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Frontiers in Immunology 2024Swine influenza viruses (SIVs) pose significant economic losses to the pig industry and are a burden on global public health systems. The increasing complexity of the...
INTRODUCTION
Swine influenza viruses (SIVs) pose significant economic losses to the pig industry and are a burden on global public health systems. The increasing complexity of the distribution and evolution of different serotypes of influenza strains in swine herds escalates the potential for the emergence of novel pandemic viruses, so it is essential to develop new vaccines based on swine influenza.
METHODS
Here, we constructed a self-assembling ferritin nanoparticle vaccine based on the hemagglutinin (HA) extracellular domain of swine influenza A (H1N1) virus using insect baculovirus expression vector system (IBEVS), and after two immunizations, the immunogenicities and protective efficacies of the HA-Ferritin nanoparticle vaccine against the swine influenza virus H1N1 strain in mice and piglets were evaluated.
RESULTS
Our results demonstrated that HA-Ferritin nanoparticle vaccine induced more efficient immunity than traditional swine influenza vaccines. Vaccination with the HA-Ferritin nanoparticle vaccine elicited robust hemagglutinin inhibition titers and antigen-specific IgG antibodies and increased cytokine levels in serum. MF59 adjuvant can significantly promote the humoral immunity of HA-Ferritin nanoparticle vaccine. Furthermore, challenge tests showed that HA-Ferritin nanoparticle vaccine conferred full protection against lethal challenge with H1N1 virus and significantly decreased the severity of virus-associated lung lesions after challenge in both BALB/c mice and piglets.
CONCLUSION
Taken together, these results indicate that the hemagglutinin extracellular-based ferritin nanoparticle vaccine may be a promising vaccine candidate against SIVs infection.
Topics: Animals; Influenza A Virus, H1N1 Subtype; Ferritins; Influenza Vaccines; Swine; Mice; Orthomyxoviridae Infections; Nanoparticles; Hemagglutinin Glycoproteins, Influenza Virus; Antibodies, Viral; Mice, Inbred BALB C; Swine Diseases; Female; Nanovaccines
PubMed: 38835763
DOI: 10.3389/fimmu.2024.1361323 -
Open Biology Jun 2024Succinate dehydrogenase (SDH) is a protein complex that functions in the tricarboxylic acid cycle and the electron transport chain of mitochondria. In most eukaryotes,...
Succinate dehydrogenase (SDH) is a protein complex that functions in the tricarboxylic acid cycle and the electron transport chain of mitochondria. In most eukaryotes, SDH is highly conserved and comprises the following four subunits: SdhA and SdhB form the catalytic core of the complex, while SdhC and SdhD anchor the complex in the membrane. is an apicomplexan parasite that infects one-third of humans worldwide. The genome of encodes homologues of the catalytic subunits SdhA and SdhB, although the physiological role of the SDH complex in the parasite and the identity of the membrane-anchoring subunits are poorly understood. Here, we show that the SDH complex contributes to optimal proliferation and O consumption in the disease-causing tachyzoite stage of the life cycle. We characterize a small membrane-bound subunit of the SDH complex called mitochondrial protein ookinete developmental defect (MPODD), which is conserved among myzozoans, a phylogenetic grouping that incorporates apicomplexan parasites and their closest free-living relatives. We demonstrate that MPODD is essential for SDH activity and plays a key role in attaching the SdhA and SdhB proteins to the membrane anchor of the complex. Our findings highlight a unique and important feature of mitochondrial energy metabolism in apicomplexan parasites and their relatives.
Topics: Toxoplasma; Succinate Dehydrogenase; Protozoan Proteins; Humans; Mitochondrial Proteins; Mitochondria; Phylogeny; Animals
PubMed: 38835243
DOI: 10.1098/rsob.230463 -
Gut Microbes 2024The facultative anaerobic Gram-positive bacterium is a ubiquitous member of the human gut microbiota. However, it has gradually evolved into a pathogenic and multidrug...
