149 results on '"Reinaldo B. Oriá"'
Search Results
2. Susceptibility of solid organ transplant recipients to viral pathogens with zoonotic potential: A mini-review
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Karine C. Bezerra, Carlos Meton A.G. Vieira, Edmilson F. de Oliveira-Filho, Christian Robson S. Reis, and Reinaldo B. Oriá
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Zoonosis ,Virus ,Immunosuppression ,Solid organ transplantation ,Clinical outcomes ,Transplantation failure ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
A substantial number of zoonotic diseases are caused by viral pathogens, representing a significant menace to public health, particularly to susceptible populations, such as pregnant women, the elderly, and immunocompromised individuals. Individuals who have undergone solid organ transplantation frequently experience immunosuppression, to prevent organ rejection, and, thus are more prone to opportunistic infections. Furthermore, the reactivation of dormant viruses can threaten transplant recipients and organ viability. This mini-review examines the up-to-date literature covering potential zoonotic and organ rejection-relevant viruses in solid organ transplant recipients. A comprehensive list of viruses with zoonotic potential is highlighted and the most important clinical outcomes in patients undergoing transplantation are described. Moreover, this mini-review calls attention to complex multifactorial events predisposing viral coinfections and the need for continuous health surveillance and research to understand better viral pathogens' transmission and pathophysiology dynamics in transplanted individuals.
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- 2024
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3. The double burden of malnutrition and environmental enteric dysfunction as potential factors affecting gut-derived melatonin in children under adverse environments
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Alane N. Bezerra, Caroline L. Peixoto, Synara C. Lopes, Veralice M. S. Bruin, Pedro Felipe C. Bruin, and Reinaldo B. Oriá
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melatonin ,the double burden of malnutrition ,environmental enteric dysfunction ,intestinal microbiota ,poverty ,COVID-19 ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Graphical AbstractPoor environmental conditions combined with continuous unhealthy and unsafe diets may substantially increase the risk of a vicious cycle of enteric infections (EED–environmental enteric dysfunction) and malnutrition (DBM–double burden of malnutrition) in children. Gut melatonin, mainly produced by the intestinal microbiota, can modulate the composition, variety, and dynamics of the microbiota itself and may affect and be affected by intestinal microbiota alterations due to DBM and EED.
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- 2023
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4. Do APOE4 and long COVID-19 increase the risk for neurodegenerative diseases in adverse environments and poverty?
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Gabriella C. V. Ciurleo, José Wagner Leonel Tavares-Júnior, Carlos Meton A. G. Vieira, Pedro Braga-Neto, and Reinaldo B. Oriá
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long COVID-19 ,Alzheimer's disease ,antagonistic pleiotropy ,apolipoprotein E ,malnutrition ,poverty ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2023
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5. Editorial: Nutritional factors and interventions in environmental-borne diseases
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Reinaldo B. Oriá, Ronald F. Pinheiro, and Jacqueline I. Alvarez-Leite
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environmental enteric dysfunction (EED) ,pollutants ,congenital heart defect ,metabolic syndrome risk factor ,malnutrition ,trace elements ,Nutrition. Foods and food supply ,TX341-641 - Published
- 2023
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6. Myeloperoxidase as a biomarker for intestinal-brain axis dysfunction induced by malnutrition and Cryptosporidium infection in weanling mice
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Reinaldo B. Oriá, Deiziane V.S. Costa, Pedro Henrique Q.S. de Medeiros, Cássia R. Roque, Ronaldo P. Dias, Cirle A. Warren, David T. Bolick, and Richard L. Guerrant
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Cryptosporidium parvum ,Malnutrition ,Gut ,Neuroinflammation ,Myeloperoxidase ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
Cryptosporidiosis is a waterborne protozoal infection that may cause life-threatening diarrhea in undernourished children living in unsanitary environments. The aim of this study is to identify new biomarkers that may be related to gut-brain axis dysfunction in children suffering from the malnutrition/infection vicious cycle is necessary for better intervention strategies. Myeloperoxidase (MPO) is a well-known neutrophil-related tissue factor released during enteropathy that could drive gut-derived brain inflammation. We utilized a model of environmental enteropathy in C57BL/6 weanling mice challenged by Cryptosporidium and undernutrition. Mice were fed a 2%-Protein Diet (dPD) for eight days and orally infected with 107-C. parvum oocysts. C. parvum oocyst shedding was assessed from fecal and ileal-extracted genomic DNA by qRT-PCR. Ileal histopathology scores were assessed for intestinal inflammation. Prefrontal cortex samples were snap-frozen for MPO ELISA assay and NF-kb immunostaining. Blood samples were drawn by cardiac puncture after anesthesia and sera were obtained for serum amyloid A (SAA) and MPO analysis. Brain samples were also obtained for Iba-1 prefrontal cortex immunostaining. C. parvum-infected mice showed sustained stool oocyst shedding for six days post-infection and increased fecal MPO and inflammation scores. dPD and cryptosporidiosis led to impaired growth and weight gain. C. parvum-infected dPD mice showed increased serum MPO and serum amyloid A (SAA) levels, markers of systemic inflammation. dPD-infected mice showed greater MPO, NF-kB expression, and Iba-1 immunolabeling in the prefrontal cortex, an important brain region involved in executive function. Our findings suggest MPO as a potential biomarker for intestinal-brain axis dysfunction due to environmental enteropathy.
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- 2023
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7. ApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers
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Reinaldo B. Oriá, Raul S. Freitas, Cássia R. Roque, José Carlos R. Nascimento, Ana Paula Silva, João O. Malva, Richard L. Guerrant, and Michael P. Vitek
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apoE mimetic peptides ,environmental enteric dysfunction ,blood-brain barrier ,gut-brain axis ,intestinal inflammation ,malnutrition ,Pharmacy and materia medica ,RS1-441 - Abstract
Apolipoprotein E (apoE) mimetic peptides are engineered fragments of the native apoE protein’s LDL-receptor binding site that improve the outcomes following a brain injury and intestinal inflammation in a variety of models. The vicious cycle of enteric infections and malnutrition is closely related to environmental-driven enteric dysfunction early in life, and such chronic inflammatory conditions may blunt the developmental trajectories of children with worrisome and often irreversible physical and cognitive faltering. This window of time for microbiota maturation and brain plasticity is key to protecting cognitive domains, brain health, and achieving optimal/full developmental potential. This review summarizes the potential role of promising apoE mimetic peptides to improve the function of the gut-brain axis, including targeting the blood-brain barrier in children afflicted with malnutrition and enteric infections.
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- 2023
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8. Risk Factors for Severe COVID-19 and Hepatitis C Infections: The Dual Role of Apolipoprotein E4
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Felipe B. Lima, Karine C. Bezerra, José Carlos R. Nascimento, Gdayllon C. Meneses, and Reinaldo B. Oriá
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COVID-19 ,liver ,apolipoprotein E4 ,hepatitis C (HCV) infection ,inflammation ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2022
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9. Impact of apolipoprotein E genetic polymorphisms on liver disease: An essential review
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José C.R. Nascimento, Gabriella A. Matos, Lianna C. Pereira, Anderson E.C.C.B. Mourão, Aline M. Sampaio, Reinaldo B. Oriá, and Pierluigi Toniutto
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Apolipoprotein E ,Polymorphisms ,Liver cirrhosis ,Liver diseases ,Liver transplantation ,Specialties of internal medicine ,RC581-951 - Abstract
Cirrhosis is an advanced stage of liver disease, compromising liver function with systemic health implications and poor quality of life. Hepatitis C virus (HCV) infection and alcoholic liver disease are the main causes of this pathology. However, since genetic factors may play a large role in the progression and severity of liver disease, and as apolipoprotein E (apoE) has been recognised to be mainly synthesised in the liver, apoE polymorphism studies are important to better understand the causal mechanisms in liver diseases. In this review, we summarise up-to-date studies addressing how apoE polymorphisms influence liver cirrhosis and liver transplantation outcomes and potential protective mechanisms. Although more clinical studies are needed to support these findings, the apoE ɛ4 allele seems to be protective against the progression of liver cirrhosis in the majority of aetiologies and the postoperative serum apoE phenotype of the transplanted subject receptors was converted to that of the donor, indicating that >90% of apoE in plasma is synthesised in the hepatic system.
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- 2020
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10. Chronic Methylmercury Intoxication Induces Systemic Inflammation, Behavioral, and Hippocampal Amino Acid Changes in C57BL6J Adult Mice
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Tyciane S. Nascimento, Daniel V. Pinto, Ronaldo P. Dias, Ramon S. Raposo, Paulo Iury G. Nunes, Cássia R. Roque, Flávia A. Santos, Geanne M. Andrade, José Lucas Viana, Anne H. Fostier, Alessandra Sussulini, Jacqueline I. Alvarez-Leite, Carlos Fontes-Ribeiro, João O. Malva, and Reinaldo B. Oriá
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methylmercury ,metabolism ,hippocampus ,neurotransmission ,oxidative stress ,neuroinflammation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Methylmercury (MeHg) is highly toxic to the human brain. Although much is known about MeHg neurotoxic effects, less is known about how chronic MeHg affects hippocampal amino acids and other neurochemical markers in adult mice. In this study, we evaluated the MeHg effects on systemic lipids and inflammation, hippocampal oxidative stress, amino acid levels, neuroinflammation, and behavior in adult male mice. Challenged mice received MeHg in drinking water (2 mg/L) for 30 days. We assessed weight gain, total plasma cholesterol (TC), triglycerides (TG), endotoxin, and TNF levels. Hippocampal myeloperoxidase (MPO), malondialdehyde (MDA), acetylcholinesterase (AChE), amino acid levels, and cytokine transcripts were evaluated. Mice underwent open field, object recognition, Y, and Barnes maze tests. MeHg-intoxicated mice had higher weight gain and increased the TG and TC plasma levels. Elevated circulating TNF and LPS confirmed systemic inflammation. Higher levels of MPO and MDA and a reduction in IL-4 transcripts were found in the hippocampus. MeHg-intoxication led to increased GABA and glycine, reduced hippocampal taurine levels, delayed acquisition in the Barnes maze, and poor locomotor activity. No significant changes were found in AChE activity and object recognition. Altogether, our findings highlight chronic MeHg-induced effects that may have long-term mental health consequences in prolonged exposed human populations.
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- 2022
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11. The Transition From Undernutrition to Overnutrition Under Adverse Environments and Poverty: The Risk for Chronic Diseases
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Paola Caroline L. Leocádio, Synara C. Lopes, Ronaldo P. Dias, Jacqueline I. Alvarez-Leite, Richard L. Guerrant, João O. Malva, and Reinaldo B. Oriá
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malnutrition ,obesity ,intestinal microbiota ,diet ,COVID-19 ,dysbiosis ,Nutrition. Foods and food supply ,TX341-641 - Published
- 2021
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12. Methylmercury Interactions With Gut Microbiota and Potential Modulation of Neurogenic Niches in the Brain
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Daniel V. Pinto, Ramon S. Raposo, Gabriella A. Matos, Jacqueline I. Alvarez-Leite, João O. Malva, and Reinaldo B. Oriá
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methylmercury ,neurogenesis ,brain ,intestinal microbiota ,neurodegenerative diseases ,gut dysbiosis ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2020
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13. Editorial: Interplay Between Nutrition, the Intestinal Microbiota and the Immune System
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Reinaldo B. Oriá, Nuno Empadinhas, and João O. Malva
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gut microbiota ,nutrients ,inflammation ,immune system ,intestinal barrier function ,autoimmunity ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2020
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14. Obesity: More Than an Inflammatory, an Infectious Disease?
