Microalgae polyphosphate nanoparticles deliver bioavailable calcium against phytate antagonism: Ex vivo and in vivo studies.

Biogenic nanoparticles are promising carriers to deliver essential minerals. Here, calcium-enriched polyphosphate nanoparticles (CaPNPs) with a Ca/P molar ratio > 0.5 were produced by Synechococcus sp. PCC 7002 in the growth medium containing 1.08 g/L CaCl2, and had nearly spherical morphologies with a wide size distribution of 5-75 nm and strongly anionic surface properties with an average ζ-potential of -39 mV, according to dynamic light-scattering analysis, transmission and scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The ex-vivo ligated mouse ileal loop assays found that calcium in CaPNPs was readily available to intestinal absorption via both ion channel-mediated and endocytic pathways, specifically invoking macropinocytic internalization, lysosomal degradation, and transcytosis. Rat oral pharmacokinetics revealed that CaPNPs had a calcium bioavailability approximately 100 % relative to that of CaCl2 and more than 1.6 times of that of CaCO3. CaPNPs corrected the retinoic acid-induced increase in serum calcium, phosphorus, and bone-specific alkaline phosphatase, and decrease in serum osteocalcin, bone mineral content/density, and femoral geometric parameters with an efficacy equivalent to CaCl2 and markedly greater than CaCO3. In contrast to CaCl2, CaPNPs possessed desirable resistance against phytate's antagonistic action on calcium absorption in these ex vivo and in vivo studies. Overall, CaPNPs are attractive as a candidate agent for calcium supplementation, especially to populations on high-phytate diets.

Gum Arabic-Derived Hydroxyproline-Rich Peptides Stimulate Intestinal Nonheme Iron Absorption via HIF2α-Dependent Upregulation of Iron Transport Proteins.

The stimulation of host iron absorption is a promising antianemia strategy adjunctive/alternative to iron intervention. Here, gum arabic (GA) containing 3.14 ± 0.56% hydroxyproline-rich protein with repetitive X-(Pro/Hyp)n motifs was found to increase iron reduction, uptake, and transport to upregulate duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferroportin, and hephaestin to inhibit hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) and to stabilize HIF2α in polarized Caco-2 cell monolayers in a dose-dependent manner, and this was dependent on its protein fraction, rather than the polysaccharide fraction. Three abundant GA-derived hydroxyproline-containing dipeptides of Hyp-Hyp, Pro-Hyp, and Ser-Hyp were detected by liquid chromatography-mass spectrometry in the lysates of polarized Caco-2 cell monolayers at the maximum levels of  0.167 ± 0.021, 0.134 ± 0.017, and 0.089 ± 0.015 µg/mg of protein, respectively, and showed desirable docking affinity energy values of -7.53, - 7.91, and -7.39 kcal/mol, respectively, against human PHD3. GA-derived peptides also acutely increased duodenal HIF2α stability and Dcytb, DMT1, ferroportin, and hephaestin transcription in rats (P < 0.05). Overall, GA-derived hydroxyproline-rich peptides stimulated intestinal iron absorption via PHD inhibition, HIF2α stabilization, and subsequent upregulation of iron transport proteins.

Microalgae polysaccharides exert antioxidant and anti-inflammatory protective effects on human intestinal epithelial cells in vitro and dextran sodium sulfate-induced mouse colitis in vivo.

