Characterization of hOAT4 and mOat5 as functional orthologs for renal anion uptake and efflux transport.

Organic anions (OA) are compounds including drugs or toxicants that are negatively charged at physiological pH and are typically transported by Organic Anion Transporters (OATs). Human OAT4 (SLC22A11) is expressed in the apical membrane of renal proximal tubules. Although there is no rodent ortholog of hOAT4, rodents express Oat5 (Slc22a19), an anion exchanger that is also localized to the apical membrane of renal proximal tubule cells. The purpose of this study was to determine the functional similarity between mouse Oat5 and human OAT4. Chinese hamster ovary (CHO) cells expressing SLC22A11 or Slc22a19 were used to assess the transport characteristics of radiolabeled ochratoxin (OTA). We determined the kinetics of OTA transport; the resulting Kt and Jmax values were very similar for both hOAT4 and mOat5: Kt 3.9 and 7.2 µM, respectively, & Jmax 4.4 and 3.9 pmol/cm2, respectively. For the profile of OTA inhibition by OAs, IC50 values were determined for several clinically important drugs and toxicants. The resulting IC50 values ranged from 9 µM for indomethacin to ~600 µM for the diuretic hydrochlorothiazide. We measured the efflux of OTA from preloaded cells; both hOAT4 and mOat5 supported the efflux of OTA. These data support the hypothesis that OAT4 and Oat5 are functional orthologs and share selectivity for OTA both for reabsorption and secretion. Significance Statement This study compares the selectivity profile between human OAT4 and mouse Oat5. Our data revealed a similar selectivity profile for OTA reabsorption and secretion by these two transporters, thereby supporting the hypothesis that hOAT4 and mOat5, while not genetic orthologs, behave as functional orthologs for both uptake and efflux. These data will be instrumental in selecting an appropriate animal model when studying the renal disposition of anionic drugs and toxicants.

Low molecular weight acids and OATP1B mediated hepatic clearance: In vitro and in vivo evaluation using novel hypoxia-inducible factor prolyl hydroxylase inhibitors (Dustats).

Organic anion transporting polypeptide (OATP1B) plays a key role in the hepatic clearance of a majority of high molecular weight (MW) acids and zwitterions. Here, we evaluated the role of OATP1B-mediated uptake in the clearance of novel hypoxia-inducible factor prolyl hydroxylase inhibitors ("Dustats"), which are typically low MW (300-400 daltons) aliphatic carboxylic acids. Five acid dustats, namely daprodustat, desidustat, enarodustat, roxadustat and vadadustat, showed specific transport by OATP1B1/1B3 in transporter-transfected HEK293 cells. Neutral compound, molidustat, was not a substrate to OATP1B1/1B3. None of the dustats showed transport by other hepatic uptake transporters, including NTCP, OAT2 and OAT7. In the primary human hepatocytes, uptake of all acids was significantly reduced by rifampin (OATP1B inhibitor); with an estimated fraction transported by OATP1B (ft ,OATP1B) of up to >80% (daprodustat). Molidustat uptake was minimally inhibited by rifampin; and low permeability acids (desidustat and enarodustat) also showed biliary efflux in sandwich culture human hepatocytes. In vivo, intravenous pharmacokinetics of all 5 acids was significantly altered by a single-dose rifampin (30 mg/kg) in Cynomolgus monkey. Hepatic clearance (non-renal) was about 4-fold (vadadustat) to >11-fod (daprodustat and roxadustat) higher in control group compared to rifampin-treated subjects. In vivo ft ,OATP1B was estimated to be ~70-90%. In the case of molidustat, rifampin had a minimal effect on overall clearance. Rifampin also considerably reduced volume of distribution of daprodustat and roxadustat. Overall, OATP1B significantly contribute to the hepatic clearance and pharmacokinetics of several dustats, which are low MW carboxylic acids. OATP1B activity should therefore by evaluated in this property space. Significance Statement Our in vitro and in vivo results suggest that OATP1B-mediated hepatic uptake play a significant role in the pharmacokinetics of low MW acidic dustats, which are being developed or approved for the treatment of anemia in chronic kidney disease. Significant active uptake mechanisms are not apparent for the neutral compound, molidustat. Characterization of uptake mechanisms is therefore important in predicting human pharmacokinetics and evaluating drug-drug interactions for low MW acids.