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Paola C. L. Leocádio, Reinaldo B. Oriá, Maria Elena Crespo-Lopez, and Jacqueline I. Alvarez-Leite
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obesity ,microbiota ,diet ,dysbiosis ,inflammation ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2020
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15. Causal Pathways from Enteropathogens to Environmental Enteropathy: Findings from the MAL-ED Birth Cohort Study
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Margaret N. Kosek, Tahmeed Ahmed, Zulfiquar Bhutta, Laura Caulfield, Richard Guerrant, Eric Houpt, Gagandeep Kang, Margaret Kosek, Gwenyth Lee, Aldo Lima, Benjamin J.J. McCormick, James Platts-Mills, Jessica Seidman, Rebecca R. Blank, Michael Gottlieb, Stacey L. Knobler, Dennis R. Lang, Mark A. Miller, Karen H. Tountas, Zulfiqar A. Bhutta, William Checkley, Richard L. Guerrant, Carl J. Mason, Laura E. Murray-Kolb, William A. Petri, Jr., Jessica C. Seidman, Pascal Bessong, Rashidul Haque, Sushil John, Aldo A.M. Lima, Estomih R. Mduma, Reinaldo B. Oriá, Prakash Sunder Shrestha, Sanjaya Kumar Shrestha, Erling Svensen, Anita K.M. Zaidi, Cláudia B. Abreu, Angel Mendez Acosta, Imran Ahmed, A.M. Shamsir Ahmed, Asad Ali, Ramya Ambikapathi, Leah Barrett, Aubrey Bauck, Eliwaza Bayyo, Ladaporn Bodhidatta, Anuradha Bose, J. Daniel Carreon, Ram Krishna Chandyo, Vivek Charu, Hilda Costa, Rebecca Dillingham, Alessandra Di Moura, Viyada Doan, Jose Quirino Filho, Jhanelle Graham, Christel Hoest, Iqbal Hossain, Munirul Islam, M. Steffi Jennifer, Shiny Kaki, Beena Koshy, Álvaro M. Leite, Noélia L. Lima, Bruna L.L. Maciel, Mustafa Mahfuz, Cloupas Mahopo, Angelina Maphula, Monica McGrath, Archana Mohale, Milena Moraes, Francisco S. Mota, Jayaprakash Muliyil, Regisiana Mvungi, Gaurvika Nayyar, Emanuel Nyathi, Maribel Paredes Olortegui, Reinaldo Oria, Angel Orbe Vasquez, William K. Pan, John Pascal, Crystal L. Patil, Laura Pendergast, Silvia Rengifo Pinedo, Stephanie Psaki, Mohan Venkata Raghava, Karthikeyan Ramanujam, Muneera Rasheed, Zeba A. Rasmussen, Stephanie A. Richard, Anuradha Rose, Reeba Roshan, Barbara Schaefer, Rebecca Scharf, Srujan L. Sharma, Binob Shrestha, Rita Shrestha, Suzanne Simons, Alberto M. Soares, Rosa M.S. Mota, Sajid Soofi, Tor Strand, Fahmida Tofail, Rahul J. Thomas, Ali Turab, Manjeswori Ulak, Vivian Wang, Ladislaus Yarrot, Pablo Peñataro Yori, Didar Alam, Caroline Amour, Cesar Banda Chavez, Sudhir Babji, Rosa Rios de Burga, Julian Torres Flores, Jean Gratz, Ajila T. George, Dinesh Hariraju, Alexandre Havt, Priyadarshani Karunakaran, Robin P. Lazarus, Ila F. Lima, Dinesh Mondal, Pedro H.Q.S. Medeiros, Rosemary Nshama, Josiane Quetz, Shahida Qureshi, Sophy Raju, Anup Ramachandran, Rakhi Ramadas, A. Catharine Ross, Mery Siguas Salas, Amidou Samie, Kerry Schulze, E. Shanmuga Sundaram, Buliga Mujaga Swema, and Dixner Rengifo Trigoso
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Enteropathy ,Undernutrition ,Stunting ,Enteropathogen ,Child growth ,Child health ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. Methods: Non-diarrheal stool samples (N = 22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N = 6363) and plasma alpha-1-acid glycoprotein (AGP) (N = 2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0–2 years of age. Findings: Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. Interpretation: The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation. Funding: Bill & Melinda Gates Foundation.
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- 2017
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16. Effect of Hypoproteic and High-Fat Diets on Hippocampal Blood-Brain Barrier Permeability and Oxidative Stress
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Cristhyane Costa de Aquino, Ricardo A. Leitão, Luís A. Oliveira Alves, Vanessa Coelho-Santos, Richard L. Guerrant, Carlos F. Ribeiro, João O. Malva, Ana P. Silva, and Reinaldo B. Oriá
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high-fat diet ,regional basic diet ,blood-brain barrier ,neuroinflammation ,oxidative stress ,malnutrition ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Worldwide, millions of people are exposed to dietary imbalance that impacts in health and quality of life. In developing countries, like in Brazil, in poor settings, dietary habits, traditionally hypoproteic, are changing rapidly to western-type high-fat foods. These rapidly changing dietary habits are imposing new challenges to human health and there are many questions in the field that remain to be answered. Accordingly, we currently do not know if chronic consumption of hypoproteic (regional basic diet, RBD) or high-fat diets (HFD) may impact the brain physiology, contributing to blood-brain barrier (BBB) dysfunction and neuroinflammatory events. To address this issue, mice were challenged by breastfeeding from dams receiving standard, RBD or HFD from suckling day 10 until weaning. Immediately after weaning, mice continued under the same diets until post-natal day 52. Herein, we show that both RBD and HFD cause not only a peripheral but also a consistent central neuroinflammatory response, characterized by an increased production of Reactive Oxygen Species (ROS) and pro-inflammatory cytokines. Additionally, BBB hyperpermeability, accounted by an increase in hippocampal albumin content, a decrease in claudin-5 protein levels and collagen IV immunostaining, was also observed together with an upregulation of vascular cell adhesion molecule 1 (VCAM-1). Interestingly, we also identified a significant astrogliosis, manifested by upregulation of GFAP and S100β levels and an intensification of arbor complexity of these glial cells. In sum, our data show that dietary imbalance, related with hypoproteic or high-fat content, impairs BBB properties potentially favoring the transmigration of peripheral immune cells and induces both a peripheral and central neuroinflammatory status. Noteworthy, neuroinflammatory events in the hippocampus may cause neuronal malfunction leading to cognitive deficits and long-term persistence of this phenomenon may contribute to age-related neurodegenerative diseases.
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- 2019
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17. Cellular and Molecular Mechanisms Mediating Methylmercury Neurotoxicity and Neuroinflammation
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João P. Novo, Beatriz Martins, Ramon S. Raposo, Frederico C. Pereira, Reinaldo B. Oriá, João O. Malva, and Carlos Fontes-Ribeiro
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mercury cycle ,Methylmercury ,neuroinflammation ,neurotoxicity ,microglia ,oligodendrocytes ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Methylmercury (MeHg) toxicity is a major environmental concern. In the aquatic reservoir, MeHg bioaccumulates along the food chain until it is consumed by riverine populations. There has been much interest in the neurotoxicity of MeHg due to recent environmental disasters. Studies have also addressed the implications of long-term MeHg exposure for humans. The central nervous system is particularly susceptible to the deleterious effects of MeHg, as evidenced by clinical symptoms and histopathological changes in poisoned humans. In vitro and in vivo studies have been crucial in deciphering the molecular mechanisms underlying MeHg-induced neurotoxicity. A collection of cellular and molecular alterations including cytokine release, oxidative stress, mitochondrial dysfunction, Ca2+ and glutamate dyshomeostasis, and cell death mechanisms are important consequences of brain cells exposure to MeHg. The purpose of this review is to organize an overview of the mercury cycle and MeHg poisoning events and to summarize data from cellular, animal, and human studies focusing on MeHg effects in neurons and glial cells. This review proposes an up-to-date compendium that will serve as a starting point for further studies and a consultation reference of published studies.
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- 2021
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18. Revisiting Inbred Mouse Models to Study the Developing Brain: The Potential Role of Intestinal Microbiota
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Reinaldo B. Oriá, João O. Malva, Patricia L. Foley, Raul S. Freitas, David T. Bolick, and Richard L. Guerrant
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mouse models ,developing brain ,immune system ,environment ,intestinal microbiota ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2018
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19. Genetic Susceptibility to Neurodegeneration in Amazon: Apolipoprotein E Genotyping in Vulnerable Populations Exposed to Mercury
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Gabriela P. F. Arrifano, Rosa C. R. Martín-Doimeadios, María Jiménez-Moreno, Sergio Fernández-Trujillo, Marcus Augusto-Oliveira, José R. Souza-Monteiro, Barbarella M. Macchi, Jacqueline I. Alvarez-Leite, José L. M. do Nascimento, Marcos T. Amador, Sidney Santos, Ândrea Ribeiro-dos-Santos, Liz C. Silva-Pereira, Reinaldo B. Oriá, and Maria E. Crespo-Lopez
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ApoE ,Tapajós ,Tucuruí ,human ,methylmercury ,ancestry ,Genetics ,QH426-470 - Abstract
Human exposure to mercury is a serious problem of public health in Amazon. As in other vulnerable populations throughout the world, Amazonian riverine populations are chronically exposed to this metal and some symptoms of mercury intoxication were already detected in these populations. However, studies on the genetic susceptibility to mercury toxicity in the Amazon are scarce, and they tested a limited number of individuals. In this context, apolipoprotein E gene (APOE) is a key element with a well-established association among their alleles and the neurodegenerative consequences of mercury intoxication. However, no studies have addressed APOE genotyping in Amazonian exposed populations. Additionally, epidemiological studies with APOE genotyping in Amazon have been restricted to indigenous populations. Therefore, this work analyzed for the first time the genotypic and allelic profiles of APOE in Amazonian riverine populations chronically exposed to mercury. Eight hundred and twenty three individuals were enrolled in our study donating blood (794) and/or hair (757). APOE genotyping was analyzed by real-time PCR. Total mercury and mercury species were quantified by ICP-MS and GC-pyro-AFS, respectively. Genomic ancestry markers were evaluated by multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. The 𝜀3 and 𝜀3/𝜀3 were the most frequent allele and genotype, respectively, followed by 𝜀4 allele and 𝜀3/𝜀4 genotype. Only 𝜀2/𝜀2 genotype was not found, suggesting that the absence of this genotype is a generalized phenomenon in Amazon. Also, our data supported an association between the presence of APOE4 and the Amerindian origin in these populations. Fifty-nine individuals were identified at maximum risk with levels of mercury above 10 μg/g and the presence of APOE4. Interestingly, among individuals with high mercury content, APOE4-carriers had high mercury levels than APOE2-carriers, pointing to a different heavy metal accumulation according to the APOE allele. These data suggest that APOE4, in addition to a possible pharmacodynamic effect, may influence pharmacokinetically the mercury exposure causing its higher accumulation and leading to worse deleterious consequences. Our results may aid in the development of prevention strategies and health policy decision-making regarding these at-risk vulnerable populations.
