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Frontiers in Immunology 2023Severe COVID-19 results initially in pulmonary infection and inflammation. Symptoms can persist beyond the period of acute infection, and patients with Post-Acute...
INTRODUCTION
Severe COVID-19 results initially in pulmonary infection and inflammation. Symptoms can persist beyond the period of acute infection, and patients with Post-Acute Sequelae of COVID (PASC) often exhibit a variety of symptoms weeks or months following acute phase resolution including continued pulmonary dysfunction, fatigue, and neurocognitive abnormalities. We hypothesized that dysregulated NAD metabolism contributes to these abnormalities.
METHODS
RNAsequencing of lungs from transgenic mice expressing human ACE2 (K18-hACE2) challenged with SARS-CoV-2 revealed upregulation of NAD biosynthetic enzymes, including NAPRT1, NMNAT1, NAMPT, and IDO1 6 days post-infection.
RESULTS
Our data also demonstrate increased gene expression of NAD consuming enzymes: PARP 9,10,14 and CD38. At the same time, SIRT1, a protein deacetylase (requiring NAD as a cofactor and involved in control of inflammation) is downregulated. We confirmed our findings by mining sequencing data from lungs of patients that died from SARS-CoV-2 infection. Our validated findings demonstrating increased NAD turnover in SARS-CoV-2 infection suggested that modulating NAD pathways may alter disease progression and may offer therapeutic benefits. Specifically, we hypothesized that treating K18-hACE2 mice with nicotinamide riboside (NR), a potent NAD precursor, may mitigate lethality and improve recovery from SARS-CoV-2 infection. We also tested the therapeutic potential of an anti- monomeric NAMPT antibody using the same infection model. Treatment with high dose anti-NAMPT antibody resulted in significantly decreased body weight compared to control, which was mitigated by combining HD anti-NAMPT antibody with NR. We observed a significant increase in lipid metabolites, including eicosadienoic acid, oleic acid, and palmitoyl carnitine in the low dose antibody + NR group. We also observed significantly increased nicotinamide related metabolites in NR treated animals.
DISCUSSION
Our data suggest that infection perturbs NAD pathways, identify novel mechanisms that may explain some pathophysiology of CoVID-19 and suggest novel strategies for both treatment and prevention.
Topics: Humans; Mice; Animals; NAD; COVID-19; SARS-CoV-2; Mice, Transgenic; Inflammation; Nicotinamide-Nucleotide Adenylyltransferase
PubMed: 37457744
DOI: 10.3389/fimmu.2023.1158455 -
Sensors (Basel, Switzerland) Mar 2021Propolis contains many effective antifungal compounds that have not yet been identified and evaluated. In addition, distinguishing samples of propolis with high...
Propolis contains many effective antifungal compounds that have not yet been identified and evaluated. In addition, distinguishing samples of propolis with high antifungal activity from less active ones would be beneficial for effective therapy. Propolis samples were collected from four different geographical regions in Hungary and used to prepare ethanol extracts for analysis. First, an antifungal susceptibility test was performed on . Then, gas chromatography-mass spectrometry (GC-MS) and an opto-electronic nose were applied for the classification of propolis samples. In three propolis samples, the IC was measured between 72 and 134 µg/mL, but it was not calculable in the fourth sample. GC-MS analysis of the four propolis samples identified several compounds belonging to the various chemical classes. In the antifungal samples, the relative concentration of 11,14-eicosadienoic acid was the highest. Based on the opto-electronic electronic nose measurements, 98.4% of the original grouped antifungal/non-antifungal cases were classified correctly. We identified several molecules from propolis with potential antifungal properties. In addition, this is the first report to demonstrate the usefulness of a portable opto-electronic nose to identify propolis samples with high antifungal activity. These results may contribute to the rapid and efficient selection of new fungicide-candidate molecules and effective propolis samples for treatment.
