Di-2-pyridylketone 4, 4-dimethyl-3-thiosemicarbazone effectively induces human colorectal carcinoma cell apoptosis via mTOR pathway

Background: To investigate the anticancer mechanisms of di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) in human colon cancer cells. Human colorectal carcinoma (HCC) is one of the most commonly diagnosed cancers in both males and females. Current studies have found that iron chelators can be used as novel anticancer drugs; however, the anticancer activity of iron chelators and their target genes in HCC has been rarely reported. Methods: Dp44mT was used to treat two colorectal tumor cell lines, SW480 and HT-29. The proapoptotic effects of different concentrations of Dp44mt were measured using flow cytometry and Hoechst 33258 staining. Ferric ammonium citrate (FAC) was used as an additional iron donor to inhibit the effects of Dp44mT. Apoptosis and DNA damage-related proteins were examined by Western blot analysis. Results: In this study, we found that the iron chelators Dp44mT could induce the apoptosis in two colorectal tumor cell lines SW480 and HT-29, upregulate the expression level of p-histone H2A.X, and inhibit the phosphorylation level of mTOR in a dose-dependent way. Those effects could be reversed by the additional iron donor FAC. Conclusion: These data indicate that iron depletion and/or the presence of iron can modulate the HCC apoptosis progression in vitro, which may be a potential target for future HCC therapy.

Anemia Prevalence and Iron Supplementation Practices Among Pregnant Women in Vancouver, Canada

Objectives Health Canada recommends supplementation with 16–20 mg iron during pregnancy to maintain adequate iron stores and reduce the prevalence of iron deficiency. Most prenatal vitamins contain 27 mg iron (the recommended dietary allowance). In the case of diagnosed iron deficiency (typically defined as a ferritin concentration < 15–50 µg/L), some pregnant women may be recommended to take additional iron. Iron is an essential nutrient and adequate intake is needed for a healthy pregnancy; however, excess iron can also be harmful. We aimed to evaluate the hematological profile, prevalence of anemia, and iron supplementation practices of healthy pregnant women in Vancouver, Canada. Methods As part of an ongoing clinical trial, 40 healthy pregnant women (aged 19–42 years) received prenatal vitamins containing 27 mg iron over 16 weeks of pregnancy, starting at 9–21 weeks gestation. A complete blood count was measured at baseline and endline. Anemia was defined as hemoglobin < 110 g/L in the first/third trimesters and < 105 g/L in the second trimester. Microcytic anemia (most commonly caused by iron deficiency) was defined as having both anemia and a MCV concentration < 80 fL. Participants reported other supplement use throughout the study, including additional iron prescribed for treatment of iron deficiency and/or anemia. Results At baseline and endline, the mean ± SD of hemoglobin was 124 ± 9 g/L and 127 ± 11 g/L; and for MCV was 89 ± 3 fL and 91 ± 3 fL, respectively. Based on hemoglobin (trimester-specific) and MCV thresholds, no participants were classified as having anemia or microcytic anemia at either timepoint, respectively. At endline, a total of n = 8 women (20%) reported that following their baseline visit (during the intervention period) they were informed by their health care provider to increase their supplemental dose of iron up to 300 mg, in addition to the 27 mg in the study prenatal vitamin. Conclusions Whether recommendation for additional iron was warranted in 20% of women is unclear, as none had microcytic anemia based on hemoglobin and MCV values. Measurement of ferritin is warranted for the definitive diagnosis of iron deficiency, and to elucidate if there is a need for improved clinical practices for recommending additional iron supplementation. Funding Sources Healthy Starts Catalyst Grant (BC Children's Hospital Research Institute, Vancouver, Canada).

PSIV-9 A Multistate Evaluation of an Additional Iron Injection Administered to Piglets Before Weaning

