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Neurocognitive impairment (NCI) and gut microbiota dysbiosis are prevalent in patients with HIV infection. Docosahexanoic acid (DHA) supplementation may alleviate multiple neurocognitive diseases symptoms and plays important role in regulating gut microbiota. However, it is not known whether DHA algae oil supplements can alleviate neurocognitive impairment (NCI) and regulate gut microbiota and fecal metabolites. A randomized, double-blind, placebo-controlled trial was performed on 68 HIV-infected patients with NCI. Participants were randomized to receive a 3.15 g daily DHA algae oil supplement or placebo for 6 months. We collected blood and fecal samples from these patients before and after the trial. Mini mental state examination (MMSE) and neuropsychological tests (NP tests) were administered to assess the cognitive status of participants. The influence of DHA algae oil on the gut microbiota, fecal metabolomics, plasma proinflammatory, and oxidative stress factors was also investigated. There were no significant changes in NCI according to global diagnosis score (GDS) and MMSE score within the two groups, while patients receiving DHA had improvement in several blood lipids, pro-inflammatory and oxidative stress factors. The DHA supplement increased α-diversity indexes, increased abundances of Blautia, Bifidobacterium, Dorea, Lactobacillus, Faecalibacterium, Fusobacterium, and Agathobacter, and decreased abundances of Bacteroides and Prevotella_9. Furthermore, DHA supplement was correlated with improved fecal lipid metabolites as indicated by ceramides, bile acids, glycerophospholipids. In addition, the DHA supplement was associated with altered cholesterol metabolism and purine metabolism pathways. A daily supplement of DHA algae oil for 6 months has been shown to promote favorable transformations in gut microbiota, profiles of fecal metabolomic, and factors responsible for proinflammatory and oxidative stress, which might be beneficial for the prognosis of HIV-infected patients with NCI in the long-term.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04242004, identifier: NCT04242004.

Docosahexaenoic acid (DHA) is an essential ω-3 long-chain polyunsaturated fatty acid (LCPUFA) and represents the dominant structural fatty acid in the retina and in the brain's gray matter. Due to its active participation in the development of the nervous system, DHA is one of the most studied LCPUFA and is currently considered a critical nutrient during pregnancy and breastfeeding. Increasing evidence in literature suggests that an adequate concentration of DHA is required from the fetal stage through to early life to ensure optimal neurological development. Likewise, many studies in literature demonstrated that an adequate supply of DHA during pregnancy and lactation is essential to promote proper brain development in utero and in early life. Daily supplementation of DHA in newborns has potentially stronger effects compared to maternal supplementation during pregnancy. Supplementation initiated in the second year of life in children born preterm did not result in global cognitive development improvements. Preliminary findings arising from metabolomics has reported that mother's milk and infant formula supplementation of Vitamin D associated with DHA results in a higher antioxidant and protective action, with a possible positive influence on renal function and body fat on preterm infants compared to those receiving only vitamin D. Recent applications of metabolomic studies on newborns may lead to a better understanding of the metabolic process linked to early nutrition and, subsequently, to the development of targeted and personalized nutritional strategies.

The consumption of some long chain polyunsaturated fatty acids (LCPUFA), in particular docosahexanoic (DHA), eicosapentanoic (EPA) and conjugated linoleic (CLA) acids is beneficial for human health, thus its incorporation to meat gives added value, but sensory characteristics could be altered, causing rejection by the consumer. The objective of the present study was to evaluate the effect of adding these three LCPUFA to pig diet on physiochemical and sensory meat quality. The experimental design was randomized blocks with the following treatments: T1) diet+CLA; T2) diet+DHA+EPA; T3) diet+DHA+EPA+CLA; T4) diet (control). The data were analyzed using ANOVA and principal component analysis (PCA). Means were compared with Tukey test (p≤0.05). Thirty-two Pietrain × Landrace × York × Duroc castrated pigs were used in two fattening phases: 4 weeks of development and 4 weeks of finishing. They were then electroanesthetized and sacrificed. To carry out the physiochemical analyses (pH, water activity, hardness and cooking loss) and qualitative description (flavor, texture and aroma) samples were taken from the Longissimus dorsi muscle. Flavor and aroma of pork meat fed with LCPUFA was described as roasted, beef-like, and sheep-like, with soft and juicy texture, although less acceptable than the control. Roasted flavor, a desirable attribute in meats, decreased in samples obtained from pigs with diets including DHA and EPA, and fishy aroma and flavor were not detected. [ABSTRACT FROM AUTHOR]

