Recent Metabolic Advances for Preventing and Treating Acute and Chronic Graft Versus Host Disease.

The therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by the development of graft-versus-host disease (GVHD). In GVHD, rigorous pre-conditioning regimen resets the immune landscape and inflammatory milieu causing immune dysregulation, characterized by an expansion of alloreactive cells and a reduction in immune regulatory cells. In acute GVHD (aGVHD), the release of damage- and pathogen- associated molecular patterns from damaged tissue caused by the conditioning regimen sets the stage for T cell priming, activation and expansion further exacerbating tissue injury and organ damage, particularly in the gastrointestinal tract. Studies have shown that donor T cells utilize multiple energetic and biosynthetic pathways to mediate GVHD that can be distinct from the pathways used by regulatory T cells for their suppressive function. In chronic GVHD (cGVHD), donor T cells may differentiate into IL-21 producing T follicular helper cells or tissue resident T helper cells that cooperate with germinal center B cells or memory B cells, respectively, to produce allo- and auto-reactive antibodies with subsequent tissue fibrosis. Alternatively, donor T cells can become IFN- γ/IL-17 cytokine expressing T cells that mediate sclerodermatous skin injury. Patients refractory to the first line standard regimens for GVHD treatment have a poor prognosis indicating an urgent need for new therapies to restore the balance between effector and regulatory immune cells while preserving the beneficial graft-versus-tumor effect. Emerging data points toward a role for metabolism in regulating these allo- and auto-immune responses. Here, we will discuss the preclinical and clinical data available on the distinct metabolic demands of acute and chronic GVHD and recent efforts in identifying therapeutic targets using metabolomics. Another dimension of this review will examine the changing microbiome after allo-HSCT and the role of microbial metabolites such as short chain fatty acids and long chain fatty acids on regulating immune responses. Lastly, we will examine the metabolic implications of coinhibitory pathway blockade and cellular therapies in allo-HSCT. In conclusion, greater understanding of metabolic pathways involved in immune cell dysregulation during allo-HSCT may pave the way to provide novel therapies to prevent and treat GVHD.

Nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma.

Bile acid profiles are altered in obese individuals with asthma. Thus, we sought to better understand how obesity-related systemic changes contribute to lung pathophysiology. We also test the therapeutic potential of nitro-oleic acid (NO2-OA), a regulator of metabolic and inflammatory signaling pathways, to mitigate allergen and obesity-induced lung function decline in a murine model of asthma. Bile acids were measured in the plasma of healthy subjects and individuals with asthma and serum and lung tissue of mice with and without allergic airway disease (AAD). Lung function, indices of inflammation and hepatic bile acid enzyme expression were measured in obese mice with house dust mite-induced AAD treated with vehicle or NO2-OA. Serum levels of glycocholic acid and glycoursodeoxycholic acid clinically correlate with body mass index and airway hyperreactivity whereas murine levels of ß-muricholic acid and tauro-ß-muricholic acid were significantly increased and positively correlated with impaired lung function in obese mice with AAD. NO2-OA reduced murine bile acid levels by modulating hepatic expression of bile acid synthesis enzymes, with a concomitant reduction in small airway resistance and tissue elastance. Bile acids correlate to body mass index and lung function decline and the signaling actions of nitroalkenes can limit AAD by modulating bile acid metabolism, revealing a potential pharmacologic approach to improving the current standard of care.

Angioedema and Fatty Acids.

Angioedema is a life-threatening emergency event that is associated with bradykinin and histamine-mediated cascades. Although bradykinin-mediated angioedema currently has specific therapeutic options, angioedema is sometimes intractable with current treatments, especially histamine-mediated angioedema, suggesting that some other mediators might contribute to the development of angioedema. Fatty acids are an essential fuel and cell component, and act as a mediator in physiological and pathological human diseases. Recent updates of studies revealed that these fatty acids are involved in vascular permeability and vasodilation, in addition to bradykinin and histamine-mediated reactions. This review summarizes each fatty acid's function and the specific receptor signaling responses in blood vessels, and focuses on the possible pathogenetic role of fatty acids in angioedema.