Topics: Antifungal Agents; Hungary; Microbial Sensitivity Tests; Odorants; Propolis
PubMed: 33801571
DOI: 10.3390/s21072334 -
Metabolites Mar 2022Perturbations of metabolite profiles in human and canine enteropathies have been reported before. However, data in dogs are scarce and inconsistent. Currently, the...
Perturbations of metabolite profiles in human and canine enteropathies have been reported before. However, data in dogs are scarce and inconsistent. Currently, the metabolite profile in Yorkshire Terrier enteropathy (YTE) and the impact of treatment is unknown. The objective of this study was to investigate the plasma metabolome of 13 Yorkshire Terriers with YTE and compare it to 20 healthy Yorkshire Terriers. Furthermore, we studied the impact of treatment on the metabolome. In this prospective observational study, plasma metabolite profiles were analyzed by flow injection analysis-tandem mass spectrometry (FIA-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a targeted metabolomics kit. Metabolite analysis revealed that YTE is accompanied by changes in lipid and bile acid metabolism. YTE was associated with a significant decrease of long-chain fatty acids (octadecenoic acid, eicosadienoic acid, eicosatrienoic acid) and lower levels of long-chain acylcarnitines (tetradecanoylcarnitine, hexadecanoylcarnitine, hexadecenoylcarnitine, octadecenoylcarnitine) compared with healthy controls. Furthermore, taurodeoxycholic acid, a secondary bile acid, was decreased in plasma from YTE patients. These changes might be breed-specific and might be involved in the pathogenesis of YTE. Interestingly, changes in metabolite levels were not recovered after treatment and differed considerably from healthy controls.
PubMed: 35323707
DOI: 10.3390/metabo12030264 -
Meat Science Jan 2022This study aimed to describe the multivariate structure of Semimembranosus muscle and backfat fatty acid (FA) composition in 798 Italian Large White heavy pigs and to...
This study aimed to describe the multivariate structure of Semimembranosus muscle and backfat fatty acid (FA) composition in 798 Italian Large White heavy pigs and to investigate the effects of environmental factors and carcass characteristics on FA variations. The total FA variability in muscle and backfat was characterized by a negative correlation between saturated and polyunsaturated FAs, which strongly depended on the carcass adiposity. Slaughtering season was also relevant, with pigs slaughtered in autumn having more n-6 FAs and eicosadienoic acid in backfat, while pigs slaughtered in winter displayed more saturated FAs. Regarding Semimembranosus muscle, pigs with heavier belly cuts and slaughtered in autumn had higher proportions of cis-vaccenic and palmitoleic acids, while those slaughtered in summer had more saturated FAs. Slaughtering season emerged as a relevant factor shaping both backfat and muscle FA composition, indicating that more studies and attention should be paid to environmental factors, which may have effects on FA metabolism and deposition in finishing pigs.
Topics: Adipose Tissue; Animals; Fatty Acids; Female; Hamstring Muscles; Male; Pork Meat; Seasons; Sus scrofa
PubMed: 34399151
DOI: 10.1016/j.meatsci.2021.108645 -
Journal of Nutritional Science 2022Although chronic pain (CP) is classified as inflammatory or non-inflammatory, the involvement of fatty acid intake in this process has not yet been examined in detail....
Relationship between fatty acid intake and chronic neck/shoulder/upper limb pain without elevated CRP in a Japanese population: a cross-sectional analysis of the Shika study.