Microalgae polysaccharides (MAPS) have emerged as novel prebiotics, but their direct effects on intestinal epithelial barrier are largely unknown. Here, MAPS isolated from Chlorella pyrenoidosa, Spirulina platensis, and Synechococcus sp. PCC 7002 were characterized as mainly branched heteropolysaccharides, and were bioavailable to Caco-2 cells based on fluorescein isothiocyanate labeling and flow cytometry analysis. These MAPS were equally effective to scavenge hydroxyl and superoxide radicals in vitro and to attenuate the H2O2-, dextran sodium sulfate-, tumor necrosis factor α-, and interleukin 1ß-induced burst of intracellular reactive oxygen species and mitochondrial superoxide radicals, interleukin-8 production, cyclooxygenase-2 and inducible nitric oxide synthase expression, and/or tight junction disruption in polarized Caco-2 cells. MAPS and a positive drug Mesalazine were intragastrically administered to C57BL/6 mice daily for 7 d during and after 4-d dextran sodium sulfate exposure. Clinical signs and colon histopathology revealed equivalent anti-colitis efficacies of MAPS and Mesalazine, and based on biochemical analysis of colonic tight junction proteins, goblet cells, mucin 2 and trefoil factor 3 transcription, and colonic and peripheral pro-inflammatory cytokines, MAPS alleviated dextran sodium sulfate-induced intestinal epithelial barrier dysfunction, and their activities were even superior than Mesalazine. Overall, MAPS confer direct antioxidant and anti-inflammatory protection to intestinal epithelial barrier function.

Influence of the Essential Oil of Foeniculum vulgare Mill. on Sunflower Oil during the Deep-frying Process of Chinese Maye.

Sunflower oil (SFO) is faced with serious oxidation problems during the deep-frying of Chinese Maye, and the search for natural antioxidants has become a focus of scientific research due to the potential toxicity of synthetic antioxidants. In the present study, the Foeniculum vulgare Mill. essential oil (FVEO), tert-butylhydroquinone (TBHQ) were added to SFO for a 30 h deep frying experiment and the results showed that FVEO added to sunflower oil at 1 g/kg was similar to that of TBHQ-0.01 g/kg, and FVEO-1.5 g/kg would promote the oxidation of SFO. FVEO to sunflower oil also prominently restrained the decrease of the sensory properties of the fried product, Chinese Maye, including appearance, taste, flavor and overall acceptance by 24.2%, 20.2%, 46.1% and 56.0% (p < 0.01 or p < 0.05), respectively. The results indicated that FVEO could be used as a natural antioxidant to replace TBHQ in the deep-frying process of SFO, but further research is needed on the key antioxidant constituent of FVEO.

Enhancement of Oxidative Stability of Deep-Fried Sunflower Oil by Addition of Essential Oil of Amomum villosum Lour.

In this study, the essential oil of the fruits of Amomum villosum Lour. (AVEO) was extracted through steam distillation and the components of the AVEO were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS). Additionally, the antioxidant capacity in vitro of the AVEO was gauged using radical scavenging activity (DPPH, ABTS, superoxide anion) and ferric ion reducing antioxidant power (FRAP) assays; the antioxidant effect of a certain concentration of AVEO is even comparable to 0.08 mg/mL of butylated hydroxytoluene (BHT). Moreover, AVEO was applied to sunflower oil in a 30 h successive deep-frying experiment. Throughout the frying procedure, the sunflower oil-added antioxidant showed different degrees of benign changes in the physical and chemical parameters compared to the blank group, with 1 g/kg of AVEO being more consistent with 0.01 g/kg of tert-butyl hydroquinone (TBHQ), while 1.5 g/kg of essential oil revealed a stronger antioxidative capability. Meanwhile, the organoleptic characteristics of Chinese Maye, including its appearance, taste, flavor, and overall acceptability, were ameliorated when AVEO was added at 1.5 g/kg. Consequently, AVEO can be applied to substitute synthetic antioxidants as a natural antioxidant and flavoring agent during the deep-frying course of food.

Gum Arabic-Stabilized Ferric Oxyhydroxide Nanoparticles for Efficient and Targeted Intestinal Delivery of Bioavailable Iron.