The Role of Fatty Acids in Ceramide Pathways and Their Influence on Hypothalamic Regulation of Energy Balance: A Systematic Review.

Obesity is a global health issue for which no major effective treatments have been well established. High-fat diet consumption is closely related to the development of obesity because it negatively modulates the hypothalamic control of food intake due to metaflammation and lipotoxicity. The use of animal models, such as rodents, in conjunction with in vitro models of hypothalamic cells, can enhance the understanding of hypothalamic functions related to the control of energy balance, thereby providing knowledge about the impact of diet on the hypothalamus, in addition to targets for the development of new drugs that can be used in humans to decrease body weight. Recently, sphingolipids were described as having a lipotoxic effect in peripheral tissues and the central nervous system. Specifically, lipid overload, mainly from long-chain saturated fatty acids, such as palmitate, leads to excessive ceramide levels that can be sensed by the hypothalamus, triggering the dysregulation of energy balance control. However, no systematic review has been undertaken regarding studies of sphingolipids, particularly ceramide and sphingosine-1-phosphate (S1P), the hypothalamus, and obesity. This review confirms that ceramides are associated with hypothalamic dysfunction in response to metaflammation, endoplasmic reticulum (ER) stress, and lipotoxicity, leading to insulin/leptin resistance. However, in contrast to ceramide, S1P appears to be a central satiety factor in the hypothalamus. Thus, our work describes current evidence related to sphingolipids and their role in hypothalamic energy balance control. Hypothetically, the manipulation of sphingolipid levels could be useful in enabling clinicians to treat obesity, particularly by decreasing ceramide levels and the inflammation/endoplasmic reticulum stress induced in response to overfeeding with saturated fatty acids.

Queen cells acceptance rate and royal jelly production in worker honey bees of two Apis mellifera races.

Royal jelly (RJ) is an acidic yellowish-white secretion of worker honey bee glands, used as food material of worker bee larvae for the first three days and queen bee larvae for the entire life. It is commercially used in cosmetics and medicinal industry in various parts of the world. This study determined the queen cell acceptance rate and RJ production difference among Italian and Carniolan bee races. Furthermore, the effect of plastic cup cell priming media, diets and seasons were tested on the larval cell acceptance rate and RJ yield of both races. The results indicated that average queen cell acceptance rate was significantly (p<0.001) higher in Italian race (75.53 ± 1.41%) than Carniolan race (58.20 ± 1.30%). Similarly, mean RJ yield per colony significantly (p<0.001) differed between both bee races, which were 13.10 ± 0.42 g and 9.66 ± 0.43 g, in Italian and Carniolan races, respectively. Moreover, priming media, diets and seasons significantly (p<0.001) affected queen cell acceptance rate and RJ production of both bee races. This study would help breeders to select the bees with higher-level of queen cell acceptance rate and RJ production in the future.

A Low-Carbohydrate Ketogenic Diet and Treadmill Training Enhanced Fatty Acid Oxidation Capacity but Did Not Enhance Maximal Exercise Capacity in Mice.

The low-carbohydrate ketogenic diet (LCKD) is a dietary approach characterized by the intake of high amounts of fat, a balanced amount of protein, and low carbohydrates, which is insufficient for metabolic demands. Previous studies have shown that an LCKD alone may contribute to fatty acid oxidation capacity, along with endurance. In the present study, we combined a 10-week LCKD with an 8-week forced treadmill running program to determine whether training in conjunction with LCKD enhanced fatty acid oxidation capacity, as well as whether the maximal exercise capacity would be affected by an LCKD or training in a mice model. We found that the lipid pool and fatty acid oxidation capacity were both enhanced following the 10-week LCKD. Further, key fatty acid oxidation related genes were upregulated. In contrast, the 8-week training regimen had no effect on fatty acid and ketone body oxidation. Key genes involved in carbohydrate utilization were downregulated in the LCKD groups. However, the improved fatty acid oxidation capacity did not translate into an enhanced maximal exercise capacity. In summary, while favoring the fatty acid oxidation system, an LCKD, alone or combined with training, had no beneficial effects in our intensive exercise-evaluation model. Therefore, an LCKD may be promising to improve endurance in low- to moderate-intensity exercise, and may not be an optimal choice for those partaking in high-intensity exercise.

