4 antibody positivity, thrombocytopenia, D-dimer elevation, plasmatic thromboinflammatory markers, and platelet functional assays following Ad26.COV2·S vaccination in Rio de Janeiro, Brazil. METHODS: From July to September 2021, participants were assessed prior, 1, and 3 weeks post-vaccination. Platelet count and D-dimer were measured at each visit and anti-PF4 at week 3. A positive anti-PF4 prompted retrospective testing of the sample from week 0. Individuals with new thrombocytopenia or elevated D-dimer, positive anti-PF4, and 38 matched controls without laboratory abnormalities were evaluated for plasmatic p-selectin, tissue factor, and functional platelet activation assays. RESULTS: 630 individuals were included; 306 (48.57%) females, median age 28 years. Forty-two (6.67%) presented ≥1 laboratory abnormality in week 1 or 3. Five (0.79%) had thrombocytopenia, 31 (4.91%) elevated D-dimer, and 9 (1.57%) had positive anti-PF4 at week 3. Individuals with laboratory abnormalities and controls showed a slight increase in plasmatic p-selectin and tissue factor. Ten individuals with laboratory abnormalities yielded increased surface expression of p-selectin, and their ability to activate platelets in a FcγRIIa dependent manner was further evaluated. Two were partially inhibited by high concentrations of heparin and blockage of FcγRII with IV.3 antibody. Plasma obtained before vaccination produced similar results, suggesting a lack of association with vaccination. CONCLUSIONS: Vaccination with Ad26.COV2·S vaccine led to a very low frequency of low-titer positive anti-PF4 antibodies, elevation of D-dimer, and mild thrombocytopenia, with no associated clinically relevant increase in thromboinflammatory markers and platelet activation.
Assuntos
COVID-19 , Produtos de Degradação da Fibrina e do Fibrinogênio , Ativação Plaquetária , Fator Plaquetário 4 , Humanos , Feminino , Masculino , Brasil/epidemiologia , Adulto , Fator Plaquetário 4/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Pessoa de Meia-Idade , Trombocitopenia/induzido quimicamente , SARS-CoV-2/imunologia , Adulto Jovem , Ad26COVS1 , Contagem de Plaquetas , Vacinação , Estudos Retrospectivos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Adolescente , Trombose/imunologia , Trombose/prevenção & controleRESUMO
Microbial life forms are among the most ubiquitous on Earth, yet many remain understudied in Caribbean estuaries. We report on the prokaryote community composition of the Urabá Estuary in the Colombian Caribbean using 16S rRNA gene-transcript sequencing. We also assessed potential functional diversity through 38 metabolic traits inferred from 16S rRNA gene data. Water samples were collected from six sampling stations at two depths with contrasting light-penetration conditions along an approximately 100 km transect in the Gulf of Urabá in December 2019. Non-metric multidimensional scaling analysis grouped the samples into two distinct clusters along the transect and between depths. The primary variables influencing the prokaryote community composition were the sampling station, depth, salinity, and dissolved oxygen levels. Twenty percent of genera (i.e., 58 out 285) account for 95% of the differences between groups along the transect and among depths. All of the 38 metabolic traits studied showed some significant relationship with the tested environmental variables, especially salinity and except with temperature. Another non-metric multidimensional scaling analysis, based on community-weighted mean of traits, also grouped the samples in two clusters along the transect and over depth. Biodiversity facets, such as richness, evenness, and redundancy, indicated that environmental variations-stemming from river discharges-introduce an imbalance in functional diversity between surface prokaryote communities closer to the estuary's head and bottom communities closer to the ocean. Our research broadens the use of 16S rRNA gene transcripts beyond mere taxonomic assignments, furthering the field of trait-based prokaryote community ecology in transitional aquatic ecosystems.IMPORTANCEThe resilience of a dynamic ecosystem is directly tied to the ability of its microbes to navigate environmental gradients. This study delves into the changes in prokaryote community composition and functional diversity within the Urabá Estuary (Colombian Caribbean) for the first time. We integrate data from 16S rRNA gene transcripts (taxonomic and functional) with environmental variability to gain an understanding of this under-researched ecosystem using a multi-faceted macroecological framework. We found that significant shifts in prokaryote composition and in primary changes in functional diversity were influenced by physical-chemical fluctuations across the estuary's environmental gradient. Furthermore, we identified a potential disparity in functional diversity. Near-surface communities closer to the estuary's head exhibited differences compared to deeper communities situated farther away. Our research serves as a roadmap for posing new inquiries about the potential functional diversity of prokaryote communities in highly dynamic ecosystems, pushing forward the domain of multi-trait-based prokaryote community ecology.
