One-carbon metabolite supplementation to nutrient-restricted beef heifers affects placental vascularity during early pregnancy.

We hypothesized that restricted maternal nutrition and supplementation of one-carbon metabolites (OCM; methionine, folate, choline, and vitamin B12) would affect placental vascular development during early pregnancy. A total of 43 cows were bred, and 32 heifers successfully became pregnant with female calves, leading to the formation of four treatment groups: CON - OCM (n = 8), CON + OCM (n = 7), RES - OCM (n = 9), and RES + OCM (n = 8). The experimental design was a 2 × 2 factorial, with main factors of dietary intake affecting average daily gain: control (CON; 0.6 kg/d ADG) and restricted (RES; -0.23 kg/d ADG); and OCM supplementation (+OCM) in which the heifers were supplemented with rumen-protected methionine (7.4 g/d) and choline (44.4 g/d) and received weekly injections of 320 mg of folate and 20 mg of vitamin B12, or received no supplementation (-OCM; corn carrier and saline injections). Heifers were individually fed and randomly assigned to treatment at breeding (day 0). Placentomes were collected on day 63 of gestation (0.225 of gestation). Fluorescent staining with CD31 and CD34 combined with image analysis was used to determine the vascularity of the placenta. Images were analyzed for capillary area density (CAD) and capillary number density (CND). Areas evaluated included fetal placental cotyledon (COT), maternal placental caruncle (CAR), whole placentome (CAR + COT), intercotyledonary fetal membranes (ICOT, or chorioallantois), intercaruncular endometrium (ICAR), and endometrial glands (EG). Data were analyzed with the GLM procedure of SAS, with heifer as the experimental unit and significance at P ≤ 0.05 and a tendency at P > 0.05 and P < 0.10. Though no gain × OCM interactions existed (P ≥ 0.10), OCM supplementation increased (P = 0.01) CAD of EG, whereas nutrient restriction tended (P < 0.10) to increase CAD of ICOT and CND of COT. Additionally, there was a gain × OCM interaction (P < 0.05) for CAD within the placentome and ICAR, such that RES reduced and supplementation of RES with OCM restored CAD. These results indicate that maternal rate of gain and OCM supplementation affected placental vascularization (capillary area and number density), which could affect placental function and thus the efficiency of nutrient transfer to the fetus during early gestation.

In cow­calf production, periods of poor forage availability or quality can result in nutrient restriction during pregnancy. Previous studies have shown that even moderate maternal feed restriction during pregnancy, including very early in pregnancy, has profound effects on fetal and placental development, potentially having lasting impacts on calf growth and body composition later in life. One-carbon metabolites (OCM) in the diet are biomolecules required for methylation reactions and participate in the regulation of gene expression. Our objective was to evaluate the effects of nutrient restriction and OCM supplementation (specifically methionine, choline, folate, and vitamin B12) on placental vascular development during early pregnancy. Proper placental vascular development is necessary for healthy pregnancy outcomes, reflected by normal birth weight and healthy offspring. Our results indicated that maternal rate of gain and OCM supplementation affect placental vascularization, which could affect placental function and thereby fetal development throughout gestation. In the context of beef cattle production, our study sheds light on strategies that could enhance placental vascular development during early pregnancy. However, it is essential to recognize the nuances in our data, highlighting the need for further research to fully comprehend these intricate processes.

Lactation stages modulate the hematological, serum biochemical, and endocrinological profiles and oxidative stress markers in crossbred cows under tropical humid island ecosystem of Andaman and Nicobar Islands.