Peroxisome Proliferator-Activated Receptors (PPAR), fatty acids and microRNAs: Implications in women delivering low birth weight babies.

Low birth weight (LBW) babies are associated with neonatal morbidity and mortality and are at increased risk for noncommunicable diseases (NCDs) in later life. However, the molecular determinants of LBW are not well understood. Placental insufficiency/dysfunction is the most frequent etiology for fetal growth restriction resulting in LBW and placental epigenetic processes are suggested to be important regulators of pregnancy outcome. Early life exposures like altered maternal nutrition may have long-lasting effects on the health of the offspring via epigenetic mechanisms like DNA methylation and microRNA (miRNA) regulation. miRNAs have been recognized as major regulators of gene expression and are known to play an important role in placental development. Angiogenesis in the placenta is known to be regulated by transcription factor peroxisome proliferator-activated receptor (PPAR) which is activated by ligands such as long-chain-polyunsaturated fatty acids (LCPUFA). In vitro studies in different cell types indicate that fatty acids can influence epigenetic mechanisms like miRNA regulation. We hypothesize that maternal fatty acid status may influence the miRNA regulation of PPAR genes in the placenta in women delivering LBW babies. This review provides an overview of miRNAs and their regulation of PPAR gene in the placenta of women delivering LBW babies.Abbreviations: AA - Arachidonic Acid; Ago2 - Argonaute2; ALA - Alpha-Linolenic Acid; ANGPTL4 - Angiopoietin-Like Protein 4; C14MC - Chromosome 14 miRNA Cluster; C19MC - Chromosome 19 miRNA Cluster; CLA - Conjugated Linoleic Acid; CSE - Cystathionine γ-Lyase; DHA - Docosahexaenoic Acid; EFA - Essential Fatty Acids; E2F3 - E2F transcription factor 3; EPA - Eicosapentaenoic Acid; FGFR1 - Fibroblast Growth Factor Receptor 1; GDM - Gestational Diabetes Mellitus; hADMSCs - Human Adipose Tissue-Derived Mesenchymal Stem Cells; hBMSCs - Human Bone Marrow Mesenchymal Stem Cells; HBV - Hepatitis B Virus; HCC - Hepatocellular Carcinoma; HCPT - Hydroxycamptothecin; HFD - High-Fat Diet; Hmads - Human Multipotent Adipose-Derived Stem; HSCS - Human Hepatic Stellate Cells; IUGR - Intrauterine Growth Restriction; LA - Linoleic Acid; LBW - Low Birth Weight; LCPUFA - Long-Chain Polyunsaturated Fatty Acids; MEK1 - Mitogen-Activated Protein Kinase 1; MiRNA - MicroRNA; mTOR - Mammalian Target of Rapamycin; NCDs - NonCommunicable Diseases; OA - Oleic Acid; PASMC - Pulmonary Artery Smooth Muscle Cell; PLAG1 - Pleiomorphic Adenoma Gene 1; PPAR - Peroxisome Proliferator-Activated Receptor; PPARα - PPAR alpha; PPARγ - PPAR gamma; PPARδ - PPAR delta; pre-miRNA - precursor miRNA; RISC - RNA-Induced Silencing Complex; ROS - Reactive Oxygen Species; SAT - Subcutaneous Adipose Tissue; WHO - World Health Organization.

Lipid accumulation patterns and role of different fatty acid types towards mitigating salinity fluctuations in Chlorella vulgaris.

