Iron deficiency in astrocytes alters cellular status and impacts on oligodendrocyte differentiation.

Iron deficiency (ID) has been shown to affect central nervous system (CNS) development and induce hypomyelination. Previous work from our laboratory in a gestational ID model showed that both oligodendrocyte (OLG) and astrocyte (AST) maturation was impaired. To explore the contribution of AST iron to the myelination process, we generated an in vitro ID model by silencing divalent metal transporter 1 (DMT1) in AST (siDMT1 AST) or treating AST with Fe3+ chelator deferoxamine (DFX; DFX AST). siDMT1 AST showed no changes in proliferation but remained immature. Co-cultures of oligodendrocyte precursors cells (OPC) with siDMT1 AST and OPC cultures incubated with siDMT1 AST-conditioned media (ACM) rendered a reduction in OPC maturation. These findings correlated with a decrease in the expression of AST-secreted factors IGF-1, NRG-1, and LIF, known to promote OPC differentiation. siDMT1 AST also displayed increased mitochondrial number and reduced mitochondrial size as compared to control cells. DFX AST also remained immature and DFX AST-conditioned media also hampered OPC maturation in culture, in keeping with a decrease in the expression of AST-secreted growth factors IGF-1, NRG-1, LIF, and CNTF. DFX AST mitochondrial morphology and number showed results similar to those observed in siDMT1 AST. In sum, our results show that ID, induced through two different methods, impacts AST maturation and mitochondrial functioning, which in turn hampers OPC differentiation.

Both nanoplastic and iron mineral types determine their heteroaggregation: Aggregation kinetics and interface process.

Nanoplastics (NPs) inevitably interact with iron minerals (IMs) after being released into aquatic environments, changing their transport and fate. In this study, batch heteroaggregation kinetics of four types of NPs, i.e., polymethyl methacrylate (PMMA), polystyrene (PS-Bare), amino-polystyrene (PS-NH2), and carboxyl-polystyrene (PS-COOH), with two different IMs (hematite and magnetite) were conducted. We found that the heteroaggregation of NPs and IMs and the associated interfacial interaction mechanisms are both NPs-dependent and IMs-dependent. Specifically, the NPs had stronger heteroaggregation with hematite than magnetite; the heteroaggregation order of two IMs with NPs was PMMA > PS-NH2 > PS-Bare > PS-COOH. Moreover, hydrogen bond, complexation, hydrophobic, cation-π, and electrostatic interaction were involved in the interfacial reaction between NPs and hematite, and electrons were transferred from the NPs to the hematite, causing the reduction of Fe3+ into Fe2+. Furthermore, we first revealed that both pre-homoaggregation of NPs and IMs could affect their subsequent heteroaggregation, and the homoaggregates of IMs could be interrupted by PMMA or PS-COOH NPs introduction. Therefore, the emerging NPs pollution is likely to generate an ecological effect in terms of elemental cycles such as iron cycle. This work provides new insights into assessing the environmental transfer and ecological effects of NPs in aquatic environments.

Removal of Cu(II) by sodium hexametaphosphate and nano zero-valent iron modified calcium bentonite: characteristic, adsorption performance and mechanism.

Cu (II) is a toxic heavy metal commonly identified in groundwater contaminants. Bentonite-based cutoff wall is the most used method in isolating and adsorbing contaminants, while the bentonite in it easily to fail due to Cu(II) exchange. This study synthesized a novel material through the modification of calcium bentonite (CaB) utilizing sodium hexametaphosphate (SHMP) and nano zero-valent iron (NZVI). The characteristics, adsorption performance, and mechanism of the NZVI/SHMP-CaB were investigated comprehensively. The results showed that SHMP can disperse CaB and reduce flocculation, while NZVI can be further stabilized without agglomeration. The best adsorption performance of NZVI/SHMP-CaB could be obtained at the dosage of 2% SHMP and 4% NZVI. The NZVI/SHMP-CaB exhibited an outstanding removal efficiency of over 60% and 90% at a high Cu(II) concentration (pH = 6, Cu(II) = 300 mg/L) and acidic conditions (pH = 3-6, Cu(II) = 50 mg/L), respectively. The adsorption of Cu(II) by NZVI/SHMP-CaB followed a pseudo-second-order kinetic model, and fitting results from the Freundlich isothermal model suggested that the adsorption process occurred spontaneously. Besides the rapid surface adsorption on the NZVI/SHMP-CaB and ion exchange with interlayer ions in bentonite, the removal mechanism of Cu(II) also involved the chemical reduction to insoluble forms such as Cu0 and Cu2O. The generated FePO4 covered the surface of the homogenized NZVI particles, enhancing the resistance of NZVI/SHMP-CaB to acidic and oxidative environments. This study indicates that NZVI/SHMP-CaB is a promising alternative material which can be used for heavy metal removal from contaminated soil and water.