Although chronic pain (CP) is classified as inflammatory or non-inflammatory, the involvement of fatty acid intake in this process has not yet been examined in detail. Therefore, the present study investigated whether the relationship between CP and fatty acid intake differs between high and low C-reactive protein (CRP) levels in middle-aged and elderly individuals in the Shika study. One-thousand and seven males and 1216 females with mean ages of 68⋅78 and 69⋅65 years, respectively, participated in the present study. CRP was quantified by blood sampling from participants who responded to a CP questionnaire. The brief-type self-administered diet history questionnaire (BDHQ) was used to assess fatty acid intake. Interactions were observed between CP and CRP on monounsaturated fatty acids (MUFA) and eicosadienoic acid in a two-way analysis of covariance adjusted for sex, age, lack of exercise, lack of sleep, current smoking and drinking status, and BMI. MUFA (OR 1⋅359) and eicosadienoic acid (OR 1⋅072) were identified as significant independent variables for CP in a multiple logistic regression analysis, but only in the low CRP group. Only a high intake of MUFA and eicosadienoic acid was associated with chronic neck/shoulder/upper limb pain without elevated CRP. In psychogenic and neuropathic pain without elevated CRP, an increased intake of MUFA and eicosadienoic acid, a family member of -6 fatty acids, appears to affect CP. Further longitudinal studies are needed to elucidate this relationship.
Topics: Cross-Sectional Studies; Fatty Acids; Humans; Japan; Pain; Shoulder; Upper Extremity
PubMed: 35720172
DOI: 10.1017/jns.2022.37 -
Frontiers in Rehabilitation Sciences 2022The relationship between many fatty acids and respiratory outcomes remains unclear, especially with regard to mechanistic actions. Altered regulation of the process of...
RATIONALE
The relationship between many fatty acids and respiratory outcomes remains unclear, especially with regard to mechanistic actions. Altered regulation of the process of lung repair is a key feature of chronic lung disease and may impact the potential for pulmonary rehabilitation, but underlying mechanisms of lung repair following injury or inflammation are not well-studied. The epidermal growth factor receptor agonist amphiregulin (AREG) has been demonstrated to promote lung repair following occupational dust exposure in animals. Studies suggest the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) may enhance the production of AREG. The objective of this study was to determine the relationship between fatty acids and lung function in a population of veterans and determine if fatty acid status is associated with concentrations of AREG.
MATERIALS AND METHODS
Data were collected from a cross-sectional study of veterans within the Nebraska-Western Iowa Health Care System. Whole blood assays were performed to quantify AREG concentrations via a commercially available ELISA kit. Fatty acids from plasma samples from the same patients were measured using gas-liquid chromatography. Intakes of fatty acids were quantified with a validated food frequency questionnaire. Linear regression models were used to determine whether plasma fatty acids or intakes of fatty acids predicted lung function or AREG concentrations. A < 0.05 was considered statistically significant.
RESULTS
Ninety participants were included in this analysis. In fully adjusted models, plasma fatty acids were associated with AREG production, including the PUFA eicosapentaenoic acid (EPA) (β = 0.33, = 0.03) and the monounsaturated fatty acid octadecenoic acid: (β = -0.56, = 0.02). The omega-3 PUFA docosapentaenoic acid (DPA) was positively associated with lung function (β = 0.28, = 0.01; β = 26.5, = 0.05 for FEV/FVC ratio and FEV % predicted, respectively), as were the omega-6 PUFAs eicosadienoic acid (β = 1.13, < 0.001; β = 91.2, = 0.005 for FEV/FVC ratio and FEV % predicted, respectively) and docosadienoic acid (β = 0.29, = 0.01 for FEV/FVC ratio). Plasma monounsaturated and saturated fatty acids were inversely associated with lung function.
CONCLUSION
Opposing anti- and pro-inflammatory properties of different fatty acids may be associated with lung function in this population, in part by regulating AREG induction.
PubMed: 36188926
DOI: 10.3389/fresc.2022.773835 -
Animals : An Open Access Journal From... Dec 2022The effects of the replacement of dry ground corn (GC) with corn-grain silage rehydrated with water (RCSwater), cactus pear mucilage (RCSmucilage), and whey (RCSwhey) on...
