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Critical Care Research and Practice 2024Present day Jehovah's Witness (JW) religion accounts for 8.5 million followers. A tenant feature of the JW faith is religious objection to transfusions of blood and... (Review)
Review
Present day Jehovah's Witness (JW) religion accounts for 8.5 million followers. A tenant feature of the JW faith is religious objection to transfusions of blood and blood products. Interpatient variability, as it pertains to blood and blood products may occur; hence, a confidential interview will determine which products individual may consent to (Marsh and Bevan, 2002). This belief and practice place great restrictions on treating medical professionals in scenarios of life-threatening anaemia and active haemorrhage. The review to follow explores the physiological and pathophysiological consequences of severe anaemia. Non-blood transfusion practices are explored, many of which are potentially lifesaving. Particular attention is drawn to the evolving science involving artificial oxygen carriers and their use in emergency situations. A greater safety profile ensures its future use amongst religious objectors to be greatly beneficial. Intravenous iron supplementation has enjoyed a lively debate within the critical care community. A review of recent systematic and meta-analysis supports its use in the ICU; however, more investigation is needed into the complementary use of hepcidin.
PubMed: 38813134
DOI: 10.1155/2024/1913237 -
Research Square May 2024Salmonellosis, caused by Salmonella enterica serovar Typhimurium, is a significant global threat. Host immunity limits bacterial replication by inducing hepcidin, which...
Salmonellosis, caused by Salmonella enterica serovar Typhimurium, is a significant global threat. Host immunity limits bacterial replication by inducing hepcidin, which degrades ferroportin, reducing iron transfer. However, this boosts macrophage iron storage, aiding intracellular pathogens like Salmonella. Mice lacking ferritin heavy chain (FTH1) in myeloid cells suffer worsened Salmonella infection. Nuclear receptor co-activator 4 (NCOA4) regulates iron release via FTH1 degradation during low iron, but its role in salmonellosis is unclear. Here, we reveal that myeloid NCOA4 deficiency augments spleen iron levels and increases cellular iron accumulation, oxidative stress, and ferroptosis in bone marrow-derived macrophages. This deficiency also increases susceptibility to Salmonella-induced colitis in mice. Mechanistically, NCOA4 suppresses oxidative stress by directly binding to the E3 ubiquitin ligase Kelch-like ECH-associated protein 1 (KEAP1) and stabilizing the antioxidant transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2). Activation of NRF2 protects myeloid NCOA4 knockout mice from Salmonella-induced colitis. Antioxidant Tempol and myeloid cell-targeted curcumin offer protection against colitis in myeloid NCOA4-deficient mice. A low iron diet and ferroptosis inhibition also mitigate the heightened colitis in these mice. Overexpression of myeloid cell- specific NCOA4 confers protection against Salmonella-induced colitis via upregulating NRF2 signaling. Serum iron was reduced in myeloid NCOA4-overexpressing mice, but not in NCOA4- deficient mice. Targeted serum metabolomics analysis revealed that many lipids were decreased in myeloid NCOA4-deficient mice, while several of them were increased in myeloid NCOA4-overexpressing mice. Together, this study not only advances our understanding of NCOA4/KEAP1/NRF2/ferroptosis axis but also paves the way for novel myeloid cell-targeted therapies to combat salmonellosis.
PubMed: 38798412
DOI: 10.21203/rs.3.rs-4278310/v1 -
Asia Pacific Journal of Clinical... Jun 2024This study aimed to assess the associations of maternal iron status and placental iron transport proteins expression with the risk of pre-eclampsia (PE) in Chinese...
BACKGROUND AND OBJECTIVES
This study aimed to assess the associations of maternal iron status and placental iron transport proteins expression with the risk of pre-eclampsia (PE) in Chinese pregnant women.
METHODS AND STUDY DESIGN
A total of 94 subjects with PE and 112 healthy pregnant women were enrolled. Fasting blood samples were collected to detect maternal iron status. The placenta samples were collected at delivery to detect the mRNA and protein expression of divalent metal transporter 1 (DMT1) and ferroportin-1 (FPN1). Logistic analysis was used to explore the associations of maternal iron status with PE risk. The associations of placental iron transport proteins with maternal iron status were explored.