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- 2018
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20. Effects of glutamine alone or in combination with zinc and vitamin A on growth, intestinal barrier function, stress and satiety-related hormones in Brazilian shantytown children
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Aldo A.M. Lima, Gregory M. Anstead, Qiong Zhang, Ítalo L. Figueiredo, Alberto M. Soares, Rosa M.S. Mota, Noélia L. Lima, Richard L. Guerrant, and Reinaldo B. Oriá
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Micronutrients ,Stress ,Growth and Development ,Intestinal Barrier Function ,Hormonal Biomarkers ,Medicine (General) ,R5-920 - Abstract
OBJECTIVE: To determine the impact of supplemental zinc, vitamin A, and glutamine alone or in combination on growth, intestinal barrier function, stress and satiety-related hormones among Brazilian shantytown children with low median height-for-age z-scores. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in children aged two months to nine years from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for testing (a total of 120 children) were as follows: (1) glutamine alone, n = 38; (2) glutamine plus vitamin A plus zinc, n = 37; and a placebo (zinc plus vitamin A vehicle) plus glycine (isonitrogenous to glutamine) control treatment, n = 38. Leptin, adiponectin, insulin-like growth factor (IGF-1), and plasma levels of cortisol were measured with immune-enzymatic assays; urinary lactulose/mannitol and serum amino acids were measured with high-performance liquid chromatography. ClinicalTrials.gov: NCT00133406. RESULTS: Glutamine treatment significantly improved weight-for-height z-scores compared to the placebo-glycine control treatment. Either glutamine alone or all nutrients combined prevented disruption of the intestinal barrier function, as measured by the percentage of lactulose urinary excretion and the lactulose:mannitol absorption ratio. Plasma leptin was negatively correlated with plasma glutamine (p = 0.002) and arginine (p = 0.001) levels at baseline. After glutamine treatment, leptin was correlated with weight-for-age (WAZ) and weight-for-height z-scores (WHZ) (p≤0.002) at a 4-month follow-up. In addition, glutamine and all combined nutrients (glutamine, vitamin A, and zinc) improved the intestinal barrier function in these children. CONCLUSION: Taken together, these findings reveal the benefits of glutamine alone or in combination with other gut-trophic nutrients in growing children via interactions with leptin.
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- 2014
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21. Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning
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Aldo A. M. Lima, Michelle P. Kvalsund, Paula P. E. de Souza, Ítalo L Figueiredo, Alberto M. Soares, Rosa M. S. Mota, Noélia L. Lima, Relana C. Pinkerton, Peter P. Patrick, Richard L. Guerrant, and Reinaldo B. Oriá
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Malnutrition ,Cognition ,Zinc ,Vitamin A ,Glutamine ,Child ,Medicine (General) ,R5-920 - Abstract
OBJECTIVE: To identify the impact of supplemental zinc, vitamin A, and glutamine, alone or in combination, on long-term cognitive outcomes among Brazilian shantytown children with low median height-for-age z-scores. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in children aged three months to nine years old from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for cognitive testing (total of 167 children) were: (1) placebo, n = 25; (2) glutamine, n = 23; (3) zinc, n = 18; (4) vitamin A, n = 19; (5) glutamine+zinc, n = 20; (6) glutamine+vitamin A, n = 21; (7) zinc+vitamin A, n = 23; and (8) glutamine+zinc+vitamin A, n = 18. Neuropsychological tests were administered for the cognitive domains of non-verbal intelligence and abstraction, psychomotor speed, verbal memory and recall ability, and semantic and phonetic verbal fluency. Statistical analyses were performed using SPSS, version 16.0. ClinicalTrials.gov: NCT00133406. RESULTS: Girls receiving a combination of glutamine, zinc, and vitamin A had higher mean age-adjusted verbal learning scores than girls receiving only placebo (9.5 versus 6.4, p = 0.007) and girls receiving zinc+vitamin A (9.5 versus 6.5, p = 0.006). Similar group differences were not found between male study children. CONCLUSIONS: The findings suggest that combination therapy offers a sex-specific advantage on tests of verbal learning, similar to that seen among female patients following traumatic brain injury.
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- 2013
22. Modulation of Intestinal Immune and Barrier Functions by Vitamin A: Implications for Current Understanding of Malnutrition and Enteric Infections in Children
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Pedro Henrique Q. S. de Medeiros, Daniel V. Pinto, Juliana Zani de Almeida, Juliana M. C. Rêgo, Francisco A. P. Rodrigues, Aldo Ângelo M. Lima, David T. Bolick, Richard L. Guerrant, and Reinaldo B. Oriá
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vitamin A supplementation ,vitamin A deficiency ,intestinal immune response ,intestinal barrier function ,enteric infections ,Nutrition. Foods and food supply ,TX341-641 - Abstract
The micronutrient vitamin A refers to a group of compounds with pleiotropic effects on human health. These molecules can modulate biological functions, including development, vision, and regulation of the intestinal barrier. The consequences of vitamin A deficiency and supplementation in children from developing countries have been explored for several years. These children live in an environment that is highly contaminated by enteropathogens, which can, in turn, influence vitamin A status. Vitamin A has been described to modulate gene expression, differentiation and function of diverse immune cells; however, the underlying mechanisms are not fully elucidated. This review aims to summarize the most updated advances on elucidating the vitamin A effects targeting intestinal immune and barrier functions, which may help in further understanding the burdens of malnutrition and enteric infections in children. Specifically, by covering both clinical and in vivo/in vitro data, we describe the effects of vitamin A related to gut immune tolerance/homeostasis, intestinal barrier integrity, and responses to enteropathogens in the context of the environmental enteric dysfunction. Some of the gaps in the literature that require further research are also highlighted.
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- 2018
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23. Estudo das alterações relacionadas com a idade na pele humana, utilizando métodos de histo-morfometria e autofluorescência Study of age-related changes in human skin using histomorphometric and autofluorescence approaches
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Reinaldo B. Oriá, Francisco Valdeci A. Ferreira, Érika N. Santana, Mariana R. Fernandes, and Gerly A. C. Brito
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derme ,envelhecimento ,envelhecimento da pele ,epiderme ,pele ,dermis ,aging ,skin aging ,epidermis ,skin ,Dermatology ,RL1-803 - Abstract
FUNDAMENTOS: O processo de envelhecimento tecidual é evidente nas modificações visíveis na pele, resultando em importantes implicações psicológicas para o indivíduo e crescente interesse científico. OBJETIVOS: O presente trabalho objetivou analisar as alterações da pele normal com o envelhecimento mediante estratégias de histomorfometria e autofluorescência. MÉTODOS: Foram coletadas amostras de pele do abdômen de 18 cadáveres, incluindo cinco indivíduos jovens (menos de 20 anos), sete indivíduos com idade intermediária (20-60 anos) e seis indivíduos idosos (mais de 60 anos). Foram feitos cortes histológicos em parafina seguidos de coloração pela Hematoxilina-Eosina (H&E) e pelo tricrômio de Van Gieson-elastina. Avaliaram-se a espessura da epiderme e derme, e a superfície de contato epidermo-dérmica. Investigaram-se ainda as modificações qualitativas do aparelho colágeno-elástico, considerando sua disposição espacial na derme. Espécimes corados em H&E também foram utilizados para autofluorescência. RESULTADOS: A espessura da epiderme e derme do grupo idoso foi significativamente diminuída (pBACKGROUND: Age-related changes are easily recognized by examining the skin and lead to important psychological implications, motivating increased scientific interest. OBJECTIVES: This study aimed to analyze, by histomorphometric and autofluorescence approaches, the aged-related alterations in normal human skin. METHODS: Normal abdominal skin samples were taken from eighteen cadavers, including five young subjects (below 20 years old), seven subjects with intermediate age (20-60 years old) and six elderly subjects (over 60 years old). Paraffin-embedded sections were prepared and stained by Hematoxylin and Eosin (H&E) and Van Gieson-elastin trichrome. Afterwards, the H&E specimens were also used for autofluorescence technique. RESULTS: The thickness of elderly epidermis and dermis was reduced compared to middle-aged and young age groups (p
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- 2003
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24. Motor neuron diseases in the University Hospital of Fortaleza (Northeastern Brazil): a clinico-demographic analysis of 87 cases
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CARLOS M. DE CASTRO-COSTA, REINALDO B. ORIÁ, OTONI C. DO VALE, JOSÉ ARNALDO M. DE ARRUDA, WAGNER G. HORTA, JOSÉ ARTUR C. D'ALMEIDA, TEREZINHA J.T. SANTOS, RODRIGO S.N. RAMOS, and MARCUS A.C. GIFONI
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motor neuron diseases ,amyotrophic lateral sclerosis ,Fortaleza (Brazil) ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
In this retrospective (1980-1998) study, we have analyzed clinico-demographically, from the records of the University Hospital of Fortaleza (Brazil), a group of 87 patients showing signs and symptoms of motor neuron diseases (MNDs). Their diagnosis was determined clinically and laboratorially. The WFN criteria were used for amyotrophic lateral sclerosis (ALS) diagnosis. The clinico-demographic analysis of the 87 cases of MNDs showed that 4 were diagnosed as spinal muscular atrophy (SMA), 5 cases as ALS subsets: 2 as progressive bulbar paralysis (PBP), 2 as progressive muscular atrophy (PMA) and 1 as monomelic amyotrophy (MA), and 78 cases of ALS. The latter comprised 51 males and 27 females, with a mean age of 42.02 years. They were sub-divided into 4 groups according to age: from 15 to 29 years (n= 17), 30 to 39 years (n= 18), 40 to 69 years (n= 39) and 70 to 78 years (n= 4). From the 78 ALS patients, 76 were of the classic sporadic form whilst only 2 were of the familial form. The analysis of the 87 patients with MNDs from the University Hospital of Fortaleza showed a predominance of ALS patients, with a high number of cases of juvenile and early onset adult sporadic ALS.
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- 2000
25. In vitro cytotoxic effects of 5-Fluorouracil on isolated murine ovarian preantral follicles
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Cláudio Cabral Campello, C. Maside, Reinaldo B. Oriá, Ramon da Silva Raposo, Johan Smitz, Juliana Zani de Almeida, Valdevane Rocha Araújo, H.H.V. Correia, José Ricardo de Figueiredo, L.A. Vieira, Naiza Arcângela Ribeiro de Sá, A.C.A. Ferreira, Pathology/molecular and cellular medicine, Clinical Biology, and Follicle Biology
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mice ,Population ,Antineoplastic Agents ,Ovary ,Biology ,Andrology ,Follicle ,Ovarian Follicle ,Food Animals ,Follicular phase ,medicine ,Animals ,meiosis ,oocytes ,Small Animals ,education ,Antrum ,education.field_of_study ,Equine ,Oocyte ,In vitro maturation ,medicine.anatomical_structure ,Fluorouracil/pharmacology ,Female ,Animal Science and Zoology ,Fluorouracil ,Hormone - Abstract
5 fluorouracil (5FU), an antineoplastic drug, is often utilized in the therapeutic regimen for several types of cancer, including the hepatoblastoma in children. The effects of 5FU on the population of ovarian preantral follicles, which is the largest oocyte reservoir, is still poorly understood. The integrity of the ovarian preantral follicle pool is important for lifelong fertility. The better understanding of such effects may favor intervention strategies to protect fertility in 5FU-treated children and women coping with cancer. To analyze the effects of 5FU on isolated murine secondary follicles in vitro, ovaries were collected from young mice (28-30 days old), and secondary follicles were isolated and cultured for 12 days in basic culture medium, with or without 5FU at concentrations of 0.3 mM, 1 mM, 3 mM, 10 mM, and 30 mM. In the in vitro study, we analyzed the percentage of morphologically normal follicles, antrum formation, follicular diameter, and hormone production. On day 12, oocytes were recovered for in vitro maturation. 5FU treatment did not alter the percentage of morphologically normal follicles. On day 12, only 1, 10, and 30 mM 5FU significantly reduced the percentage of antrum. From day 4 onwards, 5FU treatments significantly reduced follicle diameter. The meiosis resumption rate was significantly lower in all 5FU treatments. 5FU concentrations ≥3 mM reduced estradiol levels. In conclusion, 5FU does not affect follicular morphology. However, 5FU deleteriously affects follicular growth, estradiol production, and oocyte maturation in isolated ovarian follicles.