A cooperative study utilizing 514 weanling pigs from 7 experiment stations was conducted to determine the effects of an additional iron injection administered to piglets before weaning on growth performance and hematological measures. All pigs received an initial iron injection at the time of processing postfarrowing. At each station, pigs were assigned to either the control or an added-injection treatment by pairing two same-sex pigs with a BW difference ≤ 0.453 kg within a litter. One pig within each pair received the additional iron injection (same dose received at processing) 3 to 5 days preweaning. Once weaned, both the control and added-injection group received common station-specific nursery diets. Body weight was recorded weekly by all stations. Blood samples were also collected at second injection, weaning, 14 and 28 days postweaning by 3 of the 7 stations. All data were subjected to ANOVA with the model containing the terms treatment, station, and treatment by station interaction. Average daily gain (Table 1) was greater for the added-injection group during d 0 to 14 (212.5 vs. 202.6 g, P = 0.03) which resulted in an increase in d 14 BW (P = 0.05). Although there was no treatment effect for overall ADG (d -4 to d 28), the tendency for a treatment by station interaction (P = 0.09) illustrated both responsive and nonresponsive stations, indicating that iron status was not the most limiting factor for growth at all stations. Hemoglobin concentration was greater (P < 0.0001) for the added-injection group at weaning and d 14 postweaning. In conclusion, an additional iron injection administered before weaning may lead to early success in the nursery resulting in a heavier BW in subsequent periods; however, the beneficial effects of an additional iron injection are likely dependent on herd status and characteristics.

The additional iron cable fixation between proximal patella and tibial tuberosity to treat AO/OTA 34C3 patellar fracture

Background:It is very difficult to deal with AO/OTA 34C3 patellar fracture. Although the modified Kirschner wire tension band, the cerclage and plate has been proposed to treat it, the result is not very good. We found that if the fixation was not firm enough after the modified Kirschner wire tension band with or without the cerclage had been carried out, the additional iron cable fixation between proximal patella and tibial tuberosity could resolve it effectively.Methods:Retrospective analysis was completed. 21 patients with AO/OTA 34C3 patellar fracture were treated in our department from January 2014 to January 2018. They were divided into 2 groups according to the operation plan. Group 1 (normal group), with 12 patients, was treated with modified Kirschner wire tension band with or without cerclage cable. Group 2 (cable group), with 9 patients, was treated with the additional iron cable fixation between proximal patella and tibial tuberosity when the fixation was not firm enough after the modified Kirschner wire tension band with or without the cerclage had been completed.Results:The two groups of the age, sex ratio, trauma mechanism, operation time, free articular fragment, comorbidity and follow-up time had no significant statistical difference (P>0.05). There was no significant statistical difference between the two groups of the clinical results. (such as Bostman total score and its specific individual score, the excellent and good ratio, the complications, and the bone union time, etc.) (P>0.05).Conclusions:To deal with AO/OTA 34C3 patellar fracture, when the fixation of modified Kirschner wire tension band with or without the cerclage cable is not firm enough, the additional iron cable fixation between proximal patella and tibial tuberosity can resolve it effectively.

Impact of Iron Formulations on Topramezone Injury to Bermudagrass

Goosegrass control options in bermudagrass are limited. Topramezone is one option that offers excellent control of mature goosegrass, but application to bermudagrass results in unacceptable symptoms of bleaching and necrosis typical of HPPD inhibitors. Previous research has shown that adding chelated iron reduced the phytotoxicity of topramezone without reducing the efficacy of the herbicide resulting in safening when applied to bermudagrass. Our objective was to examine additional iron sources to determine if similar safening effects occur with other sources. Field trials were conducted in the summers of 2016 - 2018 (Auburn University). Mixtures of topramezone and MSO were combined with 6 different commercial iron sources, including FeEDDHA, FeDTPA, iron citrate, FeSO4, and a combination of iron oxide/sucrate/sulfate, some of which contained nitrogen. Bermudagrass necrosis and bleaching symptoms were visually rated on a 0 to 100% scale. Reflectance (NDVI) and clipping yield measurements were also collected. Application of FeDTPA and FeSO4 reduced symptoms of bleaching and necrosis when applied with topramezone. Other treatments which contained nitrogen did not reduce injury but did reduce bermudagrass recovery time following the appearance of necrosis. Inclusion of small amounts of nitrogen often negated the safening effects of FeSO4. The iron oxide/sucrate/sulfate product had no effect on bleaching or necrosis. Data suggests that iron source had a differential effect on bleaching and necrosis reduction when applied in combination with topramezone to bermudagrass. Overall, FeSO4 and FeDTPA safened the topramezone the most on bermudagrass.

Iron metabolism in high-altitude residents

Residents at high altitude cope with decreasing inspiratory oxygen partial pressure by stimulating erythropoiesis. The increase in hemoglobin levels requires high amounts of additional iron supplied from the diet. Here, we review available data on how iron metabolism adapts when living in a hypoxic environment. Our analysis reveals that long-term adaptation to high altitude enables healthy individuals to maintain their iron stores within the physiological range despite elevated requirements for erythropoiesis. However, in vulnerable populations with increased iron demand (e.g., pregnant women or exercising individuals), iron stores are less likely to be replenished quickly when living at high altitude. Future studies need to address whether different ethnicities have acquired genetic mechanisms to adapt to the elevated iron demand for erythropoiesis at high altitude.