Assuntos
Bactérias , Biodiversidade , Ecossistema , Estuários , RNA Ribossômico 16S , Salinidade , RNA Ribossômico 16S/genética , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Filogenia , Água do Mar/microbiologia , Água do Mar/química , Região do Caribe , Microbiota/genética , Colômbia , Microbiologia da Água , Clima TropicalRESUMO
BACKGROUND: Histological techniques are essential for the microscopic study and investigation of the human dental pulp. The aim of this study was to evaluate the impact of decalcification-free technique by examining dental pulp morphology by histological staining with haematoxylin and eosin and immunohistochemistry. MATERIALS AND METHODS: The sample consisted of 30 healthy third molars extracted for orthodontic indication, the pulp tissue was obtained by removing the mineralized tissues, separating the enamel and dentine and by marking with a flexible diamond disc on the coronal surface and longitudinal axis of the root. These guides made it possible to separate the fragments and obtain the pulp tissue for fixation and staining with H&E and subsequent immunohistochemistry with CD34 and S-100 antibodies. RESULTS: The technique showed preservation of pulp morphology with adequate preservation of microscopic structures. No alterations in tissue viability were observed. The staining allowed an accurate assessment of vascular and nervous components by means of CD34 and S-100 markers, respectively. CONCLUSIONS: This technique allows preservation of pulp tissue, maintaining viable tissue for histological analysis and immunohistochemistry tests, as well as reducing sample processing time.
RESUMO
A total of 231 blood samples from wild mammals belonging to the orders Rodentia (n = 142) and Didelphimorphia (n = 89) were screened by real-time PCR assay (qPCR), being six Rhipidomys sp., 118 Thrichomys laurentius, nine Rattus rattus, four Kerodon rupestris, five Necromys lasiurus, 42 Didelphis albiventris and 47 Monodelphis domestica. Results using qPCR showed that 32 of the total 231 (13.85 %) samples were positive for hemoplasma sequences of the 16S rRNA gene. Sequences from two D. albiventris showed 99.77-99.89 % identity with 'Candidatus Mycoplasma haemoalbiventris' and 99.09 % with 'Candidatus Mycoplasma haemodidelphidis', respectively. Furthermore, one M. domestica and five T. laurentius showed 99.72-99.77 % identity with Mycoplasma sp., and one K. rupestris showed 98.13 % identity with 'Candidatus Mycoplasma haematohydrochaerus'; and from two Rattus rattus showed 99.65-99.89 % identity with Mycoplasma sp. and 'Candidatus Mycoplasma haemomuris'. The 23S rRNA gene sequences obtained from the two D. albiventris showed 100 % identity with 'Ca. M. haemoalbiventris' whereas the sequences from the R. rattus showed only 85.31 % identity with 'Candidatus Mycoplasma haematohydrochaerus'. Two T. laurentius and one K. rupestris showed 84.66-92.97 % identity with 'Candidatus Mycoplasma haemosphiggurus'. Based on phylogenetic and Neighbor-Net network analyses of the 16S and 23S rRNA genes, potential novel species are described. In addition, 'Ca. M. haemoalbiventris' was detected in Didelphis albiventris, and Mycoplasma sp. was detected in Rattus sp. rodents from the Caatinga biome, Brazil.
