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1.
Food Chem ; 399: 133912, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36029677

RESUMO

Iron deficiency anemia (IDA) is a common nutritional disease affecting 2 billion people. To develop a new iron-fortified food, we designed a novel type of iron-chelating peptide [Sea cucumbers peptides (SCP)-Fe] from sea cucumbers. SCP can chelate ferrous ions. The neutral protease hydrolysate have the highest iron chelating activity (117.17 ± 2.62 mg/g). Single factors including pH, material ratio, and molecular weight, had a significant effect on the iron chelating activity. The characterization of the SCP-Fe chelate revealed a loose and blocky structure with increased particle size. The amino acid composition, peptide identification and molecular docking indicated that Asp, Glu, Gly and Pro played an important role in binding to ferrous ions. After chelation, SCP-Fe chelate had dual nutrition effects of stronger radical scavenging ability and potential high-efficiency iron supplementation ability. These results might provide insights into the methods for developing functional foods such as iron-fortified seafood.


Assuntos
Pepinos-do-Mar , Animais , Antioxidantes/química , Humanos , Íons , Ferro/química , Quelantes de Ferro/química , Simulação de Acoplamento Molecular , Peptídeos/química , Pepinos-do-Mar/química
2.
Biol Pharm Bull ; 45(9): 1291-1299, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36047197

RESUMO

Here, we searched for microRNAs (miRNAs) in silico that could interact with SLC11A2 mRNA, a solute carrier (SLC) iron-ion transporter, and investigated their effects on SLC11A2 gene expression using the cultured human colon carcinoma cell line, Caco-2. In silico analysis using the miRWalk2.0 database revealed that several types of miRNAs interact with the human SLC11A2 gene; we focused on three miRNAs, miR-149-5p, miR-362-5p, and miR-539-5p as candidates in this study. We first revealed that the three miRNAs interact with the SLC11A2 3'-untranslated region (3'-UTR) using a luciferase assay in a Caco-2 cell line. We then examined whether the expression of each miRNA affected the expression of SLC11A2 mRNAs and their transcribed transporter proteins. We found transiently expressed miRNAs significantly reduced the reporter activity of the SLC11A2 3'-UTR site in Caco-2 cells by significantly decreasing the SLC11A2 gene and protein expression in the miRNA-transfected Caco-2 cells. Subsequently, we investigated the effects of these miRNAs on SLC11A2's iron-ion transporting activity by measuring iron-ion concentration in Caco-2 cells. Administration of ammonium iron (II) sulfate hexahydrate to Caco-2 cells significantly increased the intracellular iron-ion concentration. However, in iron-ion-pretreated cells, overexpression of each of the three miRNAs resulted in decreased intracellular iron-ion concentration. This indicated that overexpressed miRNAs inhibited iron-ion influx into Caco-2 cells by attenuating SLC11A2 transporting activity. Using in silico analysis, we predicted that three studied miRNAs could bind to the iron-ion influx transporter SLC11A2 and revealed that they regulate SLC11A2 gene expression and iron-ion transporting function in an in vitro system.


Assuntos
Proteínas de Transporte de Cátions , MicroRNAs , Regiões 3' não Traduzidas , Células CACO-2 , Proteínas de Transporte de Cátions/genética , Humanos , Ferro/metabolismo , MicroRNAs/genética , RNA Mensageiro/genética
3.
Acta Crystallogr C Struct Chem ; 78(Pt 9): 507-514, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36063378