Ferroptosis resists intracellular Vibrio splendidus AJ01 mediated by ferroportin in sea cucumber Apostichopus japonicus.

Ferroptosis, a kind of programmed cell death, is characterized with iron-dependent lipid ROS buildup, which is considered as an important cellular immunity in resisting intracellular bacterial infection in mammalian macrophages. In this process, lipid ROS oxidizes the bacterial biofilm to inhibit intracellular bacteria. However, the function of ferroptosis in invertebrate remains unknown. In this study, the existence of ferroptosis in Apostichopus japonicus coelomocytes was confirmed, and its antibacterial mechanism was investigated. First, our results indicated that the expression of glutathione peroxidase (AjGPX4) was significantly inhibited by 0.21-fold (p < 0.01) after injecting A. japonicus with the ferroptosis inducer RSL3, and the contents of MDA (3.70-fold, p < 0.01), ferrous iron (1.40-fold, p < 0.01), and lipid ROS (3.10-fold, p < 0.01) were all significantly increased under this condition and simultaneously accompanied with mitochondrial contraction and disappearance of cristae, indicating the existence of ferroptosis in the coelomocytes of A. japonicus. Subsequently, the contents of ferrous iron (1.40-fold, p < 0.05), MDA (2.10-fold, p < 0.01), ROS (1.70-fold, p < 0.01), and lipid ROS (2.50-fold, p < 0.01) were all significantly increased, whereas the mitochondrial membrane potential and GSH/GSSG were markedly decreased by 0.68-fold (p < 0.05) and 0.69-fold (p < 0.01) under Vibrio splendidus (AJ01) infection. This process could be reversed by the iron-chelating agent deferoxamine mesylate, which indicated that AJ01 could induce coelomocytic ferroptosis. Moreover, the results demonstrated that the intracellular AJ01 load was clearly decreased to 0.49-fold (p < 0.05) and 0.06-fold (p < 0.01) after treating coelomocytes with RSL3 and ferrous iron, which indicated that enhanced ferroptosis could inhibit bacterial growth. Finally, subcellular localization demonstrated that ferrous iron efflux protein ferroportin (AjFPN) and intracellular AJ01 were co-localized in coelomocytes. After AjFPN interference (0.58-fold, p < 0.01), the signals of ferrous iron and lipid ROS levels in intracellular AJ01 were significantly reduced by 0.38-fold (p < 0.01) and 0.48-fold (p < 0.01), indicating that AjFPN was an important factor in the introduction of ferroptosis into intracellular bacteria. Overall, our findings indicated that ferroptosis could resist intracellular AJ01 infection via AjFPN. These findings provide a novel defense mechanism for aquatic animals against intracellular bacterial infection.

Identification and management of preoperative anaemia in adults: A British Society for Haematology Guideline update.

This updated British Society for Haematology guideline provides an up-to-date literature review and recommendations regarding the identification and management of preoperative anaemia. This includes guidance on thresholds for the diagnosis of anaemia and the diagnosis and management of iron deficiency in the preoperative context. Guidance on the appropriate use of erythropoiesis-stimulating agents and preoperative transfusion is also provided.

Exploring progress in iron supplement formulation approaches for treating iron deficiency anemia through bibliometric and thematic analysis.