Assuntos
Marsupiais , Infecções por Mycoplasma , Mycoplasma , Filogenia , RNA Ribossômico 16S , Roedores , Animais , Mycoplasma/genética , Mycoplasma/classificação , Mycoplasma/isolamento & purificação , Brasil , RNA Ribossômico 16S/genética , Roedores/microbiologia , Infecções por Mycoplasma/veterinária , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/epidemiologia , Marsupiais/microbiologia , Análise de Sequência de DNA , DNA Bacteriano/genética , DNA Ribossômico/genética , Reação em Cadeia da Polimerase em Tempo Real , Animais Selvagens/microbiologia , Dados de Sequência MolecularRESUMO
Vicuñas (Vicugna vicugna) are wild South American camelids (SACs) protected by law in Argentina, and information on pathogens that infect them is scarce. In this study, an adult vicuña found dead in the province of Salta was examined, and evidence of infection by Sarcocystis sp. protozoans was sought. Infection of skeletal muscles by S. aucheniae, with the production of macroscopic sarcocysts, a disease known as SAC sarcocystosis, has been described in the other three SACs - llamas, alpacas, and guanacos - but its occurrence in vicuñas has so far remained unknown. In the analyzed individual, many macroscopic cysts compatible with S. aucheniae were found upon necropsy in the muscular tissue of the neck and diaphragm. Analysis of 18 S rRNA and cytochrome c oxidase subunit 1 (cox-1) gene sequences by BLAST searches and construction of phylogenetic trees demonstrated that the etiological agent was S. aucheniae. Our results show for the first time that vicuñas act as intermediate hosts in the life cycle of this parasite. In addition, this study provides the first cox-1 sequences for S. aucheniae isolates from the four SAC species acting as intermediate hosts and suggests that this marker could be useful for genotypification of this parasite species. The impact of SAC sarcocystosis on the health, well-being, and fitness of vicuñas, and the relevance of vicuña infections in the epidemiology of S. auchaniae, remain to be elucidated.
Assuntos
Filogenia , Sarcocystis , Sarcocistose , Animais , Sarcocystis/genética , Sarcocystis/isolamento & purificação , Sarcocystis/classificação , Sarcocistose/veterinária , Sarcocistose/parasitologia , Argentina , RNA Ribossômico 18S/genética , RNA Ribossômico 18S/análise , Camelídeos Americanos/parasitologia , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/análiseRESUMO
Introduction: In recent decades, Caribbean coral reefs have lost many vital marine species due to diseases. The well-documented mass mortality event of the long-spined black sea urchin Diadema antillarum in the early 1980s stands out among these collapses. This die-off killed over 90% of D. antillarum changing the reefscape from coral to algal-dominated. Nearly 40 years later, D. antillarum populations have yet to recover. In early 2022, a new mortality event of D. antillarum was reported along the Caribbean, including Puerto Rico. Methods: This study identifies the gut microbiota changes associated with the D. antillarum during this mortality event. It contrasts them with the bacterial composition of gut samples from healthy individuals collected in 2019 by using 16S rRNA sequencing analyses. Results: Notably, the die-off group's core microbiome resembled bacteria commonly found in the human skin and gut, suggesting potential anthropogenic contamination and wastewater pollution as contributing factors to the 2022 dysbiosis. The animals collected in 2022, especially those with signs of disease, lacked keystone taxa normally found in Diadema including Photobacterium and Propionigenium. Discussion: The association between human microbes and disease stages in the long-spined urchin D. antillarum, especially in relation to anthropogenic contamination, highlights a complex interplay between environmental stressors and marine health. While these microbes might not be the direct cause of death in this species of sea urchins, their presence and proliferation can indicate underlying issues, such as immune depletion due to pollution, habitat destruction, or climate change, that ultimately compromise the health of these marine organisms.
RESUMO
BACKGROUND: Peripheral venous catheters (PVCs) remain the primary mode of short-term venous access for managing intravenous fluid, obtaining blood samples, and peripheral parenteral nutrition. They may get contaminated and require regular monitoring to prevent complications. This study evaluated the occurrence of phlebitis and its associated-clinical and microbiological indicators. METHODS: The frequency of phlebitis was evaluated in hospitalized patients of both medical and surgical fields. Subsequently, the dichotomous association between the presence of phlebitis and the clinical aspects was investigated. In parallel, the bacterial contamination of PVCs was assessed through culture-based methods, microscopy observation, and 16S rRNA gene sequencing. RESULTS: Approximately one in four patients presented phlebitis (28.4%). The most frequent symptom was erythema at access site, with or without pain, corresponding to Score 1 on the phlebitis scale (17.9%). Colonization of both lumen and external surface of PVC was observed in 31.3% of the samples. Staphylococcus and Pseudomonas were the most isolated bacterial genera on the PVC surface. No significant association was observed between the presence of phlebitis and the clinical aspects, as well as the presence of microorganisms. CONCLUSION: Microorganism were present on both internal and external PVC surface, without being associated to phlebitis.