Nanostructured iron(III) compounds are promising food fortificants with desirable iron bioavailability and food compatibility. Here, gum arabic (GA) solubilized 252 mg of iron(III) per g at neutral pH in the form of GA-stabilized ferric oxyhydroxide nanoparticles (GA-FeONPs) with Z-average size of 142.7 ± 5.9 nm and ζ-potential of -20.50 ± 1.25 mV. Calcein-fluorescence-quenching assay revealed well-absorbed iron from GA-FeONPs by polarized Caco-2 cells due to efficient macropinocytic internalization and asialoglycoprotein receptor-mediated specific endocytosis facilitated by the polypeptide and arabinogalactan fractions of GA, respectively, with endocytosed GA-FeONPs being in part basolaterally transcytosed and in another part degraded into cellular labile iron pool. GA-FeONPs showed good colloidal stability under varied pH, gastrointestinal, thermal processing, and spray/freeze drying conditions and displayed remarkably weaker pro-oxidant activity than FeSO4 in glyceryl trilinoleate emulsion (P < 0.05). Oral pharmacokinetics unveiled desirable iron bioavailability of GA-FeONPs relative to FeSO4, i.e., 124.27 ± 5.91% in aqueous solution and 161.64 ± 5.01% in milk. Overall, GA-FeONPs are a promising novel iron fortificant with food-compatible, efficient, and targeted intestinal iron delivery and sustained iron-release properties.

Imaging characteristics and treatment strategies of traumatic diaphragmatic hernia with aortic dissection: a report of 3 cases.

BACKGROUND: Traumatic aortic dissection with traumatic diaphragmatic hernia is a rare traumatic disease. The purpose of this article is to investigate the imaging characteristics and treatment strategies for traumatic diaphragmatic hernia with aortic dissection. CASE PRESENTATION: The imaging and clinical data of 3 patients with traumatic diaphragmatic hernia combined with aortic dissection were analyzed retrospectively. Of the three cases, two were males, and one was female; their mean age was 52.7 years (range, 47-62 years). Plain chest CT scans revealed diaphragmatic hernia in 2 patients, but no traumatic aortic dissection was found. Diaphragmatic hernia repair was performed in all patients. Aortic dilatation was found during intraoperative exploration, and aortic dissection was confirmed by postoperative enhanced CT. One patient underwent stent implantation and recovered smoothly (Case 1). The other patient refused stent implantation and died of thoracic hemorrhage (Case 2). The third patient underwent preoperative enhanced CT to identify traumatic diaphragmatic hernia with aortic dissection (Case 3). Aortic covered stent implantation was performed immediately, and diaphragmatic hernia repair was performed at a selected time. The patient's postoperative recovery was good. CONCLUSION: A preoperative plain chest CT scan indicated diaphragmatic hernia in major blunt thoracic trauma patients with a history of trauma and blurred periaortic spaces accompanied by hematocele and other imaging manifestations. Chest-enhanced CT should be performed to improve the diagnostic accuracy of aortic dissection.

Collagen Peptides as a Hypoxia-Inducible Factor-2α-Stabilizing Prolyl Hydroxylase Inhibitor to Stimulate Intestinal Iron Absorption by Upregulating Iron Transport Proteins.

Iron intervention is not always safe and effective to correct iron deficiency. Host iron absorption stimulation is emerging as a promising adjunctive/alternative treatment. Here, porcine collagen hydrolysate (CH) and collagen-derived dipeptide prolyl-hydroxyproline, rather than collagen amino acids, namely, glycine, proline, and hydroxyproline, were found to increase cellular iron reduction, absorption, and transportation, to upregulate duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferroportin (FPN), and hephaestin, and to nongenomically activate hypoxia-inducible factor-2α signaling in polarized Caco-2 cells. Prolyl-hydroxyproline showed both competitive and uncompetitive inhibition of recombinant human prolyl hydroxylase-3 activity with EC50 and Ki values of 10.62 and 6.73 µM, respectively. Docking simulations revealed collagen peptides as iron chelators and/or steric hindrances for prolyl hydroxylase-3. CH and prolyl-hydroxyproline acutely increased duodenal hypoxia-inducible factor-2α stability and Dcytb, DMT1, FPN, and hephaestin transcription in rats. Overall, collagen peptides act as a hypoxia-inducible factor-2α-stabilizing prolyl hydroxylase inhibitor to stimulate intestinal iron absorption.