Mangrove-dwelling microalgae are well adapted to frequent encounters of salinity fluctuations across their various growth phases but are lesser studied. The current study explored the adaptive changes (in terms of biomass, oil content and fatty acid composition) of mangrove-isolated C. vulgaris UMT-M1 cultured under different salinity levels (5, 10, 15, 20, 30 ppt). The highest total oil content was recorded in cultures at 15 ppt salinity (63.5% of dry weight) with uncompromised biomass productivity, thus highlighting the 'trigger-threshold' for oil accumulation in C. vulgaris UMT-M1. Subsequently, C. vulgaris UMT-M1 was further assessed across different growth phases under 15 ppt. The various short, medium and long-chain fatty acids (particularly C20:0), coupled with a high level of C18:3n3 PUFA reported at early exponential phase represents their physiological importance during rapid cell growth. Accumulation of C18:1 and C18:2 at stationary growth phase across all salinities was seen as cells accumulating substrate for C18:3n3 should the cells anticipate a move from stationary phase into new growth phase. This study sheds some light on the possibility of 'triggered' oil accumulation with uninterrupted growth and the participation of various fatty acid types upon salinity mitigation in a mangrove-dwelling microalgae.

Recent advances in bio-chemical, molecular and physiological aspects of membrane lipid derivatives in plant pathology.

Plant pathogens pose a significant threat to the food industry and food security accounting for 10-40% crop losses annually on a global scale. Economic losses from plant diseases are estimated at $300B for major food crops and are associated with reduced food availability and accessibility and also high food costs. Although strategies exist to reduce the impact of diseases in plants, many of these introduce harmful chemicals to our food chain. Therefore, it is important to understand and utilize plants' immune systems to control plant pathogens to enable more sustainable agriculture. Lipids are core components of cell membranes and as such are part of the first line of defense against pathogen attack. Recent developments in omics technologies have advanced our understanding of how plant membrane lipid biosynthesis, remodelling and/or signalling modulate plant responses to infection. Currently, there is limited information available in the scientific literature concerning lipid signalling targets and their biochemical and physiological consequences in response to plant pathogens. This review focusses on the functions of membrane lipid derivatives and their involvement in plant responses to pathogens as biotic stressors. We describe major plant defense systems including systemic-acquired resistance, basal resistance, hypersensitivity and the gene-for-gene concept in this context.

Bee products as a source of promising therapeutic and chemoprophylaxis strategies against COVID-19 (SARS-CoV-2).

The emergence of novel coronavirus (SARS-CoV-2) in 2019 in China marked the third outbreak of a highly pathogenic coronavirus infecting humans. The novel coronavirus disease (COVID-19) spread worldwide, becoming an emergency of major international concern. However, even after a decade of coronavirus research, there are still no licensed vaccines or therapeutic agents to treat the coronavirus infection. In this context, apitherapy presents as a promising source of pharmacological and nutraceutical agents for the treatment and/or prophylaxis of COVID-19. For instance, several honeybee products, such as honey, pollen, propolis, royal jelly, beeswax, and bee venom, have shown potent antiviral activity against pathogens that cause severe respiratory syndromes, including those caused by human coronaviruses. In addition, the benefits of these natural products to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells, and stimulation of the innate and adaptive immune responses. Thus, in the absence of specific antivirals against SARS-CoV-2, apitherapy could offer one hope toward mitigating some of the risks associated with COVID-19.

Dietary fatty acids modulate cortisol concentrations and social dominance during social confrontations in adolescent male guinea pigs.

The hypothalamic-pituitary-adrenal (HPA)-axis and related glucocorticoid concentrations regulate physiology and behavior, which can be modulated by nutritional conditions, particularly by the dietary fatty acid composition. Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to promote hypothalamic-pituitary-adrenal (HPA)-axis functions, whereas saturated fatty acids (SFAs) in general produce adverse effects and even increase baseline glucocorticoid concentrations. Glucocorticoids (e.g. cortisol) were further documented to modulate the establishment of dominance relationships, while the involvement of dietary fatty acids remains understudied. This study focused on different effects of PUFAs and SFAs on cortisol concentrations and social dominance in male guinea pigs. Three groups of animals were maintained on diets high in PUFAs (10 % w/w walnut oil), SFAs (10 % w/w coconut fat), or on an untreated control diet starting already prenatally. During adolescence, at an age of 60, 90, and 120 days, each individual's saliva cortisol concentrations and hierarchy index (calculated by initiated and received agonistic behavior) were measured during basal group housing conditions and stressful social confrontations with unfamiliar individuals of the other groups. SFA males showed highest baseline cortisol concentrations, lowest cortisol responses to social confrontations, and became subdominant. PUFA and control males showed significant cortisol responses. However, while control males became dominant during social confrontations, the hierarchy index in PUFA males decreased with age. Individual hierarchy indices during consecutive social confrontations revealed a high consistency. The findings presented here indicate that dietary fatty acids differently affect HPA-axis functions and social dominance but the underlying mechanisms remain to be determined.

