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Lipotoxicity has been considered the main cause of pancreatic beta-cell failure during type 2 diabetes development. Lipid droplets (LD) are believed to regulate the beta-cell sensitivity to free fatty acids (FFA), but the underlying molecular mechanisms are largely unclear. Accumulating evidence points, however, to an important role of intracellular sphingosine-1-phosphate (S1P) metabolism in lipotoxicity-mediated disturbances of beta-cell function. In the present study, we compared the effects of an increased irreversible S1P degradation (S1P-lyase, SPL overexpression) with those associated with an enhanced S1P recycling (overexpression of S1P phosphatase 1, SGPP1) on LD formation and lipotoxicity in rat INS1E beta-cells. Interestingly, although both approaches led to a reduced S1P concentration, they had opposite effects on the susceptibility to FFA. Overexpression of SGPP1 prevented FFA-mediated caspase-3 activation by a mechanism involving an enhanced lipid storage capacity and prevention of oxidative stress. In contrast, SPL overexpression limited LD biogenesis, content, and size, while accelerating lipophagy. This was associated with FFA-induced hydrogen peroxide formation, mitochondrial fragmentation, and dysfunction, as well as ER stress. These changes coincided with the upregulation of proapoptotic ceramides but were independent of lipid peroxidation rate. Also in human EndoC-βH1 beta-cells, suppression of SPL with simultaneous overexpression of SGPP1 led to a similar and even more pronounced LD phenotype as that in INS1E-SGPP1 cells. Thus, intracellular S1P turnover significantly regulates LD content and size and influences beta-cell sensitivity to FFA.

Although a high amount of brown adipose tissue (BAT) is associated with low plasma triglyceride concentration, the mechanism responsible for this relationship in people is not clear. Here, we evaluate the interrelationships among BAT, very-low-density lipoprotein triglyceride (VLDL-TG), and free fatty acid (FFA) plasma kinetics during thermoneutrality in women with overweight/obesity who had a low (

Carbon-13 isotopomics of triacylglycerol (TAG) fatty acids or free fatty acids in biological matrices holds considerable potential in food authentication, forensic investigations, metabolic studies, and medical research. However, challenges arise in the isotopic analysis of short- and medium-chain (C4 to C10) fatty acid methyl esters (SMCFAMEs) through gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). The high volatility of these esters results in losses during their preparation, leading to isotopic fractionation. Moreover, the methoxy group added to acyl chains requires the correction of δ13C values, thereby increasing the uncertainty of the final results. Analyzing free fatty acids (FFAs) addresses both issues encountered with SMCFAMEs. To achieve this objective, we have developed a new protocol enabling the isotopomics of individual fatty acids (FAs) by GC-C-IRMS. The same experiment also provides the FA profile, i.e., the relative percentage of each FA in the TAG hydrolysate or its concentration in the studied matrix. The method exhibited high precision, as evidenced by the repeatability and within-lab reproducibility of results when tested on TAGs from both animal and vegetal origins. Compared to the analysis of FAMEs by GC-C-IRMS, the current procedure also brings several improvements in alignment with the principles of green analytical chemistry and green sample preparation. Thus, we present a two-in-one method for 13C-isotopomic and metabolomic biomarker quantitation within quasi-universal TAG compounds, encompassing the short- and medium-acyl chains. [ABSTRACT FROM AUTHOR]

In this study we separated the chemical components of cork from Quercus variabilis by various solvent extraction and alcoholysis methods. We identified the content and chemical composition of suberin and dichloromethane extract with gas chromatography-mass spectrometry (GC-MS) and analyzed the antifungal effects of different cork extracts against wood-decaying fungi. The results showed that the main structural component of cork, suberin, averaging 36.34% of the total dry weight, exhibited a pronounced inhibitory effect on wood-decaying fungi, compared to the dichloromethane extract. By the end of the entire culture period, the colony diameter of white rot fungi was 5 mm in the 40 mg/mL suberin treatment group, 19 mm for brown rot fungi, both significantly smaller than the control group (90 mm). Hydroxy fatty acids, free fatty acids, and α,ω-diacids may be the key components contributing to the antifungal activity of suberin. The inhibitory mechanism of suberin components on wood-decaying fungi may involve suppressing the respiratory metabolism of the fungi and increasing the permeability of their cell membranes, thereby limiting their normal life activities. [ABSTRACT FROM AUTHOR]

Background: Phospholipase A2 (PLA2) is a large family of enzymes involved in the inflammatory process that catalyzes the hydrolysis of membrane phospholipids, leading to the production of free fatty acids and lysophospholipids, starting the arachidonic acid cascade. Their expression has been related to the behavior of several cancers. Our objective is to search for PLA2 expression in prostate cancer (PCa) tissue that correlates with prognosis and survival. Methods: Using qRT-PCR, we analyzed the expression levels of PLA2G1B, PLA2G2A, PLA2G2D, PLA2G4A, PLA2G4B, PLA2G4C, PLA2G4D, PLA2G4E, PLA2G4F, PLA2G6, PLA2G7, PLA2G16, PNPLA1, and PNPLA2 in PCa tissue from 108 patients submitted to radical prostatectomy, followed by a mean time of 163 months. Results: All PLA2 was overexpressed in PCa compared to normal tissue. Interestingly, higher expression of some PLA2 was related to favorable prognostic factors: lower levels of PSA (PLA2G2A, PLA2G4D), lower rates of lymph node metastasis (PLA2G16 and PLA2G1B), and organ-confined disease (PLA2G4A). Most importantly, PLAG4B was independently related to longer disease-free survival. Conclusion: This is the first study exploring comprehensively the expression levels of PLA2 in PCa, showing that the higher expression of some PLA2 should be used as biomarkers of good prognosis and longer disease-free survival. [ABSTRACT FROM AUTHOR]

Manouri, a protected designation of origin (PDO) cheese, is one of the most popular whey cheeses produced in Greece. The objective of the current study was to investigate if there are differences between artisanal and industrial Manouri cheeses regarding microbiological quality, volatile organic compounds (VOCs) profile and other quality parameters (colour, texture), sensory attributes and spectral characteristics detected by Fourier transform infrared spectroscopy (FT-IR) that may discriminate the samples. Differences were detected in the population of the dominant microbial groups, especially for lactic acid bacteria (LAB), Enterobacteriaceae and yeast counts. No discrimination was attained from the physicochemical analyses, except for the pH values. A total of 50 VOCs were identified, including ketones, lactones, free fatty acids, aldehydes, esters, alcohols and hydrocarbons. Sensory evaluation was carried out using a quantitative descriptive analysis (QDA) panel and a consumer panel. Consumers showed a preference for the artisanal Manouri, and the QDA panel revealed significant differences in 11 out of the 17 sensory attributes. Colour and texture analyses were also performed and showed specific differences in yellowness, as well as in fracturability and hardness. FT-IR spectral analysis demonstrated potential discrimination related to the phospholipid content and profile of artisanal and industrial Manouri. [ABSTRACT FROM AUTHOR]

Background: Altered gut metabolites, especially short-chain fatty acids (SCFAs), in feces and plasma are observed in patients with Parkinson's disease (PD). Objective: We aimed to investigate the colonic expression of two SCFA receptors, free fatty acid receptor (FFAR)2 and FFAR3, and gut barrier integrity in patients with PD and correlations with clinical severity. Methods: In this retrospective study, colonic biopsy specimens were collected from 37 PD patients and 34 unaffected controls. Of this cohort, 31 participants (14 PD, 17 controls) underwent a series of colon biopsies. Colonic expression of FFAR2, FFAR3, and the tight junction marker ZO-1 were assayed by immunofluorescence staining. The You Only Look Once (version 8, YOLOv8) algorithm was used for automated detection and segmentation of immunostaining signal. PD motor function was assessed with the Movement Disorder Society (MDS)-Unified Parkinson's Disease Rating Scale (UPDRS), and constipation was assessed using Rome-IV criteria. Results: Compared with controls, PD patients had significantly lower colonic expression of ZO-1 (p < 0.01) and FFAR2 (p = 0.01). On serial biopsy, colonic expression of FFAR2 and FFAR3 was reduced in the pre-motor stage before PD diagnosis (both p < 0.01). MDS-UPDRS motor scores did not correlate with colonic marker levels. Constipation severity negatively correlated with colonic ZO-1 levels (r = -0.49, p = 0.02). Conclusions: Colonic expression of ZO-1 and FFAR2 is lower in PD patients compared with unaffected controls, and FFAR2 and FFAR3 levels decline in the pre-motor stage of PD. Our findings implicate a leaky gut phenomenon in PD and reinforce that gut metabolites may contribute to the process of PD. [ABSTRACT FROM AUTHOR]

Summary: Crude fats and oils may have high free fatty acid (FFA) content depending on raw material quality and processing conditions. Their refining is always a challenge due to refining loss and the formation of some process contaminants such as 3‐monochloropropane‐1,2‐diol esters (3‐MCPDE), and glycidyl esters (GE). In this study, crude hazelnut oil having 12.10% FFA was degummed, bleached, and pre‐deacidified by a molecular distillation (MD) unit before neutralisation and deodorisation. Changes in FFA, diglyceride(DG), 3‐MCPDE, GE, and tocopherol contents were monitored. Almost no changes were detected in FFA and DG contents during degumming and bleaching while the latter resulted in the 3‐MCPDE formation and GE reduction. Some tocopherol losses were also observed after these steps. On the other hand, a huge amount of FFA was distilled (from 12.10% to 1.71%) by the MD process performed at 200 °C, 0.25 mbar, as well as with a 53.6% loss of tocopherol. The samples were then subjected to deodorisation before (MD‐PHY) and after neutralisation (MD‐CHE) at 230 °C under 2 mbar absolute pressure for 2, 4, and 8 h. While some 3‐MCPDE and GE formations were detected during MD‐CHE, there were almost no formations in these contaminants after MD‐PHY. When the bleached oil having 12.10% FFA was also directly deodorised at given conditions, no formations but some reductions in 3‐MCPDE and GE contents of the oils were determined, possibly because of esterification of FFA with DGs that are an important precursor of these contaminants. [ABSTRACT FROM AUTHOR]