Use of ancient grains for the management of diabetes mellitus: A systematic review and meta-analysis.

AIMS: A systematic review and meta-analysis of published randomized controlled trials was conducted to collate evidence from studies implementing ancient grains and investigate the impact of ancient grain consumption on health outcomes of patients with Diabetes Mellitus (DM). DATA SYNTHESIS: Twenty-nine randomized controlled trials were included, and 13 were meta-analyzed. Interventions ranged from 1 day to 24 weeks; most samples were affected by DM type 2 (n = 28 studies) and the ancient grains used were oats (n = 10 studies), brown rice (n = 6 studies), buckwheat (n = 4 studies), chia (n = 3 studies), Job's Tears (n = 2 studies), and barley, Khorasan and millet (n = 1 study). Thirteen studies that used oats, brown rice, and chia provided data for a quantitative synthesis. Four studies using oats showed a small to moderate beneficial effect on health outcomes including LDL-c (n = 717, MD: 0.30 mmol/l, 95% CI: 0.42 to -0.17, Z = 4.61, p < 0.05, I2 = 0%), and TC (n = 717, MD: 0.44 mmol/l, 95% CI: 0.63 to -0.24, Z = 4.40, p < 0.05, I2 = 0%). Pooled analyses of studies using chia and millet did not show significant effects on selected outcomes. CONCLUSIONS: For adults affected by DM type 2, the use of oats may improve lipidic profile. Further experimental designs are needed in interventional research to better understand the effects of ancient grains on diabetes health outcomes. PROSPERO REGISTRATION: CRD42023422386.

Ruminal methane emission and lactational performance of cows fed rapeseed cake and oats on a grass silage-based diet.

The objective of this experiment was to investigate the effect of lipid from rapeseed cake and oats on ruminal CH4 emission and lactational performance of dairy cows. Twelve lactating Nordic Red cows, of which 4 were primiparous, and averaging (±SD) 48 ± 22.9 DIM, 37.8 ± 7.14 kg/d milk yield were enrolled in a switch-back design experiment with 3 periods of 4 wk each. The cows were assigned into 6 pairs based on parity, DIM, milk yield, and BW at the beginning of the experiment. The experimental treatments were (1) rapeseed cake and oats (RSC+O), and (2) rapeseed meal and barley (RSM+B) as the concentrate feeds. Cows in each pair were randomly assigned to 1 of the 2 groups, which received the treatments in 2 different sequences (i.e., group 1 received RSC+O in period 1 and 3, and RSM+B in period 2, whereas group 2 was fed RSM+B in period 1 and 3, and RSC+O in period 2). The diets consisted of a partially mixed ration with grass silage mixed with either oats or barley, according to the treatment sequence, and the rapeseed cake or meal being mixed into a pellet with either oats or barley according to the treatments, and a mineral mix. The pellet was delivered at a fixed amount (i.e., 6 kg/d for multiparous and 5 kg/d for the primiparous cows) from the milking robot. The actual forage to concentrate ratios for RSC+O and RSM+B were 51:49 and 52:48, respectively, with NDF concentrations of 41.5% and 36.0% and CP concentrations of 17.0% and 16.7% of diet DM. Dry matter intake, milk yield, and gas exchange (with a GreenFeed system attached to the milking robot) were recorded daily, and milk composition and spot fecal samples were collected during the last week of each period. Based on feed analysis, and DMI of the cows during the experiment, the total fat content of the experimental diets was 4.1% and 2.7% of DM for RSC+O and RSM+B diets, respectively. Dry matter intake was 1.6 kg/d lower, and milk yield tended to be 1.0 kg/d greater for RSC+O versus RSM+B. There were no differences in ECM yield and milk composition between the treatments, whereas milk ME efficiency was greater for cows fed RSC+O than RSM+B. Methane yield (g/kg DMI) did not differ between treatments, but CH4 production (g/d) was 9.4% and CH4 intensity as g/kg ECM was 11.7% lower for RSC+O versus RSM+B. The lower CH4 production was likely caused by the lower DMI and fiber digestibility, observed with the RSC+O diet. In addition, the greater lipid intake also contributed to lower rate of fermentation and subsequent decrease in CH4 production. Overall, feeding rapeseed cake with oats in a grass silage-based diet increased feed efficiency while decreasing CH4 emission intensity in lactating cows. This provides a practical way of mitigating ruminal CH4 emission from dairy operations while maintaining milk production with commonly used feedstuffs in Nordic conditions.

