-
Ecotoxicology and Environmental Safety Jul 2024The contamination of water by arsenic (As) has emerged as a significant environmental concern due to its well-documented toxicity. Environmentally relevant...
The contamination of water by arsenic (As) has emerged as a significant environmental concern due to its well-documented toxicity. Environmentally relevant concentrations of As have been reported to pose a considerable threat to fish. However, previous studies mainly focused on the impacts of As at environmentally relevant concentrations on adult fish, and limited information is available regarding its impacts on fish at early life stage. In this study, zebrafish embryos were employed to evaluate the environmental risks following exposure to different concentrations (0, 25, 50, 75 and 150 μg/L) of pentavalent arsenate (AsV) for 120 hours post fertilization. Our findings indicated that concentrations ≤ 150 μg/L AsV did not exert significant effects on survival or aberration; however, it conspicuously inhibited heart rate of zebrafish larvae. Furthermore, exposure to AsV significantly disrupted mRNA transcription of genes associated with cardiac development, and elongated the distance between the sinus venosus and bulbus arteriosus at 75 μg/L and 150 μg/L treatments. Additionally, AsV exposure enhanced superoxide dismutase (SOD) activity at 50, 75 and 150 μg/L treatments, and increased mRNA transcriptional levels of Cu/ZnSOD and MnSOD at 75 and 150 μg/L treatments. Concurrently, AsV suppressed metallothionein1 (MT1) and MT2 mRNA transcriptions while elevating heat shock protein70 mRNA transcription levels in zebrafish larvae resulting in elevated malondialdehyde (MDA) levels. These findings provide novel insights into the toxic effects exerted by low concentrations of AsV on fish at early life stage, thereby contributing to an exploration into the environmental risks associated with environmentally relevant concentrations.
Topics: Animals; Zebrafish; Arsenates; Water Pollutants, Chemical; Oxidative Stress; Embryo, Nonmammalian; Heart; Superoxide Dismutase; Metallothionein; Larva; Heart Rate; Dose-Response Relationship, Drug
PubMed: 38843745
DOI: 10.1016/j.ecoenv.2024.116529 -
Frontiers in Plant Science 2024
PubMed: 38841279
DOI: 10.3389/fpls.2024.1430708 -
BMC Genomics Jun 2024Broussonetia papyrifera is an economically significant tree with high utilization value, yet its cultivation is often constrained by soil contamination with heavy metals...
BACKGROUND
Broussonetia papyrifera is an economically significant tree with high utilization value, yet its cultivation is often constrained by soil contamination with heavy metals (HMs). Effective scientific cultivation management, which enhances the yield and quality of B. papyrifera, necessitates an understanding of its regulatory mechanisms in response to HM stress.
RESULTS
Twelve Metallothionein (MT) genes were identified in B. papyrifera. Their open reading frames ranged from 186 to 372 bp, encoding proteins of 61 to 123 amino acids with molecular weights between 15,473.77 and 29,546.96 Da, and theoretical isoelectric points from 5.24 to 5.32. Phylogenetic analysis classified these BpMTs into three subclasses: MT1, MT2, and MT3, with MT2 containing seven members and MT3 only one. The expression of most BpMT genes was inducible by Cd, Mn, Cu, Zn, and abscisic acid (ABA) treatments, particularly BpMT2e, BpMT2d, BpMT2c, and BpMT1c, which showed significant responses and warrant further study. Yeast cells expressing these BpMT genes exhibited enhanced tolerance to Cd, Mn, Cu, and Zn stresses compared to control cells. Yeasts harboring BpMT1c, BpMT2e, and BpMT2d demonstrated higher accumulation of Cd, Cu, Mn, and Zn, suggesting a chelation and binding capacity of BpMTs towards HMs. Site-directed mutagenesis of cysteine (Cys) residues indicated that mutations in the C domain of type 1 BpMT led to increased sensitivity to HMs and reduced HM accumulation in yeast cells; While in type 2 BpMTs, the contribution of N and C domain to HMs' chelation possibly corelated to the quantity of Cys residues.
CONCLUSION
The BpMT genes are crucial in responding to diverse HM stresses and are involved in ABA signaling. The Cys-rich domains of BpMTs are pivotal for HM tolerance and chelation. This study offers new insights into the structure-function relationships and metal-binding capabilities of type-1 and - 2 plant MTs, enhancing our understanding of their roles in plant adaptation to HM stresses.
Topics: Metallothionein; Metals, Heavy; Phylogeny; Broussonetia; Gene Expression Regulation, Plant; Plant Proteins; Stress, Physiological; Amino Acid Sequence; Protein Binding
PubMed: 38840042
DOI: 10.1186/s12864-024-10477-x -
Open Heart Jun 2024Iron deficiency (ID) has been reported in patients with congenital heart disease. There is, however, a scarcity of data on its prevalence in patients with a Fontan...
BACKGROUND
Iron deficiency (ID) has been reported in patients with congenital heart disease. There is, however, a scarcity of data on its prevalence in patients with a Fontan circulation. The aim of this study is to investigate the prevalence of ID in Fontan patients and to investigate the association between ID and exercise capacity in this population.
METHODS AND RESULTS
Blood count and haematological parameters were determined in plasma of 61 Fontan patients (51% female, mean age 29±9 years). ID was defined as transferrin saturation (TSAT) ≤19.8%. The prevalence of ID was 36% (22/61 patients). Especially among women, the diagnosis of ID was highly prevalent (52%) despite normal haemoglobin levels (153.7±18.4 g/L). Mean ferritin levels were 98±80 µg/L and mean TSAT levels were 22%±12%. Cardiopulmonary exercise testing was performed in 46 patients (75%). Patients with ID had a lower peak oxygen uptake (V̇Opeak) (1397±477 vs 1692±530 mL/min; p=0.039), although this relationship was confounded by sex. The presence of ID increased the likelihood of not achieving a respiratory exchange ratio (RER) ≥1.1 by 5-fold (p=0.035).
CONCLUSION
ID is highly prevalent among patients with a Fontan circulation. V̇Opeak is lower in patients with ID. Fontan patients with ID are less likely to achieve an RER≥1.1 during cardiopulmonary exercise testing.
Topics: Humans; Female; Male; Fontan Procedure; Heart Defects, Congenital; Exercise Tolerance; Adult; Prevalence; Exercise Test; Young Adult; Biomarkers; Anemia, Iron-Deficiency; Oxygen Consumption; Iron; Iron Deficiencies; Adolescent; Ferritins
PubMed: 38839367
DOI: 10.1136/openhrt-2024-002693 -
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