Summary: Cocoa butter is the most important ingredient of chocolate, which determines its melting behaviour. Variations in the melting characteristics of cocoa butter can profoundly affect the performance and suitability for their industrial utilisation. Over time, researchers have been attempting to establish a logical relationship between cocoa butter's unique thermal properties and the amount of saturated to unsaturated fatty acids in mono, di and triglycerides, and fatty acids (as major components), and free fatty acids, soap, primary oxidation products, minerals, moisture, phospholipids, tocopherols, unsaponifiable matters and metals (as minor components) found in cocoa butter. In this research, the thermal behaviours of thirteen samples of cocoa butter with different origins were investigated using isothermal differential scanning calorimetry. The cocoa butters starting temperature of crystallisation, temperature of maximum heat release, temperature of completed crystallisation and the enthalpy of heat release during recrystallisation were evaluated. In addition, the chemical composition (moisture, acidity, peroxide, minerals and soap content), fatty acid and triacylglycerol composition were used to establish an MLP‐ANN with fourteen input neurons connected by two flexible, sigmoid activation function layers. The back‐propagation was used to train the artificial neural network (ANN) structure and optimise the error of prediction. The study showed that the MLP algorithm can predict the thermal behaviour of CB samples with trace error, regardless of plant growth and extract process condition. [ABSTRACT FROM AUTHOR]

BACKGROUND: Glasswort represents a novel alternative to KCl for replacing sodium in meat products. To evaluate the effects of Na reduction on the quality changes of a traditional dry cured belly due to storage, fresh bellies were dry‐salted with 2% NaCl (BCON), with 2% of a mixture containing 50% NaCl and 50% KCl (BKCl) or with 1% of a mixture of 90% NaCl and 10% powdered glasswort (BGW), dry‐cured, sliced, vacuum packaged and stored under refrigeration for 60 days. RESULTS: The BKCl and BGW bellies were lower in sodium by one‐third to one‐half compared to BCON (with 1.6 g Na/100 g). Neither BKCl, nor BGW significantly differed from BCON in free fatty acids (FFA) before and after storage, whereas BGW showed almost twice as much 2‐methylbutanal content as BCON. All bellies showed microbiological stability during storage. Micrococcaceae was the most abundant microbial group with values of 105 to 106 colony‐forming units g−1. The BGW presented higher Micrococcaceae counts (approximately one log unit) but lower microbial biodiversity than BCON. CONCLUSION: The two alternative dry salting methods reduced the sodium content in bellies, at the same time as ensuring chemical and microbiological stability during refrigerated vacuum storage. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

This study aims to address critical challenges such as global warming and energy sustainability by targeting the reduction of high NOx emissions in diesel engines. The effects of acetone (AC) and magnesium oxide (MgO) nanoparticles (NPs) as additives in improving the physicochemical properties of biodiesel derived from renewable, nonedible Pistacia terebinthus oil, which is abundant in Turkey and has a high free fatty acid (FFA) content of 5.8%, were investigated. Due to the high FFA content, a two‐step (esterification followed by transesterification [TR]) method was used for biodiesel production. Additionally, a quantitative analysis of biodiesel obtained by both single (TR) and two‐step methods was performed to address a gap in the literature. The addition of AC and MgO NPs to B20 (80% diesel fuel and 20% biodiesel) fuel resulted in reductions in the rate of pressure rise, instantaneous energy release, cylinder pressure, mean gas temperature, and cumulative heat release rate. However, brake‐specific fuel consumption increased, and brake thermal efficiency decreased. Emissions analyses showed a reduction in CO emissions by 6.65% with AC and 2.10% with AC + MgO, and a reduction in NOx emissions by 41.64% with AC and 46.03% with AC + MgO. However, hydrocarbon emissions increased by 26.48%. The study highlights the synergistic benefits of AC and MgO additives in biodiesel, presenting a viable strategy for improving the environmental and performance metrics of biodiesel blends. It provides new insights into alternative fuel formulations. [ABSTRACT FROM AUTHOR]

One of the main concerns in the production and processing of fishery products is the issue of storage and increasing its shelf life. In this regard, this study aims to investigate the effect of chitosan -chia seed gum coating (2% and 1.5% of the sample weight, respectively) on some chemical properties (the amount of free fatty acids, peroxide, thiobarbituric acid index, volatile nitrogenous bases and pH)., microbial (number of Escherichia coli bacteria) and sensory of phytophagous fish during storage period (0, 3, 6, 9 and 12 days) was done at refrigerator temperature. The results showed that the amount of free fatty acids, peroxide, thiobarbituric index, volatile nitrogenous bases and the number of Escherichia coli bacteria in all the samples increased with the increase in storage time, and this increase was less intense in the samples coated with chitosan -chia seed gum solution. The findings indicated that with increasing storage time, the pH level increased in the uncoated samples, but in the coated samples, the pH level decreased at first and then increased. The sensory evaluation of the samples also revealed that the overall acceptance of the samples decreased with the increase in storage time and after the third day of storage, the coated samples received more points than the uncoated samples from the evaluators. Finally, this study showed that the use of chitosan -chia seed gum coating can help increase the shelf life of fish fillets in the refrigerator [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the liquid-liquid equilibrium data for a ternary system of water, ethyl acetate and oil from the microalgae Scenedesmus obliquus at 298.15, 308.15, and 318.15 K. The potential of the ternary system was also investigated for the selective extraction of free fatty acids and neutral lipids from crude microalgae oil. The equilibrium data were obtained using a model oil formulated from a mixture of refined vegetable oils, with a fatty acid profile analogous to the dark and opaque algae oil. The experimental equilibrium curves and tie lines were provided as a function of temperature for a free fatty acid content of 2%, 20% and 40% (w/w). The free fatty acids in the model oil migrated preferentially to the ethyl acetate-rich phase in each of the systems under study, with extraction efficiencies ranging from 79.4% to 97.1%. However, the extraction efficiencies for the neutral lipids were lower (51.5–70.1%), indicating the preferential extraction of free fatty acids. The distribution coefficients of neutral lipids (1.06–2.34) and free fatty acids (3.85–33.2) were determined in order to better understand the selectivity of the green solvent, ethyl acetate, in the purification of crude oil from algae. The selectivity values varied from 1.84 to 28.6, indicating that the solvent was effective in concentrating neutral lipids and free fatty acids in the ethyl acetate-rich phase. The increase in free fatty acid content therefore reduced the partition coefficient for neutral lipids, improving its selectivity, and making it possible to concentrate this lipid class by liquid-liquid separation with ethyl acetate. [ABSTRACT FROM AUTHOR]

Efforts to meet the constantly increasing global energy demand without adverse environmental impacts have led to the development of alternative energy sources. Biodiesel, a biomass alternative, has been identified as a source with a potential substitute for fossil fuel-derived diesel for transportation purposes. Oxidation degradation is one of the primary obstacles hindering the commercialization of biodiesel, which has been established as a viable alternative to diesel derived from fossil fuels. In this research, the Rancimat method is used to find out how well three antioxidants—vitamins A, C, and E—improve the stability of biodiesel made from waste cooking oil. At a concentration of 1000 ppm, the selected antioxidants improved the oxidation stability of biodiesel. Vitamin C improved the waste cooking oil biodiesel induction period from 0.79 to 7 h most effectively. These results are because of the low bond dissociation energy (318.5 kJ/mol), the molecular weight (176.16 g/mol), and the formation of acetyl palmitate, known to possess antioxidant properties in oils. When antioxidants A and C (induction period = 12.9 h) and C and E (induction period = 7 h) were combined in a ratio of 1:1, they were more effective. The combination of A and E negatively affected the oxidation stability of waste cooking oil biodiesel, resulting in an induction period of 0.33 h. Herein, the present research has demonstrated that using antioxidant C, either alone or in conjunction with other natural antioxidants, positively impacts the oxidation stability of waste cooking oil biodiesel. [ABSTRACT FROM AUTHOR]

Uveal melanoma is a malignant tumor originating from melanocytes in the eye's uvea, often detected during routine ophthalmic examinations due to its typically asymptomatic nature. Despite effective local treatments, up to 50% of patients develop hematogenous metastases, highlighting the need for better prognostic markers and therapeutic targets. In this study, we developed an innovative Metastasis-Related Gene Signature (MERGS) score to classify patients from various cohorts. By establishing this scoring method, we discovered underlying mechanisms responsible for significant differences between samples with high and low MERGS scores. We identified a set of ten genes to construct MERGS, which showed a high predictive accuracy for patient survival. Further, Monoglyceride Lipase (MGLL) emerged as the most important gene in distinguishing uveal melanoma metastasis. Functional studies demonstrated that knocking down MGLL significantly inhibited proliferation, invasion, and migration of uveal melanoma cells in vitro and in vivo, while overexpression of MGLL enhanced these malignant behaviors. Additionally, MGLL modulated free fatty acid (FFA) levels within these cells. Our findings reveal MGLL as a crucial player in uveal melanoma progression and propose it as a novel therapeutic target, potentially leading to improved management and outcomes for patients with this disease. [ABSTRACT FROM AUTHOR]

For patients with type 1 diabetes mellitus complicated by severe hypoglycemia, clinical islet transplantation is an efficacious alternative to whole pancreas transplantation. While islet transplantation has improved over the last few years, there remain questions regarding its cost‐effectiveness and donor allosensitization, which is exacerbated when islets from more than one donor are required. Understanding the features of a pancreas that would provide viable islets prior to isolation may lead to development of an accurate assay that could identify suitable pancreases and provide significant cost savings to a clinical islet transplantation program. In this pilot study, solid‐state high‐resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy was used to assess samples of convenience of human pancreatic tissue taken prior to islet isolation both before and after incubation using the two‐layer perfluorocarbon (PFC)/University of Wisconsin (UW) solution cold‐storage method. We observed that, prior to incubation, human pancreatic tissue exhibited evidence of hypoxia with decreased peak integrals associated with glucose and increased peak integrals corresponding to lactate and free fatty acids. After incubation, we observed a reversal of the hypoxia‐induced damage, as integrals corresponding to glucose increased, and those corresponding to lactate and free fatty acid resonances decreased. Interestingly, a significant correlation between the ratio of the glucose integral (at 3.0–4.5 ppm) to the sum of the fatty acid (at 0.9 ppm) and lactate + fatty acid (at 1.3 ppm) integrals and glucose responsiveness, a measure of islet viability, of the isolated islets, was observed after incubation in PFC/UW solution for pancreases that responded to PFC/UW solution incubation (p = 0.02). Notably, pancreases with little or no change in the integral ratio after PFC/UW solution incubation had poor recovery. These results suggest that tissue recovery is a key feature for determining islet cell viability, and further that HRMAS NMR may be a practical method to quickly assess human donor pancreatic tissue prior to islet isolation for clinical transplantation. [ABSTRACT FROM AUTHOR]

