Non-Pharmacological Interventions for Anemia Treatment: Systematic Review

The global prevalence of anemia in non-pregnant women, of childbearing age, is estimated at 29.0% and is more common in low- and middle-income countries, women belonging to low socioeconomic strata. iron deficiency can cause direct or risky disability. To determine the effectiveness of Non-Pharmacological Interventions for the treatment of anemia. The method used is with the help of electronic databases from journals that have been published through PubMed, Proquest, EBSCOhost, and Science Direct as many as 6 articles were reviewed from 1186 articles. The 6 articles reviewed in this study with varied respondents using patients, male rats, nurses, Sprague-Dawley (SD) Rattus norvegicus Domestica, bovine serum, premature neonates. Non-pharmacological interventions developed in the treatment of anemia in both human and animal samples as well as the development of treatment and laboratory examinations in the treatment of anemia are Nursing Delirium Screening scale, Hepcidin expression, pain identification, HM10760A, Divalent metal transporter DMT1/SLC11A2, conservative management.

Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Ferroptosis is a new form of regulated cell death, which is mediated by intracellular iron. Although it is reported that bavachin has antitumour effects on several tumour cells and prompts the reactive oxygen species (ROS) generation, it is unclear whether ferroptosis can be induced by bavachin in osteosarcoma (OS) cells. In this study, we found that bavachin inhibits the viability of MG63 and HOS OS cell lines along with an increase in the ferrous iron level, ROS accumulation, malondialdehyde overexpression, and glutathione depletion. Moreover, iron chelators (deferoxamine), antioxidants (Vit E), and ferroptosis inhibitors (ferrostatin-1 and liproxstatin-1) reverse bavachin-induced cell death. Bavachin also altered the mitochondrial morphology of OS cells, leading to smaller mitochondria, higher density of the mitochondrial membrane, and reduced mitochondrial cristae. Further investigation showed that bavachin upregulated the expression of transferrin receptor, divalent metal transporter-1, and P53, along with downregulating the expression of ferritin light chain, ferritin heavy chain, p-STAT3 (705), SLC7A11, and glutathione peroxidase-4 in OS cells. More importantly, STAT3 overexpression, SLC7A11 overexpression, and pretreatment with pifithrin-α (P53 inhibitor) rescued OS cell ferroptosis induced by bavachin. The results show that bavachin induces ferroptosis via the STAT3/P53/SLC7A11 axis in OS cells.

Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery

Pro-inflammatory cytokines promote cellular iron-import through enhanced divalent metal transporter-1 (DMT1) expression in pancreatic β-cells, consequently cell death. Inhibition of β-cell iron-import by DMT1 silencing protects against apoptosis in animal models of diabetes. However, how alterations of signaling networks contribute to the protective action of DMT1 knock-down is unknown. Here, we performed phosphoproteomics using our sequential enrichment strategy of mRNA, protein, and phosphopeptides, which enabled us to explore the concurrent molecular events in the same set of wildtype and DMT1-silenced β-cells during IL-1β exposure. Our findings reveal new phosphosites in the IL-1β-induced proteins that are clearly reverted by DMT1 silencing towards their steady-state levels. We validated the levels of five novel phosphosites of the potential protective proteins using parallel reaction monitoring. We also confirmed the inactivation of autophagic flux that may be relevant for cell survival induced by DMT1 silencing during IL-1β exposure. Additionally, the potential protective proteins induced by DMT1 silencing were related to insulin secretion that may lead to improving β-cell functions upon exposure to IL-1β. This global profiling has shed light on the signal transduction pathways driving the protection against inflammation-induced cell death in β-cells after DMT1 silencing.

Melatonin Alleviates Acute Sleep Deprivation-Induced Memory Loss in Mice by Suppressing Hippocampal Ferroptosis

Objectives: Memory decline caused by insufficient sleep is a critical public health issues and currently lacks effective treatments. This study objective was to explore alleviative effect of melatonin on sleep deprivation (SD)-induced deficiencies in learning and memory.Materials and Methods: A continuous 72 h SD mouse model, with or without melatonin or Fer-1 supplementation were established. The changes of cognitive function, iron homeostasis, lipid peroxidation and intracellular signal pathways in mice were detected by Morris water maze, antioxidant assay, immunohistochemistry, western blot, RT-PCR and Prussian blue staining. In vitro, we treated HT-22 cells with ferroptosis inducer (Erastin) to further explore the specific mechanism of melatonin in ferroptosis.Results: Mice subjected to SD had significantly elevated latency and path length to reach hidden platform, as well as a decrease in number of entries and time spent in the target zone when the hidden platform was removed (p < 0.05). Nevertheless, supplementation with ferroptosis inhibitor (Fer-1) mitigated the memory impairment associated with SD. Further evaluation revealed an up-regulation of intracellular iron accumulation, transferrin receptor 1 and divalent metal transporter 1 expression and ROS and MDA production, and a down-regulation of ferroportin and antioxidant enzyme (GPX4 and SOD) expression in SD mice. SD decreased expression of MT2 receptor rather than of MT1, and inhibited ERK/Nrf2 signaling activation in the hippocampus (p < 0.05). In contrast, the aforementioned SD-inductions were reversed by supplementation using 20 and 40 mg/kg melatonin in SD mice. In vitro, melatonin pretreatment reversed Erastin-induced ferroptosis, abnormalities in iron transporter protein and antioxidant enzyme expression and suppression of ERK/Nrf2 signaling in HT-22 cells, however this protective effect of melatonin was blocked by MT2-, ERK- and Nrf2-specific antagonists (p < 0.05).Conclusion: Our finding suggested SD may induce ferroptosis, in turn leading to cognitive deficits. Melatonin alleviated memory loss and hippocampal ferroptosis caused by acute SD through binding to the MT2 receptor to activate ERK/Nrf2 signaling.