RESUMO

Both trans and cis iron-CTMC complexes, namely, trans-dichlorido[(5SR,7RS,12RS,14SR)-5,7,12,14-tetramethyl-1,4,8,11-tetraazacyclotetradecane]iron(III) tetrachloridoferrate, [Fe(C14H32N4)Cl2][FeCl4] (1a), the analogous chloride methanol monosolvate, [Fe(C14H32N4)Cl2]Cl·CH3OH (1b), and cis-dichlorido[(5SR,7RS,12SR,14RS)-5,7,12,14-tetramethyl-1,4,8,11-tetraazacyclotetradecane]iron(III) chloride, [Fe(C14H32N4)Cl2]Cl (2), were successfully synthesized and structurally characterized using X-ray diffraction. The coordination geometry of the macrocycle is dependent on the stereoisomerism of CTMC. The packing of these complexes appears to be strongly influenced by extensive hydrogen-bonding interactions, which are in turn determined by the nature of the counter-anions (1a versus 1b) and/or the coordination geometry of the macrocycle (1a/1b versus 2). These observations are extended to related ferric cis- and trans-dichloro macrocyclic complexes.


Assuntos
Ciclamos , Cloretos , Cristalografia por Raios X , Compostos Férricos , Ligação de Hidrogênio , Ferro , Ligantes
4.
J Nanobiotechnology ; 20(1): 405, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064371

RESUMO

BACKGROUND: Septic heart failure accounts for high mortality rates globally. With a strong reducing capacity, zero-valent iron nanoparticles (nanoFe) have been applied in many fields. However, the precise roles and mechanisms of nanoFe in septic cardiomyopathy remain unknown. RESULTS: NanoFe was prepared via the liquid-phase reduction method and functionalized with the biocompatible polymer sodium carboxymethylcellulose (CMC). We then successfully constructed a mouse model of septic myocardial injury by challenging with cecal ligation and puncture (CLP). Our findings demonstrated that nanoFe has a significant protective effect on CLP-induced septic myocardial injury. This may be achieved by attenuating inflammation and oxidative stress, improving mitochondrial function, regulating endoplasmic reticulum stress, and activating the AMPK pathway. The RNA-seq results supported the role of nanoFe treatment in regulating a transcriptional profile consistent with its role in response to sepsis. CONCLUSIONS: The results provide a theoretical basis for the application strategy and combination of nanoFe in sepsis and septic myocardial injury.


Assuntos
Insuficiência Cardíaca , Traumatismos Cardíacos , Nanopartículas , Sepse , Animais , Insuficiência Cardíaca/metabolismo , Ferro , Camundongos , Miocárdio/metabolismo , Sepse/metabolismo
5.
J Cell Biol ; 221(10)2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36066504

RESUMO

A ferritin particle consists of 24 ferritin proteins (FTH1 and FTL) and stores iron ions within it. During iron deficiency, ferritin particles are transported to lysosomes to release iron ions. Two transport pathways have been reported: macroautophagy and ESCRT-dependent endosomal microautophagy. Although the membrane dynamics of these pathways differ, both require NCOA4, which is thought to be an autophagy receptor for ferritin. However, it is unclear whether NCOA4 only acts as an autophagy receptor in ferritin degradation. Here, we found that ferritin particles form liquid-like condensates in a NCOA4-dependent manner. Homodimerization of NCOA4 and interaction between FTH1 and NCOA4 (i.e., multivalent interactions between ferritin particles and NCOA4) were required for the formation of ferritin condensates. Disruption of these interactions impaired ferritin degradation. Time-lapse imaging and three-dimensional correlative light and electron microscopy revealed that these ferritin-NCOA4 condensates were directly engulfed by autophagosomes and endosomes. In contrast, TAX1BP1 was not required for the formation of ferritin-NCOA4 condensates but was required for their incorporation into autophagosomes and endosomes. These results suggest that NCOA4 acts not only as a canonical autophagy receptor but also as a driver to form ferritin condensates to facilitate the degradation of these condensates by macroautophagy (i.e., macroferritinophagy) and endosomal microautophagy (i.e., microferritinophagy).