The effects of the replacement of dry ground corn (GC) with corn-grain silage rehydrated with water (RCSwater), cactus pear mucilage (RCSmucilage), and whey (RCSwhey) on the growth, physicochemical composition, and fatty acid profile of goat kids’ meat were investigated. Thirty-two crossbred goat kids (16.4 ± 2.50 kg initial weight) were assigned in a randomized block design with four treatments and eight repetitions. The NDF intake of goat kids fed with RCSmucilage was higher in comparison to RCSwater and RCSwhey (p = 0.0009). The dietary replacement of GC by RCSmucilage increased the final weight (p = 0.033) and meat-cooking losses (p = 0.0001) of kids. The concentrations of oleic (p = 0.046), 11,14-eicosadienoic (p = 0.033), and EPA (p = 0.010) were higher in the meat of kids fed with RCSmucilage and RCSwhey, and the α-linolenic concentration was higher (p = 0.019) for animals feeding with RCSmucilage. Meat from kids fed with RCSwhey presented the lowest ∑SFA and the highest ∑MUFA. In contrast, the ∑PUFA (p < 0.012) was higher for goats fed with RCSwater. The ∑ω3 (p < 0.0001) was higher in animals fed with RCSmucilage and RCSwhey. Desirable fatty acids were higher (p = 0.044) in animals fed with RCSmucilage and RCSwhey, and the atherogenicity (p = 0.044) and thrombogenicity (p < 0.0001) indexes were lower for goats fed the RCSwhey diet. The enzymatic activities of Δ9desaturase (C16) were higher (p = 0.027) in goat kids fed with GC and RCSmucilage, and Δ9desaturase (C18) was higher (p = 0.0497) when goats were fed with RCSmucilage and RCSwhey. Elongase activities were higher (p = 0.045) in goat kids fed with GC and RCSwater. The total replacement of GC by RCSmucilage is recommended in the diet of goat kids due to improvements in the weight gain and proportion of desirable fatty acids in the meat. In addition, RCSmucilage promoted better conservation of the silage at a lower cost when compared to commercial additives.
PubMed: 36611641
DOI: 10.3390/ani13010031 -
Iranian Journal of Biotechnology Jan 2022is one of the most important oilseeds that has a proportionate profile of essential unsaturated fatty acids that are suitable for human nutrition. In this regard, we...
BACKGROUND
is one of the most important oilseeds that has a proportionate profile of essential unsaturated fatty acids that are suitable for human nutrition. In this regard, we can mention a high percentage and a reasonable ratio of omega 3 and omega 6.
OBJECTIVES
In the current study, the created variation of second-generation mutant (M2) camelina lines in terms of fatty acid profiles and ISSR molecular markers in was evaluated.
MATERIALS AND METHODS
For this purpose, while producing the first-generation of mutant plants (M1), 200 M2 seeds with 0.1% and 0.5% ethyl methanesulfonate (EMS) mutations were treated in two replications for 8 and 16 hours based on a completely randomized design.
RESULTS
The results of mean comparisons showed that there was no significant difference between treatments in terms of fatty acids of palmitic acid, stearic acid, linoleic acid, eicosadienoic acid, oleic acid and erucic acid. The cluster analysis revealed that all the treatments used with five replications were divided into eight groups. It was found that all replications of the treatment with a concentration of 0.1% and a time of 16 hours (C1T2) were in the second group with the lowest palmitic acid was present among other treatments. Therefore, C1T2 treatment is recommended as the best treatment to reduce palmitic acid. Examination of the information content of ISSR molecular markers also showed that markers 2, 5, and 6 were the best informative markers in the detection of camelina fatty acid profiles.
CONCLUSION
A significant variation has been created in the fatty acids profile and it can be applied in future breeding programs depending on the intended purpose.
PubMed: 35891951
DOI: 10.30498/ijb.2021.263748.2948 -
Cancer Immunology, Immunotherapy : CII Jan 2022Lipids have immunomodulatory functions and the potential to affect cancer immunity. (Observational Study)
Observational Study
BACKGROUND
Lipids have immunomodulatory functions and the potential to affect cancer immunity.