The present study was designed to assess the interrelationship between hematological, serum biochemical, and endocrinological profiles and oxidative stress markers and lactational stages in crossbred (CB) dairy cows of Andaman and Nicobar Islands (ANI). Healthy (n = 6) CB cows (50-62.50% exotic inheritance; Holstein Friesian × Andaman local) of 4th parity with age of 7-9 years and body weight of 350-400 kg were selected from Cattle Breeding Farm, ICAR-Central Island Agricultural Research Institute (ICAR-CIARI), Port Blair, ANI. These experimental cows were synchronized with Ovsynch protocol, and parturition was planned to happen in the month of May-June. Lactation was allowed for 305 days. Hematological profiles, serum biochemical profiles, oxidative stress markers and endocrinological profiles were measured at a 15-day interval from day 07 to 305 of lactation (after 6 days of colostrum). The lactation period was divided into first (day 07 to 90), second (day 91 to 180), and third (day 181 to 305) stage of lactation. Average daily milk yield (L) did not vary among the stages of lactations; however, first (8.56 ± 1.26) and second (9.79 ± 0.87) stages had higher milk yield compared to third (7.93 ± 0.79) stage of lactation. Hematological profiles did not vary among the stages of lactation; however, these values were within the range of bovine species at lactation. Serum glucose, triglyceride, total cholesterol, total protein, globulin, and blood urea nitrogen (BUN) increased (P < 0.05) and albumin and creatinine decreased (P < 0.05) gradually as lactation stages advanced. Activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and concentration of calcium, phosphorous, and magnesium were nearly similar among the stages of lactation. Similarly, triiodothyronine (T3), and thyroxine (T4) increased and prolactin and cortisol decreased (P < 0.05) gradually as stages of lactation advanced. Total antioxidant capacity (TAC) increased and malondialdehyde (MDA) decreased (P < 0.05) as lactation stages advanced. The results of the present study indicated that the lactating CB cows suffered nutritional stress (deficiency of protein, carbohydrate, lipids, and minerals), physiological stress (higher cortisol), oxidative stress (higher MDA and deficiency of total antioxidant capacity), and hormonal imbalance (higher prolactin and cortisol and deficiency of thyroid hormones) during the early stages of lactation. Thus, the first and second stages are more stressful events compared to the third stage of lactation in the CB cows in ANI. Therefore, regular monitoring of blood components and accordingly suitable feeding strategies with balanced nutrients and minerals, supplementation of suitable antioxidants, and appropriate management practices need to be implemented to mitigate these stresses and to prevent metabolic disorders with maximum milk production during different stages of lactation in CB cows under humid tropical island ecosystem of Andaman and Nicobar Islands.

Comparison of R1ρ Imaging Between Rapid Acquisition with Relaxation Enhancement (RARE) and Ultrashort TE (UTE) Sequence in the Assessment of Rat Liver Iron Overload at 11.7T.

INTRODUCTION: Since the most prominent effect of iron is increasing R2* and R2 relaxation rates, the iron-overload liver shows little signal with conventional T1ρ sequences like RARE. Whereas UTE MR imaging sequences can detect the signal from short T2/T2* relaxation components in tissues. This study aims to evaluate the difference in R1ρ profiles and compare the correlations between RARE-based and UTE-based sequences with LIC in assessing rat liver iron overload. METHODS: Iron dextran (Sigma, 100 mg Fe/ml) was injected into thirty-five rats (25-100 mg/kg body weight), while the rats in the control group were injected with saline (n=5). The liver specimen was taken after one week. A portion of the largest hepatic lobe was extracted to quantify the LIC by inductively coupled plasma, and the remaining liver tissue was stored in 4% buffered paraformaldehyde for 24 h before MRI. Spin-lock preparation with RARE readout and 2D UTE readout pulses were developed to quantify R1ρ on a Bruker 11.7T MR system. RESULTS: The mean R1ρ value of the rat liver with UTE-based R1ρ sequence was significantly higher compared to the RARE-based R1ρ sequence (p<0.001). Spearman's correlation analysis (two-tailed) indicated that the R1ρ values were significantly correlated with LIC for both UTE-R1ρ and RARER1ρ sequences (r = 0.727, P < 0.001, and r = 0.712, P < 0.001, respectively). CONCLUSION: The current study adds to evidence that there is a correlation between iron concentration and R1ρ. Moreover, the UTE-based R1ρ sequence is more sensitive to the liver iron than the RAREbased R1ρ sequence. R1ρ might serve as a complementary imaging biomarker for liver iron overload quantification.

Identification and Registration for High-Yielding Strain through ST and MLT of Curcuma caesia Roxb. (Jor Lab KH-2): A High-Value Medicinal Plant.

(1) Background: Curcuma caesia Roxb. is a high valued crop which is extensively used in pharmaceuticals, flavour and fragrances. C. caesia is recognised as an endangered species due to its extensive collection from the wild through human intervention. Therefore, to prevent the species from extinction, it is very necessary to conserve and cultivate this plant species for the sustainable availability of the raw material. (2) Methods: In the present plant breeding programme, a multi-year study was performed for the identification of superior genotypes which will help in conservation. To fulfil this objective, a total of 135 accessions of C. caesia were collected from different regions of India and were set up for experimental selection trial for three years (2016-2018). After proper evaluation of the genotypes based on six agronomical traits, five high-yielding genotypes were identified which underwent multilocation trial for two years (2019 and 2020). The stability analysis using the Eberhart-Russell method, AMMI and GGE biplot were used to study the consistency of the genotypes in varied environments compared with the check variety. (3) Results: Analysis of variance indicated significant genotype and environment interaction for the yield traits, i.e., dry rhizome recovery, rhizome yield and essential oil yield. The coefficient of variation (CV) was highest for tillers per plant (21.76) and lowest for the plant height (4.93). All the results clearly demonstrated Jor Lab KH-2 as the highest yielding and stable genotype in varied environments compared with the check variety and other selected genotypes. (4) Conclusions: This genotype was then submitted to ICAR-NBPGR, New Delhi, for germplasm registration and received its confirmation vide registration number INGR 21159. This genotype will greatly benefit the breeders and will also help in the conservation of this endangered species. This is the first report on the identification and registration of a high-yielding variety of C. caesia.