Assuntos
Autofagia , Ferritinas , Coativadores de Receptor Nuclear , Endossomos/metabolismo , Ferritinas/genética , Ferritinas/metabolismo , Ferro/metabolismo , Lisossomos/metabolismo , Coativadores de Receptor Nuclear/genética , Coativadores de Receptor Nuclear/metabolismo , Fagossomos/metabolismo , Fatores de Transcrição/metabolismo
6.
J Neuroinflammation ; 19(1): 219, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068571

RESUMO

Since the twenty-first century, the development of technological advances in anesthesia and surgery has brought benefits to human health. However, the adverse neurological effects of perioperative-related factors (e.g., surgical trauma, anesthesia, etc.) as stressors cannot be ignored as well. The nervous system appears to be more "fragile" and vulnerable to damage in developing and aging individuals. Ferroptosis is a novel form of programmed cell death proposed in 2012. In recent years, the regulation of ferroptosis to treat cancer, immune system disorders, and neurodegenerative diseases have seen an unprecedented surge of interest. The association of ferroptosis with perioperative neurocognitive disorders has also received much attention. Cognitive impairment can not only affect the individual's quality of life, but also impose a burden on the family and society. Therefore, the search for effective preventive and therapeutic methods to alleviate cognitive impairment caused by perioperative-related factors is a challenge that needs to be urgently addressed. In our review, we first briefly describe the connection between iron accumulation in neurons and impairment of brain function during development and aging. It is followed by a review of the pathways of ferroptosis, mainly including iron metabolism, amino acid metabolism, and lipid metabolism pathway. Furthermore, we analyze the connection between ferroptosis and perioperative-related factors. The surgery itself, general anesthetic drugs, and many other relevant factors in the perioperative period may affect neuronal iron homeostasis. Finally, we summarize the experimental evidence for ameliorating developmental and degenerative neurotoxicity by modulating ferroptosis. The suppression of ferroptosis seems to provide the possibility to prevent and improve perioperative neurocognitive impairment.


Assuntos
Disfunção Cognitiva , Ferroptose , Apoptose , Humanos , Ferro/metabolismo , Qualidade de Vida
7.
Methods Cell Biol ; 172: 37-50, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36064225

RESUMO

Lipid peroxidation occurs under conditions where reactive oxygen species (ROS) readily react with vulnerable lipids on cell membranes. Polyunsaturated fatty acids (PUFAs) are highly susceptible to lipid peroxidation because of their unstable double bonds. Because the cell membrane is particularly rich in PUFAs, it is often the site at which many lipid peroxidation chain reactions occur. Lipid peroxidation is considered the ultimate trigger of ferroptosis, an iron-dependent form of non-apoptotic cell death. Radiotherapy is a common cancer treatment that uses high-energy ionizing radiation to kill cancer cells, and radiation-induced cell death is partially attributed to lipid peroxidation-driven ferroptosis. Here, we describe methods to assess lipid peroxidation in irradiated cells. The same techniques can be applied to a variety of lipid peroxidation measurements under different treatment conditions.


Assuntos
Ferro , Morte Celular/fisiologia , Membrana Celular/metabolismo , Ferro/metabolismo , Peroxidação de Lipídeos/fisiologia , Espécies Reativas de Oxigênio/metabolismo
8.
Br J Hosp Med (Lond) ; 83(8): 1-3, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-36066297

RESUMO

Anaemia affects a third of surgical patients and is associated with increased morbidity and mortality. Iron deficiency is the most common cause of anaemia and can be absolute or functional. Patients may require treatment with oral or intravenous iron.


Assuntos
Anemia Ferropriva , Anemia , Deficiências de Ferro , Administração Intravenosa , Anemia/etiologia , Anemia/terapia , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Humanos , Ferro/uso terapêutico
9.
Zhonghua Yan Ke Za Zhi ; 58(9): 715-716, 2022 Sep 11.
Artigo em Chinês | MEDLINE | ID: mdl-36069095

RESUMO

A patient complained of vision loss of his left eye which was crushed by iron ore for 11 months. The cornea of the injured eye was thin and swollen, and a large amount of rust-like material was observed to be deposited. An intraocular foreign body was found by orbital CT. During vitrectomy, a piece of metal sheet was found near the ora serrate, and the intraocular structure was severely damaged, and characterized by vitreous brown turbidity, a white optic disc, occlusion of blood vessels in the fundus, and peripheral retinal atrophy with degeneration. The patient was diagnosed as ocular siderosis in the left eye.