METHODS
The associations of pretreatment serum cholesterol and long-chain fatty acids with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated in 148 patients with non-small cell lung cancer who received nivolumab.
RESULTS
When each lipid was separately evaluated, increased low-density lipoprotein (LDL)-cholesterol (P < 0.001), high-density lipoprotein (HDL)-cholesterol (P = 0.014), total cholesterol (P = 0.007), lauric acid (P = 0.015), myristic acid (P = 0.022), myristoleic acid (P = 0.035), stearic acid (P = 0.028), linoleic acid (P = 0.005), arachidic acid (P = 0.027), eicosadienoic acid (P = 0.017), dihomo-γ-linolenic acid (P = 0.036), and behenic acid levels (P = 0.032) were associated with longer PFS independent of programmed death ligand 1 (PD-L1) expression. Meanwhile, increased LDL-cholesterol (P < 0.001), HDL-cholesterol (P = 0.009), total cholesterol (P = 0.036), linoleic acid (P = 0.014), and lignoceric acid levels (P = 0.028) were associated with longer OS independent of PD-L1 expression. When multiple lipids were evaluated simultaneously, LDL-cholesterol (P = 0.003), HDL-cholesterol (P = 0.036), and lauric acid (P = 0.036) were independently predictive of PFS, and LDL-cholesterol (P = 0.008) and HDL-cholesterol (P = 0.031) were predictive of OS. ORR was not associated with any serum lipid.
CONCLUSIONS
Based on the association of prolonged survival in patients with increased serum cholesterol and long-chain fatty acid levels, serum lipid levels may be useful for predicting the efficacy of immune checkpoint inhibitor therapy.
Topics: Aged; Antineoplastic Agents, Immunological; Carcinoma, Non-Small-Cell Lung; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Disease-Free Survival; Fatty Acids; Female; Gene Expression Regulation, Neoplastic; Humans; Immune Checkpoint Inhibitors; Lipids; Lung Neoplasms; Male; Middle Aged; Nivolumab; Prospective Studies; Treatment Outcome
PubMed: 34091744
DOI: 10.1007/s00262-021-02979-4 -
Plant Diversity Feb 2021Nervonic acid (NA, cis-15-tetracosenoic acid) is a very long-chain monounsaturated fatty acid that has been shown to be a core component of nerve fibers and nerve cells....
Nervonic acid (NA, cis-15-tetracosenoic acid) is a very long-chain monounsaturated fatty acid that has been shown to be a core component of nerve fibers and nerve cells. It can be used to treat and prevent many neurological diseases. At present, commercially available NA is mainly derived from seeds, which contain about 5%-6% NA in their seed oil. The aim of this study were to identify and analyze NA-containing species that could be used as NA resource plants. For this purpose, 46 species seeds were collected in China and in some or all of the seed oils from these species 15 fatty acids were detected, including linoleic acid, oleic acid (C18:1, C18:1), erucic acid, palmitic acid, NA, linolenic acid (C18:3, C18:3), eicosenoic acid (C20:1, C20:1), stearic acid, behenic acid, tetracosanoic acid, arachidic acid, and docosadienoic acid. Nervonic acid was detected in all samples, but the content was highly variable among species. NA content over 9% was detected in eleven species, of which had the highest levels (13.90%). The seed oil content, seed weight, and fatty acid profiles varied among species, but the comprehensive evaluation value (W) showed that could be a new potential NA resources plant. The results also showed that NA was significantly negatively correlated with palmitic acid, oleic acid, and eicosenoic acid, but positively correlated with eicosadienoic acid, behenic acid, erucic acid, and tetracosanoic acid, which indicate the probable pathway for NA biosynthesis in plants. This study has identified species that may serve as NA resources and will help guide subsequent species breeding programs.
PubMed: 33778229
DOI: 10.1016/j.pld.2020.10.003