Bovine pyruvate carboxylase gene proximal promoter activity is regulated by saturated and unsaturated fatty acids in Madin-Darby bovine kidney cells.

An increase in bovine pyruvate carboxylase (PC; EC 6.4.1.1) at calving and during feed restriction corresponds with increased circulating nonesterified fatty acids as a consequence of negative energy balance. Regulation of PC mRNA and effect of specific combinations of saturated and unsaturated fatty acid profiles has yet to be explored. Our objective was to determine the effects of chain length, degree of saturation, and copresence of saturated and unsaturated fatty acids on activity of bovine PC promoter 1 (PCP1). For these experiments, Madin-Darby bovine kidney cells were transfected with a full-length bovine PCP1 construct from -1002 to +3 bp relative to the bovine PC gene transcription start site (bovine PCP1(-1002_+3)) ligated to a Firefly luciferase reporter, or with one of a series of nested 5' serial truncations (bovine PCP1(-773_+3), bovine PCP1(-494_+3), or bovine PCP1(-222_+3)). Cells were exposed for 23 h to either individual fatty acids (C16:0, C18:0, or C18:3n-3 cis) bound to BSA or to fatty acid mixtures in ratios of 90:10, 75:25, 50:50, or 25:75, corresponding to combinations of C16:0: C18:3n-3 cis or C18:0: C18:3n-3 cis. Total fatty acid concentration was 1.00 mM. Exposure to either C16:0 or C18:3n-3 cis alone elicited a significant increase in capacity to drive bovine PCP1(-1002_+3) activity compared with 1% BSA in Dulbecco's Modified Eagle's Medium control treatment (2.29, 2.89, and 1.00 ± 0.26 fold of promoter induction for C16:0, C18:3n-3 cis, and control, respectively). Treatment with C18:3n-3 cis alone caused a greater increase in promoter activity compared with C16:0 alone, indicating a lesser response to C16:0 alone for bovine PCP1(-1002_+3). Interestingly, inclusion of C18:3n-3 cis, at any level of fatty acid ratios examined, in combination with C16:0 increased promoter activity of bovine PCP1(-773_+3) or bovine PCP1(-222_+3) compared with treatment with C16:0 alone or control. Data from the bovine PCP1 truncation and fatty acid copresence experiments reveal the potential for response elements of unsaturated fatty acids or fatty acid ligands in several bovine PCP1 promoter regions. In silico analysis of bovine PCP1 identified putative peroxisome proliferator-activated receptor α and sterol regulatory element binding protein binding sites which may be implicated in fatty acid signaling to alter bovine PCP1 activity. Pyruvate carboxylase promoter 1 activity that is mediated by unsaturated fatty acids acting through elements within -1002 and -222 bp of bovine PCPI may determine PC response during periods of negative energy balance in dairy cows.

Seminal plasma components from fertile stallions involved in the epididymal sperm freezability.