A Comparison of Treatment of OCD Lesions of the Capitellum With Osteochondral Autograft and Allograft Transplantation.

Osteochondritis dissecans (OCD) of the capitellum occurs relatively infrequently but can be found in young overhead-throwing athletes, most commonly in baseball players and gymnasts. Although non-operative management can effectively treat stable lesions, unstable lesions can lead to debilitating symptoms of the elbow and diminished quality of life without surgical intervention. This article reviews methods of treating OCD of the capitellum categorized by stability, size, and patient characteristics, and seeks to familiarize the reader with the appropriate selection of osteochondral allograft versus autograft in treating large, unstable lesions. We complement this review with 3 case examples, each using either an osteochondral autograft or allograft, and discuss the decision-making methodology used in each case.

Three decades of rust surveys in the United States reveal drastic virulence changes in oat crown rust.

To better understand how the pathogenicity of the oat crown rust pathogen, Puccinia coronata f. sp. avenae (Pca), has changed in the United States, 30 years of USDA survey isolates (n=5,456) tested on 30-40 differential lines were analyzed for overall and Pc resistance gene specific virulence trends and correlations. Pca is incredibly pathologically diverse with 88% of races represented by a single isolate. There are a slightly higher proportion of unique races from the Northern region of the United States and for one fourth of the years, Northern region isolates were significantly more virulent than Southern isolates which supports the idea that sexual recombination in this region is mediated by the alternate host as a major factor in creating new races. However, there is also support for regular isolate movement between North and South regions as isolates in the United States are steadily accumulating virulences at a rate of 0.35 virulences per year. Virulence significantly increased for 23 and decreased for 4 of the 40 differential lines. In the past few years, virulence has reached 90% or greater for 16 differential lines. There were also strong correlations in virulence for certain Pc genes that are likely identical, allelic, or target the same or closely linked pathogen effectors (e.g. Pc39, Pc55, and Pc71), and the results were largely in concordance with recent GWAS effector studies using USDA isolate subsets. Understanding changes in Pca pathogenicity is essential for the responsible deployment and management of Pc resistance genes for sustainable and profitable oat production.

Favorable long-term clinical and radiologic outcomes with high survivorship after autologous osteochondral transplantation of the talus.

PURPOSE: To evaluate long-term clinical and radiologic outcomes of patients undergoing autologous osteochondral transplantation (AOT) for osteochondral lesions of the talus (OLT) and to perform a correlation analysis between clinical and radiologic outcomes. METHODS: Thirty-five patients with a mean age of 32.2 ± 8.9 years undergoing AOT for OLT between 1997 and 2003 were available for follow-up after an average of 19.1 ± 1.4 years. Demographic, surgical, and injury-related data were collected. After a minimum 18-year follow-up, patient-reported outcome scores (PROs) were collected, including the American Orthopaedic Foot & Ankle Society (AOFAS) score, the Foot and Ankle Outcome Score (FAOS), Tegner Activity Scale, and Visual Analogue Scale (VAS) for pain of the ankle. The Lysholm Score and VAS for pain of the knee were collected to assess donor-site morbidity. Magnetic resonance imaging scans were obtained to conduct an assessment of the replaced cartilage using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 scoring system. Any revision surgery (except symptomatic hardware removal and arthroscopic debridement) was defined as clinical failure. RESULTS: Favorable clinical and radiologic (MOCART score, 73.7 ± 16.7 points) outcomes without any donor-site morbidities were observed. Twenty-three (65.7%) patients were satisfied or very satisfied with the surgical treatment. Fourteen (40.0%) and 25 (71.4%) patients had no or minor limitations in their athletic and working performance, respectively. A significant correlation between the MOCART and the FAOS Sport and Recreational activities subscale was found (rs, 0.491; p = 0.033). Six (17.1%) patients met the criteria for clinical failure an average of 12.2 ± 6.6 years after AOT. Survival analysis demonstrated a mean estimated time of survival of 21.3 years (95% CI [19.55, 22.96]) and a 20-year survival rate of 77.9%. CONCLUSION: Autologous osteochondral transplantation to treat OLT achieves high patient satisfaction and favorable PROs with a 20-year survival rate of almost 80%. Given the high clinical efficacy of AOT, this procedure can be recommended as a safe and promising technique for the long-term therapy of OLT. LEVEL OF EVIDENCE: Level IV.