Abstract: Cutinases (E.C. 3.1.1.74) belong to the α/β-hydrolase superfamily. They were initially discovered because they are secreted by fungi to hydrolyze the ester bonds of the plant polymer cutin. Since then, they have been shown to catalyze the hydrolysis of a variety of polymers, insoluble triacylglycerols, and low-molecular-weight soluble esters. Cutinases are also capable of catalyzing esterification and transesterification reactions. These relatively small, versatile, secreted catalysts have shown promise in a number of industrial applications. This review begins by describing the characteristics of cutinases, pointing out key differences among cutinases, esterases and lipases, and reviewing recent progress in engineering improved cutinases. It continues with a review of the methods used to produce cutinases, with the goal of obtaining sufficient quantities of material for use in industrial processes. Finally, the uses of cutinases in the textile industry are described. The studies presented here demonstrate that the cutinases are poised to become important industrial catalysts, replacing older technologies with more environmentally friendly processes. [Copyright &y& Elsevier]

Dietary ratios of n-3/n-6 polyunsaturated fatty acids (PUFAs) have been implicated in controlling markers of metabolic disorders, including obesity, insulin resistance (IR), inflammation, and lipid profiles, which are also presumed to be partly related to type 2 diabetes mellitus (T2DM). However, molecular mechanisms of the different PUFAs related to metabolic disorders have not been systematically addressed. The present study aimed to investigate the impact of dietary n-3/n-6 PUFA ratios on obesity and IR and, further, to determine the underlying mechanisms. For 16 weeks, 32 SD male rats, randomly divided into four groups (n = 8 per group), received one of the following diets: normal chow, high saturated fatty acid (SFA), high n-3/n-6 PUFA ratio (1∶1, PUFA1:1), or low n-3/n-6 PUFA ratio (1∶4, PUFA1:4). Following the experimental diet period, metabolic parameters related to obesity and IR were measured. Compared to SFA diet-fed rats, PUFA1:1 diet-fed rats exhibited decreased body and visceral fat weight, lowered blood lipids, and improved glucose tolerance and insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of circulating pro-inflammatory cytokines, including tumor necrosis factor α, interleukin-6, and C-reactive protein. Moreover, the TLR4 protein and mRNA levels were markedly down-regulated by PUFA1:1 compared with SFA; however, PUFA1:4 diet-fed rats failed to exhibit these changes. Cumulatively, our data highlight a role for a PUFA1:1 diet in the prevention of obesity and related metabolic disorders by suppressing the activation of TLR4, a critical modulator of pro-inflammatory cytokines. [Copyright &y& Elsevier]

Abstract: Background: Determining if associations exist between child neurodevelopment and environmental exposures, especially low level or background ones, is challenging and dependent upon being able to measure specific and sensitive endpoints. Psychometric or behavioral measures of CNS function have traditionally been used in such studies, but do have some limitations. Auditory neurophysiologic measures examine different nervous system structures and mechanisms, have fewer limitations, can more easily be quantified, and might be helpful additions to testing. To date, their use in human epidemiological studies has been limited. We reviewed the use of auditory brainstem responses (ABR) and otoacoustic emissions (OAE) in studies designed to determine the relationship of exposures to methyl mercury (MeHg) and nutrients from fish consumption with neurological development. We included studies of experimental animals and humans in an effort to better understand the possible benefits and risks of fish consumption. Objectives: We reviewed the literature on the use of ABR and OAE to measure associations with environmental exposures that result from consuming a diet high in fish. We focused specifically on long chain polyunsaturated fatty acids (LCPUFA) and MeHg. Methods: We performed a comprehensive review of relevant studies using web-based search tools and appropriate search terms. Results: Gestational exposure to both LCPUFA and MeHg has been reported to influence the developing auditory system. In experimental studies supplemental LCPUFA is reported to prolong ABR latencies and human studies also suggest an association. Experimental studies of acute and gestational MeHg exposure are reported to prolong ABR latencies and impair hair cell function. In humans, MeHg exposure is reported to prolong ABR latencies, but the impact on hair cell function is unknown. Conclusion: The auditory system can provide objective measures and may be useful in studying exposures to nutrients and toxicants and whether they are associated with children's neurodevelopment. [Copyright &y& Elsevier]