Assuntos
Oftalmopatias , Corpos Estranhos no Olho , Siderose , Oftalmopatias/diagnóstico , Oftalmopatias/etiologia , Corpos Estranhos no Olho/complicações , Corpos Estranhos no Olho/diagnóstico , Corpos Estranhos no Olho/cirurgia , Fundo de Olho , Humanos , Ferro , Siderose/diagnóstico , Siderose/etiologia , Siderose/cirurgia
10.
Wei Sheng Yan Jiu ; 51(4): 544-549, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-36047256

RESUMO

OBJECTIVE: To analyze the status of dietary micronutrient in takes among the children of 12-17 years old in China from 2016 to 2017. METHODS: Multistage stratified random sampling method was used to collect data in 275 monitoring sites of the China National Nutrition and Health Survey of Chinese children and lactating mothers in 31 provinces of China from 2016 to 2017. Three consecutive 24-hour recalls method wasused to collect the information of food intake, and household or school canteen edible oil and condiments weighing were adopted. The dietary micronutrient were analyzed based on theChina Food Composition table. RESULTS: The average daily intakes of vitamin A(retinol activity equivalents), vitamin B_1(thiamine), vitamin B_2(riboflavin), vitamin C(ascorbic acid), calcium, iron, zinc and sodium were 356.8 µ g, 0.8 mg, 0.8 mg, 60.5 mg, 342.8 mg, 19.2 mg, 9.8 mg and 5 230.4 mg, respectively. The proportion ofdaily average intakes of vitamin A, vitamin B_1, vitamin B_2, vitamin C and calcium lower than 60% of the recommended value were 74.3%, 59.4%, 57.7%, 62.6% and 93.0%, respectively. The proportion of daily intake of iron and zinc reaching 80% of the recommended value were 73.8% and 64.8%, respectively. The proportion of daily average intake of sodium exceeded the appropriate intake by 94.4%. The average daily intakes of micronutrients increased with age among the children of 12-17 years old. There were differences of daily intake of vitamin A in gender, urban and rural areas(P<0.05), there was difference of vitamin C in urban and rural areas(P<0.01), there were differences of daily intake of vitamin B_1, vitamin B_2, calcium, iron and zinc in age, gender, urban and rural areas(P<0.01), there were differences in the average daily intake of sodium in age, gender(P<0.01). CONCLUSION: The average daily dietary of iron and zinc intakes in the diet were basically enough in most children of 12-17 years old in China, that of sodium was too much, and that of some micronutrients was insufficient.


Assuntos
Micronutrientes , Oligoelementos , Adolescente , Ácido Ascórbico , Cálcio , Cálcio na Dieta , Criança , China , Dieta , Ingestão de Alimentos , Ingestão de Energia , Feminino , Humanos , Ferro , Lactação , Estado Nutricional , Sódio , Vitamina A , Vitaminas , Zinco
11.
Biomed Pharmacother ; 153: 113516, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076514

RESUMO

Ferroptosis, an iron-dependent form of regulated cell death, was recently demonstrated to be closely associated with the immune system. Regulators of ferroptosis may be the cells and secretions of the immune system. Ferroptosis has contributed to the progression of various diseases, namely, cancer, ischemia, and degenerative diseases. However, research on the relationship between ferroptosis and asthma remains fragmented. Non-immune cells associated with asthma are also closely associated with ferroptosis. Further studies on cross-linking asthma inflammation with ferroptosis signaling pathways could help identify several key molecules, known as ferroptosis regulators, that regulate asthma. Ferroptosis provides a new perspective to interpret and understand the manifestations of asthma, potential drug discovery targets, and new therapeutic options to effectively intervene in the imbalance caused by abnormal inflammation in asthma. Thus, the pathogenesis of ferroptosis and its contribution to the pathogenesis of asthma is essential in deepening the understanding and improving the prognosis and cure rate of the patients. Herein, we introduce the main molecular mechanisms of ferroptosis and asthma, describe the relationship between ferroptosis and asthma based on their common regulatory cells or molecules, and discuss potential drug discovery targets and therapeutic applications of ferroptosis in the context of immunomodulation and symptom alleviation.