Antioxidant and anti-inflammatory protective effects of yellowtail (Seriola quinqueradiata) milt hydrolysates on human intestinal epithelial cells in vitro and dextran sodium sulphate-induced mouse colitis in vivo.

Milt is an underutilized fish processing by-product containing valuable nutrients for human health. Here, a gastrointestinal hydrolysate of degreased yellowtail (Seriola quinqueradiata) milt contained 70.6% arginine-rich protein, 20% nucleic acids, 7.1% minerals and 2.3% carbohydrates. Yellowtail milt hydrolysates (YMH) effectively attenuated the H2O2-induced burst of intracellular reactive oxygen species, plasma membrane impairment, loss of cell viability, interleukin 8 production and the expression of claudin-4 and occludin in Caco-2 cells with its protein fraction playing a greater antioxidant role than its nucleic acid fraction. YMH also significantly counteracted the tumor necrosis factor α- and interleukin 1ß-stimulated interleukin 8 production and cyclooxygenase-2 and inducible nitric oxide synthase expression in Caco-2 cells and inhibited the production of nitric oxide and proinflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells depending on its protein fraction, rather than its nucleic acid fraction. YMH and a positive drug 5-aminosalicylic acid were intragastrically administered to C57BL/6 mice daily for 7 days during and after 4-day dextran sodium sulphate exposure. Based on clinical signs, colon histopathology and biochemical analysis of colonic tight junction proteins, mucus compositions and goblet cells, YMH ameliorated mouse colitis symptoms and intestinal epithelial barrier dysfunction more effectively than 5-aminosalicylic acid. According to myeloperoxidase activity, proinflammatory cytokines and NF-κB, YMH and 5-aminosalicylic acid exerted equivalent inhibitory effects on colonic and systemic inflammation. Overall, YMH have considerable antioxidant and anti-inflammatory efficacies to maintain gut health.

Epithelial-Myoepithelial Carcinoma of the Esophagus: A Case Report.

Epithelial-myoepithelial carcinoma (EMC) of the esophagus is a rare biphasic tumor with low malignant potential, which has not previously been reported in the published literature. The present study describes the case of an asymptomatic, 53-year-old male who presented with EMC in the esophagus during a gastroscopic examination. Esophageal computed tomography (CT) showed thickening of the wall of the lower esophagus with a thickness of about 0.7 cm, and an enhanced scan showed uneven enhancement of the thickened esophageal wall. Thoracoscopic esophagectomy was performed because the tumor was malignant. Histopathology revealed that the tumor was characterized by a biphasic architecture consisting of cuboidal ductal cells and myoepithelial cells. The patient's postoperative recovery was eventful, an anastomotic fistula occurred, and the patient was discharged from the hospital after 84 days. One year postsurgery, the patient remained in good health, with no evidence of metastasis and recurrence.

Phycocyanin ameliorates mouse colitis via phycocyanobilin-dependent antioxidant and anti-inflammatory protection of the intestinal epithelial barrier.