The facultative anaerobic Gram-positive bacterium is a ubiquitous member of the human gut microbiota. However, it has gradually evolved into a pathogenic and multidrug resistant lineage that causes nosocomial infections. The establishment of high-level intestinal colonization by enterococci represents a critical step of infection. The majority of current research on has been conducted under aerobic conditions, while limited attention has been given to its physiological characteristics in anaerobic environments, which reflects its natural colonization niche in the gut. In this study, a high-density transposon mutant library containing 26,620 distinct insertion sites was constructed. Tn-seq analysis identified six genes that significantly contribute to growth under anaerobic conditions. Under anaerobic conditions, deletion of (encoding Fe-S cluster assembly protein B) results in more extensive and significant impairments on carbohydrate metabolism compared to aerobic conditions. Consistently, the pathways involved in this utilization-restricted carbohydrates were mostly expressed at significantly lower levels in mutant compared to wild-type under anaerobic conditions. Moreover, deletion of or (encoding pyruvate formate lyase-activating protein A) led to failure of gastrointestinal colonization in mice. These findings contribute to our understanding of the mechanisms by which maintains proliferation under anaerobic conditions and establishes colonization in the gut.
Topics: Enterococcus faecium; Animals; Mice; Bacterial Proteins; Anaerobiosis; Iron-Sulfur Proteins; Gastrointestinal Tract; Gastrointestinal Microbiome; Gram-Positive Bacterial Infections; Humans; DNA Transposable Elements; Carbohydrate Metabolism; Female; Acetyltransferases
PubMed: 38831611
DOI: 10.1080/19490976.2024.2359665 -
The Pan African Medical Journal 2024Chronic kidney disease (CKD) is commonly complicated by anemia. Treating dialysis-dependent patients with anemia, including daprodustat and other inhibitors of prolyl... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Chronic kidney disease (CKD) is commonly complicated by anemia. Treating dialysis-dependent patients with anemia, including daprodustat and other inhibitors of prolyl hydroxylase of hypoxia-inducible factor, recombinant human erythropoietin (rhEPO), and iron supplements. We conducted this study to test our postulation; daprodustat is superior to rhEPO and other conventional treatments respecting efficacy and safety parameters. We made systematic search through PubMed, Web of Science, Scopus, and Cochrane. Seven unique trials were eventually included for systematic review; six of them with a sample size of 759 patients entered our network meta-analysis (NMA). Daprodustat 25-30 mg was associated with the greatest change in serum hemoglobin (MD=1.86, 95%CI= [1.20; 2.52]), ferritin (MD= -180.84, 95%CI= [-264.47; -97.20]), and total iron binding capacity (TIBC) (MD=11.03, 95%CI= [3.15; 18.92]) from baseline values. Dialysis-dependent patients with anemia had a significant increment in serum Hemoglobin and TIBC and a reduction in serum ferritin, in a dose-dependent manner, when administered daprodustat.