Assuntos
Asma , Ferroptose , Asma/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Ferro/metabolismo , Transdução de Sinais
12.
Biomed Pharmacother ; 153: 113402, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076527

RESUMO

This study was aimed to explore the effects of fucoidan on iron overload and ferroptosis-induced liver injury, and the underlying mechanisms in rats exposed to alcohol. Sprague-Dawley rats were used to establish alcoholic liver injury model by intragastric administration with alcohol for 16 weeks. The results showed that fucoidan treatment reversed alcohol-induced increases in reactive oxygen species and malondialdehyde levels, and increased glutathione peroxidase and glutathione levels, thus protecting against liver damage. Long-term alcohol feeding resulted in abnormal increase of serum ferritin, liver total iron and the "free" iron levels. Fucoidan treatment reduced serum ferritin level and alleviated liver iron deposition. Fucoidan reversed the reduction of hepcidin induced by alcohol exposure and decreased divalent metal transporter 1 (DMT1) and ferroportin1 (FPN1) expressions in the duodenum. Electron microscope observation of liver tissues showed that alcohol exposure induced ferroptosis changes in the liver. However, fucoidan treatment could alleviate alcohol-induced ferroptosis via upregulating the expressions of p62, Nrf2, SLC7A11 and GPX4. The liver endogenous metabolites analysis by liquid chromatography and mass spectrometry showed that after fucoidan intervention, mineral absorption, biosynthesis of amino acids pathways and lipid metabolism were changed. Fucoidan intervention reduced the levels of oxidized glutathione and regulated the levels of phosphatidylethanolamines in liver tissues. Our data showed that fucoidan supplementation could inhibit iron load via regulating hepcidin-intestinal DMT1/FPN1 axis, alleviate the liver oxidative damage and protect hepatocytes from ferroptosis induced by long-term alcohol exposure through upregulating p62/Nrf2/SLC7A11 pathway in rats.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Ferroptose , Sobrecarga de Ferro , Animais , Etanol , Ferritinas , Hepcidinas/metabolismo , Ferro/metabolismo , Sobrecarga de Ferro/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Polissacarídeos , Ratos , Ratos Sprague-Dawley
13.
Biomed Pharmacother ; 153: 113524, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076606

RESUMO

Colorectal cancer (CRC) is a common malignant tumor characterized by unchecked division and survival of abnormal cells in the colon or rectum with high morbidity and mortality. Despite the rapid development of early screening methods and improved therapies, the prognosis of CRC is not satisfactory. Identification of new biomarkers for early detection and development of more effective therapies are still urgent tasks in current studies to achieve ideal treatment of CRC. Ferroptosis is a recently emerged novel regulated form of cell death characterized by a massive accumulation of iron-dependent lipid peroxidates, making it morphologically and molecularly distinct from apoptosis, cell death, and autophagy. Accumulating studies have shown that induction of ferroptosis in CRC successfully eliminates cancer cells resistant to other modes of cell death. Thus, ferroptosis may become a new direction for the design of CRC therapy. Although many research articles have investigated the possible roles of ferroptosis in CRC, a study that summarizes the main findings, including the regulators and mechanisms of action, of ferroptosis in CRC is not available. Herein, the studies in recent literature regarding the roles of ferroptosis on the progression and treatment of CRC were summarized, mainly focusing on molecular and biological mechanisms in vitro and in vivo. In particular, the roles of numerous ferroptosis regulators, such as SLC7A11, reactive oxygen species (ROS), glutathione (GSH), and iron, in CRC, were discussed and the application of ferroptosis-associated genes for the early diagnosis and prognosis of CRC was explored. In addition, an outlook for future studies of ferroptosis in CRC treatment and the possible barriers and the corresponding solutions were discussed.