Phycocyanin is a typical microalgal active compound with antioxidant and anti-inflammatory efficacy, and the pigment moiety phycocyanobilin has been recently proposed as its active structural component. Here, to explore the structural basis for phycocyanin's intestinal protective action, we evaluated the therapeutic effects and mechanism of action of phycocyanin and phycocyanobilin in dextran sodium sulphate (DSS)-induced colitis mice and in Caco-2 and RAW 264.7 cells. Phycocyanobilin was obtained by solvothermal alcoholysis of phycocyanin and characterized by spectroscopy and mass spectrometry methods. Phycocyanin, phycocyanobilin and a positive drug mesalazine were intragastrically administered to C57BL/6 mice daily for 7 days during and after 4-day DSS exposure. Clinical signs and colon histopathology revealed that phycocyanin and phycocyanobilin had an equivalent anti-colitis efficacy that was even superior to mesalazine. Based on biochemical analysis of colonic tight junction proteins, mucus compositions and goblet cells, and colonic and peripheral proinflammatory cytokines, phycocyanin and phycocyanobilin displayed equivalent intestinal epithelial barrier-protecting and anti-inflammatory potential that was evidently superior to that of mesalazine. Flow cytometry analysis of phycocyanobilin fluorescence in Caco-2 cells unveiled a similar uptake efficacy of phycocyanin and phycocyanobilin by intestinal epithelial cells. According to lactic dehydrogenase release, 2',7'-dichlorodihydrofluorescein fluorescence and methylthiazolyldiphenyl-tetrazolium bromide assay in Caco-2 cells, phycocyanin and phycocyanobilin could equally and effectively protect the intestinal epithelial barrier from oxidant-induced disruption. Phycocyanin and phycocyanobilin also showed equivalent anti-inflammatory effects in tumor necrosis factor-α-stimulated Caco-2 cells and in lipopolysaccharides- and tumor necrosis factor-α-activated RAW264.7 cells. Overall, our results demonstrate the phycocyanobilin-dependent anti-colitis role of phycocyanin via antioxidant and anti-inflammatory mechanisms.

Polyphosphates as an effective vehicle for delivery of bioavailable nanoparticulate iron(III).

Polyphosphates are widely used food additives with the potential to increase iron bioavailability but chemical nature of their soluble complexes with iron remains largely unknown. Here, pyrophosphate, tripolyphosphate, hexametaphosphate and ∼25-chain-length polyphosphate solubilized 896, 896, 1120 and 1344 mg Fe(III) per g, respectively, at neutral pH by mediating the formation of highly-negatively-charged ferric hydroxide-polyphosphate nanoparticles (PolyP-FeONPs). PolyP-FeONPs displayed fading yellow color with increasing initial dissolved P/Fe ratio ((P/Fe)init) and decreasing polyphosphate length due to rising proportion of Fe(III)-phosphate bonds, and specifically, pyrophosphate resulted colorless PolyP-FeONPs at (P/Fe)init ≥ 4. PolyP-FeONPs had weak pro-oxidant activity in glyceryl trilinoleate emulsion and good colloidal stability under spray/freeze-drying and gastrointestinal conditions. Serum iron kinetics in rats revealed sustained iron release and ∼170% iron bioavailability of oral PolyP-FeONPs relative to FeSO4. Calcein-fluorescence-quenching assay in polarized Caco-2 cells unveiled divalent-metal-transporter-1-independent and macropinocytosis-dependent iron uptake from PolyP-FeONPs. This study helps develop food-compatible, highly-bioavailable and sustained-release iron preparations.

Plasma Exosome-Derived SENP1 May Be a Potential Prognostic Predictor for Melanoma.