RESULTS
After adjusting for covariates, dietary total iron, non-heme iron intake and serum hepcidin were negatively associated with PE, with adjusted ORs (95%CIs) were 0.40 (0.17, 0.91), 0.42 (0.18, 0.94) and 0.02 (0.002, 0.13) for the highest versus lowest tertile, respectively. For the highest tertile versus lowest tertile, serum iron (4.08 (1.58, 10.57)) and ferritin (5.61 (2.36, 13.31)) were positively associated with PE. The mRNA expressions and protein levels of DMT1 and FPN1 in placenta were up-regulated in the PE group (p < 0.05). The mRNA expressions of DMT1 and FPN1 in placenta showed a negative correlation with the serum hepcidin (r = -0.71, p < 0.001; r = -0.49, p < 0.05).
CONCLUSIONS
In conclusion, the maternal iron status were closely associated with PE risk, placental DMT1 and FPN1 were upregulated in PE which may be a promising target for the prevention of PE.
Topics: Humans; Female; Pregnancy; Pre-Eclampsia; Case-Control Studies; Adult; Iron; Placenta; Cation Transport Proteins; Hepcidins; Risk Factors; China; Nutritional Status
PubMed: 38794978
DOI: 10.6133/apjcn.202406_33(2).0005 -
Animals : An Open Access Journal From... May 2024This study investigated the effects of glucose (GLU), tapioca starch (TS), gelatinized tapioca starch (GTS), potato starch (PS) and gelatinized potato starch (GPS) on...
This study investigated the effects of glucose (GLU), tapioca starch (TS), gelatinized tapioca starch (GTS), potato starch (PS) and gelatinized potato starch (GPS) on growth and physiological responses in juvenile largemouth bass . After 8 weeks, fish fed with starch diets had better weight gain and growth rates. Counts of red blood cells and monocytes were increased in the PS and GPS groups, compared to GLU group. Contents of serum triglyceride and total cholesterol were markedly elevated in the TS, PS and GPS groups. There were lower levels of serum glucose, insulin and cholecystokinin, and higher agouti-related peptide contents in the PS group compared to GLU group. PS and GPS could enhance glycolysis and TCA cycle by increasing their enzyme activities and transcriptional levels. Additionally, starch sources markedly heightened mRNA levels of key genes involved in the respiratory electron transport chain. Additionally, elevated mRNA levels of key antioxidant genes were shown in the TS and GTS groups. Moreover, TS and PS could promote immunity by upregulating transcriptional levels of the complement system, lysozyme and hepcidin. Taken together, starch exhibited better growth via increasing glycolysis and TCA cycle compared with GLU, and PS could improve antioxidant and immune capacities in largemouth bass.
PubMed: 38791708
DOI: 10.3390/ani14101492 -
Aging May 2024Hepcidin antimicrobial peptide (HAMP) is a small peptide hormone recognized for its role in iron metabolism and cancer treatment. The purpose of this study was to...
BACKGROUND
Hepcidin antimicrobial peptide (HAMP) is a small peptide hormone recognized for its role in iron metabolism and cancer treatment. The purpose of this study was to examine the influence of HAMP in NSCLC.
METHODS
The profile of NSCLC cells and tissues was characterized via HAMP. Gain- or loss-of-function cell models of HAMP were constructed, and CCK8, colony formation, and Transwell analyses were used to confirm the influence of HAMP on NSCLC cells. Upstream and downstream HAMP mechanisms in NSCLC were also analysed. Dual-luciferase reporter and pull-down assays confirmed the associations of miR-873-5p with HAMP, miR-873-5p, and the lncRNA KCNQ1OT1/SNHG14/XIST. Moreover, a xenograft model was established in nude mice for confirming the role of HAMP in NSCLC cell growth.
RESULTS
In addition, HAMP expression increased in NSCLC cells and tissues. In terms of cellular functions, the HAMP-overexpressing group exhibited elevated NSCLC cell proliferation, invasion, and migration. HAMP knockdown reversed these changes. Bioinformatics analysis indicated that miR-873-5p targeted HAMP, which affected the nuclear factor kappa B (NF-κB) pathway in NSCLC. HAMP activated the NF-κB pathway, which was negatively modulated by miR-873-5p. NF-κB inhibitor JSH-23 can partly suppress the proliferation, invasion, and migration in HAMP-overexpressed cells. Moreover, miR-873-5p was the target miRNA of long noncoding RNAs (lncRNAs), which included KCNQ1OT1, SNHG14, and XIST, and these three lncRNAs promoted HAMP.
CONCLUSION
Noncoding RNA-mediated HAMP promotes NSCLC cell proliferation, migration, and invasion by initiating the NF-κB pathway.
