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Ferrous sulphate (FS) is a cost effective, readily available iron supplement for iron deficiency (ID). The pro-oxidant effect of oral ferrous iron is known to induce inflammation, causing gastric side-effects and resulting in poor compliance. Curcumin is a potent antioxidant and has also been shown to exhibit iron chelation in-vitro, although it is not established whether these effects are retained in-vivo. The aim of this study was therefore to assess the influence of a formulated bioavailable form of curcumin (HydroCurcTM; 500 mg) on acute iron absorption and status in a double blind, placebo-controlled randomized trial recruiting 155 healthy participants (79 males; 26.42 years ± 0.55 and 76 females; 25.82 years ± 0.54). Participants were randomly allocated to five different treatment groups: iron and curcumin placebo (FS0_Plac), low dose (18 mg) iron and curcumin placebo (FS18_Plac), low dose iron and curcumin (FS18_Curc), high dose (65 mg) iron and curcumin placebo (FS65_Plac), and high dose iron and curcumin (FS65_Curc). Participants were provided with the supplements according to their relevant treatment groups at baseline (0 min), and blood collection was carried out at 0 min and at 180 min following supplementation. In the treatment groups, significant difference was observed in mean serum iron between baseline (0 min) and at end-point (180 min) (F (1, 144) = 331.9, p < 0.0001) with statistically significant intra-group increases after 180 min (p < 0.0001) in the FS18_Plac (8.79 µmol/L), FS18_Curc (11.41 µmol/L), FS65_Plac (19.09 µmol/L), and FS65_Curc (16.39 µmol/L) groups. A significant difference was also observed between the two time points in serum TIBC levels and in whole blood haemoglobin (HGB) in the treatment groups, with a significant increase (1.55%/2.04 g/L) in HGB levels from baseline to end-point observed in the FS65_Curc group (p < 0.05). All groups receiving iron demonstrated an increase in transferrin saturation (TS%) in a dose-related manner, demonstrating that increases in serum iron are translated into increases in physiological iron transportation. This study demonstrates, for the first time, that regardless of ferrous dose, formulated curcumin in the form of HydroCurc™ does not negatively influence acute iron absorption in healthy humans.

With a small amount of maleimide modification on the liposome surface, enhanced cellular uptake of liposomes and drug-delivery efficiency can be obtained both in vitro and in vivo. Herein, we describe the mechanisms underlying this enhanced cellular uptake. Suppression of the cellular uptake of maleimide-modified liposomes (M-GGLG, composed of 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate [GGLG]/cholesterol/poly(ethylene glycol) - 1,2-distearoyl-sn-glycero-3-phosphoethanolamine [PEG₅₀₀₀-DSPE]/maleimide [M]-PEG₅₀₀₀-Glu2C18 at a molar ratio of 5:5:0.03:0.03) caused by temperature block and addition of serum was alleviated compared with that of liposomes without maleimide modification (GGLG liposomes, composed of GGLG/cholesterol/PEG₅₀₀₀-DSPE/PEG₅₀₀₀-Glu2C₁₈ at a molar ratio of 5:5:0.03:0.03). When 0.01 nM N-ethylmaleimide was used to pre-block cellular thiols, the cellular uptake of M-GGLG liposomes was decreased to approximately 70% in HeLa, HCC1954, MDA-MB-468, and COS-7 cell lines. Moreover, inhibition of a thiol-related reductase such as protein disulfide isomerase resulted in a 15%-45% inhibition of the cellular uptake of M-GGLG liposomes, whereas GGLG liposomes were not influenced. Further, single and mixed inhibitors of clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis did not efficiently inhibit the cellular uptake of M-GGLG liposomes. Using confocal microscopy, we verified that M-GGLG liposomes were localized partially in lysosomes after inhibition of the mentioned conventional endocytic pathways. Therefore, it was hypothesized that the mechanisms underlying the enhanced cellular uptake of liposomes by maleimide modification was thiol-mediated membrane trafficking, including endocytosis and energy-independent transport.