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- 2022
26. Healthy living and active aging in Latin America and the Caribbean countries: biological, demographic, and epidemiological challenges
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João M. Coelho-Filho, Reinaldo B. Oriá, Karla C. Giacomin, Gerly A.C. Brito, Marcos Santos, Veronica Aran, Manoela Heringer, Deiziane V.S. Costa, Ronaldo P. Dias, and Vivaldo M. Neto
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- 2023
27. List of contributors
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Margarida Abrantes, Raquel Alves, Sharath Anugula, Veronica Aran, Lina Badimon, Jorge N. Barreto, Grzegorz Bartosz, Fernanda Borges, Consuelo Borrás, Maria Filomena Botelho, Jean Bousquet, António M.D. Brehm, Gerly A.C. Brito, Daan Bultje, Ana Cristina Cabral, André Caetano, Helena Canhão, Isabel Marques Carreira, Ana Maria Carriazo, Cristina Carvalho, Eugenia Carvalho, Margarida Castel-Branco, Yaohua Chen, João M. Coelho-Filho, Vera Constâncio, António Correia e Silva, Deiziane V.S. Costa, Elísio Costa, Inês Costa, Teresa Cunha-Oliveira, Paulo de Carvalho, Vicenzo De Luca, Edoardo R. de Natale, Jorge Dias, Ronaldo P. Dias, Ana I. Duarte, John Farrel, Fernando Fernandez-Llimos, Lino Ferreira, Luigi Ferrucci, Isabel Vitoria Figueiredo, Jamie K. Ford, Claudio Franceschi, Alex A. Freitas, Maja Furlan de Brito, Karla C. Giacomin, Henrique Girao, Ilias Gkikas, Bárbara Gomes, Rodrigo M. Gomes, Ana Cristina Gonçalves, Peter Goulden, Marcus Grant, Luís F. Grilo, Nick Guldemond, Jorge Henriques, Manoela Heringer, Maddalena Illario, Carmen Jerónimo, John G. Jones, Joana Jorge, Yaschar Kabiri, Agnieszka Karkucinska-Wieckowska, George Kelly, James L. Kirkland, Kristina Kitaeva, Andrey Kiyasov, Viktor I. Korolchuk, Mafalda Laranjo, Thomas J. LaRocca, Marta Lavrador, Magdalena Lebiedzinska-Arciszewska, Zhiquan Li, Yuezhong Liu, Alexandre Lourenço, Lina Ma, João O. Malva, Christopher R. Martens, Cristina Mas-Bargues, Paulo Matafome, Joana Barbosa Melo, Maria L. Lima Mendonça, Athanasios Metaxakis, Lefkos T. Middleton, Paula I. Moreira, Judite M. Nascimento, Vivaldo M. Neto, Paulo J. Oliveira, Alessandro Ori, Reinaldo B. Oriá, Susan E. Ozanne, Miguel Padeiro, Teresa Padro, Carlos M. Palmeira, Yiming Pan, Simão Paredes, João F. Passos, Edith Pereira, Francisco B. Pereira, Susana P. Pereira, Paolo Pinton, Joana F. Pires, Salomé Pires, M. Cristina Polidori, Marios Politis, Nuno Raimundo, João Ramalho-Santos, Lene Juel Rasmussen, Fernando J. Regateiro, Dario D. Reis, Caio Ribeiro, Ilda Patrícia Ribeiro, Teresa M. Ribeiro-Rodrigues, Albert Rizvanov, Teresa Rocha, Susanne Röhr, Anabela P. Rolo, Aurora Román-Domínguez, Roman Romero-Ortuno, Manuel Santos Rosa, Catrin Rutland, Izabela Sadowska-Bartosz, Paula Santana, Deolinda Santinha, Marcos Santos, Ana Bela Sarmento Ribeiro, Deisa S.R.C. Semedo, João Sequeira, Felipe Sierra, Maria Natalina L. Silva, Rafael Solana, Valeriya Solovyeva, Hélder Spínola, Renata S. Tavares, Nektarios Tavernarakis, Tamar Tchkonia, Yin-Leng Theng, Vicente Traver-Salcedo, Chi Udeh-Momoh, Rakhi Verma, Stella Victorelli, Andreia Vilaça, Gemma Vilahur, José Viña, Thomas von Zglinicki, Devin Wahl, Berenice Maria Werle, Mariusz R. Wieckowski, Heather Wilson, Erin O. Wissler Gerdes, Lucyna A. Wozniak, Barbara Zavan, Yi Zhu, and Hans Zischka
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- 2023
28. Hair mercury is associated with dyslipidemia and cardiovascular risk: An anthropometric, biochemical and genetic cross-sectional study of Amazonian vulnerable populations
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Amanda Lopes-Araújo, Gabriela P. Arrifano, Barbarella M. Macchi, Marcus Augusto-Oliveira, Letícia Santos-Sacramento, Rosa C. Rodríguez Martín-Doimeadios, María Jiménez-Moreno, Arnaldo J. Martins Filho, Jacqueline I. Alvarez-Leite, Reinaldo B. Oriá, José Luiz M. do Nascimento, and Maria Elena Crespo-Lopez
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Biochemistry ,General Environmental Science - Published
- 2023
29. Urinary tubular biomarkers as predictors of death in critically ill patients with COVID-19
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Gabriela F Bezerra, Gdayllon C Meneses, Polianna LMM Albuquerque, Nicole C Lopes, Ranieri SS Santos, Juliana C da Silva, Sandra MB Mota, Rodrigo R Guimarães, Fábio R Guimarães, Álvaro R Guimarães, Caio MC Adamian, Paula R de Lima, Izabel CJ Bandeira, Márcia MP Dantas, Geraldo BS Junior, Reinaldo B Oriá, Elizabeth F Daher, and Alice MC Martins
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Lipocalin-2 ,Critical Illness ,Biochemistry (medical) ,Clinical Biochemistry ,Drug Discovery ,COVID-19 ,Humans ,Hepatitis A Virus Cellular Receptor 1 ,Prospective Studies ,Acute Kidney Injury ,Biomarkers - Abstract
Aim: To evaluate the prediction capacity of urinary biomarkers for death in critically ill patients with COVID-19. Methods: This is a prospective study with critically ill patients due to COVID-19 infection. The urinary biomarkers NGAL, KIM-1, MCP-1 and nephrin were quantified on ICU admission. Results: There was 40% of death. Urinary nephrin and MCP-1 had no association with death. Tubular biomarkers (proteinuria, NGAL and KIM-1) were predictors of death and cut-off values of them for death were useful in stratify patients with worse prognosis. In a multivariate cox regression analysis, only NGAL remains associated with a two-mount survival chance. Conclusion: Kidney tubular biomarkers, mostly urinary NGAL, had useful capacity to predict death in critically ill COVID-19 patients.
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- 2022
30. 5-Fluorouracil disrupts ovarian preantral follicles in young C57BL6J mice
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A.C.A. Ferreira, Laritza Ferreira de Lima, C. Maside, Ramon da Silva Raposo, L.A. Vieira, Valdevane Rocha Araújo, José G. Abreu, Thayse Pinheiro da Costa, José Ricardo de Figueiredo, Juliana Zani de Almeida, Sônia Nair Báo, Reinaldo B. Oriá, Cláudio Cabral Campello, Ana Beatriz Graça Duarte, and Luiz F. S. Oliveira
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0301 basic medicine ,Pharmacology ,Cancer Research ,Wnt signaling pathway ,Histology ,Ovary ,Biology ,Toxicology ,Andrology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,In vivo ,WNT2 ,030220 oncology & carcinogenesis ,medicine ,Pharmacology (medical) ,Viability assay ,Ovarian follicle ,Immunostaining - Abstract
5-Fluorouracil (5-FU), an anti-cancer drug, has been used for hepatoblastoma (HB) chemotherapy in children, who may have impaired ovarian follicle pool reserve with lasting effects to reproduction. Therefore, this study aimed to investigate 5-FU effects on survival, growth, and morphology of ovarian preantral follicles from C57BL6J young mice. Experiments were carried-out both in vivo and in vitro. Mice were treated with 5-FU injection (450 mg/kg i.p) or saline and sacrificed 3 days after to obtain ovaries for histology and molecular biology. Ovaries for in vitro studies were obtained from unchallenged mice and cultured under basic culture medium (BCM) or BCM plus 5-FU (9.2, 46.1, 92.2 mM). Preantral follicles were classified according to developmental stages, and as normal or degenerated. To assess cell viability, caspase-3 immunostaining was performed. Transcriptional levels for apoptosis (Bax, Bcl2, p53, Bax/Bcl2) and Wnt pathway genes (Wnt2 and Wnt4) were also analyzed. Ultrastructural analyses were carried-out on non-cultured ovaries. In addition, β-catenin immunofluorescence was assessed in mouse ovaries. The percentage of all-types normal follicles was significantly lower after 5-FU challenge. A total loss of secondary normal follicles was found in the 5-FU group. The highest 5-FU concentrations reduced the percentage of cultured normal primordial follicles. Large vacuoles were seen in granulosa cells and ooplasm of preantral follicles by electron microscopy. A significantly higher gene expression for Bax and Bax/Bcl2 ratio was seen after 5-FU treatment. A marked reduction in β-catenin immunolabeling was seen in 5-FU-challenged preantral follicles. In the in vitro experiments, apoptotic and Wnt gene transcriptions were significantly altered. Altogether, our findings suggest that 5-FU can deleteriously affect the ovarian follicle reserve by reducing preantral follicles survival.
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- 2021
31. Oral methylmercury intoxication aggravates cardiovascular risk factors and accelerates atherosclerosis lesion development in ApoE knockout and C57BL/6 mice
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Cláudia Carvalhinho Windmöller, Janayne L Silva, Flávia A. Santos, Anderson J. Ferreira, Luciano S. A. Capettini, Giselle Foureaux, Gianne Paul Campos, Paola Caroline Lacerda Leocádio, Jonas Martins Reis, Maria Elena Crespo-Lopez, Reinaldo B. Oriá, and Jacqueline I. Alvarez-Leite
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Apolipoprotein E ,C57BL/6 ,medicine.medical_specialty ,Health, Toxicology and Mutagenesis ,Inflammation ,010501 environmental sciences ,Toxicology ,030226 pharmacology & pharmacy ,01 natural sciences ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine.artery ,Medicine ,0105 earth and related environmental sciences ,Aorta ,biology ,business.industry ,biology.organism_classification ,Blood pressure ,Endocrinology ,Knockout mouse ,Original Article ,Liver function ,medicine.symptom ,business - Abstract
Methylmercury (MeHg) intoxication is associated with hypertension, hypercholesterolemia, and atherosclerosis by mechanisms that are not yet fully understood. We investigated the effects of MeHg intoxication in atherosclerosis-prone (ApoE-KO) and resistant C57BL/6 mice. Mice were submitted to carotid stenosis surgery (to induce atherosclerosis faster) and received water or MeHg solution (20 mg/L) for 15 days. Tail plethysmography was performed before and after MeHg exposure. Food and MeHg solution intakes were monitored weekly. On the 15th day, mice were submitted to intravital fluorescence microscopy of mesenteric vasculature to observe in vivo leukocyte rolling and adhesion. Results showed that despite the high hair and liver Hg concentrations in the MeHg group, food and water (or MeHg solution) consumption and liver function marker levels were similar to those in controls. MeHg exposure increased total cholesterol, the atherogenic (non-HDL) fraction and systolic and diastolic blood pressure. MeHg exposure also induced inflammation, as seen by the increased rolling and adhered leukocytes in the mesenteric vasculature. Atherosclerosis lesions were more extensive in the aorta and carotid sites of MeHg-ApoE knockout mice. Surprisingly, MeHg exposure also induced atherosclerosis lesions in C57BL/6 mice, which are resistant to atherosclerosis formation. We concluded that MeHg intoxication might represent a risk for cardiovascular diseases since it accelerates atherogenesis by exacerbating several independent risk factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s43188-020-00066-x) contains supplementary material, which is available to authorized users.