RESUMO
Bisphenol S (BPS) is widely used in the manufacture products and increase the risk of cardiovascular diseases. The effect of the association between obesity and BPS on cardiac outcomes is still unknown. Male C57BL/6 mice were divided into standard chow diet (SC; 15 kJ/g), standard chow diet + BPS (SCB), high-fat diet (HF; 21 kJ/g), and high-fat diet + BPS (HFB). Over 12 weeks, the groups were exposed to BPS through drinking water (dose: 25 µg/kg/day) and/or a HF diet. We evaluated: body mass (BM), total cholesterol, systolic blood pressure (SBP), left ventricle (LV) mass, and cardiac remodeling. In the SCB group, BM, total cholesterol, and SBP increase were augmented in relation to the SC group. In the HF and HFB groups, these parameters were higher than in the SC and SCB groups. Cardiac hypertrophy was evidenced by augmented LV mass and wall thickness, and ANP protein expression in all groups in comparison to the SC group. Only the HFB group had a thicker LV wall than SCB and HF groups, and increased cardiomyocyte area when compared with SC and SCB groups. Concerning cardiac fibrosis, SCB, HF, and HFB groups presented higher interstitial collagen area, TGFß, and α-SMA protein expression than the SC group. Perivascular collagen area was increased only in the HF and HFB groups than SC group. Higher IL-6, TNFα, and CD11c protein expression in all groups than the SC group evidenced inflammation. All groups had elevated CD36 and PPARα protein expression in relation to the SC group, but only HF and HFB groups promoted cardiac steatosis with increased perilipin 5 protein expression than the SC group. BPS exposure alone promoted cardiac remodeling with pathological concentric hypertrophy, fibrosis, and inflammation. Diet-induced remodeling is aggravated when associated with BPS, with marked hypertrophy, alongside fibrosis, inflammation, and lipid accumulation.
Assuntos
Cardiomegalia , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Fenóis , Animais , Masculino , Dieta Hiperlipídica/efeitos adversos , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Camundongos , Fenóis/toxicidade , Remodelação Ventricular/efeitos dos fármacos , SulfonasRESUMO
Mammalian and reptilian vascular tissues present basal release of 6-nitrodopamine, which is reduced when the tissues are pre-incubated with the NO synthase inhibitor L-NG-Nitro arginine methyl ester (L-NAME), or when the endothelium is mechanically removed. 6-Nitrodopamine induces vasorelaxation in pre-contracted vascular rings by antagonizing the dopaminergic D2-like receptor. Here it was investigated whether male swine vessels (including carotid, left descendent coronary, renal, and femoral arteries) release 6-nitrodopamine, dopamine, noradrenaline, and adrenaline, as measured by liquid chromatography coupled to tandem mass spectrometry. The in vitro vasorelaxant action of 6-nitrodopamine was evaluated in carotid, coronary, renal, and femoral arteries precontracted by U-46619 (3 nM), and compared to that induced by the dopamine D2-receptor antagonist L-741,626. Expression of tyrosine hydroxylase and the neuromaker calretinin was investigated by immunohistochemistry. All vascular tissues presented basal release of endothelium-derived catecholamines. The relaxation induced by 6-nitrodopamine was not affected by preincubation of the tissues with either L-NAME (100 µM, 30-min preincubation) or the heme-site inhibitor of soluble guanylyl cyclase ODQ (100 µM, 30-min preincubation). Electrical field stimulation (EFS)-induced contractions were significantly potentiated by previous incubation with L-NAME, but unaffected by ODQ preincubation. The contractions induced by EFS were reduced by preincubation with either 6-nitrodopamine or L-741,626. Immunohistochemistry in all arteries revealed the presence of tyrosine hydroxylase in the endothelium, whereas immunoreactivity for calretinin was negative. Swine vessels present basal release of endothelium-derived catecholamines and expression of tyrosine hydroxylase in the endothelium. The vasodilation induced by 6-nitrodopamine is due to blockade of dopaminergic D2-like receptors.