Natural stocks of Japanese eel (Anguilla japonica) have decreased drastically because of overfishing, habitat destruction, and changes in the ocean environment over the past few decades. However, to date, artificial mass production of glass eels is far from reality because of the lack of appropriate feed for the eel larvae. In this study, wild glass eel, leptocephali, preleptocephali, and embryos were collected to conduct RNA-seq. Approximately 279 million reads were generated and assembled into 224,043 transcripts. The transcript levels of genes coding for digestive enzymes and nutrient transporters were investigated to estimate the capacities for nutrient digestion and absorption during early development. The results showed that the transcript levels of protein digestion enzymes were higher than those of carbohydrate and lipid digestion enzymes in the preleptocephali and leptocephali, and the transcript levels of amino acid transporters were also higher than those of glucose and fructose transporters and the cholesterol transporter. In addition, the transcript levels of glucose and fructose transporters were significantly raising in the leptocephali. Moreover, the transcript levels of protein, carbohydrate, and lipid digestion enzymes were balanced in the glass eel, but the transcript levels of amino acid transporters were higher than those of glucose and cholesterol transporters. These findings implied that preleptocephali and leptocephali prefer high-protein food, and the nutritional requirements of monosaccharides and lipids for the eel larvae vary with growth. An online database (http://molas.iis.sinica.edu.tw/jpeel/) that will provide the sequences and the annotated results of assembled transcripts was established for the eel research community.

Operative hysteroscopy is accompanied by the use of distention medium. Its absorption can lead to volume overload and hemodynamic disturbances that can lead to serious complications. We investigated the impact of the type of anesthesia on decreasing these complications with the use of noninvasive thoracic bioimpedance. A prospective, randomized, blind study. Sixty women, with American Society of Anesthesiologists classifications I-III, undergoing operative hysteroscopy were randomly allocated into 2 groups. Spinal anesthesia group received intrathecal 0.5% hyperbaric bupivacaine 12.5 mg and 25 μg fentanyl; the other group received general anesthesia with intravenous analgesia, propofol, and rocuronium followed by endotracheal intubation. Total glycine absorption, cardiac output, systemic vascular resistance, thoracic fluid content (noninvasive thoracic bioimpedance), and serum sodium were measured. Women in the general anesthesia group showed more significant changes in the total glycine absorption, thoracic fluid content, and hemodynamic parameters. Serum sodium decreased significantly postoperatively in the general anesthesia group. Spinal anesthesia is associated with less glycine absorption, less thoracic fluid load, better control of hemodynamics, and better patient satisfaction in operative hysteroscopy. •Anesthesia has an impact on hemodynamics and glycine absorption in hysteroscopy.•Thoracic bioimpedance measures the hemodynamics and thoracic fluid.•Spinal anesthesia provides less glycine absorption than general anesthesia.•Spinal anesthesia provides better hemodynamic and thoracic fluid control.•Spinal anesthesia provides more patient satisfaction.

The objective of the study is to determine the effect of copper (Cu) plus the reducing agent ascorbic acid (AA) on the absorption of non-heme iron (Fe). Experimental study with block design in which each subject was his own control. After signing an informed consent, 14 adult women using an effective method of contraception and negative pregnancy test received 0.5 mg Fe, as ferrous sulfate, alone or with Cu, as copper sulfate, plus ascorbic acid (AA/Cu 2/1 molar ratio) at 4/1; 6/1 and 8/1 Cu/Fe molar ratios as an aqueous solution on days 1, 2, 14, and 15 of the study. Fe absorption was assessed by erythrocyte incorporation of iron radioisotopes ⁵⁵Fe and ⁵⁹Fe. Geometric mean (range ± SD) absorption of Fe at 4/1 and 6/1 Cu/Fe molar ratios (and AA/Cu 2/1 molar ratio) and Fe alone was 57.4 % (35.7–92.1 %), 64.2 % (45.8–89.9 %), and 38.8 % (20.4–73.8 %), respectively (ANOVA for repeated measures p 

Abstract Background and Aims The pathways whereby foliar-applied nutrients move across the leaf surface remain unclear. The aim of the present study was to examine the pathways by which foliar-applied Zn moves across the sunflower (Helianthus annuus) leaf surface, considering the potential importance of the cuticle, stomata and trichomes. Methods Using synchrotron-based X-ray florescence microscopy and nanoscale secondary ion mass spectrometry (NanoSIMS), the absorption of foliar-applied ZnSO4 and nano-ZnO were studied in sunflower. The speciation of Zn was also examined using synchrotron-based X-ray absorption spectroscopy. Key Results Non-glandular trichomes (NGTs) were particularly important for foliar Zn absorption, with Zn preferentially accumulating within trichomes in ≤15 min. The cuticle was also found to have a role, with Zn appearing to move across the cuticle before accumulating in the walls of the epidermal cells. After 6 h, the total Zn that accumulated in the NGTs was approx. 1.9 times higher than in the cuticular tissues. No marked accumulation of Zn was found within the stomatal cavity, probably indicating a limited contribution of the stomatal pathway. Once absorbed, the Zn accumulated in the walls of the epidermal and the vascular cells, and trichome bases of both leaf sides, with the bundle sheath extensions that connected to the trichomes seemingly facilitating this translocation. Finally, the absorption of nano-ZnO was substantially lower than for ZnSO4, with Zn probably moving across the leaf surface as soluble Zn rather than nanoparticles. Conclusions In sunflower, both the trichomes and cuticle appear to be important for foliar Zn absorption.

