De novo assembly of Idesia polycarpa transcriptome and unsaturated fatty acid biosynthesis candidate genes Mining and functional Identification.

Unsaturated fatty acids (UFA) in lipids are the key to nutraceutical oil applications, with various potential applications in nutraceutical functional foods and pharmaceutical industries. In Idesia polycarpa (Salicaceae), more than 80 % of UFA have been found in the fruits; yet, the underlying genetic mechanism remains poorly understood. Due to the lack of theoretical research on the genes related to lipid biosynthesis and the complete genetic transformation system of I. polycarpa fruit, the selection and breeding of I. polycarpa, an excellent oil tree, has been severely restricted. In-depth understanding of the molecular mechanism and gene function of lipid biosynthesis of I. polycarpa fruit is therefore of great significance for the development of I. polycarpa resources. This is not only conducive to the genetic improvement of I. polycarpa by molecular breeding technologies but can also provide a reference for the study of the gene functions of other oil plants. In this study, the FA accumulation patterns of I. polycarpa fruits during 8 growth periods were analysed. Fruit from two developmental periods with different UFA levels were analysed for RNA sequencing by an Illumina NovaSeq 6000 HiSeq platform. De novo transcriptome assembly presented 115,350 unigenes and 4382 differentially expressed genes (DEGs). Functional annotation in the KEGG pathway and combined with DEG data revealed candidate genes potentially involved in UFA biosynthesis. Expression analysis of q-PCR of IpDGAT2, IpGPAT, IpKASII, IpSAD, IpFAD2, IpFAD3 and IpFAD8 suggested that these genes are highly involved in UFA biosynthesis. Full-length candidate genes were cloned and analysed by bioinformatic tools, and function analysis of IpSAD and IpFAD3 showed that these genes regulated the products of linoleic acid metabolism. This study provides a foundation for UFA biosynthesis in Idesia polycarpa, facilitating its genetic breeding in the future.

Palmitoleate protects against Lipopolysaccharide-induced Inflammation and Inflammasome Activity.

Inflammation is part of natural immune defense mechanism against any form of infection or injury. However, prolonged inflammation could perturb cell homeostasis and contribute to the development of metabolic and inflammatory diseases including maternal obesity, diabetes, cardiovascular diseases, and metabolic dysfunction-associated steatotic liver diseases. Polyunsaturated fatty acids have been shown to mitigate inflammatory response by generating specialized pro-resolving lipid mediators which take part in resolution of inflammation. Here, we show that palmitoleate, an omega-7 monounsaturated fatty acid exerts anti-inflammatory properties in response to lipopolysaccharide (LPS)-mediated inflammation. Exposure of bone-marrow derived macrophages (BMDMs) to LPS or TNFα induces robust increase in the expression of pro-inflammatory cytokines and supplementation of palmitoleate inhibited LPS-mediated upregulation of pro-inflammatory cytokines. We also observed that palmitoleate was able to block LPS+ATP-induced inflammasome activation mediated cleavage of pro-caspase 1 and pro-interleukin (IL)-1ß. Further, treatment of palmitoleate protects against LPS-induced inflammation in human THP-1 derived macrophages and trophoblasts. Co-exposure of LPS and palmitate (saturated free fatty acid) induces inflammasome and cell death in BMDMs, however, treatment of palmitoleate blocked LPS and palmitate-induced cell death in BMDMs. Further, LPS and palmitate together results in the activation of mitogen activated protein kinases (MAPK) and pretreatment of palmitoleate inhibited the activation of MAPKs and nuclear translocation of nuclear factor kappa B (NF-kB) in BMDMs. In conclusion, palmitoleate shows anti-inflammatory properties against LPS-induced inflammation and LPS+palmitate/ATP-induced inflammasome activity and cell death.

Effect of alterations in phospholipids and free fatty acids on aroma-active compounds in instant-boiled chuck tender, sirloin and silverside beef.