Assuntos
Vasodilatação , Animais , Masculino , Vasodilatação/efeitos dos fármacos , Suínos , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/metabolismo , Artéria Femoral/fisiologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiologia , Vasos Coronários/metabolismo , Artéria Renal/efeitos dos fármacos , Artéria Renal/metabolismo , Artéria Renal/fisiologia , Dopamina/metabolismo , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/metabolismo , Artérias Carótidas/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Vasodilatadores/farmacologiaRESUMO
OBJECTIVE: To identify the difference in breast cancer mortality rates among young women according to countries' economic classification. METHODS: A systematic literature review included retrospective studies on breast cancer mortality rates in women aged 20 to 49 years. Databases used were PubMed, Web of Science, Scopus, and Virtual Health Library, with articles selected in English, Portuguese, and Spanish. The study selection and analysis were conducted by two pairs of researchers. Data from 54 countries were extracted, including 39 high-income, 12 upper-middle-income, and 3 lower-middle-income countries. A meta-analysis was performed with the quantitative data from two studies. RESULTS: Six articles met the inclusion criteria. Four were analyzed descriptively due to data diversity, and two were included in the meta-analysis. The pooled mortality rate for high-income countries was 10.2 per 100,000 women (95% CI: 9.8-10.6), while for upper-middle-income countries, it was 15.5 per 100,000 women (95% CI: 14.9-16.1). Lower-middle-income countries had a pooled mortality rate of 20.3 per 100,000 women (95% CI: 19.5-21.1). The decrease in mortality rates in high-income countries was statistically significant (p<0.05). CONCLUSION: Mortality rates for breast cancer among young women have decreased significantly in high-income countries but have increased in lower-income countries. This disparity underscores the impact of insufficient investment in preventive measures, health promotion, early diagnosis, and treatment on young women's mortality in lower-income countries.
Assuntos
Neoplasias da Mama , Países Desenvolvidos , Países em Desenvolvimento , Humanos , Feminino , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Prognóstico , Adulto Jovem , Adulto , Taxa de Sobrevida , Renda , Pessoa de Meia-Idade , Fatores SocioeconômicosRESUMO
OBJECTIVE: Individuals with Down Syndrome (DS) exhibit a higher susceptibility to infections, suggesting potential immunological alterations within this population. Consequently, this study aims to assess the immune response profile in children with DS to identify potential immune dysfunctions associated with recurrent infections. METHODS: The authors conducted a retrospective analysis involving 49 DS patients, examining various epidemiological, clinical, cytogenetic, and laboratory variables. The study's sample comprised patients aged 2-20 years, with a predominance of males. These patients were categorized into two groups based on the presence or absence of recurrent infections, as indicated by the Jeffrey Modell Foundation alert signs. RESULTS: Immunoglobulin (Ig) A, G, and M levels were deemed normal, although individuals with DS experiencing recurrent infections exhibited significantly lower IgA levels. Additionally, CD3, CD4, CD8, and CD19 lymphocyte counts were found to be within normal ranges, with no significant differences between the two groups. While overall data indicated normal seroconversion levels of pneumococcal polysaccharide antibodies, a notable impairment in seroconversion was observed among DS patients with recurrent infections compared to those without such infections. CONCLUSION: The deficiency of anti-polysaccharide antibodies in individuals with DS may constitute an important immunological comorbidity. Therefore, it warrants further investigation, particularly among individuals with recurrent infections.