OBJECTIVE: To evaluate plasma exosome-derived SUMO-specific protease (SENP)1 levels and assess their prognostic value in melanoma. PATIENTS AND METHODS: We extracted exosomes from the plasma of 126 melanoma patients, and identified them with transmission electron microscopy, nanoparticle tracking analysis and western blotting. The plasma exosome-derived SENP1 levels of melanoma patients and healthy controls were detected with ELISA. RESULTS: Plasma exosome-derived SENP1 levels in melanoma patients were significantly upregulated than in healthy controls (P < 0.001). Plasma exosome-derived SENP1 levels in melanoma patients with tumor size >10 cm, located in the mucosa or viscera, with Clark level IV/V, with lymph node metastasis, and TNM stages IIb-IV were significantly higher than in patients in with tumor size <10 cm, located in the skin, with Clark level I-III, without lymph node metastasis, and TNM stages IIb-IV (all P < 0.05). Disease-free survival (DFS) and overall survival (OS) were worse in melanoma patients who had higher plasma exosome-derived SENP1 levels than lower plasma exosome-derived SENP1 levels (both P < 0.001). Area under the receiver operating characteristic curve (AUROC) of plasma exosome-derived SENP1 for predicting 3-year DFS of melanoma patients was 0.82 [95% confidence interval (CI): 0.74-0.88], with a sensitivity of 81.2% (95% CI: 69.9-89.6%) and specificity of 75.4% (95% CI: 62.2-85.9%). The AUROC of plasma exosome-derived SENP1 for predicting 3-year OS of melanoma patients was 0.76 (95% CI: 0.67-0.83), with a sensitivity of 95.7% (95% CI: 85.5-99.5%) and specificity of 62.0% (95% CI: 50.4-72.7%). CONCLUSIONS: Melanoma patients with higher plasma exosome-derived SENP1 levels had worse DFS and OS. The plasma exosome-derived SENP1 levels may be a potential prognostic predictor for 3-year DFS and 3-year OS of melanoma.

Plasma exosomal caveolin-1 predicts Poor Prognosis in Ovarian Cancer.

Objective: In this study, we aimed to evaluate the levels of plasma exosomal caveolin-1(CAV1) and determine its prognostic value in ovarian cancer patients. Patients and Methods: Exosome-rich fractions were isolated from the plasma of 155 patients with ovarian cancer. TEM, NTA and western blot analysis were used to confirm the exosome integrity and purification. Results: Compared with healthy controls, plasma exosomal CAV1 levels in ovarian cancer patient were significantly down-regulated (P < 0.001). The low plasma levels of exosomal CAV1 in ovarian cancer patient plasma were related to FIGO stages, grades and lymph node metastasis (all P < 0.01). Among all ovarian cancer patients, DFS was worse in patients who had low plasma exosomal CAV1 levels compared with that in patients with high plasma exosomal CAV1 levels (P < 0.001). The OS of patients with low plasma exosomal CAV1 levels was shorter than that in patients with high plasma exosomal CAV1 levels (P < 0.001). The AUROC of plasma exosomal CAV1 was 0.76 (95% CI: 0.68-0.82) for DFS prediction in ovarian cancer patients, with a sensitivity 52.9 (95% CI: 42.8-62.9) and a specificity 88.7 (95% CI: 77.0-95.7). For OS prediction in ovarian cancer patients, the AUROC of plasma exosomal CAV1 was 0.78 (95% CI: 0.70-0.84), with a sensitivity 65.1 (95% CI: 49.1-79.0) and a specificity 81.2 (95% CI: 72.8-88.0). Conclusions: Low exosomal CAV1 levels were closely related to the FIGO stages I/II, low grade, lymph node metastasis and prognosis of ovarian cancer patients. Plasma exosomal CAV1 may be a potential biomarker for the prognosis in ovarian cancer patients.

Involvement of Scratch2 in GalR1-mediated depression-like behaviors in the rat ventral periaqueductal gray.

Galanin receptor1 (GalR1) transcript levels are elevated in the rat ventral periaqueductal gray (vPAG) after chronic mild stress (CMS) and are related to depression-like behavior. To explore the mechanisms underlying the elevated GalR1 expression, we carried out molecular biological experiments in vitro and in animal behavioral experiments in vivo. It was found that a restricted upstream region of the GalR1 gene, from -250 to -220, harbors an E-box and plays a negative role in the GalR1 promoter activity. The transcription factor Scratch2 bound to the E-box to down-regulate GalR1 promoter activity and lower expression levels of the GalR1 gene. The expression of Scratch2 was significantly decreased in the vPAG of CMS rats. Importantly, local knockdown of Scratch2 in the vPAG caused elevated expression of GalR1 in the same region, as well as depression-like behaviors. RNAscope analysis revealed that GalR1 mRNA is expressed together with Scratch2 in both GABA and glutamate neurons. Taking these data together, our study further supports the involvement of GalR1 in mood control and suggests a role for Scratch2 as a regulator of depression-like behavior by repressing the GalR1 gene in the vPAG.

