Due to the emergence of highly pathogenic and oseltamivir-resistant influenza viruses, there is an urgent need to develop new anti-influenza agents. Herein, five subseries of oseltamivir derivatives ...were designed and synthesized to improve their activity toward drug-resistant viral strains by further exploiting the 150-cavity in the neuraminidases (NAs). The bioassay results showed that compound 21h exhibited antiviral activities similar to or better than those of oseltamivir carboxylate (OSC) against H5N1, H5N2, H5N6, and H5N8. Besides, 21h was 5- to 86-fold more potent than OSC toward N1, N8, and N1-H274Y mutant NAs in the inhibitory assays. Computational studies provided a plausible rationale for the high potency of 21h against group-1 and N1-H274Y NAs. In addition, 21h demonstrated acceptable oral bioavailability, low acute toxicity, potent antiviral activity in vivo, and high metabolic stability. Overall, the above excellent profiles make 21h a promising drug candidate for the treatment of influenza virus infection.
Total polyphenols and flavonoids content, phenolics profile by HPLC, and antioxidant activity of ten fruit beer produced adding fruits during the fermentation process were analyzed. The fruits were: ...cherry, raspberry, peach, apricot, grape, plum, orange and apple. Antioxidant activity, total polyphenols and flavonoids content were considerably higher in most of the fruit beers in respect to conventional, no-fruit beers. Cherries beers exhibit the highest values, followed by grape, plum and orange beers. An enrichment was observed in catechin and quercetin content in all fruit beers examined. Myricetin and resveratrol were also detected in most of the fruit beers. Among phenolic acids, an enrichment in chlorogenic, neochlorogenic, p-coumaric and caffeic acids was measured in most of the fruit beers in respect to conventional beers. Our findings show that fruits addition during the fermentation process considerably increased the antioxidant activity of beer and qualitatively and quantitatively improved its phenolics profile.
•Fruits addition affects antioxidant activity and phenolics content of beer.•Fruits beers showed stronger antioxidant activity compared to conventional non-fruits beers.•Higher content of bioactive compounds was measured in fruits beers in respect to non-fruits beers.•Cherries, grape, plum and orange beers had the highest phenolics level and antioxidant activity.•Catechin, quercetin, myricetin, resveratrol and chlorogenic acids were detected in fruits beers.
•The aim of this study was to systematically review the concentration range of major Fatty Acids in human milk at various lactation stages.•The quality of included literature was high, assessed by ...using the agency for health care research and quality (AHRQ) scale.•These findings could shed light on the dynamic change progress of major Fatty Acids metabolism, potentially enhance the knowledge of lactation biology, and improve infant feeding practices to meet the needs of infants.
Fatty acids (FAs) in human milk are important nutrients for infants. They play important roles in energy supply, nervous system development, and metabolic function maintenance. However, how the composition of major milk FAs change with lactation stages remains controversial.
To systematically review the concentration range of major FAs in human milk at various lactation stages.
A total of 12 papers involving 50 sets of data with 3507 participants were reviewed according to the PRISMA checklist and flow diagram. The inclusion criteria was the literatures had the FAs contents in breast milk of healthy lactation mothers at three lactation stages and the dietary patterns could be calculated. The exclusion criteria were: the studies were duplicates, were unrelated to dietary patterns or breast milk composition, and/or the study populations were unhealthy. We searched PubMed, the China National Knowledge Infrastructure, WanFang, and Web of science. Agency for Health Care Research and Quality (AHRQ) was used to assess the bias of studies. The mean values of polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA), α-linolenic acid (ALA), linoleic acid (LA), monounsaturated fatty acids (MUFAs), and saturated fatty acids (SFAs, including lauric acid and palmitic acid), in human milk at three lactation stages (colostrum 1–7 d, transitional milk 8–14 d, mature milk 15 d–3 mo) of healthy lactating women were investigated in terms of the high protein dietary pattern. Publication biases were evaluated by Egger's test.
According to the percentage in total fat of colostrum, transitional milk, and mature milk (% wt/wt), respectively, the results showed that PUFA (25.72%, 24.92%, and 22.69%), AA (0.85%, 0.76%, and 0.59%), DHA (0.53%, 0.47%, and 0.39%), EPA (0.15%, 0.10%, and 0.10%), and MUFA (37.39%, 37.21%, and 36.14%) contents in breast milk decreased with lactation, while another two PUFA forms, LA (17.47%, 17.82%, and 17.48%), and ALA (1.09%, 1.39%, and 1.24%) arrived at a peak in the transitional milk and then decreased in the mature milk, SFA (37.46%, 38.64%, and 40.52%), and lauric acid contents (2.78%, 4.91%, and 4.97%) increased with the lactation stages.
These findings could shed light on the dynamic change progress of major FA metabolism, potentially enhancing the knowledge of lactation biology, and improving infant feeding practices to meet their needs.