Abstract: There is limited information regarding the intake and status of polyunsaturated fatty acids (PUFA) in Chinese pregnant women with different dietary patterns. We hypothesize that there will be significant differences in long chain n-3 and n-6 PUFA status in pregnant women from 3 regions of China (river/lake, coastal and inland). Dietary fatty acid intakes and fatty acid profiles in maternal and umbilical erythrocyte phosphatidylcholine (PC) were analyzed. The median daily intakes (mg) of eicosapentanoic acid and docosahexaenoic acid (DHA) in the coastal group (64.6 and 93.9, n = 42) were significantly higher than those in the river/lake group (27.9 and 41.8, n = 41) and the inland group (12.1 and 41.1, n = 40). Daily intake of arachidonic acid (AA) was highest (170.2 mg) in the inland group. The median DHA level (%) of maternal erythrocyte PC was comparable between river/lake and inland groups (5.7 vs. 5.6) while both were significantly lower than in coastal group (8.4). The median AA level (%) of maternal erythrocyte PC tended to be lower in the coastal group than in the inland group but the difference was not significant. The AA and DHA levels in umbilical erythrocyte PC were comparable among the 3 groups. In conclusion, differences in long chain n-3 PUFA intake between geographic regions, in particular in DHA, were reflected in differences in maternal erythrocyte PC DHA status but did not result in differences in umbilical erythrocyte PC. [Copyright &y& Elsevier]

Abstract: Consuming omega-3 fatty acids (ω-3 FA) during pregnancy and lactation benefits fetal and infant brain development and might reduce the severity of preterm births by prolonging pregnancy. However, diets that are relatively rich in ω-3 FA can adversely affect fetal and infant development and the auditory brainstem response (ABR), a measure of brain development and sensory function. We previously examined the offspring of female rats fed excessive, adequate or deficient amounts of ω-3 FA during pregnancy and lactation. The 24-day-old offspring in the Excess group, compared to the Control group, had postnatal growth retardation and poor hearing acuity and prolonged neural transmission times as evidenced by the ABR. The Deficient group was intermediate. The current study followed these offspring to see if these poor outcomes persisted into young adulthood. Based on prior findings, we hypothesized that the Excess and Deficient offspring would “catch-up” to the Control offspring by young adulthood. Female Wistar rats received one of the three diet conditions from day 1 of pregnancy through lactation. The three diets were the Control ω-3 FA condition (ω-3/ω-6 ratio~0.14), the Excess ω-3 FA condition (ω-3/ω-6 ratio~14.0) and Deficient ω-3 FA condition (ω-3/ω-6 ratio~0% ratio). The Control diet contained 7% soybean oil; whereas the Deficient and Excess ω-3 FA diets contained 7% safflower oil and 7% fish oil, respectively. One male and female offspring per litter were ABR-tested as young adults using tone pip stimuli of 2, 4, 8 and 16 kHz. The postnatal growth retardation and prolonged neural transmission times in the Excess and Deficient pups had dissipated by young adulthood. In contrast, the Excess group had elevated ABR thresholds (hearing loss) at all tone pip frequencies in comparison to the Control and Deficient groups. The Deficient group had worse ABR thresholds than the Control group in response to the 8 kHz tone pips only. The Excess group also had ABR amplitude–intensity profiles suggestive of hyperacusis. These results are consistent with the Barker hypothesis concerning the fetal and neonatal origins of adult diseases. Thus, consuming diets that are excessively rich or deficient in ω-3 FA during pregnancy and lactation seems inadvisable because of risks for long-lasting adverse effects on brain development and sensory function. [Copyright &y& Elsevier]