Assuntos
Neoplasias Colorretais , Ferroptose , Morte Celular , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Glutationa/metabolismo , Humanos , Ferro/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
Comput Math Methods Med ; 2022: 4456987, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081434

RESUMO

Objective: In this study, we used the TCGA database and ICGC database to establish a prognostic model of iron death associated with renal cell carcinoma, which can provide predictive value for the identification of iron death-related genes and clinical treatment of renal clear cell carcinoma. Methods: The gene expression profiles and clinical data of renal clear cell carcinoma and normal tissues were obtained in the TCGA database and ICGC database, and the differential genes related to iron death were screened out. The differential genes were screened out by single and multifactor Cox risk regression model. R software, "edge" package (version 4.0), was used to identify the DELs of 551 transcriptional gene samples and 522 clinical samples. The risk prediction model with genes was established to analyze the correlation between the genes in the established model and clinical characteristics, Through the final screening of iron death related genes, it can be used to predict the prognosis of renal clear cell carcinoma and provide advice for clinical targeted therapy. Results: Seven iron death differential genes (CLS2, FANCD2, PHKG2, ACSL3, ATP5MC3, CISD1, PEBP1) associated with renal clear cell carcinoma were finally screened and were refer to previous relevant studies. These genes are closely related to iron death and have great value for the prognosis of renal clear cell carcinoma. Conclusion: Seven iron death genes can accurately predict the survival of patients with renal clear cell carcinoma.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Ferro/metabolismo , Neoplasias Renais/metabolismo , Prognóstico
15.
Oncol Rep ; 48(4)2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36082808

RESUMO

Iron is an essential nutrient that facilitates cell proliferation and growth, and it can contribute to tumor growth. Although iron chelators have shown great potential in preclinical cancer models, they can cause adverse side­effects. The aim of the present study was to determine whether treatment with 5­aminolevurinic acid (5­ALA) has antitumor effects in bladder cancer, by reduction of mitochondrial iron without using an iron chelator, through activation of heme synthesis. T24 and MGH­U3 cells were treated with 5­ALA. Ferrochelatase uses iron to convert protoporphyrin IX into heme, thus additional groups of T24 and MGH­U3 cells were transfected with synthesized ferrochelatase small interfering RNA (siRNA) either to silence ferrochelatase or to provide a negative siRNA control group, and then cell viability, apoptosis, mitochondrial Fe2+, the cell cycle, and ferritin expression were analyzed in all groups and compared. As an in vivo assessment, mice with orthotopic bladder cancer induced using N­butyl­N­(4­hydro­oxybutyl) were treated with 5­ALA. Bladder weight and pathological findings were evaluated, and immunohistochemical analysis was performed for ferritin and proliferating cell nuclear antigen (PCNA). In the cells treated with 5­ALA, proliferation was decreased compared with the controls, and apoptosis was not detected. In addition, the expression of Fe2+ in mitochondria was decreased by 5­ALA, expression of ferritin was also reduced by 5­ALA, and the percentage of cells in the S phase of the cell cycle was significantly increased by 5­ALA. In T24 and MGH­U3 cells with silenced ferrochelatase, the inhibition of cell proliferation, decreased expression of Fe2+ in mitochondria, reduced expression of ferritin, and increased percentage of cells in the S phase by treatment with 5­ALA were weakened. In vivo, no mouse treated with 5­ALA developed muscle­invasive bladder cancer. The expression of ferritin was weaker in mice treated with 5­ALA and that of PCNA was higher than that in mice treated without 5­ALA. It was concluded that 5­ALA inhibited proliferation of bladder cancer cells by activating heme synthesis.