Assuntos
Síndrome de Down , Recidiva , Humanos , Síndrome de Down/imunologia , Síndrome de Down/complicações , Masculino , Criança , Feminino , Adolescente , Estudos Retrospectivos , Pré-Escolar , Adulto JovemRESUMO
Glioblastoma (GBM) is an aggressive form of cancer affecting the Central Nervous System (CNS) of thousands of people every year. Redox alterations have been shown to play a key role in the development and progression of these tumors as Reactive Oxygen Species (ROS) formation is involved in the modulation of several signaling pathways, transcription factors, and cytokine formation. The second-generation oral alkylating agent temozolomide (TMZ) is the first-line chemotherapeutic drug used to treat of GBM, though patients often develop primary and secondary resistance, reducing its efficacy. Antioxidants represent promising and potential coadjutant agents as they can reduce excessive ROS formation derived from chemo- and radiotherapy, while decreasing pharmacological resistance. S-allyl-cysteine (SAC) has been shown to inhibit the proliferation of several types of cancer cells, though its precise antiproliferative mechanisms remain poorly investigated. To date, SAC effects have been poorly explored in GBM cells. Here, we investigated the effects of SAC in vitro, either alone or in combination with TMZ, on several toxic and modulatory endpoints-including oxidative stress markers and transcriptional regulation-in two glioblastoma cell lines from rats, RG2 and C6, to elucidate some of the biochemical and cellular mechanisms underlying its antiproliferative properties. SAC (1-750 µM) decreased cell viability in both cell lines in a concentration-dependent manner, although C6 cells were more resistant to SAC at several of the tested concentrations. TMZ also produced a concentration-dependent effect, decreasing cell viability of both cell lines. In combination, SAC (1 µM or 100 µM) and TMZ (500 µM) enhanced the effects of each other. SAC also augmented the lipoperoxidative effect of TMZ and reduced cell antioxidant resistance in both cell lines by decreasing the TMZ-induced increase in the GSH/GSSG ratio. In RG2 and C6 cells, SAC per se had no effect on Nrf2/ARE binding activity, while in RG2 cells TMZ and the combination of SAC + TMZ decreased this activity. Our results demonstrate that SAC, alone or in combination with TMZ, exerts antitumor effects mediated by regulatory mechanisms of redox activity responses. SAC is also a safe drug for testing in other models as it produces non-toxic effects in primary astrocytes. Combined, these effects suggest that SAC affords antioxidant properties and potential antitumor efficacy against GBM.
RESUMO
The use of yeast to biologically control the production of ochratoxin A, which is caused by filamentous fungal growth, in coffee farms is a promising alternative to conventional methods. However, yeast strains, environmental field conditions, and the chemical composition of grains / fruits can influence the effectiveness of biological control agents. We tested the efficiency of different yeast strains in controlling three species of ochratoxigenic fungi in a coffee-based medium. The reasons and mechanisms behind the varying sensitivities of different Aspergillus species to biological control remains unclear. Aspergillus carbonarius rapidly assimilated carbon sources, giving it an advantage over yeasts in substrate colonisation. Saccharomyces cerevisiae CCMA 0159 inhibited all three fungal species, achieving efficiencies of 74.4%, 100%, and 80.9% against A. carbonarius, A. westerdijkiae, and A. ochraceus, respectively. The strategies employed by S. cerevisiae CCMA 0159 to inhibit the growth of ochratoxigenic fungi included competition, production of fungicidal volatile compounds, and alteration of the substrate's physicochemical properties. Our results indicate that among the yeast isolates tested, S. cerevisiae CCMA 0159 is the most effective in inhibiting ochratoxigenic fungi in coffee, including the more resistant A. carbonarius.
RESUMO
BACKGROUND: This study investigates the contamination level, spatial distribution, pollution sources, potential ecological risks, and human health risks associated with heavy metal(loid)s (i.e., arsenic (As), copper (Cu), iron (Fe), manganese (Mn), lead (Pb), and zinc (Zn)) in surface soils within the mining region of Matehuala, located in central Mexico. OBJECTIVES: The primary objectives are to estimate the contamination level of heavy metal(loid)s, identify pollution sources, assess potential ecological risks, and evaluate human health risks associated with heavy metal(loid) contamination. METHODS: Soil samples from the study area were analysed using various indices including Igeo, Cf, PLI, mCd, EF, and PERI to evaluate contamination levels. Source apportionment of heavy metal(loid)s was conducted using the APCS-MLR and PMF receptor models. Spatial distribution patterns were determined using the most efficient interpolation technique among five different approaches. The total carcinogenic risk index (TCR) and total non-carcinogenic index (THI) were used in this study to assess the potential carcinogenic and non-carcinogenic hazards posed by heavy metal(loid)s in surface soil to human health. RESULTS: The study reveals a high contamination level of heavy metal(loid)s in the surface soil, posing considerable ecological risks. As was identified as a priority metal for regulatory control measures. Mining and smelting activities were identified as the primary factors influencing heavy metal(loid) distributions. Based on spatial distribution mapping, concentrations were higher in the northern, western, and central regions of the study area. As and Fe were found to pose considerable and moderate ecological risks, respectively. Health risk evaluation indicated significant levels of carcinogenic risks for both adults and children, with higher risks for children. CONCLUSION: This study highlights the urgent need for monitoring heavy metal(loid) contamination in Matehuala's soils, particularly in regions experiencing strong economic growth, to mitigate potential human health and ecological risks associated with heavy metal(loid) pollution.