Anemia is a severe health issue that affects around one-third of the global population. Therefore, the present study aims to conduct a bibliometric analysis to investigate the research trends regarding advancements on iron formulations in treating iron deficiency anemia via oral or parenteral route. This study adopts thematic and bibliometric methods on existing research on novel iron formulations. It also provides perspective into the existing understanding on treatment strategies for iron deficiency anemia. This study is conducted on 543 papers on various ferrous and ferric formulations used in the treatment of iron deficiency anemia. The study period is from 1977 to 2022, and the papers are identified from the Scopus database. The bibliometric analysis was carried out using the R tool's Bibliometrix package. The study discusses performance analysis, including annual publications, geographic analysis, relevant affiliations, journal analysis, and citation analysis. In addition, the conceptual structure, including the co-occurrence network, thematic map, thematic evolution, intellectual structure highlighting co-citation analysis, and social structure depicting the collaboration network and collaboration world map, are presented. The results showed increased research on formulation strategies for the treatment of iron deficiency anemia from 2010 onwards. The top 5 contributing countries are the USA, Italy, India, Germany, and the UK, and peer-reviewed journals from the area of nutrition. The most trending areas of study are iron deficiency anemia in pregnancy, chronic kidney diseases, inflammatory bowel diseases, and various intravenous formulations used in its treatment. The authors from Europe collaborate the most with authors from other countries. The study concludes that a safer and more effective iron formulation is needed to reduce the prevalence of anemia. The findings of the study are helpful in advancing research on innovative formulations for treating iron deficiency anemia. The insights from the study are helpful to policymakers in designing specific health policies and investing more in research and development of novel formulations for the treatment of iron deficiency anemia.

Iron Metabolic Biomarkers and the Mortality Risk in the General Population: A Nationwide Population-Based Cohort Study.

Context: Iron is an essential element in the human body and plays a critical role in many physiological and cellular processes. However, the association between iron status and the risk of all-cause or cause-specific mortality has not been well-investigated. And it is unclear whether the association between iron metabolic biomarkers and the risk of mortality differs between people with and without diabetes mellitus (DM). Objective: This work aimed to investigate associations between iron metabolic biomarkers and all-cause and cause-specific mortality risk in the general population, and heterogeneities in the associations among population with and without DM.. Methods: A total of 29 166 adults from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999 to 2010 were included, with linkage to the National Death Index to December 31, 2019. Cox proportional-hazard models and Fine-Gray subdistribution hazard models were used to estimate associations between iron metabolic biomarkers and outcomes. Results: During a median follow-up of 18.83 years, 9378 deaths were observed, including 3420 cardiovascular disease (CVD) deaths and 1969 cancer deaths. A significant linear association between serum ferritin (SF) and all-cause mortality was observed among the overall population and those without DM. J-shaped associations between transferrin saturation (TSAT) and all-cause and CVD mortality were observed among all populations. In the overall population, compared to the first quartile (Q1) group, the adjusted hazard ratio (HR) (95% CI) for all-cause mortality was 1.07 (1.00-1.15), 1.05 (0.98-1.12), 1.13 (1.05-1.21) in Q2, Q3, and Q4 groups for SF, while the HR was 0.94 (0.88-0.99), 0.92 (0.86-0.97), and 0.93 (0.88-0.99) for TSAT. In individuals without DM, the adjusted HR of the Q4 of SF were 1.19 (1.03-1.37) for CVD mortality and 1.25 (1.05-1.48) for cancer mortality. In individuals with DM, the adjusted HRs of the Q4 of TSAT were 0.76 (0.62-0.93) for CVD mortality and 1.47 (1.07-2.03) for cancer mortality. Conclusion: Iron metabolism abnormalities increase mortality risk in the general population. The associations of iron status with mortality were significantly different between individuals with and without DM, which indicated tailored strategies for iron homeostasis are needed.

Haem iron versus ferrous iron salts to treat iron deficiency anaemia in Gambian children: protocol for randomised controlled trial {1}.