Asperulosidic Acid Ameliorates Renal Interstitial Fibrosis via Removing Indoxyl Sulfate by Up-Regulating Organic Anion Transporters in a Unilateral Ureteral Obstruction Mice Model.

Asperulosidic acid is a bioactive iridoid isolated from Hedyotis diffusa Willd. with anti-inflammatory and renal protective effects. However, its mechanism on renal interstitial fibrosis has not been elucidated yet. The present study aims to explore whether asperulosidic acid could retard renal fibrosis by reducing the circulating indoxyl sulfate (IS), which is a uremic toxin and accelerates chronic kidney disease progression by inducing renal fibrosis. In this paper, a unilateral ureteral obstruction (UUO) model of Balb/C mice was established. After the mice were orally administered with asperulosidic acid (14 and 28 mg/kg) for two weeks, blood, liver and kidney were collected for biochemical, histological, qPCR and Western blot analyses. Asperulosidic acid administration markedly reduced the serum IS level and significantly alleviated the histological changes in glomerular sclerosis and renal interstitial fibrosis. It is noteworthy that the mRNA and protein levels of the organic anion transporter 1 (OAT1), OAT3 and hepatocyte nuclear factor 1α (HNF1α) in the kidney were significantly increased, while the mRNA expressions of cytochrome P450 2e1 (Cyp2e1) and sulfotransferase 1a1 (Sult1a1) in the liver were not altered after asperulosidic acid administration. These results reveal that asperulosidic acid could accelerate the renal excretion of IS by up-regulating OATs via HNF1α in UUO mice, thereby alleviating renal fibrosis, but did not significantly affect its production in the liver, which might provide important information for the development of asperulosidic acid.

Core microbes closely related with the nutrients and flavor of sweet fermented oats (whole grain food) from China.

Increased attention has been given to whole grain and plant-based foods due to health concerns. Sweet fermented oats (SFOs) are such traditional fermented food from China. However, reports on their microbiota and relations with the nutrients and flavor were scarcely few, hindering their wider application. The comprehensive microbial composition, metabolic compounds and their correlations of representative SFOs from northwestern China were firstly investigated. Firmicutes predominated the microbial communities, followed by Proteobacteria. Weissella, Bacillus and Lactobacillus were dominant bacterial genera, biomarkers and core bacteria as well. GC-MS (Gas Chromatography-Mass Spectrometer) identified the metabolic compounds, among which the categories fatty acids and carboxylic acids most abundant. Eighteen chemicals showed significant differences among the five SFOs, including ethyl octanoate, neryl acetate, L-sorbose, diglycerol, cellotetraose etc. Fatty acids, carboxylic acids, amino acids, peptides, oligosaccharides, and monosaccharides were the key substances responsible for the unique flavor and rich nutrients in SFOs. The core bacteria were closely related to chemical acids, esters, flavone and alcohol. Pediococcus showed a negative correlation with 2,3-butanediol. SFOs were made in the laboratory with the core bacterial strains, obtaining a high abundance of nutrient chemicals and sensory evaluation value. The research provided a foundation for the improvement, further application and industrialization of SFOs.

Synbiotic microencapsulation of Lactobacillus brevis and Lactobacillus delbrueckii subsp. lactis using oats/oats brans as prebiotic for enhanced storage stability.

Potential probiotic strains, Lactobacillus delbrueckii subsp. lactis and Lactobacillus brevis were microencapsulated with their appropriate prebiotics, oat bran, and oats, respectively, selected by in vitro fermentation. The microencapsulation of these probiotics were done in an alginate matrix, with and without their appropriate prebiotics. Results showed that cells microencapsulated with the prebiotics had significantly more storage stability (p < 0.05) than free cells and cells microencapsulated without the prebiotics. The probiotic cells encapsulated with their appropriate prebiotic had improved survival rates when exposed to bile as compared to free cells. The survival of microencapsulated and free cells in the simulated gastric fluid and simulated intestinal fluid was also evaluated in this study. Microencapsulated probiotics, along with an appropriate prebiotic, were found to be more stable in bile, simulated gastric fluid and simulated intestinal fluid. Interestingly, this is the first work to use prebiotic such as oats and the oat bran to prepare the synbiotic microsphere.