Topics: Humans; Anemia; Renal Dialysis; Hemoglobins; Renal Insufficiency, Chronic; Glycine; Ferritins; Barbiturates; Network Meta-Analysis; Erythropoietin; Recombinant Proteins; Dose-Response Relationship, Drug; Iron
PubMed: 38828426
DOI: 10.11604/pamj.2024.47.114.37278 -
Yakugaku Zasshi : Journal of the... 2024Iron is necessary for all living organisms, and bacteria that cause infections in human hosts also need ferrous ions for their growth and proliferation. In the human... (Review)
Review
Iron is necessary for all living organisms, and bacteria that cause infections in human hosts also need ferrous ions for their growth and proliferation. In the human body, most ferric ions (Fe) are tightly bound to iron-binding proteins such as hemoglobin, transferrin, lactoferrin, and ferritin. Pathogenic bacteria express highly specific iron uptake systems, including siderophores and specific receptors. Most bacteria secrete siderophores, which are low-molecular weight metal-chelating agents, to capture Fe outside cell. Siderophores are mainly classified as either catecholate or hydroxamate. Vibrio vulnificus, a Gram-negative pathogenic bacterium, is responsible for serious infections in humans and requires iron for growth. A clinical isolate, V. vulnificus M2799, secretes a catecholate siderophore, vulnibactin, that captures ferric ions from the environment. In our study, we generated deletion mutants of the genes encoding proteins involved in the vulnibactin mediated iron-utilization system, such as ferric-vulnibactin receptor protein (VuuA), periplasmic ferric-vulnibactin binding protein (FatB), ferric-vulnibactin reductase (VuuB), and isochorismate synthase (ICS). ICS and VuuA are required under low-iron conditions for ferric-utilization in M2799, but the alternative proteins FatB and VuuB can function as a periplasmic binding protein and a ferric-chelate reductase, respectively. VatD, which functions as ferric-hydroxamate siderophores periplasmic binding protein, was shown to participate in the ferric-vulnibactin uptake system in the absence of FatB. Furthermore, the ferric-hydroxamate siderophore reductase IutB was observed to participate in ferric-vulnibactin reduction in the absence of VuuB. We propose that ferric-siderophore periplasmic binding proteins and ferric-chelate reductases represent potential targets for drug discovery in the context of infectious diseases.
Topics: Iron; Siderophores; Humans; Drug Discovery; Bacterial Infections; Molecular Targeted Therapy; Hydroxamic Acids; Iron-Binding Proteins
PubMed: 38825472
DOI: 10.1248/yakushi.23-00197-2 -
Journal of Hazardous Materials Aug 2024Bioremediation of cadmium (Cd) pollution, a recognized low-carbon green environmental protection technology, is significantly enhanced by the discovery of Cd-tolerant...
Bioremediation of cadmium (Cd) pollution, a recognized low-carbon green environmental protection technology, is significantly enhanced by the discovery of Cd-tolerant microorganisms and their underlying tolerance mechanisms. This study presents Colpoda sp., a soil ciliate with widespread distribution, as a novel bioindicator and bioremediator for Cd contamination. With a 24 h-LC of 5.39 mg l and an IC of 24.85 μg l in Cd-contaminated water, Colpoda sp. achieves a maximum bioaccumulation factor (BAF) of 3.58 and a Cd removal rate of 32.98 ± 0.74 % within 96 h. The toxic responses of Colpoda sp. to Cd stress were assessed through cytological observation with transmission electron microscopy (TEM), oxidative stress kinase activity, and analysis of Cd-metallothionein (Cd-MTs) and the cd-mt gene via qRT-PCR. The integrated biomarker response index version 2 (IBRv2) and structural equation models (SEM) were utilized to analyze key factors and mechanisms, revealing that the up-regulation of Cd-MTs and cd-mt expression, rather than the oxidative stress system, is the primary determinant of Cd accumulation and tolerance in Colpoda sp. The ciliate's ability to maintain growth under 24.85 μg l Cd stress and its capacity to absorb and accumulate Cd particles from water into cells are pivotal for bioremediation. A new mathematical formula and regression equations based on Colpoda sp.'s response parameters have been established to evaluate environmental Cd removal levels and design remediation schemes for contaminated sites. These findings provide a novel bioremediation and monitoring pathway for Cd remobilization and accumulation in soil and water, potentially revolutionizing the governance of Cd pollution.
Topics: Cadmium; Soil Pollutants; Biodegradation, Environmental; Ciliophora; Metallothionein; Oxidative Stress; Water Pollutants, Chemical
PubMed: 38823099
DOI: 10.1016/j.jhazmat.2024.134762 -
Nature Communications May 2024The human AAA-ATPase Bcs1L translocates the fully assembled Rieske iron-sulfur protein (ISP) precursor across the mitochondrial inner membrane, enabling respiratory...