BACKGROUND: The World Health Organization recommends universal iron supplementation for children aged 6-23 months in countries where anaemia is seen in over 40% of the population. Conventional ferrous salts have low efficacy due to low oral absorption in children with inflammation. Haem iron is more bioavailable, and its absorption may not be decreased by inflammation. This study aims to compare daily supplementation with haem iron versus ferrous sulphate on haemoglobin concentration and serum ferritin concentration after 12 weeks of supplementation. METHODS: This will be a two-arm, randomised controlled trial. Gambian children aged 6-12 months with anaemia will be recruited within a predefined geographical area and recruited by trained field workers. Eligible participants will be individually randomised using a 1:1 ratio within permuted blocks to daily supplementation for 12 weeks with either 10.0 mg of elemental iron as haem or ferrous sulphate. Safety outcomes such as diarrhoea and infection-related adverse events will be assessed daily by the clinical team (see Bah et al. Additional file 4_Adverse event eCRF). Linear regression will be used to analyse continuous outcomes, with log transformation to normalise residuals as needed. Binary outcomes will be analysed by binomial regression or logistic regression, Primary analysis will be by modified intention-to-treat (i.e., those randomised and who ingested at least one supplement dose of iron), with multiple imputations to replace missing data. Effect estimates will be adjusted for baseline covariates (C-reactive protein, alpha-1-acid glycoprotein, haemoglobin, ferritin, soluble transferrin receptor). DISCUSSION: This study will determine if therapeutic supplementation with haem iron is more efficacious than with conventional ferrous sulphate in enhancing haemoglobin and ferritin concentrations in anaemic children aged 6-12 months. TRIAL REGISTRATION: Pan African Clinical Trial Registry PACTR202210523178727.

A Qualitative Analysis of Urbanization and Menstrual Health Among Young Women.

This qualitative study, grounded in theory, employed inductive coding for analysis, focusing on menstrual health among urban women aged 10-25. The research aims to explore the menstrual health status, practices, and beliefs of participants. The research delves into the impact of recent government initiatives on menstrual health and assesses the role of urbanization in shaping evolving menstrual health practices among young girls. Employing in-depth qualitative methods such as interviews and focus group discussions, the study seeks a comprehensive understanding of participants' experiences and perceptions related to menstrual health. The dynamics of women's menstrual experiences are significantly influenced by urbanization, heightened exposure to social media, evolving lifestyles, and government initiatives like the distribution of menstrual products in schools and the enhancement of water, sanitation, and hygiene (WASH) facilities in government institutions. Positive shifts have been observed, including reduced restrictions on menstruating individuals, enhanced access to affordable hygiene products, and improved disposal facilitated by municipal garbage collection services. However, notable gaps persist in basic knowledge about menstruation, hygienic practices, effective interpersonal communication with schoolteachers or community health care workers, and compliance with government programs promoting weekly iron-folic acid supplementation and biannual Albendazole intake, calling for substantial improvement.

Iron and Magnesium Co-substituted Hydroxyapatite Nanoparticles in Orthodontic Composite: A Preliminary Assessment.

Aim The study aims to characterize Fe and Mg co-substituted hydroxyapatite nanoparticles (FeMgHAPn) and assess the antimicrobial properties of FeMgHAPn-incorporated orthodontic composite. Materials and methods FeMgHAPn was synthesized using the sol-gel method, and the prepared nanoparticle powder was characterized using Fourier Transform Infrared Spectroscopy (FTIR), energy-dispersive X-ray analysis (EDX)) and scanning electron microscopic (SEM) analysis. The FeMgHAPn was incorporated into a commercially available orthodontic composite in two concentrations (40 and 20 µL), and the structure was examined using SEM. The FeMgHAPn-incorporated composite was tested for its antimicrobial efficacy against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli using the agar-well diffusion method. The zones of inhibition (ZOI) were measured in millimeters (mm). Results The characterization of the FeMgHAPn indicated the successful formation of the nanoparticle without any impurities or byproducts. The high concentration (40 µL) of FeMgHAPn-incorporated orthodontic composite showed the maximum ZOI against all three microbes, followed by the low concentration (20 µL) and the control group. Conclusion The FeMgHAPn-incorporated orthodontic composite showed promising antimicrobial activity against caries-causing S. mutans, S. aureus, and E. coli.

Inpatient management of iron deficiency anemia in pediatric patients with inflammatory bowel disease: A single center experience.