De novo genome assembly and functional annotation for Fusarium langsethiae.

BACKGROUND: Fusarium langsethiae is a T-2 and HT-2 mycotoxins producing species firstly characterised in 2004. It is commonly isolated from oats in Northern Europe. T-2 and HT-2 mycotoxins exhibit immunological and haemotological effects in animal health mainly through inhibition of protein, RNA and DNA synthesis. The development of a high-quality and comprehensively annotated assembly for this species is therefore essential in providing the molecular understanding and the mechanism of T-2 and HT-2 biosynthesis in F. langsethiae to help develop effective control strategies. RESULTS: The F. langsethiae assembly was produced using PacBio long reads, which were then assembled independently using Canu, SMARTdenovo and Flye. A total of 19,336 coding genes were identified using RNA-Seq informed ab-initio gene prediction. Finally, predicting genes were annotated using the basic local alignment search tool (BLAST) against the NCBI non-redundant (NR) genome database and protein hits were annotated using InterProScan. Genes with blast hits were functionally annotated with Gene Ontology. CONCLUSIONS: We developed a high-quality genome assembly of a total length of 59 Mb and N50 of 3.51 Mb. Raw sequence reads and assembled genome is publicly available and can be downloaded from: GenBank under the accession JAFFKB000000000. All commands used to generate this assembly are accessible via GitHub: https://github.com/FadyMohareb/fusarium_langsethiae .

OMICS in Fodder Crops: Applications, Challenges, and Prospects.

Biomass yield and quality are the primary targets in forage crop improvement programs worldwide. Low-quality fodder reduces the quality of dairy products and affects cattle's health. In multipurpose crops, such as maize, sorghum, cowpea, alfalfa, and oat, a plethora of morphological and biochemical/nutritional quality studies have been conducted. However, the overall growth in fodder quality improvement is not on par with cereals or major food crops. The use of advanced technologies, such as multi-omics, has increased crop improvement programs manyfold. Traits such as stay-green, the number of tillers per plant, total biomass, and tolerance to biotic and/or abiotic stresses can be targeted in fodder crop improvement programs. Omic technologies, namely genomics, transcriptomics, proteomics, metabolomics, and phenomics, provide an efficient way to develop better cultivars. There is an abundance of scope for fodder quality improvement by improving the forage nutrition quality, edible quality, and digestibility. The present review includes a brief description of the established omics technologies for five major fodder crops, i.e., sorghum, cowpea, maize, oats, and alfalfa. Additionally, current improvements and future perspectives have been highlighted.

Effect of oat or rice flour on pulse-induced gastrointestinal symptoms and breath hydrogen in subjects sensitive to pulses and controls - a randomised cross-over trial with two parallel groups.

Pulses are healthy and sustainable but induce gut symptoms in people with a sensitive gut. Oats, on the contrary, have no fermentable oligo- di-, monosaccharides and polyols compounds and are known for the health effects of their fibres. This 4-day cross-over trial investigated the effects of oat and rice flour ingested with pulses on gut symptoms and exhaled gases (4th day only) in subjects with a sensitive gut or IBS (n 21) and controls (n 21). The sensitive group perceived more symptoms after both meals than controls (P = 0·001, P = 0·001). Frequency, intensity or quality of the symptoms did not differ between meals during the first 3 d in either group. More breath hydrogen was produced after an oat than rice containing meal in both groups (AUC, P = 0·001, P = 0·001). No between-group difference was seen in breath gases. During day 4, both sensitive and control groups perceived more symptoms after the oat flour meal (P = 0·001, P = 0·0104, respectively) as mainly mild flatulence. No difference in moderate or severe symptoms was detected. Increased hydrogen production correlated to a higher amount of perceived flatulence after the oat flour meal in both the sensitive and the control groups (P = 0·042, P = 0·003, respectively). In summary, ingestion of oat flour with pulses increases breath hydrogen levels compared with rice flour, but gastrointestinal symptoms of subjects sensitive to pulses were not explained by breath hydrogen levels. Additionally, consumer mindsets towards pulse consumption and pulse-related gut symptoms were assessed by an online survey, which implied that perceived gut symptoms hinder the use of pulses in sensitive subjects.