ABSTRACT In this study, the influence of different ratios of sheep's to goat's milk (100:0, 75:25, 50:50, 25:75, and 0:100) on the content of functional metabolites and volatiles in Lighvan cheese throughout ripening was investigated. The samples were ripened under brine for 90 days and assessed in terms of variations in chemical composition, proteolysis, angiotensin‐converting enzyme, α‐amylase, and α‐glucosidase inhibitory activities, antioxidant power, total free amino acids, gamma amino butyric acid, free fatty acids, and volatile compounds. Results showed that by increasing the proportion of goat's milk, the samples exhibited higher antioxidant effect and inhibition of the angiotensin‐converting enzyme during ripening. After 90 days, an increase in α‐glucosidase and a slight decrease in α‐amylase inhibitory activities were observed in Lighvan cheese samples that were produced with 50%, 75% and 100% of goat's milk. In contrast, higher contents of sheep's milk led to a significant increase in the concentration of esters, terpenes and alcohols and a slight increase in gamma‐aminobutyric acid. The highest concentration of saturated and unsaturated fatty acids was observed in the cheese prepared with 100% raw sheep's milk after 90 days of ripening. The results revealed the possibility of making a functional white‐brined cheese by monitoring the type and ratio of the used milk and ripening time. [ABSTRACT FROM AUTHOR]

This study investigates the hepatoprotective effects of olive oil and flaxseed oil on chemically induced hepatotoxicity in rats by evaluating key biochemical parameters, including free fatty acids, iodine value, liver enzymes (ALP, ALT, AST), cholesterol, triglycerides, and HDL levels. The results demonstrated significant improvements in these markers with the administration of olive oil and flaxseed oil, either individually or in combination. The free fatty acid percentages and iodine values were consistent with the known nutritional properties of the oils. Notably, the combination of olive oil and flaxseed oil yielded the most substantial benefits, reducing ALP (115.53 ± 0.44 U/L), ALT (50.77 ± 1.46 U/L), and AST (52.12 ± 0.36 U/L) levels while improving lipid profiles by lowering cholesterol (135.4 ± 1.43 mg/dL) and triglyceride levels (57.14 ± 2.35 mg/dL) and increasing HDL levels (49.20 ± 0.45 mg/dL). These findings suggest that olive oil and flaxseed oil, due to their antioxidant and anti‐inflammatory properties, can effectively mitigate liver damage and promote lipid metabolism. The study supports the potential therapeutic application of these oils in managing liver health and preventing hepatotoxicity. [ABSTRACT FROM AUTHOR]

Obesity is one of the primary risk factors for osteoarthritis (OA), acting through cross talk among altered biomechanics, metabolism, adipokines, and dietary free fatty acid (FA) composition. Obesity and aging have been linked to cellular senescence in various tissues, resulting in increased local and systemic inflammation and immune dysfunction. We hypothesized that obesity and joint injury lead to cellular senescence that is typically associated with increased OA severity or with aging and that the ratio of omega-6 (ω-6) to omega-3 (ω-3) FAs regulates these pathologic effects. Mice were placed on an ω-6-rich high-fat diet or a lean control diet and underwent destabilization of the medial meniscus to induce OA. Obesity and joint injury significantly increased cellular senescence in subcutaneous and visceral fat as well as joint tissues such as synovium and cartilage. Using adeno-associated virus (AAV) gene therapy for fat-1, a fatty acid desaturase that converts ω-6 to ω-3 FAs, decreasing the serum ω-6:ω-3 FA ratio had a strong senomorphic and therapeutic effect, mitigating metabolic dysfunction, cellular senescence, and joint degeneration. In vitro coculture of bone marrow-derived macrophages and chondrocytes from control and AAV8-fat1-treated mice were used to examine the roles of various FA mediators in regulating chondrocyte senescence. Our results suggest that obesity and joint injury result in a premature “aging” of the joint as measured by senescence markers, and these changes can be ameliorated by altering FA composition using fat-1 gene therapy. These findings support the potential for fat-1 gene therapy to treat obesity- and/or injury-induced OA clinically [ABSTRACT FROM AUTHOR]

Background: The association between plasma free fatty acid (FFA) and the outcomes in the heart failure (HF) patients remains unclear. Methods: A cohort study among HF patients was performed. Plasma FFA was analyzed as both a continuous and a categorical variable (grouped by tertiles) to assess its association with composite cardiovascular (CV) death and HF hospitalization (CV death & HHP), CV death alone, and all-cause mortality (ACM) using Cox regression models. Subgroup analyses of HF patients with preserved ejection fraction (HFpEF) and mildly reduced/reduced ejection fraction (HFmrEF/HFrEF) were performed. This work also assessed the effectiveness of combining FFA and NT-pro BNP biomarkers for risk stratification by calculating the concordance index (C-index). Results: Among the 4,109 HF patients, FFA levels exceeding 0.4–0.42 mmol/L were associated with increased risks of the three outcomes. Patients in the highest FFA tertile faced greater risks than those in the lowest tertile. Adjusted hazard ratios were 1.32 (95% CI: 1.11–1.58) for CV death & HHP, 1.45 (95% CI: 1.16–1.82) for CV death, and 1.39 (95% CI: 1.15–1.68) for ACM, with a maximum follow-up of 8 years (median: 25 months). Subgroup analyses revealed that elevated FFA levels consistently predicted worse outcomes in both HFmrEF/HFrEF and HFpEF patients. The C-index for predicting outcomes was significantly greater when NT-pro BNP and FFA were combined than when NT-pro BNP was used alone (P < 0.01). Conclusion: Increased plasma FFA concentrations were independently associated with greater risks of CV death & HHP, CV death, and ACM among HF patients, irrespective of the ejection fraction. The combination of FFA and NT-pro BNP biomarkers significantly improved risk stratification in HF patients. [ABSTRACT FROM AUTHOR]

Postembryonic development of animals has long been considered an internally predetermined program, while macronutrients were believed to be essential solely for providing biomatters and energy to support this process. However, in this study, by using a nematode Caenorhabditis elegans (abbreviated as C. elegans hereafter) model, we surprisingly discovered that dietary supplementation of palmitic acid alone, rather than other abundant essential nutrients such as glucose or amino acid mixture, was sufficient to initiate early postembryonic development even under complete macronutrient deprivation. Such a development was evidenced by changes in morphology, cellular markers in multiple tissues, behaviors, and the global transcription pattern and it occurred earlier than the well-known early L1 nutrient checkpoint. Mechanistically, palmitic acid did not function as a biomatter/energy provider, but rather as a ligand to activate the nuclear hormone receptor NHR-49/80, leading to the production of an unknown peroxisome-derived secretive hormone in the intestine. This hormonal signal was received by chemosensory neurons in the head, regulating the insulin-like neuropeptide secretion and its downstream nuclear receptor to orchestrate global development. Additionally, the nutrient-sensing hub mTORC1 played a negative role in this process. In conclusion, our data indicate that free fatty acids act as a primary nutrient signal to launch the early development in C. elegans, which suggests that specific nutrients, rather than the internal genetic program, serve as the first impetus for postembryonic development. Macronutrients are known to provide biomatter and energy to postembryonic development in animals. This study shows that free fatty acids act as a primary nutrient signal to trigger early development in C. elegans, expanding the traditional function of specific nutrients. [ABSTRACT FROM AUTHOR]

There is an urgent need for better biomarkers for the detection of early-stage breast cancer. Utilizing untargeted metabolomics and lipidomics in conjunction with advanced data mining approaches for metabolism-centric biomarker discovery and validation may enhance the identification and validation of novel biomarkers for breast cancer screening. In this study, we employed a multimodal omics approach to identify and validate potential biomarkers capable of differentiating between patients with breast cancer and those with benign tumors. Our findings indicated that ether-linked phosphatidylcholine exhibited a significant difference between invasive ductal carcinoma and benign tumors, including cases with inconsistent mammography results. We observed alterations in numerous lipid species, including sphingomyelin, triacylglycerol, and free fatty acids, in the breast cancer group. Furthermore, we identified several dysregulated hydrophilic metabolites in breast cancer, such as glutamate, glycochenodeoxycholate, and dimethyluric acid. Through robust multivariate receiver operating characteristic analysis utilizing machine learning models, either linear support vector machines or random forest models, we successfully distinguished between cancerous and benign cases with promising outcomes. These results emphasize the potential of metabolic biomarkers to complement other criteria in breast cancer screening. Future studies are essential to further validate the metabolic biomarkers identified in our study and to develop assays for clinical applications. [ABSTRACT FROM AUTHOR]