BACKGROUND: Screening for iron deficiency anemia (IDA) is important in managing pediatric patients with inflammatory bowel disease (IBD). Concerns related to adverse reactions may contribute to a reluctance to prescribe intravenous (IV) iron to treat IDA in this population. AIM: To track the efficacy and safety of IV iron therapy in treating IDA in pediatric IBD patients admitted to our center. METHODS: A longitudinal observational cohort study was performed on 236 consecutive pediatric patients admitted to our tertiary IBD care center between September 2017 and December 2019. 92 patients met study criteria for IDA, of which 57 received IV iron, 17 received oral iron, and 18 were discharged prior to receiving iron therapy. RESULTS: Patients treated with IV iron during their hospitalization experienced a significant increase of 1.9 (± 0.2) g/dL in mean (± SE) hemoglobin (Hb) concentration by the first ambulatory follow-up, compared to patients who received oral iron 0.8 (± 0.3) g/dL or no iron 0.8 (± 0.3) g/dL (P = 0.03). One out of 57 (1.8%) patients that received IV iron therapy experienced an adverse reaction. CONCLUSION: Our findings demonstrate that treatment with IV iron therapy is safe and efficacious in improving Hb and iron levels in pediatric patients with IDA and active IBD.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Anemia tolerance.

Anemia is a pathological condition in which the hemoglobin and red blood cell mass decrease; it is mainly defined by the concentration of hemoglobin in the blood. The World Health Organization guidelines establish specific values to define anemia in different population groups. Early detection of anemia can also be a valuable indicator of underlying medical conditions. Clinical studies have explored the relationship between perioperative anemia and morbidity, highlighting the need for more judicious therapeutic strategies, such as the use of Patient Blood Management, which aims to prevent and treat anemia in a personalized and effective way. Patient Blood Management emerges as a promising approach to dealing with anemia, recognizing that its correction through transfusion always carries risks and that personalized prevention and treatment can offer better outcomes for patients.

Remediation of acetamiprid pesticide from contaminated water by antibacterial biosorbent based on carboxymethyl tragacanth-grafted-poly(3-aminophenol) decorated with ZnO@Fe3O4.

Pesticides can have harmful impacts on the environment and living organisms. Thus, removing them from polluted water is crucial. In this study, a bionanocomposite of carboxymethyl tragacanth-grafted-poly(3-aminophenol)/zinc oxide@iron oxide (CMT-g-P3AP/ZnO@Fe3O4) synthesized by in situ copolymerization as an efficient adsorbent to eliminate the acetamiprid pesticide from polluted water. The CMT-g-P3AP/ZnO@Fe3O4 magnetic nanocomposite was analyzed utilizing various techniques including FTIR, EDX, FESEM, XRD, BET, CHNSO, and TGA. The results displayed that the resulting nanocomposite with maximum adsorption capacity (Qmax) successfully removed the acetamiprid pesticide from polluted water under optimal conditions such as pH of 7.00, 5.00 mg of adsorbent, 20.0 min duration, and 400 mg/L acetamiprid concentration. According to the linear Langmuir isotherm, the Qmax of the biosorbent was 833 mg/g. The experimental adsorption data fitted well with Temkin's nonlinear isotherm model. The adsorption kinetic data were closely related to the Weber-Morris intraparticle diffusion nonlinear model. After three repetitive cycles, CMT-g-P3AP/ZnO@Fe3O4 can be outstandingly renewed and recycled without significant reduction in its adsorption efficacy, as evidenced by the adsorption-desorption experiments. In addition, the CMT-g-P3AP/ZnO@Fe3O4 displayed the good antibacterial activity against E. coli and S. aureus.

Shared functions of Fe-S cluster assembly and Moco biosynthesis.