Zinc oxide nanoparticles reduce biofilm formation, synergize antibiotics action and attenuate Staphylococcus aureus virulence in host; an important message to clinicians.

BACKGROUND: Biofilm-related infections are difficult to be treated because of higher resistance to antimicrobial agents. Current study aims to characterize the influence of zinc oxide nanoparticles (ZnO-NPs) on both S. aureus susceptibility to antibiotics and pathogenesis. METHODS: The influence of ZnO-NPs on biofilm formation by S. aureus was characterized by the crystal violet and tube assay. The synergistic effect of ZnO-NPs in combination with antibiotics on S. aureus was characterized using the checkerboard method. The effect of ZnO-NPs on S. aureus cell surface hydrophobicity and blood hemolysis was investigated. RT-qPCR was used to investigate the effect of ZnO-NPs on the expression of biofilm related genes (icaA, icaR and sarA), katA and sigB. The impact of ZnO-NPs on S. aureus pathogenesis was evaluated using mice infection model. RESULTS: ZnO-NPs exhibited a good antibiofilm activity against S. aureus. The findings indicate a synergistic antibiofilm effect of combination between ZnO-NPs and tested antibiotics. ZnO-NPs were capable of decreasing S. aureus cell surface hydrophobicity which could account for observed decrease in bacterial biofilm forming capacity. Moreover, ZnO-NPs-treated bacteria exhibited a significant decrease in blood hemolysis relative to control untreated S. aureus. The expression of biofilm related genes was significantly repressed in ZnO-NPs treated bacteria as compared to untreated cells. Finally, the effect of ZnO-NPs on S. aureus pathogenesis was investigated using mice infection model where ZnO-NPs accelerated healing of wounds in mice as compared to control untreated mice. CONCLUSIONS: Present data support the efficiency of ZnO-NPs as antibiofilm agent in treatment of S. aureus infections. This study recommends the incorporation of ZnO-NPs as adjuvant with other antibiotics targeting S. aureus based on the promising findings obtained herein in order to control infection with this pathogen.

Outbreak of Ichthyophthirius multifiliis associated with Aeromonas hydrophila in Pangasianodon hypophthalmus: The role of turmeric oil in enhancing immunity and inducing resistance against co-infection.

Ichthyophthirius multifiliis, a ciliated parasite causing ichthyophthiriasis (white spot disease) in freshwater fishes, results in significant economic loss to the aquaculture sector. One of the important predisposing factors for ichthyophthiriasis is low water temperature (i.e., below 20°C), which affects the health and makes freshwater fishes more susceptible to parasitic infections. During ichthyophthiriasis, fishes are stressed and acute immune reactions are compromised, which enables the aquatic bacterial pathogens to simultaneously infect the host and increase the severity of disease. In the present work, we aimed to understand the parasite-bacteria co-infection mechanism in fish. Later, Curcuma longa (turmeric) essential oil was used as a promising management strategy to improve immunity and control co-infections in fish. A natural outbreak of I. multifiliis was reported (validated by 16S rRNA PCR and sequencing method) in Pangasianodon hypophthalmus from a culture facility of ICAR-CIFRI, India. The fish showed clinical signs including hemorrhage, ulcer, discoloration, and redness in the body surface. Further microbiological analysis revealed that Aeromonas hydrophila was associated (validated by 16S rRNA PCR and sequencing method) with the infection and mortality of P. hypophthalmus, confirmed by hemolysin and survival assay. This created a scenario of co-infections, where both infectious agents are active together, causing ichthyophthiriasis and motile Aeromonas septicemia (MAS) in P. hypophthalmus. Interestingly, turmeric oil supplementation induced protective immunity in P. hypophthalmus against the co-infection condition. The study showed that P. hypophthalmus fingerlings supplemented with turmeric oil, at an optimum concentration (10 ppm), exhibited significantly increased survival against co-infection. The optimum concentration induced anti-stress and antioxidative response in fingerlings, marked by a significant decrease in cortisol and elevated levels of superoxide dismutase (SOD) and catalase (CAT) in treated animals as compared with the controls. Furthermore, the study indicated that supplementation of turmeric oil increases both non-specific and specific immune response, and significantly higher values of immune genes (interleukin-1ß, transferrin, and C3), HSP70, HSP90, and IgM were observed in P. hypophthalmus treatment groups. Our findings suggest that C. longa (turmeric) oil modulates stress, antioxidant, and immunological responses, probably contributing to enhanced protection in P. hypophthalmus. Hence, the application of turmeric oil treatment in aquaculture might become a management strategy to control co-infections in fishes. However, this hypothesis needs further validation.