Assuntos
Monitoramento Ambiental , Metais Pesados , Mineração , Poluentes do Solo , México , Poluentes do Solo/análise , Medição de Risco , Metais Pesados/análise , Humanos , Monitoramento Ambiental/métodosRESUMO
Alzheimer's disease (AD) constitutes a major public-health issue of our time. Regrettably, despite our considerable understanding of the pathophysiological aspects of this disease, current interventions lead to poor outcomes. Furthermore, experimentally promising compounds have continuously failed when translated to clinical trials. Along with increased population ageing, Type 2 Diabetes Mellitus (T2DM) has become an extremely common condition, mainly due to unbalanced dietary habits. Substantial epidemiological evidence correlates T2DM with cognitive impairment as well. Considering that brain insulin resistance, mitochondrial dysfunction, oxidative stress, and amyloidogenesis are common phenomena, further approaching the common features among these pathological conditions. Metformin constitutes the first-choice drug to preclude insulin resistance in T2DM clinical management. Experimental evidence suggests that its functions might include neuroprotective effects, in addition to its hypoglycemic activity. This review aims to summarize and discuss current knowledge of experimental data on metformin on this path towards translational medicine. Finally, we discuss the controversial data of responses to metformin in vitro, and in vivo, animal models and human studies.
Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Metformina , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Metformina/uso terapêutico , Metformina/farmacologia , Humanos , Animais , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Pesquisa Translacional Biomédica/métodos , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Resistência à Insulina/fisiologiaRESUMO
Earth harbors unique environments where only microorganisms adapted to extreme conditions, known as extremophiles, can survive. This study focused on a high-altitude meltwater pond, located in the Puna de Atacama, Dry Andes. The extremophilic bacteria of this habitat must adapt to a range of extremities, including cold and dry climate, high UV radiation, high daily temperature fluctuations, low-nutrient availability, and negative water balance. This study aimed to explore the taxonomic diversity of cultivable extremophilic bacteria from sediment samples of a desiccated, high-altitude, meltwater pond using media with different organic matter contents and different incubation temperatures. Based on the 16S rRNA gene sequence analysis, the isolates were identified as members of the phyla Actinobacteria, Proteobacteria, and Firmicutes. The most abundant genera were Arthrobacter and Pseudoarthrobacter. The isolates had oligocarbophilic and psychrotrophic properties, suggesting that they have adapted to the extreme environmental parameters of their natural habitats. The results indicate a positive correlation between nutrient concentration and temperature tolerance.
Assuntos
Altitude , Bactérias , Lagoas , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Lagoas/microbiologia , Chile , Extremófilos , RNA Ribossômico 16S/genética , Microbiologia da ÁguaRESUMO
Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) control antral follicular growth by regulating several processes, such as the synthesis of hormones and signaling molecules, proliferation, survival, apoptosis, luteinization, and ovulation. To exert these effects, gonadotropins bind to their respective Gs protein-coupled receptors, activating the protein kinase A (PKA) pathway or recruiting Gq proteins to activate protein kinase C (PKC) signaling. Although the action mechanism of FSH and LH is clear, recently, it has been shown that both gonadotropins promote the synthesis of sphingosine-1-phosphate (S1P) in granulosa and theca cells through the activation of sphingosine kinase 1. Moreover, the inhibition of SPHKs reduces S1P synthesis, cell viability, and the proliferation of follicular cells in response to gonadotropins, and the addition of S1P to the culture medium increases the proliferation of granulosa and theca cells without apparent effects on sexual steroid synthesis. Therefore, we consider that S1P is a crucial signaling molecule that complements the canonical gonadotropin pathway to promote the proliferation and viability of granulosa and theca cells.