Non-volatile organic acids and amino acids are important flavor compounds in Pixian broad-bean paste, which is a traditional Chinese seasoning product. In this study, non-volatile organic acids, ...formed in the broad-bean paste due to the metabolism of large molecular compounds, are qualitatively and quantitatively determined by high-performance liquid chromatography (HPLC). Amino acids, mainly produced by hydrolysis of soybean proteins, were determined by the amino acid automatic analyzer. Results indicated that seven common organic acids and eighteen common amino acids were found in six Pixian broad-bean paste samples. The content of citric acid was found to be the highest in each sample, between 4.1 mg/g to 6.3 mg/g, and malic acid were between 2.1 mg/g to 3.6 mg/g ranked as the second. Moreover, fumaric acid was first detected in fermented bean pastes albeit with a low content. For amino acids, savory with lower sour taste including glutamine (Gln), glutamic acid (Glu), aspartic acid (Asp) and asparagines (Asn) were the most abundant, noted to be 6.5 mg/g, 4.0 mg/g, 6.4 mg/g, 4.9 mg/g, 6.2 mg/g and 10.2 mg/g, and bitter taste amino acids followed. More importantly, as important flavor materials in Pixian broad-bean paste, these two groups of substances are expected to be used to evaluate and represent the flavor quality of Pixian broad-bean paste. Moreover, the results revealed that citric acid, glutamic acid, methionine and proline were the most important flavor compounds. These findings are agreat contribution for evaluating the quality and further assessment of Pixian broad-bean paste.
Desaturation of dietary α-linolenic acid (ALA) to omega-3 (n-3) long-chain fatty acids (FAs) is mediated through FA desaturases (FADS1-FADS2) and may be influenced by dietary FA composition.
We ...investigated the effects of diets enriched in flaxseed oil (FXCO) or high-oleic acid canola oil (HOCO) compared with a Western diet (WD) and FADS1-FADS2 single nucleotide polymorphisms (SNPs) on plasma FAs and U-(13)CALA metabolism.
In a randomized crossover design, 36 hyperlipidemic subjects consumed 3 isoenergetic diets enriched in FXCO (20.6 g ALA/d), HOCO (2.4 g ALA/d), or WD (1.3 g ALA/d) for 4 wk. On day 27, blood was sampled 0, 24, and 48 h after the subjects (n = 26) consumed 45 mg U-(13)CALA. The subjects were genotyped for 4 FADS SNPs.
FXCO increased (P < 0.001) plasma ALA, EPA, and docosapentaenoic acid (DPA), with no change in DHA compared with the HOCO or WD diets. At 24 and 48 h, U-(13)CALA recovered as plasma (13)CEPA and (13)CDPA were lower (P < 0.001) after the FXCO diet than after the HOCO and WD diets. No change in (13)CDHA was observed between diets. Minor allele homozygotes of rs174545, rs174583, rs174561, and rs174537 had lower (P < 0.05) plasma EPA, arachidonic acid (AA), EPA/ALA, and AA/linoleic acid compositions and lower (P < 0.05) plasma (13)CEPA enrichment at 24 and 48 h in comparison with carriers of the major allele after all diets. SNPs were not associated with plasma composition of DHA or (13)CDHA enrichment.
An increase in ALA intake resulting in increased plasma EPA composition may be cardioprotective, especially in minor allele homozygotes. This trial was registered at www.clinicaltrials.gov as NCT00927199.
Fish oil contains a complex mixture of omega-3 fatty acids, which are predominantly eicosapentaenoic acid (EPA), docosapentaenoic acid, and docosahexaenoic acid (DHA). Each of these omega-3 fatty ...acids has distinct biological effects that may have variable clinical effects. In addition, plasma levels of omega-3 fatty acids are affected not only by dietary intake, but also by the polymorphisms of coding genes fatty acid desaturase 1-3 for the desaturase enzymes that convert short-chain polyunsaturated fatty acids to long-chain polyunsaturated fatty acids. The clinical significance of this new understanding regarding the complexity of omega-3 fatty acid biology is the purpose of this review.
FADS polymorphisms that result in either lower levels of long-chain omega-3 fatty acids or higher levels of long-chain omega-6 polyunsaturated fatty acids, such as arachidonic acid, are associated with dyslipidemia and other cardiovascular risk factors. EPA and DHA have differences in their effects on lipoprotein metabolism, in which EPA, with a more potent peroxisome proliferator-activated receptor-alpha effect, decreases hepatic lipogenesis, whereas DHA not only enhances VLDL lipolysis, resulting in greater conversion to LDL, but also increases HDL cholesterol and larger, more buoyant LDL particles.