PubMed: 38787358
DOI: 10.18632/aging.205819 -
Clinical and Experimental Pediatrics May 2024Iron deficiency (ID) tends to be overlooked compared with anemia. However, its prevalence is estimated to be twice as high as that of ID anemia, and ID without anemia...
Iron deficiency (ID) tends to be overlooked compared with anemia. However, its prevalence is estimated to be twice as high as that of ID anemia, and ID without anemia can be accompanied by clinical and functional impairments. The symptoms of ID are nonspecific, such as fatigue and lethargy, but can lead to neurodevelopmental disorders in children, restless legs syndrome, and recurrent infections due to immune system dysregulation. In particular, the risk of ID is high in the context of chronic inflammatory diseases (CIDs) due to the reaction of various cytokines and the resulting increase in hepcidin levels; ID further exacerbates these diseases and increases mortality. Therefore, the diagnosis of ID should not be overlooked through ID screening especially in high-risk groups. Ferritin and transferrin saturation levels are the primary laboratory parameters used to diagnose ID. However, as ferritin levels respond to inflammation, the diagnostic criteria differ among guidelines. Therefore, new tools and criteria for accurately diagnosing ID should be developed. Treatment can be initiated only with an accurate diagnosis. Oral iron is typically the first-line treatment for ID; however, the efficacy and safety of intravenous iron have recently been recognized. Symptoms improve quickly after treatment, and the prognosis of accompanying diseases can also be improved. This review highlights the need to improve global awareness of ID diagnosis and treatment, even in the absence of anemia, to improve the quality of life of affected children, especially those with CIDs.
PubMed: 38772411
DOI: 10.3345/cep.2023.00521 -
Age and Ageing May 2024Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and...
CONTEXT
Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation.
OBJECTIVE AND METHODS
Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73 m2; CKDG3a/b; n = 35) or normal renal function (eGFR >90 ml/min/1.73 m2; CKDG1; n = 35) received 12,000, 24,000 or 48,000 IU D3/month for 1 year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression.
RESULTS
Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNFα were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNFα significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR.
CONCLUSION
Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.
Topics: Humans; Fibroblast Growth Factor-23; Aged; Male; Female; Renal Insufficiency, Chronic; Dietary Supplements; Glomerular Filtration Rate; Biomarkers; Fibroblast Growth Factors; Iron; Kidney; Vitamin D; Aged, 80 and over; Treatment Outcome; Inflammation; Inflammation Mediators; Age Factors; Cholecalciferol; Time Factors; Bone and Bones
PubMed: 38770543
DOI: 10.1093/ageing/afae096 -
Frontiers in Microbiology 2024The increasing demand for orthopedic surgeries, including joint replacements, is driven by an aging population and improved diagnosis of joint conditions. Orthopedic...
The increasing demand for orthopedic surgeries, including joint replacements, is driven by an aging population and improved diagnosis of joint conditions. Orthopedic surgeries carry a risk of infection, especially in patients with comorbidities. The rise of antibiotic resistance exacerbates this issue, necessitating alternatives like bioengineered antimicrobial peptides (AMPs), offering broad-spectrum activity and multiple action mechanisms. This review aimed to assess the prevalence of antimicrobial potential and the yield after purification among recombinant AMP families. The antimicrobial potential was evaluated using the Minimum Inhibitory Concentration (MIC) values against the most common bacteria involved in clinical infections. This systematic review adhered to PRISMA guidelines, focusing on studies of recombinant AMPs. The search strategy was run on PubMed, Scopus and Embase up to 30 March 2023. The Population, Exposure and Outcome model was used to extract the data from studies and ToxRTool for the risk of bias analysis. This review included studies providing peptide production yield data and MIC values against pathogenic bacteria. Non-English texts, reviews, conference abstracts, books, studies focusing solely on chemical synthesis, those reporting incomplete data sets, using non-standard MIC assessment methods, or presenting MIC values as ranges rather than precise concentrations, were excluded. From 370 publications, 34 studies on AMPs were analyzed. These covered 46 AMPs across 18 families, with Defensins and Hepcidins being most common. Yields varied from 0.5 to 2,700 mg/L. AMPs were tested against 23 bacterial genera, with MIC values ranging from 0.125 to >1,152 μg/mL. Arenicins showed the highest antimicrobial activity, particularly against common orthopedic infection pathogens. However, AMP production yields varied and some AMPs demonstrated limited effectiveness against certain bacterial strains. This systematic review emphasizes the critical role of bioengineered AMPs to cope infections and antibiotic resistance. It meticulously evaluates recombinant AMPs, focusing on their antimicrobial efficacy and production yields. The review highlights that, despite the variability in AMP yields and effectiveness, Arenicins and Defensins are promising candidates for future research and clinical applications in treating antibiotic-resistant orthopedic infections. This study contributes significantly to the understanding of AMPs in healthcare, underscoring their potential in addressing the growing challenge of antibiotic resistance. https://osf.io/2uq4c/.