The additional iron cable fixation between proximal patella and tibial tuberosity to treat AO/OTA 34C3 patellar fracture

Background: It is very difficult to deal with AO/OTA 34C3 patellar fracture. Although the modified Kirschner wire tension band, the cerclage and plate has been proposed to treat it, the result is not very good. We found that if the fixation was not firm enough after the modified Kirschner wire tension band with or without the cerclage had been carried out, the additional iron cable fixation between proximal patella and tibial tuberosity could resolve it effectively.Methods: Retrospective analysis was completed. 21 patients with AO/OTA 34C3 patellar fracture were treated in our department from January 2014 to January 2018. They were divided into 2 groups according to the operation plan. Group 1 (normal group), with 12 patients, was treated with modified Kirschner wire tension band with or without cerclage cable. Group 2 (cable group), with 9 patients, was treated with the additional iron cable fixation between proximal patella and tibial tuberosity when the fixation was not firm enough after the modified Kirschner wire tension band with or without the cerclage had been completed.Results: The two groups of the age, sex ratio, trauma mechanism, operation time, free articular fragment, comorbidity and follow-up time had no significant statistical difference (P>0.05). There was no significant statistical difference between the two groups of the clinical results. (such as Bostman total score and its specific individual score, the excellent and good ratio, the complications, and the bone union time, etc.) (P>0.05).Conclusions: To deal with AO/OTA 34C3 patellar fracture, when the fixation of modified Kirschner wire tension band with or without the cerclage cable is not firm enough, the additional iron cable fixation between proximal patella and tibial tuberosity can resolve it effectively.

Risk Factors for Anemia and Micronutrient Deficiencies among Women of Reproductive Age—The Impact of the Wheat Flour Fortification Program in Uzbekistan

Food fortification can be effective in reducing the prevalence of anemia and micronutrient deficiencies. This study assessed risk factors for—and the impact of the wheat flour program in Uzbekistan on—anemia, and iron and folate deficiency (FD) in non-pregnant women (NPW) of reproductive age. National data were analyzed for risk factors using multivariable regression. Additional iron intake from fortified flour was not associated with iron deficiency (ID) and did not result in a significantly different prevalence of anemia regardless of the levels, whereas women with additional folic acid intake had a lower relative risk (RR) of FD (RR: 0.67 [95% CI: 0.53, 0.85]). RR for anemia was greater in women with ID (RR: 4.7; 95% CI: 3.5, 6.5) and vitamin A insufficiency (VAI; RR 1.5; 95% CI: 1.3, 1.9). VAI (RR: 1.4 [95% CI: 1.3, 1.6]) and breastfeeding (RR: 1.1 [95% CI: 0.99, 1.2]) were associated with increased risk of ID, while being underweight reduced the risk (RR: 0.74 [95% CI: 0.58, 0.96]). Breastfeeding (RR: 1.2 [95% CI: 1.1, 1.4]) and inflammation (RR: 1.2 [95% CI: 1.0, 1.3]) increased risk of FD. FD results indicate that the fortification program had potential for impact, but requires higher coverage of adequately fortified wheat flour and a more bioavailable iron fortificant.

Microbial feedbacks optimize ocean iron availability

Iron is the limiting factor for biological production over a large fraction of the surface ocean because free iron is rapidly scavenged or precipitated under aerobic conditions. Standing stocks of dissolved iron are maintained by association with organic molecules (ligands) produced by biological processes. We hypothesize a positive feedback between iron cycling, microbial activity, and ligand abundance: External iron input fuels microbial production, creating organic ligands that support more iron in seawater, leading to further macronutrient consumption until other microbial requirements such as macronutrients or light become limiting, and additional iron no longer increases productivity. This feedback emerges in numerical simulations of the coupled marine cycles of macronutrients and iron that resolve the dynamic microbial production and loss of iron-chelating ligands. The model solutions resemble modern nutrient distributions only over a finite range of prescribed ligand source/sink ratios where the model ocean is driven to global-scale colimitation by micronutrients and macronutrients and global production is maximized. We hypothesize that a global-scale selection for microbial ligand cycling may have occurred to maintain “just enough” iron in the ocean.