Antibiofilm Effect of Silver Nanoparticles in Changing the Biofilm-Related Gene Expression of Staphylococcus epidermidis.

Nowadays, antibiotic resistance is a major public health problem. Among staphylococci, infections caused by Staphylococcus epidermidis (S. epidermidis) are frequent and difficult to eradicate. This is due to its ability to form biofilm. Among the antibiotic substances, nanosilver is of particular interest. Based on this information, we decided to investigate the effect of nanosilver on the viability, biofilm formation and gene expression of the icaADBC operon and the icaR gene for biofilm and non-biofilm S. epidermidis strains. As we observed, the viability of all the tested strains decreased with the use of nanosilver at a concentration of 5 µg/mL. The ability to form biofilm also decreased with the use of nanosilver at a concentration of 3 µg/mL. Genetic expression of the icaADBC operon and the icaR gene varied depending on the ability of the strain to form biofilm. Low concentrations of nanosilver may cause increased biofilm production, however no such effect was observed with high concentrations. This confirms that the use of nanoparticles at an appropriately high dose in any future therapy is of utmost importance. Data from our publication confirm the antibacterial and antibiotic properties of nanosilver. This effect was observed phenotypically and also by levels of gene expression.

Form of dietary selenium affects mRNA encoding interferon-stimulated and progesterone-induced genes in the bovine endometrium and conceptus length at maternal recognition of pregnancy.

Widespread regions of the southeast United States have soils, and hence forages, deficient in selenium (Se), necessitating Se supplementation to grazing cattle for optimal immune function, growth, and fertility. We have reported that supplementation with an isomolar 1:1 mix (MIX) of inorganic (ISe) and organic (OSe) forms of Se increases early luteal phase (LP) concentrations of progesterone (P4) above that in cows on ISe or OSe alone. Increased early LP P4 advances embryonic development. Our objective was to determine the effects of the form of Se on the development of the bovine conceptus and the endometrium using targeted real-time PCR (qPCR) on day 17 of gestation, the time of maternal recognition of pregnancy (MRP). Angus-cross yearling heifers underwent 45-d Se-depletion then repletion periods, then at least 90 d of supplementation (TRT) with 35 ppm Se per day as either ISe (n = 10) or MIX (n = 10). Heifers were inseminated to a single sire after detected estrus (day 0). On day 17 of gestation, caruncular (CAR) and intercaruncular (ICAR) endometrial samples and the developing conceptus were recovered from pregnant heifers (ISe, n = 6 and MIX, n = 6). qPCR was performed to determine the relative abundance of targeted transcripts in CAR and ICAR samples, with the expression data subjected to one-way ANOVA to determine TRT effects. The effect of TRT on conceptus development was analyzed using a one-tailed Student's t-test. When compared with ISe-treated heifers, MIX heifers had decreased (P < 0.05) abundance of several P4-induced and interferon-stimulated mRNA transcripts, including IFIT3, ISG15, MX1, OAS2, RSAD2, DGAT2, FGF2 in CAR and DKK1 in ICAR samples and tended (P ≤ 0.10) to have decreased mRNA abundance of IRF1, IRF2, FOXL2, and PGR in CAR samples, and HOXA10 and PAQR7 in ICAR samples. In contrast, MIX-supplemented heifers had increased (P < 0.05) mRNA abundance of MSTN in ICAR samples and an increase in conceptus length (ISe: 17.45 ± 3.08 cm vs. MIX: 25.96 ± 3.95 cm; P = 0.05). Notably, myostatin increases glucose secretion into histotroph and contributes to advanced conceptus development. This advancement in conceptus development occurred in the presence of similar concentrations of serum P4 (P = 0.88) and whole blood Se (P = 0.07) at MRP.