Non‐alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Hepatic lipid deposition is a key factor in the development of NAFLD. N6‐methyladenosine (m6A) modification, the most prevalent mRNA modification in eukaryotic cells, plays an important role in regulating hepatic lipid metabolism. However, its potential role in hepatic lipid deposition remains poorly understood. Histological and immunohistochemistry studies were used to investigate lipid deposition in free fatty acids (FFAs)‐incubated LO2 cells, high‐fat diet‐fed mice models and clinical samples. Stable overexpression and knockdown of AlkB homolog 5 (ALKBH5) was manipulated to investigate the effects of ALKBH5 on m6A methylation and lipid metabolism in hepatocytes. RNA‐sequencing transcriptome analysis and methylated RNA immunoprecipitation‐quantitative‐PCR analysis were used to reveal the potential downstream molecular targets of ALKBH5. ALKBH5 was down‐regulated in fatty liver compared to normal liver in both humans and mice. Overexpression of ALKBH5 significantly improved FFA‐induced lipid accumulation and promoted autophagosome‐lysosome fusion in hepatocytes. Meanwhile, knockdown of ALKBH5 significantly increased the expression of microtubule‐associated protein 1A/1B‐light chain 3B and Sequestosome 1, leading to impaired autophagic flux and further lipid deposition in hepatocytes under FFA incubation. Overexpression of vacuolar protein sorting 11 (VPS11) reversed FFA‐induced lipid accumulation in ALKBH5‐silenced hepatocytes. Mechanistically, ALKBH5 alleviated hepatic lipid deposition and impaired autophagic flux by removing the m6A modification on VPS11 mRNA to promote its translation. Collectively, our findings revealed an epigenetic mechanism by which ALKBH5 alleviates hepatic lipid deposition by restoring VPS11‐dependent autophagic flux, providing a potential target to counteract NAFLD. [ABSTRACT FROM AUTHOR]

Abstract\nKEY POLICY HIGHLIGHTSMetformin is known for its antioxidant properties and ability to ameliorate metabolic dysfunction-associated fatty liver disease (MAFLD) and is the focus of this study. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is linked to MAFLD risk. This study investigated the effects of metformin on ferroptosis in free fatty acid (FFA)-treated Huh7 hepatoma cells and its association with MAFLD risk. Using Western blot, immunofluorescence, and ELISA, this study revealed that FFA treatment led to increased intracellular fat and iron accumulation, heightened Lp-PLA2 expression, reduced levels of the cysteine transporter SLC7A11 and glutathione peroxidase 4 (GPX4), altered glutathione (GSH)/oxidized glutathione (GSSG) ratios, generation of reactive oxygen species (ROS), and initiation of lipid peroxidation, which ultimately resulted in cell ferroptosis. Importantly, metformin reversed FFA-induced iron accumulation, and this effect was attenuated by ferrostatin-1 but enhanced by erastin, RSL3, and si-GPX4. Additionally, metformin activated antioxidant and antiapoptotic mechanisms, which reduced lipid peroxidation and suppressed Lp-PLA2 expression in FFA-treated Huh7 cells. In conclusion, our findings indicate that metformin may protect against MAFLD by inhibiting iron accumulation and Lp-PLA2 expression through the ROS, ferroptosis, and apoptosis signaling pathways. This study highlights potential therapeutic strategies for managing MAFLD-related risks and emphasizes the diverse roles of metformin in maintaining hepatocyte balance.Metformin lowered Lp-PLA2 levels in human Huh7 hepatoma cells.Both fatty acid and iron metabolism improved after metformin treatment.Metformin alleviated oxidative stress, apoptosis, lipid peroxidation and ferroptosis.Metformin lowered Lp-PLA2 levels in human Huh7 hepatoma cells.Both fatty acid and iron metabolism improved after metformin treatment.Metformin alleviated oxidative stress, apoptosis, lipid peroxidation and ferroptosis. [ABSTRACT FROM AUTHOR]

Changes in the physical, biochemical, and microbiological properties of Pangasius mince incorporated with 2% (w/w) sodium alginate and salt were evaluated for 120 days under frozen conditions (−20 °C). The TBARS (0.03–0.62 mg MDA/kg) and free fatty acid (FFA) (<1 mg oleic acid/100 g) were found to be significantly lower in the alginate-treated sample (T2) than in the control mince (C) and salt-added mince sample (T1). Better visual appearance, higher water retention, less moisture reduction (only 1.5%) along with lower total volatile base nitrogen (TVBN) (10–17 mg N/100 g) and TVC (<4 log cfu/g) were evident in T2 throughout the storage period than in T1 and control. [ABSTRACT FROM AUTHOR]

Background: Organisms have evolved a range of phenotypic and genetic adaptations to live in different environments along an altitudinal gradient. Herein, we studied the widely distributed Chinese toad, Bufo gargarizans, as a model and used an integrated phenotype-genotype approach to assess adaptations to different altitudinal environments. Results: Comparison of populations from four altitudes (50 m, 1200 m, 2300 m, and 3400 m) showed more effective defenses among high-altitude toads. These included thickened epidermis, more epidermal capillaries and granular glands, greater gland size in skin, and higher antioxidant enzyme activities in plasma. High-altitude toads also showed increased erythrocytes and hematocrit and elevated hemoglobin concentration, potentially improving oxygen delivery. Elevated altitude led to a metabolic shift from aerobic to anaerobic metabolism, and high-altitude populations favored carbohydrates over fatty acids to fuel for energy metabolism. Differentially expressed genes were associated with adaptive phenotypic changes. For instance, expression of genes associated with fatty acid metabolism showed greater suppression at high altitude (3400 m), consistent with decreased flux of β-hydroxybutyric acid and lower free fatty acids levels. Moreover, down-regulation of genes involved in carbon metabolism processes at high altitude (3400 m) were coincident with reduced TCA cycle flux. These results suggest that high-altitude toads adopt a metabolic suppression strategy for survival under harsh environmental conditions. Moreover, the hypoxia-inducible factor signaling cascade was activated at high altitude. Conclusions: Collectively, these results advance our comprehension of adaptation to high-altitude environments by revealing physiological and genetic mechanisms at work in Chinese toads living along altitudinal gradients. [ABSTRACT FROM AUTHOR]

SUMMARY Photosynthetic electron transport is carried out by the electron carrier, plastoquinone (PQ). Recently, another form of PQ, acylplastoquinol (APQ), was discovered in Synechocystis sp. PCC 6803 (Synechocystis), but its physiological function in photosynthesis is unclear. In the present study, we identified a lipase encoded in sll0482 gene in Synechocystis that deacylates APQ and releases a free fatty acid and a reduced PQ (plastoquinol, PQH2), which we named acylplastoquinol lipase (APL). Disruption of apl gene increased APQ content, and recovery of photodamaged PSII under low light (LL) after the exposure to very high light (vHL) at 2500 μmol photons m−2 sec−1 without aeration (vHL) for 60 min, was suppressed in the Δapl cells. Δapl cells also show the slow rate of de novo synthesis of D1, a reaction center of PSII under such condition. Under high light, the cellular growth of Δapl was inhibited; however, disruption of apl gene did not affect the photosynthetic activity or photoinhibition of PSII. In wild‐type cells, APQ content increased under vHL condition. Also, APQ was converted to PQH2 after transfer to LL with aeration by ambient air. Such striking changes in APQ were not observed in Δapl cells. The deacylation of APQ by APL may help repair PSII when PSII cannot drive photosynthetic electron transport efficiently. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Sea buckthorn (Hippophae rhamnoides L.) pulp oil is rich in functional components; however, low water solubility and stability limit its applications. This study fabricated sea buckthorn pulp oil microcapsules using whey protein isolate (WPI), soy protein isolate (SPI), sodium caseinate (NaCN), gum arabic (GA), starch sodium octenylsuccinate (OSAS) and SPI mixed with chitosan (CHI). The influences of these wall materials on physicochemical properties, release behavior and digestibility were explored.Protein‐based wall materials (WPI, NaCN, SPI) demonstrated lower bulk densities due to their porous structures and larger particle sizes, while GA and OSAS produced denser microcapsules. Encapsulation efficiency was the highest for protein‐based microcapsules (79.41–89.12%) and the lowest for GA and OSAS. The surface oil percentage of protein‐based microcapsules (1.41–4.40%) was lower than that of the other microcapsules. Protein‐based microcapsules showed concave and cracked surfaces, while GA and OSAS microcapsules were spherical and smooth. CHI improved reconstitution performance, leading to faster dissolution. During simulated gastrointestinal digestion, protein‐based microcapsules released more free fatty acids (FFAs) in the intestinal phase, while CHI‐modified SPI microcapsules showed a delayed release pattern due to thicker walls.Protein‐based wall materials were more effective for sea buckthorn pulp oil microencapsulation, providing higher encapsulation efficiency, better flow properties and releasing more FFAs. The addition of CHI led to the layer‐by‐layer self‐assembly of the microcapsule wall and resulted in sustained release during in vitro intestinal digestion. These findings suggested the potential of protein‐based microcapsules for targeted delivery and improved applications of bioactive oils in the food industry. © 2024 Society of Chemical Industry. Published by John Wiley & Sons Ltd [ABSTRACT FROM AUTHOR]

The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway in hepatocellular carcinoma (HCC) is limited. NOD-like receptors (NLRs) comprise a highly evolutionarily conserved family of cytosolic bacterial sensors, yet their impact on antitumor immunity against HCC remains unclear. In this study, we uncovered that NOD1, a well-studied member of NLR family, exhibits predominant expression in tumor-associated macrophages (TAMs) and correlates positively with improved prognosis and responses to anti-PD-1 treatments in patients with HCC. Activation of NOD1 in vivo augments antitumor immunity and enhances the effectiveness of anti-PD-1 therapy. Mechanistically, NOD1 activation resulted in diminished expression of perilipin 5, thereby hindering fatty acid oxidation and inducing free fatty acid accumulation in TAMs. This metabolic alteration promoted membrane localization of the costimulatory molecule OX40L in a lipid modification-dependent manner, thereby activating CD8+ T cells. These findings unveil a previously unrecognized role for NOD1 in fortifying antitumor T cell immunity in HCC, potentially advancing cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Subquality argan kernels are 30% cheaper than the regular kernels mandatory used to prepare edible argan oil. The use of these argan kernels for the preparation of argan oil intended to be a cosmetic ingredient, after bleaching and deodorization, is therefore particularly economically appealing. The oxidative stability of Argan oil prepared from subquality kernels is unknown. It was evaluated over a period of storage of 12 weeks at 60 °C, then compared with that of argan oil stored under the same conditions and originating from the same initial batch, but which had subsequently been simply bleached and deodorized (physical refining). Physical refining led to an increase in initial oil quality due the loss of free fatty acids (up to 30% for refined argan oil), primary and secondary oxidation products but also to a dramatic decrease of the oxidative stability of argan oil caused by the loss of tocopherols, witnessed by the up to 94% loss after 12 weeks under accelerated storage conditions. As a conclusion, the oxidative stability of argan oil prepared from subquality argan kernels remains difficult to be adequately and efficiently evaluated since the initial quality of the argan kernels is the subject of great variations. [ABSTRACT FROM AUTHOR]