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- 2020
32. Apolipoprotein E Effects on Mammalian Ovarian Steroidogenesis and Human Fertility
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Juliana Zani de Almeida, Richard L. Guerrant, José Ricardo de Figueiredo, Carolyne Neves Moreira, and Reinaldo B. Oriá
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Apolipoprotein E ,endocrine system ,medicine.medical_specialty ,Apolipoprotein E2 ,Endocrinology, Diabetes and Metabolism ,Granulosa cell ,Apolipoprotein E4 ,Apolipoprotein E3 ,030209 endocrinology & metabolism ,Biology ,Endocytosis ,03 medical and health sciences ,chemistry.chemical_compound ,Apolipoproteins E ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,Animals ,Humans ,Allele ,Gene ,chemistry.chemical_classification ,Cholesterol ,Ovary ,Amino acid ,chemistry ,Female ,lipids (amino acids, peptides, and proteins) ,Glycoprotein ,Chromosomes, Human, Pair 19 - Abstract
Apolipoprotein E (ApoE) is a glycoprotein consisting of 299 amino acids, highly produced in the mammalian ovaries. The main function of the ApoE is to transport cholesterol from the peripheral tissues to be metabolized in the liver. In humans, the ApoE gene is polymorphic, with three alleles in a single chromosome-19 locus: APOE2, APOE3, and APOE4. ApoE has also been implicated in cholesterol transport within ovarian follicles to regulate steroidogenesis. Ovarian thecal and granulosa cell cholesterol uptake requires ApoE either by participating in the lipoprotein-receptor complex or lipid endocytosis. In this review, we summarize ApoE role on mammalian ovarian steroidogenesis and on human fertility and discuss recent findings of ApoE4 as an antagonistic pleiotropy gene under adverse environments.
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- 2020
33. Hypolipidemic and reduced nitrergic effects of p-hydroxycinnamic diesters extracted from Copernicia prunifera in mice challenged by a high-fat diet
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Francisca Noélia Pereira Mendes, José Ytalo Gomes da Silva, Carla Laíne Silva Lima, Eridan Orlando Pereira Tramontina Florean, Maria Izabel Florindo Guedes, Bruno Bezerra da Silva, Sandra Machado Lira, Márcia Maria Mendes Marques, Reinaldo B. Oriá, Marcelo Oliveira Holanda, Paula Alves Salmito Rodrigues, Raquel Teixeira Terceiro Paim, Ícaro Gusmão Pinto Vieira, and Luiz Francisco Wemmenson Gonçalves Moura
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Male ,Simvastatin ,Coumaric Acids ,medicine.medical_treatment ,Carnauba wax ,Interleukin-1beta ,Administration, Oral ,Hyperlipidemias ,RM1-950 ,Arecaceae ,Pharmacology ,Diet, High-Fat ,chemistry.chemical_compound ,Copernicia prunifera ,Hyperlipidemia ,Animals ,Medicine ,Liver X receptor ,Saline ,Hypolipidemic Agents ,Liver X Receptors ,Inflammation ,p-hydroxycinnamic diesters ,biology ,Plant Extracts ,business.industry ,Standard treatment ,Body Weight ,General Medicine ,Lipid Metabolism ,medicine.disease ,biology.organism_classification ,Lipids ,Mice, Inbred C57BL ,Disease Models, Animal ,High-fat diet ,Liver ,chemistry ,Female ,Therapeutics. Pharmacology ,business ,Biomarkers ,Dyslipidemia ,medicine.drug - Abstract
Dyslipidemia is a chronic non-transmissible condition that has increased due to an unhealthy lifestyle. Statins have been used as the standard treatment to control hyperlipidemia. However, side effects and high costs may be associated with its prolonged treatment, so plants derivatives have been an attractive therapy to overcome these problems. Among the compounds extracted from plants, the p-hydroxycinnamic diesters (HCE), present in carnauba wax (CW), have been found with good pharmacological properties. Therefore, this study aimed to evaluate the potential anti-hypercholesterolemic and possible toxicological effects of HCE in C57BL/6J mice under a high-fat (HF) diet. Male C57BL/6J mice were fed during 60 days under the HF diet and therefore were either treated with HCE (200 and 400 mg/kg) or simvastatin (20 mg/kg) or received saline (controls) by gavage for 30 days under the same diet. HCE treatment was able to reduce serum total cholesterol and LDL levels. Besides, this compound increased liver X receptor (LXR) and but not significantly affected IL-1β and TNF-α liver mRNA transcription activity. In conclusion, HCE treatment was found safe and may attenuate the deleterious effects of dyslipidemia due to chronic feeding with western diets.
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- 2021
34. Acute blockade of endogenous melatonin by Luzindole, with or without peripheral LPS injection, induces jejunal inflammation and morphological alterations in Swiss mice
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Daniel Vieira Pinto, Fernanda A. Santos, P.F.C. Bruin, A.S.G. Duarte, Ana Flávia Seraine Custódio Viana, Robson Salviano de Matos, V.M.S. Bruin, and Reinaldo B. Oriá
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Lipopolysaccharides ,medicine.medical_specialty ,Medicine (General) ,LPS ,Lipopolysaccharide ,Physiology ,medicine.drug_class ,QH301-705.5 ,Immunology ,Biophysics ,Ocean Engineering ,medicine.disease_cause ,Biochemistry ,Melatonin ,chemistry.chemical_compound ,Mice ,R5-920 ,Internal medicine ,medicine ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,Biology (General) ,Receptor ,Inflammation ,Luzindole ,biology ,General Neuroscience ,Cell Biology ,General Medicine ,Receptor antagonist ,Tryptamines ,Intestine ,Endocrinology ,Jejunum ,chemistry ,Oxidative stress ,Myeloperoxidase ,biology.protein ,Tumor necrosis factor alpha ,medicine.drug ,Research Article - Abstract
This study investigated the acute blockade of endogenous melatonin (MLT) using Luzindole with or without systemic lipopolysaccharide (LPS) challenge and evaluated changes in inflammatory and oxidative stress markers in the mouse jejunum. Luzindole is an MT1/MT2 MLT receptor antagonist. Both receptors occur in the small intestine. Swiss mice were treated with either saline (0.35 mg/kg, ip), Luzindole (0.35 mg/kg, ip), LPS (1.25 mg/kg, ip), or Luzindole+LPS (0.35 and 1.25 mg/kg, ip, respectively). Jejunum samples were evaluated regarding intestinal morphometry, histopathological crypt scoring, and PAS-positive villus goblet cell counting. Inflammatory Iba-1, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, nuclear factor (NF)-kB, myeloperoxidase (MPO), and oxidative stress (NP-SHs, catalase, MDA, nitrate/nitrite) markers were assessed. Mice treated with Luzindole, LPS, and Luzindole+LPS showed villus height shortening. Crypt damage was worse in the LPS group. Luzindole, LPS, and Luzindole+LPS reduced the PAS-goblet cell labeling and increased Iba-1-immunolabelled cells compared to the saline group. Immunoblotting for IL-1β, TNF-α, and NF-kB was greater in the Luzindole group. The LPS-challenged group showed higher MPO activity than the saline and Luzindole groups. Catalase was reduced in the Luzindole and Luzindole+LPS groups compared to saline. The Luzindole group showed an increase in NP-SHs, an effect related to compensatory GSH activity. The acute blockade of endogenous MLT with Luzindole induced early changes in inflammatory markers with altered intestinal morphology. The other non-detectable deleterious effects of Luzindole may be balanced by the unopposed direct action of MLT in immune cells bypassing the MT1/MT2 receptors.
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- 2021
35. Immunoinflammatory role of apolipoprotein E4 in malnutrition and enteric infections and the increased risk for chronic diseases under adverse environments
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Ludmila Belayev, Reinaldo B. Oriá, Orleâncio Gomes Ripardo de Azevedo, Cássia Rodrigues Roque, Richard L. Guerrant, Jacqueline I. Alvarez-Leite, Raul Sousa Freitas, and Gabriella Araújo Matos
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Apolipoprotein E ,Nutrition and Dietetics ,Sanitation ,business.industry ,Apolipoprotein E4 ,Malnutrition ,Medicine (miscellaneous) ,Disease ,Malnutrition in children ,medicine.disease ,Systemic inflammation ,Biobank ,Apolipoproteins E ,Alzheimer Disease ,Immunology ,Chronic Disease ,Medicine ,Humans ,lipids (amino acids, peptides, and proteins) ,Risk factor ,medicine.symptom ,business ,Child - Abstract
Apolipoprotein E plays a crucial role in cholesterol metabolism. The immunomodulatory functions of the human polymorphic APOE gene have gained particular interest because APOE4, a well-recognized risk factor for late-onset Alzheimer's disease, has also been recently linked to increased risk of COVID-19 infection severity in a large UK biobank study. Although much is known about apoE functions in the nervous system, much less is known about APOE polymorphism effects on malnutrition and enteric infections and the consequences for later development in underprivileged environments. In this review, recent findings are summarized of apoE’s effects on intestinal function in health and disease and the role of APOE4 in protecting against infection and malnutrition in children living in unfavorable settings, where poor sanitation and hygiene prevail, is highlighted. The potential impact of APOE4 on later development also is discussed and gaps in knowledge are identified that need to be addressed to protect children's development under adverse environments.
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- 2021
36. Living in the Southern Hemisphere: Metabolic Syndrome and Its Components in Amazonian Riverine Populations
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Núbia F. S. S. Campos, Amanda Lopes-Araújo, Leticia Santos-Sacramento, Sidney Santos, Jacqueline I. Alvarez-Leite, Maria Elena Crespo-Lopez, José Luiz Martins do Nascimento, Raquel Alburquerque-Santos, Reinaldo B. Oriá, Ândrea Ribeiro-dos-Santos, Marcus Augusto-Oliveira, Gabriela P. F. Arrifano, José Rogério Souza-Monteiro, and Barbarella de Matos Macchi
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hypertension ,HDL ,diabetes ,business.industry ,dyslipidemia ,Developing country ,cholesterol ,General Medicine ,nutritional ,medicine.disease ,Obesity ,Article ,risk factor ,cardiovascular disease ,Environmental health ,Diabetes mellitus ,medicine ,Nutrition transition ,Medicine ,Metabolic syndrome ,Risk factor ,business ,Developed country ,Dyslipidemia - Abstract
The metabolic syndrome (MetS) epidemic is a global challenge. Although developing countries (including Brazil, India, and South Africa) present a higher proportion of deaths by cardiovascular diseases than developed countries, most of our knowledge is from these developed countries. Amazonian riverine populations (ARP), as well as other vulnerable populations of the Southern Hemisphere, share low-income and traditional practices, among other features. This large cross-sectional study of ARP (n = 818) shows high prevalence of hypertension (51%) and obesity (23%). MetS was diagnosed in 38% of participants (especially in women and 60–69 years-old individuals) without the influence of ancestry. Only 7–8% of adults had no cardio-metabolic abnormalities related to MetS. Atherogenic dyslipidemia (low HDL-cholesterol) was generally observed, including in individuals without MetS. Still, slight differences were detected between settings with a clear predominance of hypertension in Tucuruí. Hypotheses on possible genetic influence and factors (nutrition transition and environmental pollutants -mercury) are proposed for future studies. Moreover, a roadmap to MetS progression based on the most prevalent components is provided for the development of tailored interventions in the Amazon (initially, individuals would present low HDL-cholesterol levels, later progressing to increased blood pressure characterizing hypertension, and ultimately reaching MetS with obesity). Our alarming results support the need to improve our knowledge on these vulnerable populations.