Alterations in the Intestinal Morphology, Gut Microbiota, and Trace Mineral Status Following Intraamniotic Administration (Gallus gallus) of Genistein

Objectives Assess the effects of intraamniotic genistein administration on brush border membrane (BBM) functionality, intestinal morphology, cecal microbiome and Fe status in-vivo (Gallus gallus). Methods Broiler chickens (Gallus gallus, n = 39) were injected in ovo (day 17 of embryonic incubation) with varying concentrations of 1 mL pure genistein in 18 Ω H2O. Two treatment groups (1.25, 2.5%), two controls (water and non-injected), and a positive control (5% inulin) were administered. Upon hatch, blood was taken for hemoglobin determination and chicks were then euthanized. Nutritional status was assessed using pectoral muscle glycogen storage and body weight analysis. Duodenal and cecal tissues were excised for BBM morphometric analysis, mRNA gene expression of relevant BBM Fe transporter proteins, and 16S rRNA gene sequencing was done to evaluate gut microbiota modulation in the intestinal cecum. Results Preliminary results reveal significant increase in body weight, decrease of cecum weight, and increase in villus surface area with the higher dose of genistein administration (P < 0.05) compared to controls. Blood hemoglobin was found to be increased in the genistein-treated groups when compared to the controls (P < 0.05). Additionally, genistein administration downregulated the expression of duodenal cytochrome B (DcytB) and divalent metal transporter 1 (DMT1) and upregulated the expression of ferroportin with a dose responsive effect, indicating improved Fe physiological status. Further, administration of genistein altered the composition and function of cecal microbiota. Conclusions Genistein is a compound present in multiple staple food crops, including soybeans and chickpeas, and may be extracted and potentially used to enhance dietary Fe bioavailability and improve Fe deficiency in vulnerable populations. Recent evidence suggests a physiological role for genistein administration in improving the functionality and development of the BBM, improving Fe status, affecting the intestinal microbiome, as well as improving physiological status. Funding Sources N/A.

VTC4 Polyphosphate Polymerase Knockout Increases Stress Resistance of Saccharomyces cerevisiae Cells

Inorganic polyphosphate (polyP) is an important factor of alkaline, heavy metal, and oxidative stress resistance in microbial cells. In yeast, polyP is synthesized by Vtc4, a subunit of the vacuole transporter chaperone complex. Here, we report reduced but reliably detectable amounts of acid-soluble and acid-insoluble polyPs in the Δvtc4 strain of Saccharomyces cerevisiae, reaching 10% and 20% of the respective levels of the wild-type strain. The Δvtc4 strain has decreased resistance to alkaline stress but, unexpectedly, increased resistance to oxidation and heavy metal excess. We suggest that increased resistance is achieved through elevated expression of DDR2, which is implicated in stress response, and reduced expression of PHO84 encoding a phosphate and divalent metal transporter. The decreased Mg2+-dependent phosphate accumulation in Δvtc4 cells is consistent with reduced expression of PHO84. We discuss a possible role that polyP level plays in cellular signaling of stress response mobilization in yeast.

Salvia miltiorrhiza (SM) Injection Ameliorates Iron Overload-Associated Cardiac Dysfunction by Regulating the Expression of DMT1, TfR1, and FP1 in Rats

Previous studies have found that Salvia miltiorrhiza (SM) injection have a protective effect on the iron overloaded (IO) heart. However, the mechanisms are not completely known. In the present study, we investigated the underlying mechanisms based on the iron transport-related proteins. The rats were randomly divided into five groups: control, IO group, low-dose SM group, high-dose SM group, and deferoxamine control group. Iron dextran was injected to establish the IO model. After 14 days of treatment, cardiac histological changes were observed by hematoxylin and eosin (H&E) staining. Iron uptake-related proteins divalent metal transporter-1 (DMT-1), transferrin receptor-1 (TfR-1), and iron export-related proteins ferroportin1 (FP1) in the heart were detected by Western blotting. The results showed that SM injection decreased cardiac iron deposition, ameliorated cardiac function, and inhibited cardiac oxidation. Most important of all, SM injection downregulated the expression of DMT-1 and TfR-1 and upregulated FP1 protein levels compared with the IO group. Our results indicated that reducing cardiac iron uptake and increasing iron excretion may be one of the important mechanisms of SM injection reducing cardiac iron deposition and improving cardiac function under the conditions of IO.