Assuntos
Ferroquelatase , Neoplasias da Bexiga Urinária , Ácido Aminolevulínico/farmacologia , Ácido Aminolevulínico/uso terapêutico , Animais , Proliferação de Células , Ferritinas , Ferroquelatase/genética , Ferroquelatase/metabolismo , Heme/metabolismo , Ferro/metabolismo , Camundongos , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , RNA Interferente Pequeno , Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética
16.
BMJ Paediatr Open ; 6(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-36053580

RESUMO

INTRODUCTION: The WHO Nutrition Target aims to reduce the global prevalence of low birth weight by 30% by the year 2025. The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study will test the impact of packages of pregnancy interventions to enhance maternal nutrition and infection management on birth outcomes in rural Ethiopia. METHODS AND ANALYSIS: ENAT is a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. Eligible pregnant women presenting at antenatal care (ANC) visits at <24 weeks gestation are enrolled (n=2400). ANC quality is strengthened across all centres. Health centres are randomised to receive an enhanced nutrition package (ENP) or standard nutrition care, and within each health centre, individual women are randomised to receive an enhanced infection management package (EIMP) or standard infection care. At ENP centres, women receive a regular supply of adequately iodised salt and iron-folate (IFA), enhanced nutrition counselling and those with mid-upper arm circumference of <23 cm receive a micronutrient fortified balanced energy protein supplement (corn soya blend) until delivery. In standard nutrition centres, women receive routine counselling and IFA. EIMP women have additional screening/treatment for urinary and sexual/reproductive tract infections and intensive deworming. Non-EIMP women are managed syndromically per Ministry of Health Guidelines. Participants are followed until 1-month post partum, and a subset until 6 months. The primary study outcomes are newborn weight and length measured at <72 hours of age. Secondary outcomes include preterm birth, low birth weight and stillbirth rates; newborn head circumference; infant weight and length for age z-scores at birth; maternal anaemia; and weight gain during pregnancy. ETHICS AND DISSEMINATION: ENAT is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (001-A1-2019) and Mass General Brigham (2018P002479). Results will be disseminated to local and international stakeholders. REGISTRATION NUMBER: ISRCTN15116516.


Assuntos
Nascimento Prematuro , Etiópia/epidemiologia , Feminino , Ácido Fólico/uso terapêutico , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Ferro , Parto , Ensaios Clínicos Pragmáticos como Assunto , Gravidez , Nascimento Prematuro/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Eur Radiol Exp ; 6(1): 49, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36074209

RESUMO

BACKGROUND: Though abnormal iron deposition has been reported in specific brain regions in multiple sclerosis (MS), no data exist about whether the overall quantity of iron in the brain is altered or not. We aimed to determine whether the noted aberrant iron deposition in MS brains was a problem of overall load or regional distribution in a cohort of MS patients. METHODS: An experienced neuroradiologist, a radiology software engineer, and four neurologists analysed data from quantitative susceptibility maps reconstructed from 3-T magnetic resonance brain images of 30 MS patients and 15 age- and sex-matched healthy controls. Global brain iron load was calculated, and the regional iron concentrations were assessed in 1,000 regions of interest placed in MS lesions in different locations, normal appearing white matter, thalami, and basal ganglia. RESULTS: Global brain iron load was comparable between patients and controls after adjustment for volume (p = 0.660), whereas the regional iron concentrations were significantly different in patients than in control (p ≤ 0.031). There was no significant correlation between global iron load and clinical parameters, whereas regional iron concentrations correlated with patients' age, disease duration, and disability grade (p ≤ 0.039). CONCLUSIONS: The aberrant iron deposition noted in MS seems to be a problem of regional distribution rather than an altered global brain iron load.