In regions with soils deficient in selenium (Se), it is recommended that this trace mineral is supplemented to the diet of forage-grazing cattle. We have previously reported that the form of Se supplemented to cattle affects the function of multiple tissues, including the testis, liver, ovary, and pituitary. The objective of this study was to determine how the form of Se supplemented to heifers to achieve a Se-adequate status affects endometrial function and development of the conceptus at maternal recognition of pregnancy (MRP). Heifers were supplemented with the industry standard, an inorganic form of Se (ISe), or a 1:1 mix of organic and inorganic forms (MIX), with the reproductive tract recovered on day 17 of pregnancy. Real-time PCR was performed to determine the relative abundance of targeted mRNA transcripts in caruncular (CAR) and intercaruncular (ICAR) endometrial samples. The form of supplemental Se affected the abundance of multiple progesterone-induced and interferon-stimulated mRNA transcripts in CAR and ICAR samples, as well as the length of the conceptus that was recovered at MRP (day 17). Overall, our results indicate differences in endometrial function and increased development of the conceptus in cattle provided with MIX vs. ISe, suggesting that the MIX form of supplemental Se may increase fertility in cattle grazing soils deficient in this trace mineral.

Molecular modeling and in vitro studies of gedunin a potent alpha-amylase inhibitor and alpha-glucosidase inhibitor.

The present study explores the potential of the Azadirachta indica (Neem) plant parts (stem and bark) component gedunin for inhibition of alpha-amylase and alpha glucosidase. In contrast, Methanol at 50 mg/ml and 65 mg/ml had the lowest IC50 in alpha glucosidase and alpha amylase with noncompetitive and mixed inhibition, respectively. Azadirachta indica seeds collected from ICAR showed anti-diabetes activity in vitro and in vivo seeds collected were subjected to soxhlet and nonsoxhlet techniques followed by chromatography. HR-LCMS, HPLC, and FTIR to comprehend phytoconstituents present in the extract were used to comprehend phytoconstituents present in the extract and showed the presence gedunin. Among many hits observed, gedunin was used for docking studies using ICM software and for molecular dynamic simulation using gromacs. The results show significant alpha-amylase inhibitory activity and alpha glucosidase inhibitory activity and interaction of ligand targeting these enzymes, which can be used for cross-validation, in vitro using ligplot maps and visualization.

Iodine Supplementation Improved Antioxidant Status, Hormonal Status, Sexual Behavior, and Semen Production Performance of Bos indicus Bulls Under Tropical Climatic Condition.

Iodine is anessential micronutrient that plays a crucial role in male reproduction (sexual behavior and semen production performance) by modulating thyroid function and the antioxidant status of the animal. Nonetheless, in Bos indicus bulls, a thorough evaluation of the effects of dietary iodine supplementation on antioxidant status, seminal quality parameters, and its interaction with other minerals is not documented. Twelve Bos indicus (Sahiwal) bulls were distributed into three groups (n = 4 in each group) viz. T1 (control), T2, and T3 and fed diets containing 0.250, 0.375, and 0.500 ppm iodine/ kg dry matter intake, corresponding to 0%, 50%, and 100% higher than ICAR (2013) recommendations, respectively. The experimental feeding was carried out for 60 days and the effects on nutrient utilization, hormonal and antioxidant status, and sperm function tests were investigated. Results revealed that body weight, dry matter intake, and nutrient digestibility remained unaffected by dietary supplementation of iodine. Testosterone and thyroxine hormone concentrations were improved (p<0.05) in T2 and T3 groups. Blood and seminal iodine content were also higher (p<0.05) in both the supplemented groups (T2 and T3). Sperm functions viz. viability, physical membrane integrity, acrosomal integrity, motility, and mitochondrial membrane potential were improved (p<0.05) due to iodine supplementation. Furthermore, lipid peroxidation and membrane scrambling in spermatozoa were reduced (p<0.05) in T2 and T3 groups. Blood antioxidant status (total antioxidant activity and GPx levels) was improved (p<0.05) in T2 and T3. Sexual behavior was also improved (p<0.05) in iodine-supplemented groups. Hence, it can be concluded that iodine supplementation at the dose rate of 0.500 ppm in the Bos indicus bull diet is beneficial in improving hormonal status, antioxidant status, and semen quality.

A Comparison of International Guidelines for Rhinosinusitis.

The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), latest version EPOS2020, and the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS), latest version ICAR-RS-2021, assimilate thousands of articles on the topic of rhinosinusitis. Encompassing scores of subtopics and relying on the perspectives of many international experts, EPOS2020 and ICAR-RS-2021 reduce the existing data into consumable formats and create evidence-based recommendations. The approaches and findings are similar in many respects but have significant differences. This clinical commentary, authored by some of the principal authors of these documents, compares and contrasts EPOS2020 and ICAR-RS-2021, examining methodology, diagnostic and treatment recommendations, and each document's emphases. This commentary demonstrates that, through somewhat differing methodologies, the 2 documents arrive at largely similar conclusions. Those who care for patients suffering from rhinosinusitis will find the documents complementary and valuable in their differences as much as in their similarities.