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- 2021
37. 420.3: The Use of mTOR Inhibitors Is Associated With Reduced Mortality Among Kidney Transplant Patients Developing COVID-19
- Author
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Lúcio Requião-Moura, Luís Gustavo Modelli de Andrade, Tainá V Sandes-Freitas, Marina P Cristelli, Laila A Viana, Mônica R Nakamura, Valter D Garcia, Roberto C Manfro, Denise R Simão, Ricardo Augusto M Barros Almeida, Gustavo F Ferreira, Kellen Micheline A Henrique Costa, Paula R Lima, Alvaro Pacheco-Silva, Ida Maria M Fernandes Charpiot, Luciane M Deboni, Teresa Cristina A Ferreira, Marilda Mazzali, Carlos Alberto C Calazans, Reinaldo B Oriá, Hélio Tedesco-Silva, and José Medina-Pestana
- Subjects
Transplantation - Published
- 2022
38. The Role of Ruthenium Compounds in Neurologic Diseases: A Minireview
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Juan de Sá Roriz Caminha, Luiz Gonzaga de França Lopes, Edinilton Muniz Carvalho, Gabriella Araújo Matos, Marcio Wilker Soares Campelo, Fátima Virgínia Gama Justi, Ludmila Belayev, Cássia Rodrigues Roque, and Reinaldo B. Oriá
- Subjects
Pharmacology ,business.industry ,Brain Neoplasms ,Systems biology ,Cancer ,chemistry.chemical_element ,Antineoplastic Agents ,Neurodegenerative Diseases ,Disease ,medicine.disease ,Bioinformatics ,Motor symptoms ,Neuroprotection ,Ruthenium ,Neuroprotective Agents ,chemistry ,medicine ,Molecular Medicine ,Animals ,Humans ,Ruthenium Compounds ,Nitric Oxide Donors ,business ,Neuroinflammation - Abstract
Ruthenium (Ru) compounds, nitric oxide donors in biological systems, have emerged as a promising therapeutical alternative to conventional drugs in anticancer chemotherapy and as a potential neuroprotective agent, with less cytotoxic effects. This minireview summarizes promising studies with ruthenium complexes and their roles in cancer, neuroinflammation, neurovascular, and neurodegenerative diseases. The up-to-date evidence supports that ruthenium-based compounds have beneficial effects against gliomas, and other types of brain cancers, reduce motor symptoms in models of cerebral ischemia-reperfusion, and may act in the control of nociceptive and inflammatory events, such as seen in early Alzheimer's disease. More studies are needed to fill many current knowledge gaps about the intricate and complex ruthenium biological effects and therapeutic-related mechanisms, stimulating further research. Significance Statement In our minireview, we summarize interesting studies addressing the role of ruthenium compounds on neurological illnesses, focusing on brain cancer, neurovascular and neurodegenerative diseases. No such review is available in the literature.
- Published
- 2021
39. Intestinal permeability and inflammation mediate the association between nutrient density of complementary foods and biochemical measures of micronutrient status in young children: results from the MAL-ED study
- Author
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Erling Svensen, Gagandeep Kang, Dixner Rengifo Trigoso, M Munirul Islam, Benjamin J.J. McCormick, Ramya Ambikapathi, Sophy Raju, Rita Shrestha, Cláudia B. Abreu, Ram Krishna Chandyo, Maribel Paredes Olotegui, Gaurvika M. L. Nayyar, Archana Mohale, Margaret Kosek, Rebecca Blank, Álvaro M. Leite, Srujan Lam Sharma, Manjeswori Ulak, Richard L. Guerrant, Anup Ramachandran, Robin P. Lazarus, Josiane da Silva Quetz, AM Shamsir Ahmed, Estomih R. Mduma, Binob Shrestha, Anita K. M. Zaidi, Aubrey Bauck, Cesar Banda Chavez, Regisiana Mvungi, Silvia Rengifo Pinedo, Sanjaya K. Shrestha, Jean Gratz, Sudhir Babji, Priyadarshani Karunakaran, Pablo Peñataro Yori, José Q. Filho, Laura E. Murray-Kolb, Rosa Maria Salani Mota, Stephanie A. Richard, Ajila T. George, Sajid Bashir Soofi, Vivek Charu, Rosemary Nshama, Zeba A Rasmussen, M. Steffi Jennifer, Rahul J. Thomas, Ladislaus Blacy Yarrot, Alberto M. Soares, Noélia L. Lima, Laura L. Pendergast, Milena Lima de Moraes, Ila F. N. Lima, A. Catharine Ross, Eric R. Houpt, Ladaporn Bodhidatta, Laura E. Caulfield, Estomih Mduma, Tahmeed Ahmed, Jayaprakash Muliyil, Mery Siguas Salas, Rebecca Dillingham, Shahida Qureshi, Sushil John, Caroline Amour, Francisco Suetônio Bastos Mota, Pedro H. Q. S. Medeiros, Angel Mendez Acosta, Iqbal Hossain, Eliwaza Bayyo, Dinesh Mondal, Imran Ahmed, Buliga Mujaga Swema, H. Costa, Michael Gottlieb, Beena Koshy, Mark A. Miller, Vivian Ota Wang, Jhanelle Graham, Muneera A. Rasheed, Alexandre Havt, Bruna Leal Lima Maciel, Cloupas Mahopo, Anuradha Bose, Prakash S. Shrestha, Jessica C. Seidman, Monica McGrath, Alessandra Di Moura, Ali Turab, Viyada Doan, William Pan, Pascal O. Bessong, Didar Alam, Rakhi Ramadas, Tor A. Strand, Reinaldo B. Oriá, Stephanie Psaki, Karthikeyan Ramanujam, John M. Pascal, Rosa Burga, Amidou Samie, William A. Petri, Dinesh Hariraju, Dennis Lang, Christel Hoest, Robert E. Black, Karen H. Tountas, Mohan Venkata Raghava, Angel Orbe Vasquez, Zulfiqar A Bhutta, Emanuel Nyathi, Julian Torres Flores, Rashidul Haque, Leah J. Barrett, J. Daniel Carreon, Carl J. Mason, Zulfiqar A. Bhutta, Stacey Knobler, Rebecca J. Scharf, Suzanne Simons, Kerry Schulze, Crystal L. Patil, Aldo A. M. Lima, Reeba Roshan, Angelina Maphula, Maribel Paredes Olortegui, James A Platts-Mills, Fahmida Tofail, Shiny Kaki, Asad Ali, Gwenyth O. Lee, Sanjaya K. Shrestra, Mustafa Mahfuz, Shanmuga Sundaram, William Checkley, and Barbara A. Schaefer
- Subjects
medicine.medical_specialty ,Micronutrient deficiency ,Anemia ,030231 tropical medicine ,Nutritional Status ,Medicine (miscellaneous) ,Lower risk ,Systemic inflammation ,Permeability ,intestinal barrier function ,Cohort Studies ,Nutrient density ,Feces ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Micronutrients ,030212 general & internal medicine ,Infant Nutritional Physiological Phenomena ,Inflammation ,Nutrition and Dietetics ,biology ,business.industry ,International Nutrition ,Infant ,Bayes Theorem ,Nutrients ,medicine.disease ,Micronutrient ,environmental enteropathy ,Intestines ,micronutrient status ,Ferritin ,Intestinal Diseases ,Original Research Communications ,Malnutrition ,Endocrinology ,biology.protein ,Infant Food ,medicine.symptom ,diet ,business ,Biomarkers - Abstract
Background Environmental enteric dysfunction (EED) is thought to increase the risk of micronutrient deficiencies, but few studies adjust for dietary intakes and systemic inflammation. Objective We tested whether EED is associated with micronutrient deficiency risk independent of diet and systemic inflammation, and whether it mediates the relation between intake and micronutrient status. Methods Using data from 1283 children in the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health) birth cohort we evaluated the risk of anemia, low retinol, zinc, and ferritin, and high transferrin receptor (TfR) at 15 mo. We characterized gut inflammation and permeability by myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT) concentrations from asymptomatic fecal samples averaged from 9 to 15 mo, and averaged the lactulose:mannitol ratio z-score (LMZ) at 9 and 15 mo. Nutrient intakes from complementary foods were quantified monthly from 9 to 15 mo and densities were averaged for analyses. α-1-Acid glycoprotein at 15 mo characterized systemic inflammation. Relations between variables were modeled using a Bayesian network. Results A greater risk of anemia was associated with LMZ [1.15 (95% CI: 1.01, 1.31)] and MPO [1.16 (1.01, 1.34)]. A greater risk of low ferritin was associated with AAT [1.19 (1.03, 1.37)] and NEO [1.22 (1.04, 1.44)]. A greater risk of low retinol was associated with LMZ [1.24 (1.08, 1.45)]. However, MPO was associated with a lower risk of high transferrin receptor [0.86 (0.74, 0.98)], NEO with a lower risk of low retinol [0.75 (0.62, 0.89)], and AAT with a lower risk of low plasma zinc [0.83 (0.70, 0.99)]. Greater nutrient intake densities (vitamins A and B6, calcium, protein, and zinc) were negatively associated with EED. Inverse associations between nutrient densities and micronutrient deficiency largely disappeared after adjustment for EED, suggesting that EED mediates these associations. Conclusions EED is independently associated with an increased risk of low ferritin, low retinol, and anemia. Greater nutrient density from complementary foods may reduce EED, and the control of micronutrient deficiencies may require control of EED.
- Published
- 2019
40. Apolipoprotein E, periodontal disease and the risk for atherosclerosis: a review
- Author
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K.M. Canuto, Juliana Magalhães da Cunha Rego, José Carlos Rodrigues Nascimento, Jacqueline I. Alvarez-Leite, Maria Elena Crespo-Lopez, Reinaldo B. Oriá, Aylin Baysan, and Lianna Cavalcante Pereira
- Subjects
0301 basic medicine ,Apolipoprotein E ,medicine.medical_specialty ,Apolipoprotein E4 ,Apolipoprotein E3 ,Inflammation ,Mice ,03 medical and health sciences ,Apolipoproteins E ,0302 clinical medicine ,Risk Factors ,Epidemiology ,Animals ,Humans ,Protein Isoforms ,Medicine ,Risk factor ,General Dentistry ,Periodontal Diseases ,Periodontitis ,Mouth ,Polymorphism, Genetic ,business.industry ,Microbiota ,Genetic Pleiotropy ,030206 dentistry ,Cell Biology ,General Medicine ,Atherosclerosis ,medicine.disease ,Chronic periodontitis ,030104 developmental biology ,Pleiotropy (drugs) ,Otorhinolaryngology ,Cardiovascular Diseases ,Immunology ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,business ,Risk assessment - Abstract
The association between cardiovascular and periodontal diseases is characterized by chronic inflammatory processes, with a high prevalence worldwide and complex genetic-environment interactions. Although apolipoprotein E4 (ApoE4), one of the isoforms coded by a polymorphic APOE gene, has been widely recognized as a risk factor for cardiovascular diseases and as an immunoinflammatory factor, less is known regarding how ApoE4 affects atherosclerosis in periodontitis patients. The aim of this review was to investigate the potential underlying mechanisms related to APOE4 that could increase the risk of periodontal disease and, ultimately, of atherosclerosis. There have only been a few studies addressing apoE polymorphisms in patients with chronic periodontitis. To date, no studies have been performed that have assessed how ApoE4 affects atherosclerotic disease in chronic periodontitis patients. Although clinical studies are warranted, experimental studies have consistently documented the presence of periodontal pathogens, which are usually found in the oral cavity and saliva, in the atherosclerotic plaques of ApoE-deficient mice. In addition, in this review, the potential role of the APOE4 allele as an example of antagonistic pleiotropy during human evolution and its relation to oral health is discussed.