Overall, these results emphasize that blood concentrations of individual long-chain polyunsaturated fatty acids, which reflect both dietary intake and metabolic influences, may have independent, but also complementary- biological effects and reinforce the need to potentially provide a complex mixture of omega-3 fatty acids to maximize cardiovascular risk reduction.
BACKGROUND: Human in vivo data on dietary determinants of α-linolenic acid (ALA; 18:3n-3) metabolism are scarce. OBJECTIVE: We examined whether intakes of ALA or linoleic acid (LA; 18:2n-6) or their ...ratio influences ALA metabolism. DESIGN: During 4 wk, 29 subjects received a control diet (7% of energy from LA, 0.4% of energy from ALA, ALA-to-LA ratio = 1:19). For the next 6 wk, a control diet, a low-LA diet (3% of energy from LA, 0.4% of energy from ALA, ratio = 1:7), or a high-ALA diet (7% of energy from LA, 1.1% of energy from ALA, ratio = 1:7) was consumed. Ten days before the end of each dietary period, U-¹³CALA was administered orally for 9 d. ALA oxidation was determined from breath. Conversion was estimated by using compartmental modeling of ¹³C- and ¹²Cn-3 fatty acid concentrations in fasting plasma phospholipids. RESULTS: Compared with the control group, ALA incorporation into phospholipids increased by 3.6% in the low-LA group (P = 0.012) and decreased by 8.0% in the high-ALA group (P < 0.001). In absolute amounts, it increased by 34.3 mg (P = 0.020) in the low-LA group but hardly changed in the high-ALA group. Nearly all ALA from the plasma phospholipid pool was converted into eicosapentaenoic acid. Conversion of eicosapentaenoic acid into docosapentaenoic acid and docosahexaenoic acid hardly changed in the 3 groups and was <0.1% of dietary ALA. In absolute amounts, it was unchanged in the low-LA group, but increased from 0.7 to 1.9 mg (P = 0.001) in the high-ALA group. ALA oxidation was unchanged by the dietary interventions. CONCLUSION: The amounts of ALA and LA in the diet, but not their ratio, determine ALA conversion.
Recently, the European Food Safety Authority asserted that arachidonic acid (ARA) is an optional nutrient for the term infant even when docosahexaenoic acid (DHA) is present. The brief rationale is ...based on an explicit, widespread misapplication of the concept of “essential fatty acids” to linoleic acid that implies it is uniquely required as a nutrient per se. Linoleic acid prevents acute clinical symptoms caused by polyunsaturated fatty acid–deficient diets and is the major precursor for ARA in most human diets. Experimental diets with ARA as the sole n-6 similarly prevent symptoms but at a lower energy percentage than linoleic acid and show ARA is a precursor for linoleic acid. The absence of consistent evidence of ARA benefit from randomized controlled trials is apparently an issue as well. This review highlights basic and clinical research relevant to ARA requirements as an adjunct to DHA in infancy. ARA is a major structural central nervous system component, where it rapidly accumulates perinatally and is required for signaling. Tracer studies show that ARA-fed infants derive about half of their total body ARA from dietary preformed ARA. Clinically, of the 3 cohorts of term infants studied with designs isolating the effects of ARA (DHA-only vs DHA+ARA), none considered ARA-specific outcomes such as vascular or immune function; the study with the highest ARA level showed significant neurocognitive benefit. All breastfed term infants of adequately nourished mothers consume both DHA and ARA. The burden of proof to substantially deviate from the composition of breastmilk is greater than that available from inherently empirical human randomized controlled trial evidence. Infant formulas with DHA but without ARA risk harm from suppression of ARA-mediated metabolism manifest among the many unstudied functions of ARA.
•Acids contributed more than 90% of the total volatile profiles of dried jujubes.•Freeze drying was most effective in preserving acidic volatile compounds.•Jujube dried by DIC showed greater ...diversity in volatile compounds (26).•GC–MS coupled with an e-nose provided comprehensive aroma analysis of dried jujubes.
Volatile compounds in Chinese jujubes dried by different methods – hot-air (HAD), heat-pump (HPD), infrared radiation (IRD), vacuum (VD), vacuum freeze (VFD) and instant controlled pressure drop (DIC) drying – were analyzed using GC–MS, MOS e-nose, and flash GC e-nose. Acids comprised more than 90% of the aroma compounds in the dried jujubes, of which acetic, butanoic, propanoic, hexanoic, octanoic and decanoic acids were the most common. Jujubes dried using VFD had the highest content of total aroma compounds (1061.6 µg/kg), while DIC-dried jujubes had the most diverse profile (26 species). HPD-, IRD-, HAD- and VD-dried jujubes had similar aroma profiles based on GC–MS and flash GC e-nose results. Although the results of GC–MS, MOS e-nose, and flash GC e-nose were significant different (p < 0.05), their combination could characterize aroma profiles more comprehensively.
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