Intraperitoneal supplementation of iron alleviates dextran sodium sulfate-induced colitis by enhancing intestinal barrier function.

Iron supplementation is necessary for the treatment of anemia, one of the most frequent complications in inflammatory bowel disease (IBD). However, oral iron supplementation leads to an exacerbation of intestinal inflammation. Gut barrier plays a key role in the pathogenesis of IBD. The aim of this study was to characterize the interrelationship between systemic iron, intestinal barrier and the development of intestinal inflammation in a dextran sulfate sodium (DSS) induced experimental colitis mice model. We found that DSS-treated mice developed severe inflammation of colon, but became much healthy when intraperitoneal injection with iron. Iron supplementation alleviated colonic and systemic inflammation by lower histological scores, restorative morphology of colonic villi, and reduced expression of pro-inflammatory cytokines. Moreover, intraperitoneal supplementation of iron enhanced intestinal barrier function by upregulating the colonic expressions of tight junction proteins, restoring intestinal immune homeostasis by regulating immune cell infiltration and T lymphocyte subsets, and increasing mucous secretion of goblet cells in the colon. High-throughput sequencing of fecal 16 S rRNA showed that iron injection significantly increased the relative abundance of Bacteroidetes, which was suppressed in the gut microbiota of DSS-induced colitis mice. These results provided evidences supporting the protective effects of systemic iron repletion by intraperitoneal injection of iron on intestinal barrier functions. The finding highlights a novel approach for the treatment of IBD with iron injection therapy.

[Establishment of an Iron-overloaded Mouse Model with Tuberculosis and Analysis of the Iron Metabolism Index].

Objective To establish a mouse model of exogenous iron overload combined with tuberculosis(TB). Methods C57BL/6N mice were divided into negative control, low-, medium-, and high-dose iron groups and received intraperitoneal injection of iron dextran at 0, 3.75, 7.50, and 15.00 mg/dose(3 times/week for 4 weeks), respectively.After 4 weeks, the organ morphology and body weight of the mice were evaluated.The content of serum iron, ferritin, transferrin, and transferrin receptor was determined by ELISA.Heart, liver, spleen, lung, kidney, and small intestine were analyzed for tissue iron content and iron deposition pathology.Mycobacterium tuberculosis(Mtb)standard strain H37Rv was injected via tail vein to infect the mice receiving moderate-dose iron to establish an iron-overloaded mouse model of active TB.HE staining and Mtb culture were employed to analyze tuberculous lesions and bacterial loads of lung, spleen and liver tissues. Results The weight gain percentages of mice in the negative control, low-, medium-, and high-dose iron groups were 25.47%, 25.22%, 24.74%, and 21.36%, respectively, which was significantly lower in the high-dose group than in the negative control(F=17.235, P=0.027), low-dose(F=15.206, P=0.031), and medium-dose(F=11.061, P=0.036)groups.Liver had the highest iron content, followed by spleen, kidney, and small intestine.The iron content in heart and lung tissues of the low-dose group had no significant difference compared with those of the negative control group(F=19.023, P=0.715;F=23.193, P=0.902).Serum iron and ferritin in the iron-overloaded mice increased in a dose-dependent manner, while transferrin and transferrin receptor had no significant changes.HE and Prussian blue staining showed that the iron-overloaded mice had different degrees of iron deposition in tissues and high-dose iron caused liver and kidney damage.The lung(F=23.227, P=0.017), spleen(F=19.023, P=0.021), and liver(F=17.392, P=0.009)of the iron-overloaded mice with TB had a significantly shorter time of bacterial culture than those of the TB-infected mice without iron overload.The lung(F=21.012, P=0.007), spleen(F=20.173, P=0.002), and liver(F=19.091, P=0.005)of the iron-overloaded mice with TB had significantly higher bacterial loads than those of the TB-infected mice without iron overload. Conclusions The exogenous iron-overloaded mouse model with similar symptoms to patients with clinical iron overload can be established by intraperitoneal injection of medium-dose(7.50 mg/dose, 3 times/week for 4 weeks)iron dextran.Mtb injection through the tail vein can help construct a mouse model of iron overload combined with active TB.

Ameliorative effects and mechanisms of salvianic acid A on retinal iron overload in vivo and in vitro.