BACKGROUND: Seminal plasma (SP) plays a crucial role in sperm protection and functionality. However, the effect of SP on the sperm cryopreservation is dependent on the stallion and SP composition. The use of epididymal spermatozoa incubated in the presence of SP could help the identification of the components of SP that are able to confer protection upon the spermatozoa during freezing. OBJECTIVE: The aims of this study were (i) to identify SP components involved in the potential protection of epididymal spermatozoa during the freeze-thawing process and (ii) to identify and evaluate the proteins likely related to sperm freezability, using two-dimensional difference gel electrophoresis (2D-DIGE). MATERIALS AND METHODS: Epididymal spermatozoa from 4 stallions were incubated with SP (80%, v/v) or without SP (control) before freezing. Sperm parameters were evaluated after thawing (viability, chromatin condensation, acrosomal integrity, reactive oxygen species [ROS]) and SP composition: total antioxidant capacity (TAC), fatty acid composition, total protein concentration, and protein components by 2D-DIGE. RESULTS: After thawing, the proportions of viable and acrosome-intact spermatozoa were higher than control when SP from two stallions was used (F and O). The SP of all stallions reduced ROS production in comparison with the control. After analyzing the SP components, it was found that total protein concentration, TAC, polyunsaturated fatty acids (PUFA), and eight specific proteins identified by 2D-DIGE were different between stallions. DISCUSSION: These studies allow the identification of SP components that could be involved in sperm protection or cryotolerance. Use of this information could help in the selection of stallions according to their semen freezing capacity. CONCLUSION: The composition of the SP probably contributes to semen cryotolerance capacity. Total protein, TAC, PUFA, and some proteins such as cysteine-rich secreted protein 3 could be used as biomarkers for the selection for sperm cryotolerance.

Drought stress triggers proteomic changes involving lignin, flavonoids and fatty acids in tea plants.

Drought stress triggers a series of physiological and biochemical changes in tea plants. It is well known that flavonoids, lignin and long-chain fatty acids play important roles in drought resistance. However, changes in proteins related to these three metabolic pathways in tea plants under drought stress have not been reported. We analysed the proteomic profiles of tea plants by tandem mass tag and liquid chromatography-tandem mass spectrometry. A total of 4789 proteins were identified, of which 11 and 100 showed up- and downregulation, respectively. The proteins related to the biosynthesis of lignin, flavonoids and long-chain fatty acids, including phenylalanine ammonia lyase, cinnamoyl-CoA reductase, peroxidase, chalcone synthase, flavanone 3-hydroxylase, flavonol synthase, acetyl-CoA carboxylase 1,3-ketoacyl-CoA synthase 6 and 3-ketoacyl-CoA reductase 1, were downregulated. However, the contents of soluble proteins, malondialdehyde, total phenols, lignin and flavonoids in the tea plants increased. These results showed that tea plants might improve drought resistance by inhibiting the accumulation of synthases related to lignin, flavonoids and long-chain fatty acids. The proteomic spectrum of tea plants provides a scientific basis for studying the pathways related to lignin, flavonoid and long-chain fatty acid metabolism in response to drought stress.

Acute insulin deprivation results in altered mitochondrial substrate sensitivity conducive to greater fatty acid transport.

Type 1 and type 2 diabetes are both tightly associated with impaired glucose control. Although both pathologies stem from different mechanisms, a reduction in insulin action coincides with drastic metabolic dysfunction in skeletal muscle and metabolic inflexibility. However, the underlying explanation for this response remains poorly understood, particularly since it is difficult to distinguish the role of attenuated insulin action from the detrimental effects of reactive lipid accumulation, which impairs mitochondrial function and promotes reactive oxygen species (ROS) emission. We therefore utilized streptozotocin to examine the effects of acute insulin deprivation, in the absence of a high-lipid/nutrient excess environment, on the regulation of mitochondrial substrate sensitivity and ROS emission. The ablation of insulin resulted in reductions in absolute mitochondrial oxidative capacity and ADP-supported respiration and reduced the ability for malonyl-CoA to inhibit carnitine palmitoyltransferase I (CPT-I) and suppress fatty acid-supported respiration. These bioenergetic responses coincided with increased mitochondrial-derived H2O2 emission and lipid transporter content, independent of major mitochondrial substrate transporter proteins and enzymes involved in fatty acid oxidation. Together, these data suggest that attenuated/ablated insulin signaling does not affect mitochondrial ADP sensitivity, whereas the increased reliance on fatty acid oxidation in situations where insulin action is reduced may occur as a result of altered regulation of mitochondrial fatty acid transport through CPT-I.

AKR2A interacts with KCS1 to improve VLCFAs contents and chilling tolerance of Arabidopsis thaliana.