In this study, the effects of different raw materials, different processing temperatures, and storage temperatures on some properties of butter oil were investigated. Two different kinds of butter were produced from cream containing 40% milk fat. Both butter samples were processed into butter oil at three different temperatures (60, 90, and 120°C). Butter and butter oil samples were stored at +4°C and analyses were performed at 0, 30, and 60 days of storage. There are no significant differences between the atherogenicity index and the saturated and unsaturated fatty acid composition of butter and butter oil samples. Free fatty acid values of all samples increased during storage. Also, in all three storage periods, it was determined that free fatty acids were higher in butter samples than in butter oil samples. During storage, saturated and unsaturated free fatty acid values are generally higher in butter oil processed at 60°C than in butter oil processed at 90°C and 120°C. In total, 40 volatile compounds were detected, which included 8 ketones, each of 6 aldehydes, alcohols, acids, and hydrocarbons, 5 terpenes, and 3 esters in butter and butter oil samples. Aldehydes and ketones were generally highest in butter oil processed at 120°C. [ABSTRACT FROM AUTHOR]

Interaction between the cold rolling oil and substrate at the roll bite has always intrigued the tribologists. In plant conditions, it has been observed that occurrences of surface defects on cold‐rolled FHCR coils increase with the ageing of cold rolling emulsion. In this study, the rolling oil was aged at different lab conditions to replicate 6 and 11 months of rolling oil ageing from a particular cold rolling mill. The studies indicated an increase in acid number of the oil. Tribological studies indicated an increase in CoF along with an increase in wear phenomenon on the substrate. The removability of the surface oil becomes difficult with ageing which could lead to potential surface oil residues remaining on the strip after degreasing, resulting in surface defects and dirty coils after annealing. Deterioration in anti‐stain property is also observed as ageing progresses. The deterioration in performance is mainly governed by the depletion in additives and generation of free fatty acids within the rolling oil bath. Proper maintenance of the bath ensures lesser defect formation. [ABSTRACT FROM AUTHOR]

Lipotoxicity is defined as a prolonged metabolic imbalance of lipids that results in ectopic fat distribution in peripheral organs such as the liver, heart, and kidney. The harmful consequences of excessive lipid accumulation in cardiomyocytes cause cardiac lipotoxicity, which alters the structure and function of the heart. Obesity and diabetes are linked to lipotoxic cardiomyopathy. These anomalies might be caused by a harmful metabolic shift that accumulates toxic lipids and shifts glucose oxidation to less fatty acid oxidation. Research has linked fatty acids, fatty acyl coenzyme A, diacylglycerol, and ceramide to lipotoxic stress in cells. This stress can be brought on by apoptosis, impaired insulin signaling, endoplasmic reticulum stress, protein kinase C activation, p38 Ras-mitogen-activated protein kinase (MAPK) activation, or modification of peroxisome proliferator–activated receptors (PPARs) family members. Curcuma longa is used to extract curcumin, a hydrophobic polyphenol derivative with a variety of pharmacological characteristics. Throughout the years, curcumin has been utilized as an anti-inflammatory, antioxidant, anticancer, hepatoprotective, cardioprotective, anti-diabetic, and anti-obesity drug. Curcumin reduces cardiac lipotoxicity by inhibiting apoptosis and decreasing the expression of apoptosis-related proteins, reducing the expression of inflammatory cytokines, activating the autophagy signaling pathway, and inhibiting the expression of endoplasmic reticulum stress marker proteins. [ABSTRACT FROM AUTHOR]

Microbial biofilm formation on medical devices paves the way for device-associated infections. Staphylococcus epidermidis is one of the most common strains involved in such infections as it is able to colonize numerous devices, such as intravenous catheters, prosthetic joints, and heart valves. We previously reported the antibiofilm activity against S. epidermidis of pentadecanoic acid (PDA) deposited by drop-casting on the silicon-based polymer poly(dimethyl)siloxane (PDMS). This material exerted an antibiofilm activity by releasing PDA; however, a toxic effect on bacterial cells was observed, which could potentially favor the emergence of resistant strains. To develop a PDA-functionalized material for medical use and overcome the problem of toxicity, we produced PDA-doped PDMS by either spray-coating or PDA incorporation during PDMS polymerization. Furthermore, we created a strategy to assess the kinetics of PDA release using ADIFAB, a very sensitive free fatty acids fluorescent probe. Spray-coating resulted in the most promising strategy as the concentration of released PDA was in the range 0.8–1.5 μM over 21 days, ensuring long-term effectiveness of the antibiofilm molecule. Moreover, the new coated material resulted biocompatible when tested on immortalized human keratinocytes. Our results indicate that PDA spray-coated PDMS is a promising material for the production of medical devices endowed with antibiofilm activity. [ABSTRACT FROM AUTHOR]

As the sole producers of insulin under physiological conditions, the normal functioning of pancreatic β cells is crucial for maintaining glucose homeostasis in the body. Due to the high oxygen and energy demands required for insulin secretion, hypoxia has been shown to play a critical role in pancreatic β-cell dysfunction. Lipid metabolism abnormalities, a common metabolic feature in type 2 diabetic patients, are often accompanied by tissue hypoxia caused by metabolic overload and lead to increased free fatty acid (FFA) levels. However, the specific mechanisms underlying FFA-induced β-cell dysfunction remain unclear. Nicotinamide mononucleotide (NMN), a naturally occurring bioactive nucleotide, has garnered significant attention in recent years for its effectiveness in replenishing NAD+ and alleviating various diseases. Nevertheless, studies exploring the mechanisms through which NMN influences β-cell dysfunction remain scarce. In this study, we established an in vitro β-cell dysfunction model by treating INS-1 cells with palmitate (PA), including control, PA-treated, and PA combined with NMN or activator/inhibitor groups. Compared to the control group, cells treated with PA alone showed significantly reduced insulin secretion capacity and decreased expression of proteins related to the NAD+/AMPK/SIRT1/HIF-1α pathway. In contrast, NMN supplementation significantly restored the expression of pathway-related proteins by activating NAD+ and effectively improved insulin secretion. Results obtained using HIF-1α and AMPK inhibitors/activators further supported these findings. In conclusion, our study demonstrates that NMN reversed the PA-induced downregulation of the NAD+/AMPK/SIRT1/HIF-1α pathway, thereby alleviating β-cell dysfunction. Our study investigated the mechanisms underlying PA-induced β-cell dysfunction, examined how NMN mitigates this dysfunction and offered new insights into the therapeutic potential of NMN for treating β-cell dysfunction and T2DM. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition worldwide, demanding further investigation into its pathogenesis. Circular RNAs (circRNAs) are emerging as pivotal regulators in MASLD processes, yet their pathological implications in MASLD remain poorly understood. This study focused on elucidating the role of circular RNA ribonucleotide reductase subunit M2 (circRRM2) in MASLD progression. In this study, we used both in vitro and in vivo MASLD models using long-chain-free fatty acid (FFA)-treated hepatocytes and high-fat diet (HFD)-induced MASLD in mice, respectively. We determined the expression patterns of circRRM2, microRNA-142-5p (miR-142-5p), and neuregulin 1 (NRG1) in livers of MASLD-afflicted mice and MASLD hepatocytes by RT-qPCR. Dual-luciferase reporter assays verified the binding relationships among circRRM2, miR-142-5p, and NRG1. We conducted further analyses of their roles in MASLD hepatocytes and modulated circRRM2, miR-142-5p, and NRG1 expression in vitro by transfection. Our findings were validated in vivo. The results demonstrated reduced levels of circRRM2 and NRG1, along with elevated miR-142-5p expression in MASLD livers and hepatocytes. Overexpression of circRRM2 downregulated lipogenesis-related genes and decreased triglycerides accumulation in livers of MASLD mice. MiR-142-5p, which interacts with circRRM2, effectively counteracted the effects of circRRM2 in MASLD hepatocytes. Furthermore, NRG1 was identified as a miR-142-5p target, and its overexpression mitigated the regulatory impact of miR-142-5p on MASLD hepatocytes. In conclusion, circRRM2, via its role as a miR-142-5p sponge, upregulating NRG1, possibly influenced triglycerides accumulation in both in vitro and in vivo MASLD models. NEW & NOTEWORTHY: CircRRM2 expression was downregulated in free fatty acid (FFA)-challenged hepatocytes and high-fat diet (HFD) fed mice. Overexpressed circular RNA ribonucleotide reductase subunit M2 (circRRM2) attenuated metabolic dysfunction-associated steatotic liver disease (MASLD) development by suppressing FFA-induced triglycerides accumulation. CircRRM2 targeted microRNA-142-5p (miR-142-5p), which served as an upstream inhibitor of neuregulin 1 (NRG1) and collaboratively regulated MASLD progression. [ABSTRACT FROM AUTHOR]