Excessive iron can be accumulated in the retina and lead to retinal iron overload. Salvianic acid A (SAA) has a variety of pharmacologic effects, but there is only a limited understanding of its benefits for retinal iron overload. The aim of this study was to examine the protective effects and latent mechanisms of SAA on retinal iron overload. SAA reduced iron in the serum and retina, attenuated pathophysiological changes, and reduced retinal iron deposition in the retinas of iron-overloaded mice. It also reduced intracellular iron in ARPE-19 cells by regulating iron-handling proteins and chelating with iron. It also significantly inhibited cellular oxidative and inflammatory damage by increasing the nuclear translocation of nuclear erythroid 2-related factor 2 (Nrf2) while decreasing nuclear factor-kappa B (NF-κB), protecting the ARPE-19 cells from apoptosis by suppressing the Bax/Bcl-2 ratio, cytochrome c release, caspase activation, and poly ADP-ribose polymerase cleavage. The ability of SAA to inhibit apoptosis, increase nuclear Nrf2 expression, and decrease nuclear NF-κB expression was further confirmed in the retinas of iron-overloaded mice. This study demonstrates that SAA shows significant protective effects against retinal iron overload; its mechanisms might be associated with iron chelation; regulation of iron-handling proteins; and inhibition of oxidative stress, inflammation and apoptosis.

Gut Microbial and Metabolic Profiling Reveal the Lingering Effects of Infantile Iron Deficiency Unless Treated with Iron.

SCOPE: Iron deficiency (ID) compromises the health of infants worldwide. Although readily treated with iron, concerns remain about the persistence of some effects. Metabolic and gut microbial consequences of infantile ID were investigated in juvenile monkeys after natural recovery (pID) from iron deficiency or post-treatment with iron dextran and B vitamins (pID+Fe). METHODS AND RESULTS: Metabolomic profiling of urine and plasma is conducted with 1 H nuclear magnetic resonance (NMR) spectroscopy. Gut microbiota are characterized from rectal swabs by amplicon sequencing of the 16S rRNA gene. Urinary metabolic profiles of pID monkeys significantly differed from pID+Fe and continuously iron-sufficient controls (IS) with higher maltose and lower amounts of microbial-derived metabolites. Persistent differences in energy metabolism are apparent from the plasma metabolic phenotypes with greater reliance on anaerobic glycolysis in pID monkeys. Microbial profiling indicated higher abundances of Methanobrevibacter, Lachnobacterium, and Ruminococcus in pID monkeys and any history of ID resulted in a lower Prevotella abundance compared to the IS controls. CONCLUSIONS: Lingering metabolic and microbial effects are found after natural recovery from ID. These long-term biochemical derangements are not present in the pID+Fe animals emphasizing the importance of the early detection and treatment of early-life ID to ameliorate its chronic metabolic effects.

Establishment of an Iron-overloaded Mouse Model with Tuberculosis and Analysis of the Iron Metabolism Index / 中国医学科学院学报

Objective To establish a mouse model of exogenous iron overload combined with tuberculosis(TB). Methods C57BL/6N mice were divided into negative control, low-, medium-, and high-dose iron groups and received intraperitoneal injection of iron dextran at 0, 3.75, 7.50, and 15.00 mg/dose(3 times/week for 4 weeks), respectively.After 4 weeks, the organ morphology and body weight of the mice were evaluated.The content of serum iron, ferritin, transferrin, and transferrin receptor was determined by ELISA.Heart, liver, spleen, lung, kidney, and small intestine were analyzed for tissue iron content and iron deposition pathology.

High Prevalence of Iron Deficiency Despite Standardized High-Dose Iron Supplementation During Recombinant Erythropoietin Therapy in Extremely Low Gestational Age Newborns.

OBJECTIVE: To assess the effects of protocolized recombinant human erythropoietin (r-HuEPO) therapy and standardized high dose iron supplementation on hematologic and iron status measures in a cohort of extremely low gestational age newborns (ELGANs). STUDY DESIGN: Charts of extremely low gestational age newborns admitted from 2006 to 2016 and who had received r-HuEPO per neonatal intensive care unit protocol were reviewed. The r-HuEPO was started at a dose of 900 IU/kg per week after 7 days of age and continued until 35 weeks postmenstrual age. Oral iron supplementation at 6-12 mg/kg per day was used to maintain a transferrin saturation of >20% during r-HuEPO treatment. Data on demographic features, hematologic and iron panel indices, red blood cell transfusions, and clinical outcomes were collected. Quartile groups were created based on serum ferritin levels at the conclusion of the r-HuEPO treatment and the quartiles were compared. RESULTS: The cohort included 116 infants with mean gestational age 25.8 ± 1.5 weeks and birth weight 793 ± 174.1 g. The r-HuEPO promoted erythropoiesis as indicated by increasing hemoglobin, hematocrit, and reticulocyte count. Serum ferritin decreased over time and was ≤75 ng/mL in 60.2% of infants at the conclusion of r-HuEPO therapy; 87% received packed red blood cell transfusions. Transfusion volume, total iron intake, total iron binding capacity, and transferrin concentration differed among infants in the different serum ferritin quartiles (P < .05). CONCLUSIONS: In extremely low gestational age newborns, r-HuEPO therapy promoted erythropoiesis. Despite a biomarker-based standardized high-dose iron supplementation, the majority of infants had evidence of iron deficiency to a degree that is associated with reduced brain function.