Arabidopsis thaliana AKR2A plays an important role in plant responses to cold stress. However, its exact function in plant resistance to cold stress remains unclear. In the present study, we found that the contents of very long-chain fatty acids (VLCFAs) in akr2a mutants were decreased, and the expression level of KCS1 was also reduced. Overexpression of KCS1 in the akr2a mutants could enhance VLCFAs contents and chilling tolerance. Yeast-2-hybrid and bimolecular fluorescence complementation (BIFC) results showed that the transmembrane motif of KCS1 interacts with the PEST motif of AKR2A both in vitro and in vivo. Overexpression of KCS1 in akr2a mutants rescued akr2a mutant phenotypes, including chilling sensitivity and a decrease of VLCFAs contents. Moreover, the transgenic plants co-overexpressing AKR2A and KCS1 exhibited a greater chilling tolerance than the plants overexpressing AKR2A or KCS1 alone, as well as the wild-type. AKR2A knockdown and kcs1 knockout mutants showed the worst performance under chilling conditions. These results indicate that AKR2A is involved in chilling tolerance via an interaction with KCS1 to affect VLCFA biosynthesis in Arabidopsis.

Depression, isotretinoin, and folic acid: A practical review.

Isotretinoin (ISO) is a first-generation retinoid discovered in 1952 and approved by the FDA for the treatment of nodulocystic acne in 1982. The anti-inflammatory properties of ISO have found its use in disorders other than acne. ISO can create psychiatric problems, including depression and suicidal ideation. These neuropsychiatric problems are very similar to disorders secondary to hyperhomocysteinemia (HHcy), vitamin B12, and folic acid (vitamin B9) deficiencies. Given that previous literature suggested folate supplementation improved the efficacy of traditional antidepressant medications, clinicians may wish to consider folate supplementation for patients with depression or possible depressive symptoms, such as acne patients with genetic susceptibility. Brain-derived neurotrophic factor may be a cytokine-specific screening biomarker in immune-based antidepressive therapy.

Individual milk fatty acids are potential predictors of enteric methane emissions from dairy cows fed a wide range of diets: Approach by meta-analysis.

There is a need to quantify methane (CH4) emissions with alternative methods. For the past decade, milk fatty acids (MFA) could be used as proxies to predict CH4 emissions from dairy cows because of potential common rumen biochemical pathways. However, equations have been developed based on a narrow range of diets and with limited data. The objectives of this study were to (1) construct a set of empirical models based on individual data of CH4 emissions and MFA from a large number of lactating dairy cows fed a wide range of diets; (2) further increase the models' level of complexity (from farm to research level) with additional independent variables such as dietary chemical composition (organic matter, neutral detergent fiber, crude protein, starch, and ether extract), dairy performance (milk yield and composition), and animal characteristics (days in milk or body weight); and (3) evaluate the performance of the developed models on independent data sets including measurements from individual animals or average measurements of groups of animals. Prediction equations based only on MFA [C10:0, iso C17:0 + trans-9 C16:1,cis-11 C18:1, and trans-11,cis-15 C18:2 for CH4 production (g/d); iso C16:0, cis-11 C18:1, trans-10 C18:1, and cis-9,cis-12 C18:2 for CH4 yield (g/kg of dry matter intake, DMI); and iso C16:0, cis-15 C18:1, and trans-10 + trans-11 C18:1 for CH4 intensity (g/kg of milk)] had a root mean squared error of 65.1 g/d, 2.8 g/kg of DMI, and 2.9 g/kg of milk, respectively, whereas complex equations that additionally used DMI, dietary neutral detergent fiber, ether extract, days in milk, and body weight had a lower root mean squared error of 46.6 g/d, 2.6 g/kg of DMI, and 2.7 g/kg of milk, respectively). External evaluation with individual or mean data not used for equation development led to variable results. When evaluations were performed using individual cow data from an external data set, accurate predictions of CH4 production (g/d) were obtained using simple equations based on MFA. Better performance was observed on external evaluation with individual data for the simple equation of CH4 production (g/d, based on MFA), whereas better performance was observed on external evaluation mean data for the simple equation of CH4 yield (g/kg of DMI). The performance of evaluation of the models is dependent on the domain of validity of the evaluation data sets used (individual or mean).