Molybdenum cofactor (Moco) biosynthesis is a complex process that involves the coordinated function of several proteins. In the recent years it has become evident that the availability of Fe-S clusters play an important role for the biosynthesis of Moco. First, the MoaA protein binds two [4Fe-4S] clusters per monomer. Second, the expression of the moaABCDE and moeAB operons is regulated by FNR, which senses the availability of oxygen via a functional [4Fe-4S] cluster. Finally, the conversion of cyclic pyranopterin monophosphate to molybdopterin requires the availability of the L-cysteine desulfurase IscS, which is an enzyme involved in the transfer of sulfur to various acceptor proteins with a main role in the assembly of Fe-S clusters. In this review, we dissect the dependence of the production of active molybdoenzymes in detail, starting from the regulation of gene expression and further explaining sulfur delivery and Fe-S cluster insertion into target enzymes. Further, Fe-S cluster assembly is also linked to iron availability. While the abundance of selected molybdoenzymes is largely decreased under iron-limiting conditions, we explain that the expression of the genes is dependent on an active FNR protein. FNR is a very important transcription factor that represents the master-switch for the expression of target genes in response to anaerobiosis. Moco biosynthesis is further directly dependent on the presence of ArcA and also on an active Fur protein.

Research update for ferroptosis and cholangiocarcinoma.

Cholangiocarcinoma (CCA) is the second most common hepatobiliary malignancy after hepatocellular carcinoma. Due to the poor treatment effect and high mortality rate of CCA, it is of great significance to explore new therapeutic targets. Ferroptosis is a type of cell death caused by iron-dependent cell oxidative injury, which is closely related to the occurrence and development of numerous diseases. Novel ideas for the prevention and treatment of related diseases have been provided by ferroptosis, which has become a focus of research in recent years. This review introduces the underlying mechanisms related to ferroptosis, as well as a research update for ferroptosis in the occurrence and development of CCA. The clinical value of ferroptosis-related regulatory mechanisms in CCA will be elucidated.

Effect of calcium and phosphorus on ammonium and nitrate nitrogen adsorption onto iron (hydr)oxides surfaces: CD-MUSIC model and DFT computation.

Calcium (Ca2+) and phosphorous (PO43-) significantly influence the form and effectiveness of nitrogen (N), however, the precise mechanisms governing the adsorption of ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) are still lacking. This study employed batch adsorption experiments, charge distribution and multi-site complexation (CD-MUSIC) models and density functional theory (DFT) calculations to elucidate the mechanism by which Ca2+ and PO43- affect the adsorption of NH4+-N and NO3--N on the goethite (GT) surface. The results showed that the adsorption of NH4+-N on the GT exhibited an initial increase followed by a decrease as pH increased, peaking at a pH of 8.5. Conversely, the adsorption of NO3--N decreased with rising pH. According to the CD-MUSIC model, Ca2+ minimally affected the NH4+-N adsorption on the GT but enhanced NO3--N adsorption via electrostatic interaction, promoting the adsorption of ≡FeOH-NO3- and ≡Fe3O-NO3- species. Similarly, PO43- inhibited the adsorption of ≡FeOH-NO3- and ≡Fe3O-NO3- species. However, PO43- boosted NH4+-N adsorption by facilitating the formation of ≡Fe3O-NH4+ via electrostatic interaction and site competition. DFT calculations indicates that although bidentate phosphate (BP) was beneficial to stabilize NH4+-N than monodentate phosphate (SP), SP-NH4+ was the main adsorption configuration at pH 5.5-9.5 owing the prevalence of SP on the GT surface under site competition of NH4+-N. The results of CD-MUSIC model and DFT calculation were verified mutually, and provide novel insights into the mechanisms underlying N fixation and migration in soil.

Safety and efficacy of East Asian herbal medicine for iron deficiency anemia in children and adolescents: a systematic review and meta-analysis.