Effect of oat supplementation interventions on cardiovascular disease risk markers: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Oat supplementation interventions (OSIs) may have a beneficial effect on cardiovascular disease (CVD) risk. However, dietary background can modulate such effect. This systematic review assesses the effects of OSIs on CVD risk markers among adults, accounting for different dietary backgrounds or control arms. METHODS: We included randomized clinical trials (RCTs) that assessed the effect of oat, oat beta-glucan-rich extracts or avenanthramides on CVD risk markers. RESULTS: Seventy-four RCTs, including 4937 predominantly hypercholesterolemic, obese subjects, with mild metabolic disturbances, were included in the systematic review. Of these, 59 RCTs contributed to the meta-analyses. Subjects receiving an OSI, compared to control arms without oats, had improved levels of total cholesterol (TC) [weighted mean difference and (95% CI) - 0.42 mmol/L, (- 0.61; - 0.22)], LDL cholesterol [- 0.29 mmol/L, (- 0.37; - 0.20)], glucose [- 0.25 nmol/L, (- 0.36; - 0.14)], body mass index [- 0.13 kg/m2, (- 0.26; - 0.01)], weight [- 0.94 kg, (- 1.84: - 0.05)], and waist circumference [- 1.06 cm, (- 1.85; - 0.27)]. RCTs on inflammation and/or oxidative stress markers were scarce and with inconsistent findings. RCTs comparing an OSI to heterogeneous interventions (e.g., wheat, eggs, rice, etc.), showed lowered levels of glycated haemoglobin, diastolic blood pressure, HDL cholesterol and apolipoprotein B. The majority of included RCTs (81.1%) had some concerns for risk of bias. CONCLUSION: Dietary OSIs resulted in lowered levels of blood lipids and improvements in anthropometric parameters among participants with predominantly mild metabolic disturbances, regardless of dietary background or control. Further high-quality trials are warranted to establish the role of OSIs on blood pressure, glucose homeostasis and inflammation markers.

Above-Ground Biomass Estimation in Oats Using UAV Remote Sensing and Machine Learning.

Current strategies for phenotyping above-ground biomass in field breeding nurseries demand significant investment in both time and labor. Unmanned aerial vehicles (UAV) can be used to derive vegetation indices (VIs) with high throughput and could provide an efficient way to predict forage yield with high accuracy. The main objective of the study is to investigate the potential of UAV-based multispectral data and machine learning approaches in the estimation of oat biomass. UAV equipped with a multispectral sensor was flown over three experimental oat fields in Volga, South Shore, and Beresford, South Dakota, USA, throughout the pre- and post-heading growth phases of oats in 2019. A variety of vegetation indices (VIs) derived from UAV-based multispectral imagery were employed to build oat biomass estimation models using four machine-learning algorithms: partial least squares (PLS), support vector machine (SVM), Artificial neural network (ANN), and random forest (RF). The results showed that several VIs derived from the UAV collected images were significantly positively correlated with dry biomass for Volga and Beresford (r = 0.2-0.65), however, in South Shore, VIs were either not significantly or weakly correlated with biomass. For Beresford, approximately 70% of the variance was explained by PLS, RF, and SVM validation models using data collected during the post-heading phase. Likewise for Volga, validation models had lower coefficient of determination (R2 = 0.20-0.25) and higher error (RMSE = 700-800 kg/ha) than training models (R2 = 0.50-0.60; RMSE = 500-690 kg/ha). In South Shore, validation models were only able to explain approx. 15-20% of the variation in biomass, which is possibly due to the insignificant correlation values between VIs and biomass. Overall, this study indicates that airborne remote sensing with machine learning has potential for above-ground biomass estimation in oat breeding nurseries. The main limitation was inconsistent accuracy in model prediction across locations. Multiple-year spectral data, along with the inclusion of textural features like crop surface model (CSM) derived height and volumetric indicators, should be considered in future studies while estimating biophysical parameters like biomass.