The human AAA-ATPase Bcs1L translocates the fully assembled Rieske iron-sulfur protein (ISP) precursor across the mitochondrial inner membrane, enabling respiratory Complex III assembly. Exactly how the folded substrate is bound to and released from Bcs1L has been unclear, and there has been ongoing debate as to whether subunits of Bcs1L act in sequence or in unison hydrolyzing ATP when moving the protein cargo. Here, we captured Bcs1L conformations by cryo-EM during active ATP hydrolysis in the presence or absence of ISP substrate. In contrast to the threading mechanism widely employed by AAA proteins in substrate translocation, subunits of Bcs1L alternate uniformly between ATP and ADP conformations without detectable intermediates that have different, co-existing nucleotide states, indicating that the subunits act in concert. We further show that the ISP can be trapped by Bcs1 when its subunits are all in the ADP-bound state, which we propose to be released in the apo form.
Topics: Adenosine Triphosphate; Hydrolysis; Cryoelectron Microscopy; Electron Transport Complex III; Humans; Adenosine Diphosphate; ATPases Associated with Diverse Cellular Activities; Iron-Sulfur Proteins; Protein Conformation; Protein Folding; Models, Molecular; Protein Transport
PubMed: 38821922
DOI: 10.1038/s41467-024-49029-y -
Journal of the American Heart... Jun 2024Mendelian randomization (MR) studies suggest a causal effect of iron status on cardiovascular disease (CVD) risk, but it is unknown if these associations are confounded...
BACKGROUND
Mendelian randomization (MR) studies suggest a causal effect of iron status on cardiovascular disease (CVD) risk, but it is unknown if these associations are confounded by pleiotropic effects of the instrumental variables on CVD risk factors. We aimed to investigate the effect of iron status on CVD risk controlling for CVD risk factors.
METHODS AND RESULTS
Iron biomarker instrumental variables (total iron-binding capacity [n=208 422], transferrin saturation [n=198 516], serum iron [n=236 612], ferritin [n=257 953]) were selected from a European genome-wide association study meta-analysis. We performed 2-sample univariate MR of each iron trait on CVD outcomes (all-cause ischemic stroke, cardioembolic ischemic stroke, large-artery ischemic stroke, small-vessel ischemic stroke, and coronary heart disease) from MEGASTROKE (n=440 328) and CARDIoGRAMplusC4D (Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus the Coronary Artery Disease Genetics) (n=183 305). We then implemented multivariate MR conditioning on 7 CVD risk factors from independent European samples to evaluate their potential confounding or mediating effects on the observed iron-CVD associations. With univariate MR analyses, we found higher genetically predicted iron status to be associated with a greater risk of cardioembolic ischemic stroke (transferrin saturation: odds ratio, 1.17 [95% CI, 1.03-1.33]; serum iron: odds ratio, 1.21 [95% CI, 1.02-1.44]; total iron-binding capacity: odds ratio, 0.81 [95% CI, 0.69-0.94]). The detrimental effects of iron status on cardioembolic ischemic stroke risk remained unaffected when adjusting for CVD risk factors (all <0.05). Additionally, we found diastolic blood pressure to mediate between 7.1 and 8.8% of the total effect of iron status on cardioembolic ischemic stroke incidence. Univariate MR initially suggested a protective effect of iron status on large-artery stroke and coronary heart disease, but controlling for CVD factors using multivariate MR substantially diminished these associations (all >0.05).
CONCLUSIONS
Higher iron status was associated with a greater risk of cardioembolic ischemic stroke independent of CVD risk factors, and this effect was partly mediated by diastolic blood pressure. These findings support a role of iron status as a modifiable risk factor for cardioembolic ischemic stroke.
Topics: Humans; Mendelian Randomization Analysis; Iron; Cardiovascular Diseases; Genome-Wide Association Study; Transferrin; Biomarkers; Heart Disease Risk Factors; Risk Assessment; Ferritins; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Male; Risk Factors; Ischemic Stroke; Female
PubMed: 38818967
DOI: 10.1161/JAHA.124.034991 -
PloS One 2024The left ventricular (LV) changes which occur in Friedreich ataxia (FRDA) are incompletely understood.