PubMed: 38756724
DOI: 10.3389/fmicb.2024.1370826 -
Advances in Nutrition (Bethesda, Md.) May 2024Vaccines can prevent infectious diseases, but their efficacy varies, and factors impacting vaccine effectiveness remain unclear. Iron deficiency is the most common... (Review)
Review
Vaccines can prevent infectious diseases, but their efficacy varies, and factors impacting vaccine effectiveness remain unclear. Iron deficiency is the most common nutrient deficiency, affecting >2 billion individuals. It is particularly common in areas with high-infectious disease burden and in groups that are routinely vaccinated, such as infants, pregnant women, and the elderly. Recent evidence suggests that iron deficiency and low-serum iron (hypoferremia) not only cause anemia but also may impair adaptive immunity and vaccine efficacy. A report of human immunodeficiency caused by defective iron transport underscored the necessity of iron for adaptive immune responses and spurred research in this area. Sufficient iron is essential for optimal production of plasmablasts and IgG responses by human B cells in vitro and in vivo. The increased metabolism of activated lymphocytes depends on the high-iron acquisition, and hypoferremia, especially when occurring during lymphocyte expansion, adversely affects multiple facets of adaptive immunity, and may lead to prolonged inhibition of T-cell memory. In mice, hypoferremia suppresses the adaptive immune response to influenza infection, resulting in more severe pulmonary disease. In African infants, anemia and/or iron deficiency at the time of vaccination predict decreased response to diphtheria, pertussis, and pneumococcal vaccines, and response to measles vaccine may be increased by iron supplementation. In this review, we examined the emerging evidence that iron deficiency may limit adaptive immunity and vaccine responses. We discuss the molecular mechanisms and evidence from animal and human studies, highlight important unknowns, and propose a framework of key research questions to better understand iron-vaccine interactions.
PubMed: 38729263
DOI: 10.1016/j.advnut.2024.100238 -
The Journal of Biological Chemistry May 2024Iron is an essential element for proper cell functioning, but unbalanced levels can cause cell death. Iron metabolism is controlled at the blood-tissue barriers provided...
Iron is an essential element for proper cell functioning, but unbalanced levels can cause cell death. Iron metabolism is controlled at the blood-tissue barriers provided by microvascular endothelial cells. Dysregulated iron metabolism at these barriers is a factor in both neurodegenerative and cardiovascular diseases. Mammalian iron efflux is mediated by the iron efflux transporter ferroportin (Fpn). Inflammation is a factor in many diseases and correlates with increased tissue iron accumulation. Evidence suggests treatment with interleukin 6 (IL-6) increases intracellular calcium levels and calcium is known to play an important role in protein trafficking. We have shown that calcium increases plasma membrane localization of the iron uptake proteins ZIP8 and ZIP14, but if and how calcium modulates Fpn trafficking is unknown. In this article, we examined the effects of IL-6 and calcium on Fpn localization to the plasma membrane. In HEK cells expressing a doxycycline-inducible GFP-tagged Fpn, calcium increased Fpn-GFP membrane presence by 2 h, while IL-6 increased membrane-localized Fpn-GFP by 3 h. Calcium pretreatment increased Fpn-GFP mediated Fe efflux from cells. Endoplasmic reticulum calcium stores were shown to be important for Fpn-GFP localization and iron efflux. Use of calmodulin pathway inhibitors showed that calcium signaling is important for IL-6-induced Fpn relocalization. Studies in brain microvascular endothelial cells in transwell culture demonstrated an initial increase in Fe flux with IL-6 that is reduced by 6 h coinciding with upregulation of hepcidin. Overall, this research details one pathway by which inflammatory signaling mediated by calcium can regulate iron metabolism, likely contributing to inflammatory disease mechanisms.
PubMed: 38718866
DOI: 10.1016/j.jbc.2024.107348