Free fatty acids (FFAs) have emerged as significant risk factors for atherosclerosis (AS). Prolonged exposure to FFAs induces vascular endothelial injury, including inflammatory responses and oxidative stress, which are central events in AS. Chromofungin (CHR), a peptide derived from chromogranin A (CGA), has been implicated in various biological functions. However, its physiological roles in endothelial biology and its involvement in the pathological development of AS have not been previously reported. In the present study, we investigated the underlying mechanisms through which CHR exerts its beneficial effects on FFA‐challenged human aortic endothelial cells (HAECs). We found that treatment with CHR ameliorated the FFA‐induced reduction in cell viability and increase in lactate dehydrogenase (LDH) release. Additionally, CHR mitigated oxidative stress by reducing mitochondrial reactive oxygen species (ROS) levels and increasing superoxide dismutase (SOD) activity. Furthermore, exposure to FFAs increased NADPH oxidase (NOX) 4 expression at both the mRNA and protein levels, which were attenuated by CHR in a dose‐dependent manner. Notably, CHR reduced the levels of nucleotide‐binding domain and leucine‐rich repeat‐containing (NLR) family pyrin domain containing 3 (NLRP3), apoptosis‐associated speck‐like protein containing a CARD (ASC), and cleaved caspase‐1 (p10), key components of the NLRP3 inflammasome complex, as well as interleukin 1β (IL‐1β) and interleukin‐18 (IL‐18) expression. Mechanistically, it was demonstrated that FFAs reduced the phosphorylation of AMP‐activated protein kinase (AMPK) and acetyl‐CoA carboxylase (ACC), which were rescued by CHR in a dose‐dependent manner. Conversely, inhibition of AMPK with its specific inhibitor compound C abolished the protective effects of CHR against FFA‐induced activation of the NLRP3 inflammasome in HAECs. Based on these findings, we conclude that CHR may serve as a promising agent for maintaining normal endothelial cell function and treating AS. [ABSTRACT FROM AUTHOR]

Summary: Fish can justify a healthy human diet. Spoilage is caused due to microbial degradation and oxidative rancidity. Herbs and spices (H&S) are common ingredients in fish marination to improve quality and appeal to consumers globally. The given review delves into the potential of H&S to extend the freshness of fish while also addressing challenges in maximising their effectiveness for preservation and proposing innovative solutions. H&S with antimicrobial (AM) and antioxidative (AO) effects reduce biogenic amine (BA) formation by inhibiting the decarboxylation of free amino acids through microbial reduction and retarding lipid oxidation of free fatty acids by countering free radicals. Combining organoleptically standardised H&S with diverse microbial hurdle techniques supports extensive domestic utilisation, extending the shelf life of fish significantly compared to using them alone. The present findings recommend that H&S can maintain fish quality for 6–20 days, depending on the fish species, packaging, and AO/AM potential in refrigeration conditions. Thyme, garlic, ginger, stevia, turmeric, laurel, sage, cinnamon, cumin, mint, and rosemary are found to be the most potent preservatives that could be utilised commercially to increase fish's shelf life. Variations in H&S extracts and fish muscle composition pose challenges in optimising the effectiveness of bioactive compounds in fish preservation. Innovative approaches for utilising H&S essential oils (EOs) and advanced delivery techniques offer solutions to these challenges, leading to improved fish quality and limited shelf life. [ABSTRACT FROM AUTHOR]

ABSTRACT Context Objective Design Patients Results Conclusions Congenital Hyperinsulinism (CHI) is associated with inappropriately high levels of C‐peptide in the context of hypoglycemia.We aimed to better clarify a diagnostic threshold value of C‐peptide for children presenting with CHI.This was a retrospective case‐control analysis, examining all hypoglycemia screens, undertaken between 2009 and 2019 at a quaternary paediatrics unit. Plasma C‐peptide, insulin, free fatty acid (FFA) and B‐hydroxybutyrate (BHOB) concentrations in children diagnosed with CHI were compared with concentrations in children diagnosed with other conditions.All patients requiring hypoglycaemic screens at the quaternary children's hospital were analysed.Median [C‐peptide] were statistically significantly different between CHI (147) and non‐CHI (72) patients, p < 0.05. The Youden Index indicated that a [C‐peptide] value of 291.5 pmol/L would give the greatest optimization of sensitivity (82%) and specificity (99%) for detecting CHI. Median [insulin] differed significantly between the cohorts with a level of 64 pmol/L for CHI patients compared with 0 pmol/L with non‐CHI patients (p < 0.01). Median [BOHB] was 0 μmol/L in CHI patients as compared with 2378 μmol/L for non‐CHI patients (p < 0.01). Median [FFA] levels were 1910 μmol/L in the non‐CHI cohort, compared with 0 in the CHI cohort (p < 0.01).This study suggests that a C‐peptide concentration greater than 291.5 pmol/L is diagnostic of CHI in children. C‐peptide appears to offer the greatest utility as a biochemical diagnostic test for CHI and could be prioritised for laboratory analysis. [ABSTRACT FROM AUTHOR]

Background: Free fatty acids (FFAs) are established risk factors for various cardiovascular and metabolic disorders. Elevated FFAs can trigger inflammatory response, which may be associated with the occurrence of acute respiratory distress syndrome (ARDS) in cardiac surgery. In this prospective study, we aimed to investigate the association between circulating FFA and the incidence of ARDS, as well as the length of ICU stay, in patients undergoing off-pump coronary artery bypass grafting (CABG). Methods: We conducted a single-center, prospective, observational study among patients undergoing off-pump CABG. The primary endpoint was the occurrence of ARDS within 6 days after off-pump CABG. Serum FFA were measured at baseline and 24 h post-procedure, and the difference (Δ-FFA) was calculated. Results: A total of 180 patients were included in the primary analysis. The median FFA was 2.3 mmol/L (quartile 1 [Q1]–Q3, 1.4–3.2) at baseline and 1.5 mmol/L (Q1–Q3, 0.9–2.3) 24 h after CABG, with a Δ-FFA of 0.6 mmol/L (Q1–Q3, -0.1 to 1.6). Patients with elevated Δ-FFA levels had a significantly higher ARDS occurrence (55.6% vs. 22.2%; P < 0.001). Elevated Δ-FFA after off-pump CABG correlated with a significantly lower PaO2/FiO2 ratio, prolonged mechanical ventilation, and extended length of ICU stay. The area under the curve (AUC) of Δ-FFA for predicting ARDS (AUC, 0.758; 95% confidence interval, 0.686–0.831) significantly exceeded the AUC of postoperative FFA (AUC, 0.708; 95% CI 0.628–0.788; P < 0.001). Conclusions: Elevated Δ-FFA levels correlated with ARDS following off-pump CABG. Monitoring FFA may assist in identifying high-risk patients for ARDS, facilitating timely interventions to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

This review explores the pivotal role of the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in the pathogenesis of diabetes and its complications, highlighting the therapeutic potential of various oral hypoglycemic drugs targeting this pathway. NLRP3 inflammasome activation, triggered by metabolic stressors like hyperglycemia, hyperlipidemia, and free fatty acids (FFAs), leads to the release of pro-inflammatory cytokines interleukin-1β and interleukin-18, driving insulin resistance, pancreatic β-cell dysfunction, and systemic inflammation. These processes contribute to diabetic complications such as nephropathy, neuropathy, retinopathy, and cardiovascular diseases (CVD). Here we discuss the various transcriptional, epigenetic, and gut microbiome mediated regulation of NLRP3 activation in diabetes. Different classes of oral hypoglycemic drugs modulate NLRP3 inflammasome activity through various mechanisms: sulfonylureas inhibit NLRP3 activation and reduce inflammatory cytokine levels; sodium–glucose co-transporter 2 inhibitors (SGLT2i) suppress inflammasome activity by reducing oxidative stress and modulating intracellular signaling pathways; dipeptidyl peptidase-4 inhibitors mitigate inflammasome activation, protecting against renal and vascular complications; glucagon-like peptide-1 receptor agonists attenuate NLRP3 activity, reducing inflammation and improving metabolic outcomes; alpha-glucosidase inhibitors and thiazolidinediones exhibit anti-inflammatory properties by directly inhibiting NLRP3 activation. Agents that specifically target NLRP3 and inhibit their activation have been identified recently such as MCC950, Anakinra, CY-09, and many more. Targeting the NLRP3 inflammasome, thus, presents a promising strategy for managing diabetes and its complications, with oral hypoglycemic drugs offering dual benefits of glycemic control and inflammation reduction. Further research into the specific mechanisms and long-term effects of these drugs on NLRP3 inflammasome activity is warranted. [ABSTRACT FROM AUTHOR]