Assuntos
Esclerose Múltipla , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Ferro/análise , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem
19.
Trials ; 23(1): 763, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36076211

RESUMO

BACKGROUND: Anaemia in pregnancy is highly prevalent in African countries. High-dose oral iron is the current recommended treatment for pregnancy-related iron deficiency anaemia (IDA) in Nigeria and other African countries. This oral regimen is often poorly tolerated and has several side effects. Parenteral iron preparations are now available for the treatment of IDA in pregnancy but not widely used in Africa. The IVON trial is investigating the comparative effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate standard-of-care for pregnancy-related IDA in Nigeria. We will also measure the implementation outcomes of acceptability, feasibility, fidelity, and cost-effectiveness for intravenous ferric carboxymaltose. METHODS: This is an open-label randomised controlled trial with a hybrid type 1 effectiveness-implementation design, conducted at 10 health facilities in Kano (Northern) and Lagos (Southern) states in Nigeria. A total of 1056 pregnant women at 20-32 weeks' gestational age with moderate or severe anaemia (Hb < 10g/dl) will be randomised 1:1 into two groups. The interventional treatment is one 1000-mg dose of intravenous ferric carboxymaltose at enrolment; the control treatment is thrice daily oral ferrous sulphate (195 mg elemental iron daily), from enrolment till 6 weeks postpartum. Primary outcome measures are (1) the prevalence of maternal anaemia at 36 weeks and (2) infant preterm birth (<37 weeks' gestation) and will be analysed by intention-to-treat. Maternal full blood count and iron panel will be assayed at 4 weeks post-enrolment, 36 weeks' gestation, delivery, and 6 weeks postpartum. Implementation outcomes of acceptability, feasibility, fidelity, and cost will be assessed with structured questionnaires, key informant interviews, and focus group discussions. DISCUSSION: The IVON trial could provide both effectiveness and implementation evidence to guide policy for integration and uptake of intravenous iron for treating anaemia in pregnancy in Nigeria and similar resource-limited, high-burden settings. If found effective, further studies exploring different intravenous iron doses are planned. TRIAL REGISTRATION: ISRCTN registry ISRCTN63484804 . Registered on 10 December 2020 Clinicaltrials.gov NCT04976179 . Registered on 26 July 2021 The current protocol version is version 2.1 (080/080/2021).


Assuntos
Anemia Ferropriva , Anemia , Deficiências de Ferro , Nascimento Prematuro , Anemia/diagnóstico , Anemia/tratamento farmacológico , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/tratamento farmacológico , Feminino , Compostos Férricos/efeitos adversos , Humanos , Recém-Nascido , Ferro , Nigéria/epidemiologia , Gravidez , Gestantes , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Int J Mol Sci ; 23(17)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36076926

RESUMO

Beta-propeller protein-associated neurodegeneration (BPAN) is a subtype of neurodegeneration with brain iron accumulation (NBIA) caused by loss-of-function variants in WDR45. The underlying mechanism of iron accumulation in WDR45 deficiency remains elusive. We established a primary skin fibroblast culture of a new BPAN patient with a missense variant p.(Asn61Lys) in WDR45 (NM_007075.3: c.183C>A). The female patient has generalized dystonia, anarthria, parkinsonism, spasticity, stereotypies, and a distinctive cranial MRI with generalized brain atrophy, predominantly of the cerebellum. For the functional characterization of this variant and to provide a molecular link of WDR45 and iron accumulation, we looked for disease- and variant-related changes in the patient's fibroblasts by qPCR, immunoblotting and immunofluorescence comparing to three controls and a previously reported WDR45 patient. We demonstrated molecular changes in mutant cells comprising an impaired mitochondrial network, decreased levels of lysosomal proteins and enzymes, and altered autophagy, confirming the pathogenicity of the variant. Compared to increased levels of the ferritinophagy marker Nuclear Coactivator 4 (NCOA4) in control cells upon iron treatment, patients' cells revealed unchanged NCOA4 protein levels, indicating disturbed ferritinophagy. Additionally, we observed abnormal protein levels of markers of the iron-dependent cell death ferroptosis in patients' cells. Altogether, our data suggests that WDR45 deficiency affects ferritinophagy and ferroptosis, consequentially disturbing iron recycling.


Assuntos
Ferroptose , Autofagia/genética , Encéfalo/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Feminino , Ferroptose/genética , Humanos , Ferro/metabolismo , Imageamento por Ressonância Magnética
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