Abstract: Omega-3 fatty acids (ω-3 FA) consumption during pregnancy and lactation is beneficial to fetal and infant growth and may reduce the severity of preterm births. Thus, scientists and clinicians are recommending increasingly higher ω-3 FA doses for pregnant women and nursing babies for advancing the health of preterm, low birth weight, and normal babies. In contrast, some studies report that over-supplementation with ω-3 FA can have adverse effects on fetal and infant development by causing a form of nutritional toxicity. Our goal was to assess the effects of ω-3 FA excess and deficiency during pregnancy and lactation on the offspring''s neural transmission as evidenced by their auditory brainstem responses (ABR). Female Wistar rats were given one of three diets from day 1 of pregnancy through lactation. The three diets were the Control ω-3 FA condition (ω-3/ω-6 ratio ∼0.14), the Deficient ω-3 FA condition (ω-3/ω-6 ratio ∼0%) and the Excess ω-3 FA condition (ω-3/ω-6 ratio ∼14.0). The Control diet contained 7% soybean oil, whereas the Deficient diet contained 7% safflower oil and the Excess diet contained 7% fish oil. The offspring were ABR-tested on postnatal day 24. The rat pups in the Excess group had prolonged ABR latencies in comparison to the Control group, indicating slowed neural transmission times. The pups in the Excess group also showed postnatal growth restriction. The Deficient group showed adverse effects that were milder than those seen in the Excess group. Milk fatty acid profiles reflected the fatty acid profiles of the maternal diets. In conclusion, excess or deficient amounts of ω-3 FA during pregnancy and lactation adversely affected the offspring''s neural transmission times and postnatal thriving. Consuming either large or inadequate amounts of ω-3 FA during pregnancy and lactation seems inadvisable because of the potential for adverse effects on infant development. [Copyright &y& Elsevier]

Long chain acyl-CoA synthetase-2 (LACS-2) is a critical enzyme involved in fatty acid metabolism in the brain. The disruption of fatty acid composition and metabolism has been hypothesized to play a role in major depression. Rats exposed to the learned helplessness paradigm, an animal model of depression, were classified as either learned helpless (LH, n=8) or non-learned helpless (nLH, n=8) on the basis of escape performance. Quantitative in situ hybridization analysis was used to determine LACS-2 mRNA levels in the frontal cortex of LH, nLH and normal control rats (n=8). LACS-2 mRNA expression throughout the frontal cortex was consistently higher in LH compared to controls in all 49 regions sampled. Upregulation of LACS-2 mRNA was most prominent in the LH group, followed by nLH and controls, which exhibiting lowest expression levels. This trend was observed in 84% of the regions examined. Statistically significant increases in the LH group vs. controls (p<0.05) were seen in nine different brain regions. The results demonstrate that LACS-2 expression is significantly upregulated in distinct regions of the frontal cortex in LH rats relative to controls. This suggests that fatty acid metabolism may be altered in the learned helplessness model. [Copyright &y& Elsevier]

In this study, the role of exogenous fatty acids in the regulation of proteolipid protein (PLP) gene expression was investigated using the following model culture system: C6 glioma cells expressing the green-fluorescent protein (eGFP) driven by different segments of PLP promoter. Eicosapentanoic acid (EPA; 20:5 n-3), but not arachidonic acid (AA; 20:4 n-6), induced a significant increase in medium fluorescence intensity (MFI) determined by fluorescence-activated cell sorting (FACS). The induction of PLP promoter was time-dependent showing maximal activity between 24 and 48 h after EPA exposure. PLP promoter activation was dependent on fatty acid concentration, with maximum activation at 200 μM. Northern blot analysis confirmed the fluorescence data in C6 cells incubated with EPA. Furthermore, this treatment increased the adenylyl cyclase-cyclic AMP (cAMP) levels and the mitogen-activated protein kinase (MAPK) activation in C6 cells. PLP promoter activity was inhibited by pre-treatment with H89 (protein kinase A (PKA) inhibitor), but not with PD98059 (MAPK inhibitor), suggesting that EPA stimulates the expression of PLP via cAMP-mediated pathways. [Copyright &y& Elsevier]