BACKGROUND
The left ventricular (LV) changes which occur in Friedreich ataxia (FRDA) are incompletely understood.
METHODS
Cardiac magnetic resonance (CMR) imaging was performed using a 1.5T scanner in subjects with FRDA who are homozygous for an expansion of an intron 1 GAA repeat in the FXN gene. Standard measurements were performed of LV mass (LVM), LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF). Native T1 relaxation time and the extracellular volume fraction (ECV) were utilised as markers of left ventricular (LV) diffuse myocardial fibrosis and late gadolinium enhancement (LGE) was utilised as a marker of LV replacement fibrosis. FRDA genetic severity was assessed using the shorter FXN GAA repeat length (GAA1).
RESULTS
There were 93 subjects with FRDA (63 adults, 30 children, 54% males), 9 of whom had a reduced LVEF (<55%). A LVEDV below the normal range was present in 39%, a LVM above the normal range in 22%, and an increased LVM/LVEDV ratio in 89% subjects. In adults with a normal LVEF, there was an independent positive correlation of LVM with GAA1, and a negative correlation with age, but no similar relationships were seen in children. GAA1 was positively correlated with native T1 time in both adults and children, and with ECV in adults, all these associations independent of LVM and LVEDV. LGE was present in 21% of subjects, including both adults and children, and subjects with and without a reduced LVEF. None of GAA1, LVM or LVEDV were predictors of LGE.
CONCLUSION
An association between diffuse interstitial LV myocardial fibrosis and genetic severity in FRDA was present independently of FRDA-related LV structural changes. Localised replacement fibrosis was found in a minority of subjects with FRDA and was not associated with LV structural change or FRDA genetic severity in subjects with a normal LVEF.
Topics: Humans; Friedreich Ataxia; Male; Female; Adult; Gadolinium; Heart Ventricles; Child; Adolescent; Magnetic Resonance Imaging; Middle Aged; Young Adult; Contrast Media; Stroke Volume; Fibrosis; Frataxin
PubMed: 38814901
DOI: 10.1371/journal.pone.0303969 -
Journal of Clinical Laboratory Analysis May 2024In this study, we investigated how splenectomy affects natural killer (NK) cell levels in patients with β-thalassemia major (β-TM).
AIM
In this study, we investigated how splenectomy affects natural killer (NK) cell levels in patients with β-thalassemia major (β-TM).
MATERIALS AND METHODS
Seventy patients with β-TM (38 splenectomized and 32 nonsplenectomized) and 25 healthy controls were included in this study. The hemogram parameters, ferritin, T lymphocyte, T-helper cell, T-suppressor cell, and NK cell numbers, were measured.
RESULTS
The T lymphocyte (CD3) level was found to be significantly higher in the patient group (p < 0.05). CD3/CD4 T lymphocytes were detected to be significantly higher in the patient group (p < 0.05). Although the CD3/CD4 T lymphocyte level was significantly higher in the nonsplenectomy group (p < 0.05), this was not the case in the splenectomy group. When the patient and control groups were compared, no significant difference was detected regarding CD3/CD8 T lymphocyte levels. CD3/CD16CD56 NK cell level was found to be significantly lower only in the splenectomy group than in the control group (p < 0.05). We found that there was a significant negative correlation between serum ferritin levels and both total lymphocyte (r = -0.617) and CD3 lymphocyte (r = -0.718) levels in the control group (p < 0.05). A significant negative correlation was detected between serum ferritin levels and CD3/CD16CD56 NK cell levels in the patient group (r = -0.410) (p < 0.05).
CONCLUSION
Splenectomy reduces NK cell levels in patients with β-TM. The negative relationship between ferritin levels and NK cells indicates that ferritin levels should be kept under control in patients with β-TM.
Topics: Humans; beta-Thalassemia; Splenectomy; Killer Cells, Natural; Male; Female; Adult; Case-Control Studies; Adolescent; Young Adult; Child; Ferritins; Lymphocyte Count
PubMed: 38814004
DOI: 10.1002/jcla.25046