Distinct subtypes of proprioceptive dorsal root ganglion neurons regulate adaptive proprioception in mice.

Proprioceptive neurons (PNs) are essential for the proper execution of all our movements by providing muscle sensory feedback to the central motor network. Here, using deep single cell RNAseq of adult PNs coupled with virus and genetic tracings, we molecularly identify three main types of PNs (Ia, Ib and II) and find that they segregate into eight distinct subgroups. Our data unveil a highly sophisticated organization of PNs into discrete sensory input channels with distinct spatial distribution, innervation patterns and molecular profiles. Altogether, these features contribute to finely regulate proprioception during complex motor behavior. Moreover, while Ib- and II-PN subtypes are specified around birth, Ia-PN subtypes diversify later in life along with increased motor activity. We also show Ia-PNs plasticity following exercise training, suggesting Ia-PNs are important players in adaptive proprioceptive function in adult mice.

Orthophosphate affects iron(III) bioavailability via a mechanism involving stabilization and delivery of ferric hydroxide-phosphate nanoparticles.

Orthophosphate is endogenously present in gastrointestinal fluids and increasingly ingested as additives in processed foods. However, its effect and mechanism of action on iron bioavailability remains controversial and largely unknown. Here, at initial dissolved P/Fe ratios ((P/Fe)init) ≥ 0.6, orthophosphate completely prevents hydrolytic Fe(III) precipitation at neutral pH by mediating the formation of negatively-charged (≈-29 mV ζ-potential) ferric hydroxide-phosphate nanoparticles (Fe(OH)P-NPs) consisting of ≈3.8-nm-diameter monomers. Fe(OH)P-NPs have decreased size and Fe/P ratio with increasing (P/Fe)init. Acidic pH and balanced salts in intestinal fluid counteract orthophosphate-mediated Fe(III) solubilization by weakening colloidal stability of Fe(OH)P-NPs. Protein digests from egg white, whey, casein, and fish muscle aid Fe(III) solubilization in intestinal fluid by stabilizing Fe(OH)P-NPs with casein digest displaying the highest Fe(III)-solubilizing capacity, and in calcein-fluorescence-quenching assay, deliver nanoparticulate Fe(III) to polarized Caco-2 cells via divalent-metal-transporter-1-dependent or endocytic pathways. Overall, our study provides a new paradigm for understanding orthophosphate's role in iron bioavailability.

The Change of Systemic Immune-Inflammation Index Independently Predicts Survival of Colorectal Cancer Patients after Curative Resection.

BACKGROUND: The systemic immune-inflammation index (SII) has an important role in predicting survival in some solid tumors. However, little information is available concerning the change of the SII (∆SII) in colorectal cancer (CRC) after curative resection. This study was designed to evaluate the role of ∆SII in CRC patients who received surgery. METHODS: A total 206 patients were enrolled in this study. Clinicopathologic characteristics and survival were assessed. The relationships between overall survival (OS), disease-free survival (DFS), and ∆SII were analyzed with both univariate Kaplan-Meier and multivariate Cox regression methods. RESULTS: Based on the patient data, the receiver operating characteristic (ROC) optimal cutoff value of ∆SII was 127.7 for OS prediction. The 3-year and 5-year OS rates, respectively, were 60.4% and 36.7% in the high-∆SII group (>127.7) and 87.6% and 79.8% in the low-∆SII group (≤127.7). The 3-year and 5-year DFS rates, respectively, were 54.1% and 34.1% in the high-∆SII group and 80.3% and 78.5% in the low-∆SII group. In the univariate analysis, smoking, pathological stages III-IV, high-middle degree of differentiation, lymphatic invasion, vascular invasion, and the high-ΔSII group were associated with poor OS. Adjuvant therapy, pathological stages III-IV, vascular invasion, and ΔSII were able to predict DFS. Multivariate analysis revealed that pathological stages III-IV (HR = 0.442, 95% CI = 0.236-0.827, p = 0.011), vascular invasion (HR = 2.182, 95% CI = 1.243-3.829, p = 0.007), and the high-ΔSII group (HR = 4.301, 95% CI = 2.517-7.350, p < 0.001) were independent predictors for OS. Adjuvant therapy (HR = 0.415, 95% CI = 0.250-0.687, p = 0.001), vascular invasion (HR = 3.305, 95% CI = 1.944-5.620, p < 0.001), and the high-ΔSII group (HR = 4.924, 95% CI = 2.992-8.102, p < 0.001) were significant prognostic factors for DFS. CONCLUSIONS: The present study demonstrated that ∆SII was associated with the clinical outcome in CRC patients undergoing curative resection, supporting the role of ∆SII as a prognostic biomarker.