Treatment with glucagon-like peptide 1 receptor agonists reduces liver steatosis and cardiometabolic risk (CMR). Few data are available on lipid metabolism, and no information is available on the postprandial lipidomic profile. Thus, we investigated how exenatide treatment changes lipid metabolism and composition during fasting and after a mixed-meal tolerance test (MMTT) in adults with severe obesity without diabetes. Thirty individuals (26 females and 4 males, 30–60 years old, BMI >40 kg/m2, HbA1c 5.76%) were assigned (1:1) to diet with exenatide 10 μg twice daily treatment (n = 15) or without treatment as control (n = 15) for 3 months. Fasting and postprandial lipidomic profile (by liquid chromatography quadrupole time-of-flight mass spectrometry) and fatty acid metabolism (following a 6-h MMTT/tracer study) and composition (by gas chromatography-mass spectrometry) were evaluated before and after treatment. Both groups had slight weight loss (−5.5% vs. −1.9%, exenatide vs. control; P = 0.052). During fasting, exenatide, compared with control, reduced some ceramides (CERs) and lysophosphatidylcholines (LPCs) previously associated with CMR, while relatively increasing unsaturated phospholipid species (phosphatidylcholine [PC], LPC) with protective effects on CMR, although concentrations of total lipid species were unchanged. During MMTT, both groups showed suppressed lipolysis equal to baseline, but exenatide significantly lowered free fatty acid clearance and postprandial triacyclglycerol (TAG) concentrations, particularly saturated TAGs with 44–54 carbons. Exenatide also reduced some postprandial CERs, PCs, and LPCs previously linked to CMR. These changes in lipidomic profile remained statistically significant after adjusting for weight loss. Exenatide improved fasting and postprandial lipidomic profiles associated with CMR mainly by reducing saturated postprandial TAGs and CERs independently of weight loss and diabetes. Article Highlights: Few data are available on the effect of glucagon-like peptide 1 receptor agonists on lipid metabolism, and no information is available on the postprandial lipidomic profile. In adults without diabetes but with severe obesity, 3-month treatment with exenatide improved fasting and postprandial lipidomic profiles associated with cardiometabolic risk by decreasing saturated species (triacylglycerols [TAGs], ceramides, lysophosphatidylcholines) while increasing seven unsaturated phospholipid species (phosphatidylcholine, lysophosphatidylcholine) with protective effects on cardiometabolic risk compared with control. Exenatide blunted the rise in postprandial triglycerides, especially saturated TAGs. Postprandial triglyceride reduction was associated to decreased postprandial free fatty acid clearance, with lower saturated free fatty acid incorporation into newly synthesized lipids (TAGs and ceramides). [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Dairy cows experiencing heat stress (HS) during the precalving portion of the transition period give birth to smaller calves and produce less milk and milk protein. Supplementation of rumen-protected methionine (RPM) has been shown to modulate protein, energy, and placenta metabolism, making it a potential candidate to ameliorate HS effects. We investigated the effects of supplementing RPM to transition cows under HS induced by electric heat blanket (EHB) on cow-calf performance. Six weeks before expected calving, 53 Holstein cows were housed in a tiestall barn and fed a control diet (CON, 2.2% Met of MP) or a CON diet supplemented with SmartamineM (MET, 2.6% Met of MP, Adisseo Inc., France). Four weeks precalving, all MET and half CON cows were fitted with an EHB. The other half of the CON cows were considered thermoneutral (TN), resulting in 3 treatments: CONTN (n = 19), CONHS (n = 17), and METHS (n = 17). Respiratory rate (RR), skin temperature (ST), and rectal temperature (RT) were measured thrice weekly and core body temperatures recorded biweekly. Postcalving BW and BCS were recorded weekly, and DMI was calculated and averaged weekly. Milk yield was recorded daily and milk components were analyzed every third DIM. Biweekly AA and weekly nonesterified fatty acids (NEFA), BHB, insulin, and glucose were measured from plasma. Calf birth weight and 24 h growth, thermoregulation, and hematology profile were measured and apparent efficiency of absorption (AEA) of immunoglobulins was calculated. Data were analyzed using the MIXED procedure of SAS with 2 preplanned orthogonal contrasts: CONTN versus the average of CONHS and METHS (C1) and CONHS versus METHS (C2). Relative to TN, EHB cows had increased RT during the postcalving weeks and increased RR and ST during the entire transition period. Body weight, BCS, DMI, and milk yield were not affected by the EHB or RPM. However, protein percentage and SNF were lower in CONHS, relative to METHS cows. At calving, METHS dams had higher glucose concentrations, relative to CONHS, and during the postcalving weeks, the EHB cows had lower NEFA concentrations than TN cows. Calf birthweight and AEA were reduced by HS, whereas RR was increased by HS. Calf withers height tended to be shorter and RT were lower in CONHS, compared with METHS heifers. Overall, RPM supplementation to transition cows reverts the negative effect of HS on blood glucose concentration at calving and milk protein percentage in the dams and increases wither height while decreasing RT in the calf. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Our objective was to compare abomasal infusions of linoleic (18:2n-6) and α-linolenic (18:3n-3) acids on the enrichment of n-6 and n-3 fatty acids (FA) into the plasma lipid fractions of lactating dairy cows and evaluate their potential carryover effects in plasma lipid fractions postinfusion. Six rumen-cannulated multiparous Holstein cows (252 ± 33 DIM) were fed the same diet and assigned to 1 of 2 treatments in a completely randomized design with repeated measures. Treatments were abomasal infusions (67 g/d total FA) of (1) n-6 FA blend (N6) to provide approximately 43 g/d 18:2n-6 and 8 g/d of 18:3n-3 or (2) n-3 FA blend (N3) providing 43 g/d 18:3n-3 and 8 g/d 18:2n-6. Treatments were dissolved in ethanol, and the daily dose for each treatment was divided into 4 equal infusions, occurring every 6 h. The treatment period lasted from d 1 to 20, and the carryover period lasted from d 21 to 40. Results are presented as FA contents within each of the 4 main plasma lipid fractions: cholesterol esters (CE), phospholipids (PL); triglycerides, and plasma nonesterified fatty acids. Concentrations of individual lipid fractions in plasma were not quantified. Plasma CE and PL had the highest content of PUFA during both the treatment and carryover periods. In plasma PL, N3 increased the contents of total n-3 FA (134%), 18:3n-3 (267%), and eicosapentaenoic acid (96.3%, 20:5n-3), and decreased total n-6 FA (8.14%) and 18:2n-6 (8.16%) from d 4 to 20 compared with N6. In plasma CE, N3 increased the contents of total n-3 FA (191%) from d 4 to 20, 18:3n-3 from d 2 to 20 (178%), and 20:5n-3 from d 6 to 20 (59.9%), while N3 decreased total n-6 FA from d 4 to 20 (11.2%) and 18:2n-6 from d 2 to 20 (10.5%) compared with N6. In addition, compared with N6, N3 decreased arachidonic acid (20:4n-6) at d 2 (45%) and from d 10 to 20 (14.7%) in PL and tended to decrease 20:4n-6 without interacting with time for CE. Phospholipids were the only lipid fraction with detectable levels of docosahexaenoic acid (22:3n-6) in all samples, but we did not observe differences between treatments. In plasma trigylcerides, N3 increased the contents of total n-3 FA (135%) and 18:3n-3 (146%) from d 4 to 20, increased 20:5n-3 from d 12 to 20 (89%), decreased or tended to decrease total n-6 FA content from d 6 and 8 (26.9%), and tended to decrease 18:2n-6 at d 8 compared with N6. A similar pattern was observed for plasma nonesterified FA. We observed positive carryover effects for both N3 and N6 at different degrees in all lipid fractions, with N3 promoting more consistent outcomes and increasing total n-3 FA throughout the carryover period (from d 22 to 40) in both PL (52.8%) and CE (68.6%) compared with N6. It is important to emphasize that the higher magnitude responses observed for n-3 FA are also influenced by the content of n-3 FA being much lower than those of n-6 FA in all lipid fractions. Although these data provide important and robust information, future research quantifying changes in concentrations of individual lipid fractions in plasma and the entry and exit rates of specific FA will further enhance our understanding. In conclusion, abomasally infusing N3 and N6 increased the contents of n-3 and n-6 FA, respectively, in all plasma lipid fractions. These responses were more evident in PL and CE. We also observed positive carryover effects in all lipid fractions, where N3 had more consistent outcomes than N6. Our results indicate that dairy cows have a robust mechanism to conserve essential FA, with a pronounced preference for n-3 FA. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Mitochondrial dysfunction has been reported to occur in the mammary gland of dairy cows suffering from ketosis. Prohibitin 2 (PHB2) plays a crucial role in regulating mitophagy, which clears impaired mitochondria to maintain normal mitochondrial function. Therefore, the current study aimed to investigate how PHB2 mediates mitophagy, thereby influencing mitochondrial function in the immortalized bovine mammary epithelial cell line (MAC-T cells). First, mammary gland tissue and blood samples were collected from healthy cows (n = 15, BHB <0.6 m M) and cows with clinical ketosis (n = 15, BHB >3.0 m M). Compared with healthy cows, cows with clinical ketosis exhibited lower DMI, milk production, milk protein, milk lactose, and serum glucose. In contrast, milk fat, serum nonesterified fatty acids (NEFA) and BHB were greater in cows with clinical ketosis. The protein abundance of PHB2, peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α), mitofusin 2 (MFN2) in whole cell lysates (WCL), as well as PHB2, sequestosome-1 (SQSTM1, also called p62), microtubule-associated protein 1 light chain 3-II (MAP1LC3-II, also called LC3-II), and ubiquitinated proteins in mitochondrial fraction were significantly lower in cows with clinical ketosis. The ATP content of mammary gland tissue in cows with clinical ketosis was lower than that of healthy cows. Second, MAC-T were cultured and treated with NEFA (0, 0.3, 0.6, 1.2 m M). The MAC-T treated with 1.2 m M NEFA displayed decreased protein abundance of PHB2, PGC-1α, and MFN2 in WCL, as well as protein abundance of PHB2, p62, LC3-II, and ubiquitinated proteins in mitochondrial fraction. The content of ATP and JC-1 aggregates in 1.2 m M NEFA group were lower than in the 0 m M NEFA group. Additionally, 1.2 m M NEFA disrupted the fusion between mitochondria and lysosomes. The MAC-T were then pretreated with 100 n M rapamycin, followed by treatment with or without NEFA. Rapamycin alleviated impaired mitophagy and mitochondria dysfunction induced by 1.2 m M NEFA. Third, MAC-T were transfected with small interfering RNA to silence PHB2 or a plasmid for overexpression of PHB2, followed by treatment with or without NEFA. The silencing of PHB2 aggravated 1.2 m M NEFA-induced impaired mitophagy and mitochondrial dysfunction, whereas the overexpression of PHB2 alleviated these effects. Overall, this study provides evidence that PHB2, in regulation of mitophagy, is a mechanism for bovine mammary epithelial cells to counteract NEFA-induced mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Our overarching objective was to characterize associations between genomic merit for fertility and the reproductive function of lactating dairy cows in a prospective cohort study. In this manuscript, we present results of the association between genomic merit for fertility and indicators of metabolic status and inflammation, uterine health, endocrine status, response to synchronization, and estrous behavior in dairy cows. Lactating Holstein cows entering their first (n = 82) or second (n = 37) lactation were enrolled at