- Published
- 2019
41. Cellular and Molecular Mechanisms Mediating Methylmercury Neurotoxicity and Neuroinflammation
- Author
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Beatriz Martins, Reinaldo B. Oriá, Ramon da Silva Raposo, Frederico C. Pereira, Carlos Fontes-Ribeiro, João P Novo, and João O. Malva
- Subjects
0301 basic medicine ,microglia ,neurons ,Review ,medicine.disease_cause ,neuroinflammation ,lcsh:Chemistry ,chemistry.chemical_compound ,0302 clinical medicine ,neurotoxicity ,oxidative stress ,lcsh:QH301-705.5 ,Methylmercury ,Spectroscopy ,Microglia ,Microbiota ,Glutamate receptor ,Brain ,General Medicine ,Methylmercury Compounds ,Bioaccumulation ,Computer Science Applications ,medicine.anatomical_structure ,Toxicity ,Neurotoxicity Syndromes ,Programmed cell death ,oligodendrocytes ,Biology ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Neuroinflammation ,Inflammation ,Organic Chemistry ,Neurotoxicity ,astrocytes ,medicine.disease ,030104 developmental biology ,mercury cycle ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,Neuroscience ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
Methylmercury (MeHg) toxicity is a major environmental concern. In the aquatic reservoir, MeHg bioaccumulates along the food chain until it is consumed by riverine populations. There has been much interest in the neurotoxicity of MeHg due to recent environmental disasters. Studies have also addressed the implications of long-term MeHg exposure for humans. The central nervous system is particularly susceptible to the deleterious effects of MeHg, as evidenced by clinical symptoms and histopathological changes in poisoned humans. In vitro and in vivo studies have been crucial in deciphering the molecular mechanisms underlying MeHg-induced neurotoxicity. A collection of cellular and molecular alterations including cytokine release, oxidative stress, mitochondrial dysfunction, Ca2+ and glutamate dyshomeostasis, and cell death mechanisms are important consequences of brain cells exposure to MeHg. The purpose of this review is to organize an overview of the mercury cycle and MeHg poisoning events and to summarize data from cellular, animal, and human studies focusing on MeHg effects in neurons and glial cells. This review proposes an up-to-date compendium that will serve as a starting point for further studies and a consultation reference of published studies.
- Published
- 2021
42. Methylmercury chronic exposure affects the expression of DNA single-strand break repair genes, induces oxidative stress, and chromosomal abnormalities in young dyslipidemic APOE knockout mice
- Author
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Ramon da Silva Raposo, Cláudia Carvalhinho Windmöller, Leticia Rodrigues Sampaio, Maria Elena Crespo-Lopez, Daniel Vieira Pinto, Cássia Rodrigues Roque, Flávia A. Santos, Ronald Feitosa Pinheiro, Paulo Iury Gomes Nunes, Reinaldo B. Oriá, Mayumi N. Ito, Jacqueline I. Alvarez-Leite, and Juan de Sá Roriz Caminha
- Subjects
Senescence ,Apolipoprotein E ,Male ,medicine.medical_specialty ,Xeroderma pigmentosum ,DNA Repair ,DNA repair ,Mice, Knockout, ApoE ,DNA, Single-Stranded ,Toxicology ,medicine.disease_cause ,XRCC1 ,Mice ,Internal medicine ,medicine ,Animals ,Dyslipidemias ,Chromosome Aberrations ,Chemistry ,Neurotoxicity ,Methylmercury Compounds ,medicine.disease ,Mice, Inbred C57BL ,Oxidative Stress ,Endocrinology ,Liver ,Knockout mouse ,lipids (amino acids, peptides, and proteins) ,Environmental Pollutants ,Lipid Peroxidation ,Oxidative stress - Abstract
Mercury (Hg) is one of the most toxic environmental pollutants, especially when methylated, forming methylmercury (MeHg). MeHg affects DNA repair, increases oxidative stress, and predisposes to cancer. MeHg neurotoxicity is well-known, but recently MeHg-associated cardiovascular effects were recognized. This study evaluated circulating lipids, oxidative stress, and genotoxicity after MeHg-chronic exposure (20 mg/L in drinking water) in C57BL/6J wild-type and APOE knockout (ko) mice, the latter, being spontaneously dyslipidemic. Experimental mice were assigned to four groups: non-intoxicated and MeHg-intoxicated wild-type mice and non-intoxicated and MeHg-intoxicated APOE ko mice. Plasma levels of triglycerides, total cholesterol (TC), HDL, and LDL were analyzed. Liver lipid peroxidation and splenic gene expression of xeroderma pigmentosum complementation groups A, C, D, and G (XPA, XPC, XPD, and XPG), X-ray repair cross-complementing protein 1 (XRCC1), and telomerase reverse transcriptase (TERT) were measured. Fur Hg levels confirmed chronic MeHg intoxication. MeHg exposure raises TC levels both in wild-type and APOE ko mice. HDL and LDL-cholesterol levels were increased only in the MeHg-challenged APOE ko mice. MeHg increased liver lipid peroxidation, regardless of the genetic background. Unintoxicated APOE ko mice showed higher expression of TERT than all other groups. APOE deficiency increases XPA expression, regardless of MeHg intoxication. Furthermore, MeHg-intoxicated mice had more cytogenetic abnormalities, effect which was independent of APOE deficiency. More studies are needed to dissect the interactions between circulating lipids, MeHg intoxication, and DNA-repair pathways even at young age, interactions that likely play critical roles in cell senescence and the risk for chronic disorders later in life.
- Published
- 2021
43. Contributors
- Author
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Michelle M. Adams, Cédric Albinet, Banu Alicioglu, Paolo Amami, Nathalie André, Narin Ilgim Ardic-Avci, Elizabeth Arslanoglou, Guilherme Giannini Artioli, Michel Audiffren, Hande Ozge Aydogan, Francisco Javier Belchí, Marvin H. Berman, Ondrej Bezdicek, Cynthia Bianco, Jasmina Boban, Carlos Roberto Bueno Júnior, Blake E. Butler, Daniele Cartelli, Augusto Pietro Casani, Dilan Celebi-Birand, Zikuan Chen, Zeyuan Chen, Bihong T. Chen, Katie E. Cherry, Christian Chicherio, Jeshya A. Chio, Pere Clavé, Victoria C. Cogger, Márcia Regina Cominetti, Ma Fe P. de Guzman, Maria Clarissa O. del Moral, Eimear Dolan, Jacqueline C. Dominguez, Premchand Dommaraju, Theresa Ebo, Melissa K. Edler, Begun Erbaba, Ghazaleh Eskandari-Sedighi, Delphine Fagot, Fereshteh Farajdokht, Isabel Fariñas, Laís Francielle Francisca Felício, Luiz Felipe da Silva Figueiredo, Karen L. Fortuna, Máximo Ibo Galindo, Ekavi N. Georgousopoulou, Rahul Gokarn, Gabriel Gold, Hayley Groetz, Bruno Gualano, G.M. Halliday, Erin E. Harrington, Claudia Heidenreich, Boris Henčić, Rafael Hernández, Björn Herrmann, Jasna Jančić, R.C. Jeżewski, Hulusi Kafaligonul, Hakki Muammer Karakas, Elif Tugce Karoglu-Eravsar, Dimitris Kiosses, Dusko Kozic, Enikö Kövari, Lewis H. Kuller, Thomas J. LaRocca, David G. Le Couteur, Gary Jek Chong Lee, Unax Lertxundi, Víctor López del Amo, Mariana Luciano de Almeida, Javad Mahmoudi, João O. Malva, Patricia Regina Manzine, Beatriz Martins, Douglas B. Matthews, Derval McCormack, Juan Medrano, Duane D. Mellor, Juan C. Meléndez, Jonas Mengel-From, Jelena Milić, Jody Monkovic, Renato Sobral Monteiro-Junior, Ricardo Moreira, Emily L. Munger, Elena Navari, M. Christopher Newland, João Novo, Reinaldo B. Oriá, Fiadhnait O’Keeffe, Demosthenes B. Panagiotakos, Frederico C. Pereira, Ana Perez-Villalba, Rafaela Peron, Victor R. Preedy, Mary Ann Raghanti, Simona Raimo, Rajkumar Rajendram, Ana López Ramírez, Ramon Raposo, David Raubenheimer, Punam Rawal, Celinda Reese-Melancon, Hannah Reich, Carmen Requena, Carlos Fontes Ribeiro, Ana Carolina de Mello Alves Rodrigues, Luis Miguel Rondón García, Rosa Raquel Ruiz Trascastro, Saeed Sadigh-Eteghad, Farzad Salehpour, Janko Samardžić, Gabriella Santangelo, Encarnación Satorres, Andrew N. Shen, C.E. Shepherd, Stephen J. Simpson, Marina Yazigi Solis, Samantha M. Solon-Biet, Dunja Stankić, Timo E. Strandberg, Astrid M. Suchy-Dicey, Andrea Tapia, Majda M. Thurnher, Paula Álvarez-Merino, Noemí Tomsen, Luigi Trojano, Melek Umay Tuz-Sasik, Henryk F. Urbanski, Rodrigo Portes Ureshino, Ed van Beeck, Candice E. Van Skike, Izabela Pereira Vatanabe, Devin Wahl, David Westaway, Shawn Wong, Long Wu, Túlio Brandão Xavier-Rocha, Janko Zeković, Xin Zhang, and Liqin Zhao
- Published
- 2021
44. Inbred mouse model of brain development and intestinal microbiota
- Author
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Reinaldo B. Oriá, Ramon da Silva Raposo, Daniel Vieira Pinto, João O. Malva, Richard L. Guerrant, Ronaldo Pereira Dias, and Patricia L. Foley
- Subjects
Brain development ,biology ,Time windows ,Immunology ,Biosecurity ,medicine ,Gut flora ,medicine.symptom ,biology.organism_classification ,Systemic inflammation - Abstract
In this book chapter, we revisit laboratory animal modeling in neuroscience under modern vivarium biosecurity barriers, which have been critically important to the reproducibility and reliability of the generated data. However, limitations remain in translating data to human populations living in contaminated environments, where lifelong exposures to various levels of biohazards and chemical pollutants often occur. The majority of human populations in the developing world are still intolerably exposed to enteric pathogens and fecal coliforms (even without leading to overt diarrhea) and may be chronically afflicted with low-grade systemic inflammation, especially early in life, the same time window when dynamic events in brain plasticity happen, but also when the intestinal microbiota matures. Individuals living within a contaminated environment and having a related unhealthy gut microbiota may not achieve optimal brain development and may be more predisposed to neurodegenerative diseases later in life. Animal models are needed that better recapitulate these human living conditions and improve our understanding of the role of microbiota in these neurological conditions.