Neurocognitive impairment (NCI) and gut microbiota dysbiosis are prevalent in patients with HIV infection. Docosahexanoic acid (DHA) supplementation may alleviate multiple neurocognitive diseases symptoms and plays important role in regulating gut microbiota. However, it is not known whether DHA algae oil supplements can alleviate neurocognitive impairment (NCI) and regulate gut microbiota and fecal metabolites. A randomized, double-blind, placebo-controlled trial was performed on 68 HIV-infected patients with NCI. Participants were randomized to receive a 3.15 g daily DHA algae oil supplement or placebo for 6 months. We collected blood and fecal samples from these patients before and after the trial. Mini mental state examination (MMSE) and neuropsychological tests (NP tests) were administered to assess the cognitive status of participants. The influence of DHA algae oil on the gut microbiota, fecal metabolomics, plasma proinflammatory, and oxidative stress factors was also investigated. There were no significant changes in NCI according to global diagnosis score (GDS) and MMSE score within the two groups, while patients receiving DHA had improvement in several blood lipids, pro-inflammatory and oxidative stress factors. The DHA supplement increased α-diversity indexes, increased abundances of Blautia, Bifidobacterium, Dorea, Lactobacillus, Faecalibacterium, Fusobacterium , and Agathobacter , and decreased abundances of Bacteroides and Prevotella&#95;9 . Furthermore, DHA supplement was correlated with improved fecal lipid metabolites as indicated by ceramides, bile acids, glycerophospholipids. In addition, the DHA supplement was associated with altered cholesterol metabolism and purine metabolism pathways. A daily supplement of DHA algae oil for 6 months has been shown to promote favorable transformations in gut microbiota, profiles of fecal metabolomic, and factors responsible for proinflammatory and oxidative stress, which might be beneficial for the prognosis of HIV-infected patients with NCI in the long-term., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04242004, identifier: NCT04242004., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dong, Lin, Ding, Chen, Shi, Yuan, Li, Zhu, Xu, Shen, Wang, Ding and He.)

Docosahexaenoic acid (DHA) is an essential ω-3 long-chain polyunsaturated fatty acid (LCPUFA) and represents the dominant structural fatty acid in the retina and in the brain's gray matter. Due to its active participation in the development of the nervous system, DHA is one of the most studied LCPUFA and is currently considered a critical nutrient during pregnancy and breastfeeding. Increasing evidence in literature suggests that an adequate concentration of DHA is required from the fetal stage through to early life to ensure optimal neurological development. Likewise, many studies in literature demonstrated that an adequate supply of DHA during pregnancy and lactation is essential to promote proper brain development in utero and in early life. Daily supplementation of DHA in newborns has potentially stronger effects compared to maternal supplementation during pregnancy. Supplementation initiated in the second year of life in children born preterm did not result in global cognitive development improvements. Preliminary findings arising from metabolomics has reported that mother's milk and infant formula supplementation of Vitamin D associated with DHA results in a higher antioxidant and protective action, with a possible positive influence on renal function and body fat on preterm infants compared to those receiving only vitamin D. Recent applications of metabolomic studies on newborns may lead to a better understanding of the metabolic process linked to early nutrition and, subsequently, to the development of targeted and personalized nutritional strategies., (Copyright © 2020 Comitini, Peila, Fanos and Coscia.)

The breast-fed infant is the gold standard for infant formula research and development. The addition of long-chain polyunsaturated fatty acids and nucleotides to formula are intended to promote visual, neuro and immune development. Studies in both preterm and term infants have not consistently demonstrated efficacy with long-chain polyunsaturated fatty acids supplementation of infant formulas. Explanations for why these supplemented formulas do not always produce visual or neurodevelopmental advantages, include a small individual effect or that only a proportion of infants will benefit or the presence of confounding variables. The efficacy of nucleotides has been studied by analyzing response to vaccination in infants fed human milk versus formulas with or without additional nucleotides. Nucleotide supplemented formulas appear to enhance immune response similar to breast-fed infants with immunization. Humanizing formula with safe and well-studied nutrients may provide benefits that are discovered long after initial trials are concluded.Journal of Perinatology (2007) 27, S79–S82. doi:10.1038/sj.jp.7211711 [ABSTRACT FROM AUTHOR]