We have previously reported that resistance exercise improved the iron status in iron-deficient rats. The current study investigated the mechanisms underlying this exercise-related effect. Male 4-week-old rats were divided into a group sacrificed at the start (week 0) (n = 7), a group maintained sedentary for 6 weeks (S) or a group that performed exercise for 6 weeks (E), and all rats in the latter groups were fed an iron-deficient diet (12 mg iron/kg) for 6 weeks. The rats in the E group performed climbing exercise (5 min × 6 sets/day, 3 days/week). Compared to the week 0 rats, the rats in the S and E groups showed lower tissue iron content, and the hematocrit, hemoglobin, plasma iron, and transferrin saturation values were all low. However, the tissue iron content and blood iron status parameters, and the whole body iron content measured using the whole body homogenates of the rats, did not differ between the S group and the E group. The messenger RNA (mRNA) expression levels of hepcidin, duodenal cytochrome b, divalent metal transporter 1, and ferroportin 1 did not differ between the S group and the E group. The apparent absorption of iron was significantly lower in the E group than in the S group. Therefore, it was concluded that resistance exercise decreases iron absorption, whereas the whole body iron content is not affected, and an increase in iron recycling in the body seems to be responsible for this effect.

Phosphorus (P) is an essential macronutrient for plant growth, development and production. However, little is known about the effects of P deficiency on nutrient absorption, photosynthetic apparatus performance and antioxidant metabolism in citrus. Seedlings of ‘sour pummelo’ ( Citrus grandis ) were irrigated with a nutrient solution containing 0.2 mM (Control) or 0 mM (P deficiency) KH 2 PO 4 until saturated every other day for 16 weeks. P deficiency significantly decreased the dry weight (DW) of leaves and stems, and increased the root/shoot ratio in C . grandis but did not affect the DW of roots. The decreased DW of leaves and stems might be induced by the decreased chlorophyll (Chl) contents and CO 2 assimilation in P deficient seedlings. P deficiency heterogeneously affected the nutrient contents of leaves, stems and roots. The analysis of Chl a fluorescence transients showed that P deficiency impaired electron transport from the donor side of photosystem II (PSII) to the end acceptor side of PSI, which showed a greater impact on the performance of the donor side of PSII than that of the acceptor side of PSII and photosystem I (PSI). P deficiency increased the contents of ascorbate (ASC), H 2 O 2 and malondialdehyde (MDA) as well as the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR) and glutathione reductase (GR) in leaves. In contrast, P deficiency increased the ASC content, reduced the glutathione (GSH) content and the activities of SOD, CAT, APX and monodehydroascorbate reductase (MDHAR), but did not increase H 2 O 2 production, anthocyanins and MDA content in roots. Taking these results together, we conclude that P deficiency affects nutrient absorption and lowers photosynthetic performance, leading to ROS production, which might be a crucial cause of the inhibited growth of C . grandis .

Key Points Accumulation of neurotoxic forms of amyloid-β (Aβ) and tau proteins is the pathological hallmark of Alzheimer disease (AD) Excess deposition of Aβ results from an imbalance between its production and clearance; in both early-onset and late-onset forms of AD, Aβ clearance seems already impaired at the prodromal stage Aβ is removed from the brain by various overlapping and interacting clearance systems: degradation, blood–brain barrier (BBB) transport, interstitial fluid (ISF) bulk flow, and cerebrospinal fluid (CSF) absorption into the circulatory and peripheral lymphatic systems Although most extracellular Aβ undergoes BBB clearance, the recently discovered glymphatic pathway seems to be important for Aβ clearance Specific BBB transporters for tau have not been identified, suggesting that clearance of tau is less complex than that of Aβ, and mainly relies on degradation, ISF bulk flow, and CSF absorption Precise understanding of the mechanisms of clearance dysfunction in AD is paramount to develop strategies to reduce excess deposition of neuroxic protein and to halt the related pathological changes The elimination of amyloid-β (Aβ) from the brain is already impaired at the prodromal stage of Alzheimer disease (AD), so restoration of the clearance systems of the brain might delay the onset of AD. This Review provides a comprehensive update on the brain's clearance systems, including the recent discoveries of the glymphatic system and meningeal lymphatic vessels—findings that have important implications for understanding the disrupted elimination of toxic proteins in AD. Accumulation of toxic protein aggregates—amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles—is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood–brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.