Effect of Germination on the Avenanthramide Content of Oats and Their in Vitro Antisensitivity Activities.

In this study, a method, based on an ultraperformance liquid chromatography coupled with high-field quadrupole orbitrap high-resolution mass spectrometry (UHPLC-QE-HF-HRMS) platform, was established for the trace determination of three major avenanthramides (AVNs). The MS conditions for determining the AVNs were optimized, and the cracking methods of avenanthramides were analyzed. The linear range of the results and the correlation coefficient were 1−2000 µg/L and >0.996, respectively. Further, the established method was employed for the determination of the AVN contents of oats at different germination times, and the results indicated that the AVN contents of Zaohua and Bayou oats increased 19.26 and 6.09 times, respectively, after germination. The total AVN content of both oat varieties reached a maximum on the fifth day of germination (153.51 ± 4.08 and 126.30 ± 3.33 µg/g for the Zaohua and Bayou oats, respectively). Furthermore, this study investigated the antiallergic and antioxidant activities of the germinated oats via hyaluronidase inhibition and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-scavenging assays. The antiallergic and DPPH-scavenging abilities of the ungerminated forms of both oat varieties were weaker. However, on the fifth day of germination, the inhibition rate of anthranilamide hyaluronidase reached 72.7% and 67.3% for the Zaohua and Bayou oat varieties, respectively. The antiallergic abilities of the oats increased significantly on the fifth day of germination in terms of their antiallergic capacities and DPPH clearance (82.67% and 77.64% for the Zaohua and Bayou oats, respectively), and the two indicators exhibited similar trends. These findings demonstrated that AVNs exhibit good antisensitivity and antioxidation properties, and the antisensitivity effect correlated positively with the AVN content.

Oat polyphenol avenanthramide-2c confers protection from oxidative stress by regulating the Nrf2-ARE signaling pathway in PC12 cells.

Accumulating evidence has demonstrated that cellular antioxidant systems play essential roles in retarding oxidative stress-related diseases, such as Parkinson's disease. Because nuclear factor erythroid 2-related factor 2 (Nrf2) is a chief regulator of cellular antioxidant systems, small molecules with Nrf2-activating ability may be promising neuroprotective agents. Avenanthramide-2c (Aven-2c), avenanthramide-2f (Aven-2f) and avenanthramide-2p (Aven-2p) are the most abundant avenanthramides in oats, and they have been documented to possess multiple pharmacological benefits. In this work, we synthesized these three compounds and evaluated their cytoprotective effect against oxidative stress-induced PC12 cell injuries. Aven-2c displayed the best protective potency among them. Aven-2c conferred protection on PC12 cells by scavenging free radicals and activating the Nrf2-ARE signaling pathway. Pretreatment of PC12 cells with Aven-2c efficiently enhanced Nrf2 nuclear accumulation and evoked the expression of a set of cytoprotective molecules. The mechanistic study also supports that Nrf2 activation is the molecular basis for the cellular action of Aven-2c. Collectively, this study demonstrates that Aven-2c is a potent Nrf2 agonist, shedding light on the potential usage of Aven-2c in the treatment of neuroprotective diseases.

A Systematic Review and Meta-Analysis of Randomized Controlled Trials on the Effects of Oats and Oat Processing on Postprandial Blood Glucose and Insulin Responses.

BACKGROUND: Oats are a whole grain cereal with potentially favorable effects on the postprandial glycemic response; however, the effects of oat processing on these glycemic benefits are not well understood. OBJECTIVES: The study objective was to determine the effects of differently processed oats on the postprandial blood glucose and insulin responses relative to refined grains. METHODS: Eleven electronic databases were systematically searched to identify studies published up to and including May 2019. Randomized controlled trials comparing the postprandial blood glucose and insulin responses to oats compared with any refined grain were included, so long as the available carbohydrate content of the test meals was similar. Pooled effect sizes were computed using the difference in incremental area under the curves for blood glucose and insulin following the consumption of oats compared with the refined grain control. RESULTS: Ten publications were included, with intact oat kernels studied in 3 comparisons, thick oat flakes (>0.6 mm) in 7 comparisons, and thin/quick/instant oat flakes (≤0.6 mm) in 6 comparisons. Compared with the consumption of the refined grain control, the consumption of intact oat kernels was associated with significant reductions in postprandial blood glucose (-45.5 mmol x min/L; 95% CI: -80.1, -10.9 mmol x min/L; P = 0.010) and insulin (-4.5 nmol x min/L; 95% CI: -7.1, -1.8 nmol x min/L; P = 0.001) responses; the consumption of thick oat flakes was associated with significant reductions in postprandial blood glucose (-30.6 mmol x min/L; 95% CI: -40.4, -20.9 mmol x min/L; P < 0.001) and insulin (-3.9 nmol x min/L; 95% CI: -5.3, -2.5 nmol x min/L; P < 0.001) responses; but, the consumption of thin/quick/instant oat flakes was not associated with any effects on the postprandial blood glucose and insulin responses. CONCLUSIONS: A disruption in the structural integrity of the oat kernel is likely associated with a loss in the glycemic benefits of oats.