- Published
- 2021
45. Contributors
- Author
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Carmen Cortes, Mohamed Ahmed AboEllail, Janiel Ahkin Chin Tai, Juan C. Ahumada-Juárez, Peter J. Anderson, Vicente Andreu- Fernández, Panagiotis Antsaklis, R.A. Armstrong, Eva Ausó, Laura Avagliano, Tandy Aye, Silvia Bassani, Inês Bernardino, Reid Blanchett, Sarah J. Blossom, Gabriella Bottini, Zeina Bou Diab, Kristen R. Breit, Soledad Bárez-López, Gaetano P. Bulfamante, Miguel Castelo-Branco, Rebekah M. Charney, Karina Dale, Arij Daou, George Daskalakis, Josepheen De Asis-Cruz, George Deeb, Dana DeMaster, Briana R. De Miranda, Ronaldo P. Dias, Maja Drobnič Radobuljac, Jose R. Eguibar, Lior M. Elkaim, Ståle Ellingsen, Pietro Fazzari, Marlena S. Fejzo, Sacri R. Ferrón, Richard H. Finnell, Cecilia Flores, Patricia L. Foley, Jennifer L. Freeman, Máximo Ibo Galindo, Oscar García-Algar, Martín I. García-Castro, Timothy M. George, Robert Gerlai, Gabrielle Gloston, Joana Gonçalves, N. Granana, Paolo Grazioli, Carmen Grijota-Martínez, Ana Guadaño-Ferraz, Richard L. Guerrant, Toshiyuki Hata, Victor Hugo Hernandez Gonzalez, Grayson N. Holmbeck, George M. Ibrahim, F. Klamt, Rebecca C. Knickmeyer, Kristi A. Kohlmeier, Munekazu Komada, Steven J. Korzeniewski, Asim Kurjak, Danica Limon, Catherine Limperopoulos, Anna Lozano-Ureña, Inés López del Castillo, João O. Malva, Louis N. Manganas, Carla Marini, Mark A. Masino, Valentina Massa, Marzena Maćkowiak, Pilar Medina–Alva, Rami Mhanna, Ana Montero-Pedrazuela, Jacob E. Montgomery, Bartlett D. Moore, Patrick M. Mullin, Laura M. Nicholson, Yoshihiro Noda, Kateryna Nohejlová, Diana M. Ohanian, Reinaldo B. Oriá, Cynthia Ortinau, Chiara Parodi, R.B. Parsons, Leona Pascoe, Maria Passafaro, Mayra I. Perez, Valeria Peviani, Valeria Piazza, Daniel V. Pinto, Barbara Plemeniti Tololeski, Filip S. Polli, Shannon Pollock, Maneeshi S. Prasad, Victor R. Preedy, Rajkumar Rajendram, Ana C. Ramirez, Ramon S. Raposo, Josef Daniel Rasinger, Lauren M. Reynolds, Angela Rodríguez-Prieto, A.M. Romero Otalvaro, Sebastian Sailer, Jessica Saliba, Pina Scarpa, Sophie C. Schneider, P. Schonhofen, Giorgia Sebastiani, Sherif G. Shaaban, Merina Shrestha, Eric A. Storch, Michael A. Sustaíta, Stephanie A. Terezakis, Romana Šlamberová, D.M. Vargas, Kelly A. Vaughn, Andres G. Viana, Saira A. Weinzimmer, Eva Widerstrom-Noga, Adrien M. Winning, Marlon L. Wong, Walter Zegarra, Shao Jia Zhou, and Jill G. Zwicker
- Published
- 2021
46. Neuroinflammation and aging
- Author
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Frederico C. Pereira, Beatriz Martins, Ramon da Silva Raposo, João P Novo, Reinaldo B. Oriá, João O. Malva, Ricardo Moreira, and Carlos Fontes Ribeiro
- Subjects
business.industry ,Medicine ,business ,Neuroscience ,Neuroinflammation - Published
- 2021
47. Apolipoprotein E polymorphism influences orthotopic liver transplantation outcomes in patients with hepatitis C virus-induced liver cirrhosis
- Author
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Silvio Alencar C Sobrinho, I.R.C. Brasil, Paulo Goberlânio de Barros Silva, Edmilson Ferreira de Oliveira-Filho, James S. Owen, Reinaldo B. Oriá, José Carlos Rodrigues Nascimento, Pierluigi Toniutto, Juliana Magalhães da Cunha Rego, Gustavo Rego Coelho, Lianna Cavalcante Pereira, and Ronaldo Pereira Dias
- Subjects
Apolipoprotein E ,Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Hepatocellular carcinoma ,Hepatitis C virus ,medicine.medical_treatment ,Observational Study ,Hepacivirus ,Liver transplantation ,medicine.disease_cause ,Gastroenterology ,Cohort Studies ,Liver disease ,Apolipoproteins E ,Fibrosis ,Recurrence ,Internal medicine ,medicine ,Humans ,Polymorphism ,Aged ,Liver injury ,business.industry ,Liver Neoplasms ,General Medicine ,Middle Aged ,medicine.disease ,Hepatitis C ,Female ,Neoplasm Recurrence, Local ,business - Abstract
Background Hepatitis C virus (HCV) infection is responsible for a chronic liver inflammation, which may cause end-stage liver disease and hepatocellular carcinoma. Apolipoprotein E (protein: ApoE, gene: APOE), a key player in cholesterol metabolism, is mainly synthesized in the liver and APOE polymorphisms may influence HCV-induced liver damage. Aim To determine whether APOE alleles affect outcomes in HCV-infected patients with liver cirrhosis following orthotopic liver transplantation (OLT). Methods This was a cohort study in which 179 patients, both genders and aged 34-70 years, were included before or after (up to 10 years follow-up) OLT. Liver injury severity was assessed using different criteria, including METAVIR and models for end-stage liver disease. APOE polymorphisms were analyzed by quantitative real-time polymerase chain reaction. Results The APOE3 allele was the most common (67.3%). In inflammation severity of biopsies from 89 OLT explants and 2 patients in pre-transplant, the degree of severe inflammation (A3F4, 0.0%) was significantly less frequent than in patients with minimal and moderate degree of inflammation (≤ A2F4, 16.2%) P = 0.048, in patients carrying the APOE4 allele when compared to non-APOE4. In addition, a significant difference was also found (≤ A2F4, 64.4% vs A3F4, 0.0%; P = 0.043) and (A1F4, 57.4% vs A3F4, 0.0%; P = 0.024) in APOE4 patients when compared to APOE3 carriers. The fibrosis degree of the liver graft in 8 of 91 patients and the lack of the E4 allele was associated with more moderate fibrosis (F2) (P = 0.006). Conclusion Our results suggest that the E4 allele protects against progression of liver fibrosis and degree of inflammation in HCV-infected patients.
- Published
- 2020
48. Methylmercury Interactions With Gut Microbiota and Potential Modulation of Neurogenic Niches in the Brain
- Author
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Ramon da Silva Raposo, Gabriella Araújo Matos, João O. Malva, Jacqueline I. Alvarez-Leite, Daniel Vieira Pinto, and Reinaldo B. Oriá
- Subjects
intestinal microbiota ,Opinion ,biology ,General Neuroscience ,brain ,Neurogenesis ,methylmercury ,Gut flora ,biology.organism_classification ,Cell biology ,lcsh:RC321-571 ,chemistry.chemical_compound ,neurogenesis ,gut dysbiosis ,chemistry ,neurodegenerative diseases ,Gut dysbiosis ,Methylmercury ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Neuroscience - Published
- 2020
49. Methylmercury Impact on Adult Neurogenesis: Is the Worst Yet to Come From Recent Brazilian Environmental Disasters?
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Ricardo Moreira, Carlos Fontes Ribeiro, Reinaldo B. Oriá, Ramon da Silva Raposo, Daniel Vieira Pinto, Ronaldo Pereira Dias, and João O. Malva
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0301 basic medicine ,Cognitive Neuroscience ,Environmental disaster ,Biology ,lcsh:RC321-571 ,memory ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Environmental health ,Postnatal neurogenesis ,neurotoxicity ,medicine ,Cognitive decline ,Methylmercury ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Neurogenesis ,aging ,Neurotoxicity ,methylmercury ,medicine.disease ,Neural stem cell ,neurogenesis ,030104 developmental biology ,chemistry ,Perspective ,environmental disaster ,030217 neurology & neurosurgery ,Toxicant ,Neuroscience - Abstract
Worldwide environmental tragedies of anthropogenic origin causing massive release of metals and other pollutants have been increasing considerably. These pollution outbreaks affect the ecosystems and impact human health. Among those tragedies, recent large-scale environmental disasters in Brazil strongly affected riverside populations, leading to high-risk exposure to methylmercury (MeHg). MeHg is highly neurotoxic to the developing brain. This toxicant causes neural stem cell dysfunction and neurodevelopmental abnormalities. However, less is known about the effects of MeHg in the postnatal neurogenic niche, which harbors neural stem cells and their progeny, in the adult brain. Therefore, taking in consideration the impact of MeHg in human health it is urgent to clarify possible associations between exposure to mercury, accelerated cognitive decline, and neurodegenerative diseases. In this perspectives paper, we discuss the neurotoxic mechanisms of MeHg on postnatal neurogenesis and the putative implications associated with accelerated brain aging and early-onset cognitive decline in populations highly exposed to this environmental neurotoxicant.
- Published
- 2020
50. Early Life Experiences and Trajectories of Cognitive Development
- Author
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Reeba Roshan, Rita Shrestha, Laura E. Caulfield, Angelina Maphula, Baitun Nahar, Sayma Haque, Zeba A Rasmussen, Laura L. Pendergast, Stephanie A. Richard, Ladislaus Blacy, Beena Koshy, Benjamin J.J. McCormick, Rebecca J. Scharf, Reinaldo B. Oriá, Jessica C. Seidman, Laura E. Murray-Kolb, Muneera A. Rasheed, and Erling Svensen
- Subjects
Male ,Bayley Scales of Infant Development ,Cohort Studies ,Life Change Events ,03 medical and health sciences ,Child Development ,Cognition ,0302 clinical medicine ,030225 pediatrics ,medicine ,Cognitive development ,Humans ,Prospective Studies ,Toddler ,Socioeconomic status ,Wechsler Preschool and Primary Scale of Intelligence ,business.industry ,Infant, Newborn ,Anthropometry ,medicine.disease ,Malnutrition ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Health Resources ,Female ,business ,Follow-Up Studies ,Clinical psychology ,Cohort study - Abstract
BACKGROUND:Multiple factors constrain the trajectories of child cognitive development, but the drivers that differentiate the trajectories are unknown. We examine how multiple early life experiences differentiate patterns of cognitive development over the first 5 years of life in low-and middle-income settings.METHODS:Cognitive development of 835 children from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite observational cohort study was assessed at 6, 15, 24 (Bayley Scales of Infant and Toddler Development), and 60 months (Wechsler Preschool and Primary Scale of Intelligence). Markers of socioeconomic status, infection, illness, dietary intake and status, anthropometry, and maternal factors were also assessed. Trajectories of development were determined by latent class-mixed models, and factors associated with class membership were examined by discriminant analysis.RESULTS:Five trajectory groups of cognitive development are described. The variables that best discriminated between trajectories included presence of stimulating and learning resources in the home, emotional or verbal responsivity of caregiver and the safety of the home environment (especially at 24 and 60 months), proportion of days (0–24 months) for which the child had diarrhea, acute lower respiratory infection, fever or vomiting, maternal reasoning ability, mean nutrient densities of zinc and phytate, and total energy from complementary foods (9–24 months).CONCLUSIONS:A supporting and nurturing environment was the variable most strongly differentiating the most and least preferable trajectories of cognitive development. In addition, a higher quality diet promoted cognitive development while prolonged illness was indicative of less favorable patterns of development.
- Published
- 2020
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