Increased hippocampal TrkA expression ameliorates cranial radiation­induced neurogenesis impairment and cognitive deficit via PI3K/AKT signaling.

Cognitive deficit is one of the most serious complications of cranial radiotherapy of head and neck cancers. However, the underlying mechanism of this cognitive impairment remains unclear. In the present study, the role of tropomyosin receptor kinase A (TrkA) and its ligand neurotrophin nerve growth factor (NGF) were investigated following whole­brain irradiation (WBI). Young male Sprague­Dawley rats underwent WBI at a single dose of 10 Gy. WBI was determined to result in notable memory decline and substantial neurogenesis impairment in the hippocampus 3 months post­irradiation. Compared with the control group, TrkA protein expression was greater in irradiated rats 1 week after WBI, which then decreased significantly by the 3­month time­point. However, no difference in NGF expression was observed from 1 day to 3 months post­WBI. Overexpression of hippocampal TrkA in rats using adeno­associated virus ameliorated memory decline induced by irradiation. Additionally, upregulating TrkA expression rescued irradiation­induced hippocampal precursor cell proliferation and promoted neurogenesis. PI3K, Akt and ERK1/2 phosphorylation were also revealed to be significantly inhibited by WBI, which was ameliorated by TrkA overexpression. Findings of the present study indicated that the TrkA­dependent signaling pathway may serve a critical role in radiotherapy­induced cognitive deficit and impairments in neurogenesis.

Collagen Hydrolysate Corrects Anemia in Chronic Kidney Disease via Anti-Inflammatory Renoprotection and HIF-2α-Dependent Erythropoietin and Hepcidin Regulation.

Anemia is a common chronic kidney disease (CKD) complication contributing to increased morbidity and mortality. Collagen-based traditional Chinese nutraceuticals have long been used in antianemic therapies. This study aims to investigate the therapeutic effectiveness of porcine collagen hydrolysate (CH) and its underlying mechanism in the treatment of renal anemia by using adenine-induced CKD mice, RAW264.7 macrophages, and HepG2 hepatoma cells, with prolyl-hydroxyproline as a reference compound for collagen-derived hydroxyproline-containing di-/tripeptides. CH was found to alleviate renal filtering dysfunction, systemic and kidney inflammation, liver hepcidin overproduction and anemia and to increase erythropoietin production and hypoxia inducible factor (HIF)-2α stability in liver and kidney in CKD mice. Prolyl-hydroxyproline exerted direct anti-inflammatory effects on lipopolysaccharide-activated macrophages and elicited stimulating and inhibiting activities on erythropoietin expression and hepcidin overproduction, respectively, in HepG2 cells by HIF-2α activation. Overall, CH was effective in correcting renal anemia via anti-inflammatory renoprotection and HIF-2α-dependent erythropoietin and hepcidin regulation.