Whole-Grain Intake and Pancreatic Cancer Risk-The Danish, Diet, Cancer and Health Cohort.

BACKGROUND: Pancreatic cancer is a highly deadly disease with a poor prognosis. There is limited knowledge about prevention of the disease; thus, identification of risk factors is important to reduce the disease incidence. OBJECTIVE: The aim of the present study was to prospectively investigate associations between incidence of pancreatic cancer and whole-grain intake measured in 2 ways: as whole-grain product intake (g whole-grain products/d) and as whole-grain intake (grams of whole grains/d). Moreover, the intake of subgroups of these was also investigated: whole-grain products (rye bread, whole-grain bread, and oatmeal/muesli) and cereals (rye, wheat, and oats). METHODS: In total, 55,995 Danish adults aged 50-64 y, of whom 446 developed pancreatic cancer (17.5 y mean follow-up), were included in the study. Detailed information on daily intake of whole-grain products was available from a validated self-administered FFQ, and intake of whole-grain cereals (wheat, rye, and oats) was estimated using information from a 24-h dietary recall. The association between the whole-grain exposures and incidence of pancreatic cancer was investigated by Cox regression analyses adjusted for potential confounders. RESULTS: Total whole-grain product intake was associated with a 7% lower incidence of pancreatic cancer per serving (50 g/d) (HR: 0.93; 95% CI: 0.86, 1.00), and in the sex-specific analyses, an inverse association was found only in men. No association was found for total whole-grain intake (per 16-g serving size; HR: 0.96; 95% CI: 0.89, 1.03). When investigating specific whole-grain products and cereals individually, none were alone associated with lower incidence of pancreatic cancer. CONCLUSION: Our findings indicate that intake of whole grains is associated with lower risk of pancreatic cancer in middle-aged men. Consuming ample amounts of whole grains may prove beneficial in terms of lowering pancreatic cancer risk.

Outcomes of Osteochondral Autograft Transplantation in Pediatric Patients With Osteochondritis Dissecans of the Capitellum.

PURPOSE: To assess the outcomes of osteochondral autograft transplantations in the treatment of osteochondritis dissecans of the capitellum in the pediatric population. METHODS: Between 2011 and 2016, 15 patients who had undergone osteochondral autograft transplantation at a mean age of 13.7 years at surgery were identified. The donor site was from the superolateral, non-weight-bearing surface of the lateral femoral condyle of the ipsilateral knee. RESULTS: Mean follow-up was 29.5 months, with no patients lost to follow-up. Mean arc of motion increased significantly from 121.9° preoperatively to 139.1° postoperatively. All 9 elite athletes returned to sports at an elite level: 7 returned to the same level of competition in the same sport, 1 retired from gymnastics due to multiple injuries but began diving at an elite level, and 1 retired from baseball unrelated to elbow symptoms but continued hockey at the same level. Of the 4 recreational athletes, all returned to sport. There were no intraoperative complications. The symptoms resolved completely in all but 2 patients, who improved over their preoperative condition. The donor site knee pain resolved in all patients at an average of 2.3 months. Postoperative imaging demonstrated the healing and incorporation of the plug in all patients. CONCLUSIONS: In the treatment of osteochondritis dissecans of the capitellum, osteochondral autograft transplantation demonstrates excellent clinical and radiographic outcomes, with minimal short-term donor site morbidity and a high level of return to the sport. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.