Background: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of East Asian herbal medicine (HM) for iron deficiency anemia (IDA) in children and adolescents. Methods: Twelve electronic databases were searched in 28 May 2023 for randomized controlled trials (RCTs) evaluating the efficacy of HM in children with IDA. The primary outcome measures for treatment included blood hemoglobin and serum ferritin levels, whereas the secondary outcomes included the total effective rate (TER), incidence of adverse events (AEs), average healing time, and hematologic indicators related to IDA. Meta-analysis was performed using Review Manager 5.4 and R studio 4.3 software, and subgroup analyses were performed according to the different groups (type of intervention and duration of treatment). The effect size measures used were the risk ratio, mean difference, and standardized mean difference with 95% confidence intervals. The risk of bias was assessed using a revised Cochrane risk of bias tool for randomized trials, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation tools. Results: The meta-analysis included 28 studies. Five studies compared the efficacy of HM alone with that of oral iron alone, whereas 23 compared the efficacy of a combination of HM and oral iron with that of oral iron alone. The meta-analysis revealed that the HM treatment group showed significant improvements in all outcome measures compared to those observed in the oral iron group. Moreover, HM significantly reduced the incidence of gastrointestinal AE, compared to that associated with oral iron. Among the 28 studies, the most commonly used HM prescription was Xingpi Yanger Granules, and the most commonly used botanical drug was Astragali Radix, followed by Atractylodis Rhizoma Alba and Angelicae Sinensis Radix. Conclusion: This meta-analysis identified evidence of the efficacy and safety of HM in children with IDA. Compared to conventional oral iron therapy, HM improved IDA-related blood markers and TER, with fewer AEs and shorter mean healing times. However, further well-designed, large-scale clinical trials are necessary to strengthen the evidence of the efficacy and safety of botanical drugs. Systematic Review Registration: PROSPERO 2022 CRD42022334670. (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022334670).

Rocaglamide regulates iron homeostasis by suppressing hepcidin expression.

The anemia of inflammation (AI) is characterized by the presence of inflammation and abnormal elevation of hepcidin. Accumulating evidence has proved that Rocaglamide (RocA) was involved in inflammation regulation. Nevertheless, the role of RocA in AI, especially in iron metabolism, has not been investigated, and its underlying mechanism remains elusive. Here, we demonstrated that RocA dramatically suppressed the elevation of hepcidin and ferritin in LPS-treated mice cell line RAW264.7 and peritoneal macrophages. In vivo study showed that RocA can restrain the depletion of serum iron (SI) and transferrin (Tf) saturation caused by LPS. Further investigation showed that RocA suppressed the upregulation of hepcidin mRNA and downregulation of Fpn1 protein expression in the spleen and liver of LPS-treated mice. Mechanistically, this effect was attributed to RocA's ability to inhibit the IL-6/STAT3 pathway, resulting in the suppression of hepcidin mRNA and subsequent increase in Fpn1 and TfR1 expression in LPS-treated macrophages. Moreover, RocA inhibited the elevation of the cellular labile iron pool (LIP) and reactive oxygen species (ROS) induced by LPS in RAW264.7 cells. These findings reveal a pivotal mechanism underlying the roles of RocA in modulating iron homeostasis and also provide a candidate natural product on alleviating AI.

Identifying transcriptomic profiles of iron-quercetin complex treated peripheral blood mononuclear cells from healthy volunteers and diabetic patients.

Peripheral blood is an alternative source of stem/progenitor cells for regenerative medicine owing to its ease of retrieval and blood bank storage. Previous in vitro studies indicated that the conditioned medium derived from peripheral blood mononuclear cells (PBMCs) treated with the iron-quercetin complex (IronQ) contains potent angiogenesis and wound-healing properties. This study aims to unveil the intricate regulatory mechanisms governing the effects of IronQ on the transcriptome profiles of human PBMCs from healthy volunteers and those with diabetes mellitus (DM) using RNA sequencing analysis. Our findings revealed 3741 and 2204 differentially expressed genes (DEGs) when treating healthy and DM PBMCs with IronQ, respectively. Functional enrichment analyses underscored the biological processes shared by the DEGs in both conditions, including inflammatory responses, cell migration, cellular stress responses, and angiogenesis. A comprehensive exploration of these molecular alterations exposed a network of 20 hub genes essential in response to stimuli, cell migration, immune processes, and the mitogen-activated protein kinase (MAPK) pathway. The activation of these pathways enabled PBMCs to potentiate angiogenesis and tissue repair. Corroborating this, quantitative real-time polymerase chain reaction (qRT-PCR) and cell phenotyping confirmed the upregulation of candidate genes associated with anti-inflammatory, pro-angiogenesis, and tissue repair processes in IronQ-treated PBMCs. In summary, combining IronQ and PBMCs brings about substantial shifts in gene expression profiles and activates pathways that are crucial for tissue repair and immune response, which is promising for the enhancement of the therapeutic potential of PBMCs, especially in diabetic wound healing.