Chronic Iron Overload Restrains the Benefits of Aerobic Exercise to the Vasculature.

Physical exercise is a well-recognized effective non-pharmacological therapy for cardiovascular diseases. However, because iron is essential element in many physiological processes including hemoglobin and myoglobin synthesis, thereby playing a role on oxygen transport, many athletes use iron supplement to improve physical performance. Regarding this, iron overload is associated with oxidative stress and damage to various systems, including cardiovascular. Thus, we aimed to identify the vascular effects of aerobic exercise in a rat model of iron overload. Male Wistar rats were treated with 100 mg/kg/day iron-dextran, i.p., 5 days a week for 4 weeks, and then underwent aerobic exercise protocol on a treadmill at moderate intensity, 60 min/day, 5 days a week for 8 weeks. Exercise reduced vasoconstrictor response of isolated aortic rings by increasing participation of nitric oxide (NO) and reducing oxidative stress, but these benefits to the vasculature were not observed in rats previously subjected to iron overload. The reduced vasoconstriction in the exercised group was reversed by incubation with superoxide dismutase (SOD) inhibitor, suggesting that increased SOD activity by exercise was lost in iron overload rats. Iron overload groups increased serum levels of iron, transferrin saturation, and iron deposition in the liver, gastrocnemius muscle, and aorta, and the catalase was overexpressed in the aorta probably as a compensatory mechanism to the increased oxidative stress. In conclusion, despite the known beneficial effects of aerobic exercise on vasculature, our results indicate that previous iron overload impeded the anticontractile effect mediated by increased NO bioavailability and endogenous antioxidant response due to exercise protocol.

Comparison of Oral and Parenteral Iron Administration on Iron Homeostasis, Oxidative and Immune Status in Anemic Neonatal Pigs.

The present study was to evaluate the consequences of iron status across oral and parenteral iron administrations in prevention of iron deficiency anemia. A total of 24 one-day-old male neonatal piglets were allocated into three groups given non-iron supplementation (NON), intramuscular iron dextran injection (FeDex), and oral administration of ferrous glycine chelate (FeGly), respectively. At day 8, no significant differences in final body weight, average weight gain, and tissue coefficients were observed among three groups (P > 0.05). Both oral FeGly and FeDex injection significantly increased serum iron, ferritin, hemoglobin, and tissue iron deposition (P < 0.05). However, FeDex-injected supplementation resulted in rapidly rising hepcidin levels and hepatic iron deposition (P < 0.05). In addition, compared to parenteral iron supplementation, greater serum IgA level, SOD, and GSH-Px activities, lower expressions of IL-1ß and TNF-α in the liver, and lower expressions of IL-6 and TNF-α in the spleen were found in oral iron piglets (P < 0.05). According to our results, oral administration of ferrous glycine chelate improved iron homeostasis, and oxidative and immune status in anemic neonatal pigs.

Long-term Effect of Split Iron Dextran/Hemoglobin Supplementation on Erythrocyte and Iron Status, Growth Performance, Carcass Parameters, and Meat Quality of Polish Large White and 990 Line Pigs.

Heme is an efficient dietary iron supplement applied in humans and animals to prevent iron deficiency anemia (IDA). We have recently reported that the use of bovine hemoglobin as a dietary source of heme iron efficiently counteracts the development of IDA in young piglets, which is the common problem in pig industry. Here, we used maternal Polish Large White and terminal sire breed (L990) pigs differing in traits for meat production to evaluate the long-term effect of split supplementation with intramuscularly administered small amount of iron dextran and orally given hemoglobin on hematological indices, iron status, growth performance, slaughter traits, and meat quality at the end of fattening. Results of our study show that in pigs of both breeds split supplementation was effective in maintaining physiological values of RBC and blood plasma iron parameters as well as growth performance, carcass parameters, and meat quality traits. Our results prove the effectiveness of split iron supplementation of piglets in a far-reach perspective.