parturition and fitted with an ear-attached sensor for automated detection of estrus. Ear-notch tissue samples were collected from all cows and submitted for genotyping using a commercial genomic test. Based on genomic PTA values for daughter pregnancy rate (gDPR), cows were classified into a high (Hi-Fert; gDPR >0.6; n = 36), medium (Med-Fert; gDPR −1.3 to 0.6; n = 45), or low (Lo-Fert; gDPR <−1.3; n = 38) group. At 33 to 39 DIM, cohorts of cows were enrolled in the Presynch-Ovsynch protocol for synchronization of estrus and ovulation. Body weights, BCS, and uterine health measurements (i.e., vaginal discharge, uterine cytology) were collected from parturition to 60 DIM, and milk yield was collected through 90 DIM. Blood samples were collected weekly through 3 wk of lactation for analysis of BHB, nonesterified fatty acids (NEFA), and haptoglobin plasma concentrations. Body weight, BCS, NEFA, BHB, and haptoglobin were not associated with fertility groups from 1 to 9 wk after parturition. The proportion of cows classified as having endometritis at 33 to 36 DIM tended to be greater for the Lo-Fert than the Hi-Fert group. The proportion of cows that resumed cyclicity did not differ at any time point evaluated, and there were no significant associations between probability or duration and intensity of estrus with fertility group. Cows of superior genetic merit for fertility were more likely to ovulate, have a functional corpus luteum, have greater circulating progesterone, and have larger ovulatory size than cows of inferior fertility potential at key time points during synchronization of estrus and ovulation. Despite observing numerical differences with potential performance consequences for the proportion of cows that responded to synchronization of ovulation and were both cyclic and responded to the Ovsynch portion of the synchronization protocol, we did not observe significant differences between fertility groups. Although not consistent and modest in magnitude, the collective physiological and endocrine differences observed suggested that cows of superior genetic fertility potential might have improved reproductive performance, at least in part, because of modestly improved endocrine status, uterine health, and ability to ovulate. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Products of lipolysis released during digestion positively affect the metabolism of newborns. In contrast to the 3-layer biological membranes covering human milk (HM) fat, the lipid droplets in infant milk formula (IMF) are covered by a single membrane composed of casein and whey proteins. To reduce the differences in lipid structure between IMF and HM, studies have used milk fat globule membrane (MFGM) components such as milk polar lipids (MPL) to prepare emulsions mimicking HM fat globules However, few studies have elucidated the effect of membrane proteins (MemP) on lipid digestion in infants. In this study, 3 kinds of emulsions were prepared: one with MPL as the interface of lipid droplets (RE-1), one with membrane protein concentrate (MPC; RE-2) as the interface of lipid droplets, and one with both MPL and MPC (1:2) as the co-interface of lipid droplets (RE-3). The interfacial coverage of the emulsions was confirmed by measuring the contents of MPL and MPC at the lipid droplet interface, and by confocal laser scanning microscopy analysis. By controlling the homogenization intensity, the specific surface area of lipid droplets was controlled at the same level among the 3 emulsions. The stability constants of the emulsions varied, and RE-1 was the most stable. During simulated in vitro infant gastrointestinal digestion, the amount of free fatty acids (FFA) released from the lipid droplets was significantly higher from those with MPC at the interface (RE-2, RE-3) than from that with MPL at the interface (RE-1). The amount of FFA released at the end of intestinal digestion of RE-1, RE-2, and RE-3 was (mean ± SD; n = 3) 255.00 ± 3.54 µmol, 328.75 ± 5.30 µmol, 298.50 ± 9.19 µmol, respectively. Compared with the lipid droplets in RE-2, those with MPL at the interface (RE-1, RE-3) released more UFA during digestion. The emulsifying activity index was highest in RE-3 (MPL and MPC co-interface). The presence of MPL at the emulsion interface increased the release of UFA, and the presence of MPC increased the release of FFA. These results show that both MPL and MemP are indispensable in the construction of MFGM. Understanding their effects on digestion can provide new strategies for the development of infant foods. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. At the onset of lactation in dairy cows, inflammation and oxidative stress may occur and result in a risk of pathologies and lower milk yield. To propose an innovative management strategy for cows during this period, it is essential to better understand these physiological variations. Our objective was to evaluate the metabolic, redox, and immune status of 7 primiparous and 8 multiparous Holstein cows during late gestation and the first months of lactation. Blood samples were collected between 3 wk before calving until 12 wk postpartum. Milk samples were also collected, but only at the time points after calving. The metabolic (nonesterified fatty acids [NEFA], BHB, glucose, urea, calcium) and redox (reactive oxygen metabolites [ROM], oxidative stress index [OSI], glutathione peroxidase activity, vitamin E) statuses were analyzed in plasma or erythrocytes. The expression of genes related to antioxidant functions was determined in leukocytes collected from milk. For immune status, plasma cytokine levels and the production of reactive oxygen species (ROS) in classical and regulatory neutrophils were measured in 2 whole blood ex vivo challenges. The data were analyzed using a mixed model that included the fixed effects of parity and week and their interaction. Milk yield, plasma NEFA, and BHB in wk 2 and 4 after calving were higher in multiparous cows than in primiparous cows, whereas glucose and calcium tended to be lower. Plasma ROM and OSI levels in wk 8 were higher in multiparous than in primiparous cows. Multiparous cows also displayed higher glutathione peroxidase activity in erythrocytes, and antioxidant transcription factor and superoxide dismutase-1 expression levels in milk leukocytes. Moreover, multiparous cows had higher plasma concentrations of vitamin E but lower plasma levels of cytokines CXCL10, CCL2, IL1Rα, and IFNγ. Following ex vivo whole blood stimulation with Escherichia coli , lower IL1α and TNFα levels were measured in multiparous than in primiparous cows. Intracellular ROS production by neutrophils was lower in multiparous than in primiparous cows. These results thus indicated marked physiological changes in wk 8 compared with wk 2 and 4 of lactation. These differences in the physiological status of primiparous and multiparous cows offer interesting perspectives for potential dietary strategies to prevent pathologies which take account of parity and week relative to calving. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The objectives of this observational cohort study were to evaluate the associations of rumination time (RT) in the last week of pregnancy with transition cow metabolism, inflammation, health, and subsequent milk production, reproduction, and culling. Pregnant nulliparous (n = 199) and parous (n = 337) cows were enrolled 21 d before expected calving. Rumination time and physical activity were monitored automatically by sensors from d −21 to 15 relative to calving. Blood samples were collected on d −14, −5, 4, 8, and 12 ± 1 relative to calving. Diagnoses of clinical health problems were performed by researchers from calving to 15 DIM. In classification 1, cows were ranked based on average daily RT in the last week of pregnancy and classified into terciles as short RT (SRT), moderate RT (MRT), or long RT (LRT) for association analyses. In classification 2, RT deviation from the parity average was used in a receiver operating characteristic curve to identify the best threshold to predict postpartum clinical disease. Cows were then classified as above the threshold (AT) or below the threshold (BT). Compared with cows with LRT, cows with SRT had greater serum concentrations of nonesterified fatty acids (0.47 vs. 0.40 ± 0.01 mmol/L), BHB (0.58 vs. 0.52 ± 0.01 mmol/L), and haptoglobin (0.22 vs. 0.18 ± 0.008 g/L) throughout the transition period, and reduced concentrations of glucose, cholesterol, albumin, and magnesium in a time-dependent manner. Parous cows with SRT had higher odds of postpartum clinical disease (adjusted odds ratio [AOR] = 3.7; 95% CI: 2.1–6.4), lower odds of pregnancy by 210 DIM (AOR = 0.34; 95% CI = 0.15–0.75), and lower milk production (46.9 vs. 48.6 ± 0.5 kg/d) than parous cows with LRT. Deviation in prepartum RT had good predictive value for clinical disease in parous cows (area under the curve = 0.65; 95% CI = 0.60–0.71) but not in nulliparous (area under the curve = 0.51; 95% CI = 0.42–0.59). Separation of parous cows according to the identified threshold (≤−53 min from the parity average) resulted in differences in serum concentrations of nonesterified fatty acids (AT = 0.31 ± 0.006, BT = 0.38 ± 0.014 mmol/L), BHB (AT = 0.49 ± 0.008, BT = 0.53 ± 0.015 mmol/L), and globulin (AT = 32.3 ± 0.3, BT = 34.8 ± 0.5 g/L) throughout the transition period, as well as in serum cholesterol, urea, magnesium, albumin, and haptoglobin in a time-dependent manner. Below threshold parous cows had higher odds of clinical disease (AOR = 3.7; 95% CI = 2.1–6.4), reduced hazard of pregnancy (adjusted hazard ratio = 0.64, 95% CI: 0.47–0.89), greater hazard of culling (adjusted hazard ratio = 2.1, 95% CI: 1.2–3.6), and lower milk production (46.3 ± 0.7 vs. 48.5 ± 0.3 kg/d). External validation using data from 153 parous cows from a different herd and the established threshold in RT deviation (≤−53 min) resulted in similar predictive value, with the odds of postpartum disease 2.4 times greater in BT than AT (37.5% vs. 20.1%). In conclusion, RT in the week preceding calving was a reasonable predictor of postpartum health and future milk production, reproduction, and culling in parous cows but not in nulliparous cows. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The purpose of this experiment was to determine if nicotinic acid (NA) effects on dairy cows and rumen microbial characteristics are forage-type dependent (corn silage, CS; grass silage, GS). Four late-lactation (DIM = 225 ± 12 d) Holstein cows were used in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. The main effects were a CS (66.10% CS) based diet or a GS (79.59%) based diet with or without 12 g/d NA. Each experimental period lasted for 28 d. Milk production and milk components, blood metabolites, apparent total-tract nutrient digestibilities, minutes rumen pH were below 5.8 as an indicator of ruminal acidosis, and body temperature changes were analyzed as indicators of heat stress. Nicotinic acid supplementation did not improve apparent total-tract nutrient digestibility. Feeding a GS-based diet improved NDF and hemicellulose digestibility. Feeding a CS-based diet increased the apparent total-tract digestibility of fat, and minutes rumen pH below 5.8 for a greater proportion of the time. The CS-based diet also improved milk yield, milk fat and protein yields, and ECM yield; however, somatic cell count and BHB were also increased. Supplementing NA tended to decrease nonesterified fatty acids, especially when combined with GS where DMI was low. There was a trend for the total protozoa population to increase when GS and NA were fed but decreased when CS and NA were fed. Nicotinic acid tended to decrease rumen protozoal populations of Dasytricha , but increased populations of Ophryoscolex and Diplodiniinae with GS diets and decreased with CS diets. Entodiniinae were increased with CS but NA had no effect. Body temperature was increased when a CS-based diet was fed when compared with a GS-based diet. More research is needed to determine how NA can affect rumen microbial protein synthesis and what kind of diets will provide the optimum effect. [ABSTRACT FROM AUTHOR]