Beef flavor profiles are strongly influenced by cooking methods and lipid composition. However, the effect of instant-boiling on the aroma of different beef slices was unclear. This study investigated the lipid profiles and instant-boiling volatile profiles of chuck tender (M. Supraspinatus), sirloin (M. Longissimus dorsi) and silverside (M. Biceps femoris). Quantitative lipidomics identified 336 lipid molecular species, of which 84-112 were quantitatively different among the three beef slices. Sirloin had lower phosphatidylcholine, phosphatidylinositol, phosphatidylglycerol and free fatty acids than chuck tender and silverside. The unsaturated fatty acid acyl chains in phosphatidylethanolamine differed significantly. Solid phase microextraction-gas chromatography-olfactometry-mass spectrometry (SPME-GC-O-MS) identified hexanal, octanal, nonanal, decanal, (E)-2-octenal, (E)-2-nonenal, (E)-2-undecenal, (E,E)-2,4-nonadienal, (E,E)-2,4-decadienal, 1-octen-3-ol, 2-pentylfuran and acetoin as the aroma-active compounds of instant-boiled beef. Unsaturated free fatty acids and phosphatidylglycerols with unsaturated fatty acid residues positively correlated with the aroma-active compounds and might be crucial in flavor differences among the three beef slices. These findings provide greater understanding of the lipid and instant-boiling aroma-active compound profiles in chuck tender, sirloin and silverside, and reflect the suitability of different beef slices for instant-boiling from the aroma perspective.

Small molecule inhibitors of fungal Δ(9) fatty acid desaturase as antifungal agents against Candida auris.

Candida auris has emerged as a significant healthcare-associated pathogen due to its multidrug-resistant nature. Ongoing constraints in the discovery and provision of new antifungals create an urgent imperative to design effective remedies to this pressing global blight. Herein, we screened a chemical library and identified aryl-carbohydrazide analogs with potent activity against both C. auris and the most prevalent human fungal pathogen, C. albicans. SPB00525 [N'-(2,6-dichlorophenyl)-5-nitro-furan-2-carbohydrazide] exhibited potent activity against different strains that were resistant to standard antifungals. Using drug-induced haploinsufficient profiling, transcriptomics and metabolomic analysis, we uncovered that Ole1, a Δ(9) fatty acid desaturase, is the likely target of SPB00525. An analog of the latter, HTS06170 [N'-(2,6-dichlorophenyl)-4-methyl-1,2,3-thiadiazole-5-carbohydrazide], had a superior antifungal activity against both C. auris and C. albicans. Both SPB00525 and HTS06170 act as antivirulence agents and inhibited the invasive hyphal growth and biofilm formation of C. albicans. SPB00525 and HTS06170 attenuated fungal damage to human enterocytes and ameliorate the survival of Galleria mellonella larvae used as systemic candidiasis model. These data suggest that inhibiting fungal Δ(9) fatty acid desaturase activity represents a potential therapeutic approach for treating fungal infection caused by the superbug C. auris and the most prevalent human fungal pathogen, C. albicans.

Smartphone-Assisted Nanozyme Colorimetric Sensor Array Combined "Image Segmentation-Feature Extraction" Deep Learning for Detecting Unsaturated Fatty Acids.

Conventional methods for detecting unsaturated fatty acids (UFAs) pose challenges for rapid analyses due to the need for complex pretreatment and expensive instruments. Here, we developed an intelligent platform for facile and low-cost analysis of UFAs by combining a smartphone-assisted colorimetric sensor array (CSA) based on MnO2 nanozymes with "image segmentation-feature extraction" deep learning (ISFE-DL). Density functional theory predictions were validated by doping experiments using Ag, Pd, and Pt, which enhanced the catalytic activity of the MnO2 nanozymes. A CSA mimicking mammalian olfactory system was constructed with the principle that UFAs competitively inhibit the oxidization of the enzyme substrate, resulting in color changes in the nanozyme-ABTS substrate system. Through linear discriminant analysis coupled with the smartphone App "Quick Viewer" that utilizes multihole parallel acquisition technology, oleic acid (OA), linoleic acid (LA), α-linolenic acid (ALA), and their mixtures were clearly discriminated; various edible vegetable oils, different camellia oils (CAO), and adulterated CAOs were also successfully distinguished. Furthermore, the ISFE-DL method was combined in multicomponent quantitative analysis. The sensing elements of the CSA (3 × 4) were individually segmented for single-hole feature extraction containing information from 38,868 images of three UFAs, thereby allowing for the extraction of more features and augmenting sample size. After training with the MobileNetV3 small model, the determination coefficients of OA, LA, and ALA were 0.9969, 0.9668, and 0.7393, respectively. The model was embedded in the smartphone App "Intelligent Analysis Master" for one-click quantification. We provide an innovative approach for intelligent and efficient qualitative and quantitative analysis of UFAs and other compounds with similar characteristics.

Variation of LDL cholesterol in response to the replacement of saturated with unsaturated fatty acids: a nonrandomized, sequential dietary intervention; the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention ("RISSCI"-1) study.

BACKGROUND: Serum low density lipoprotein (LDL) cholesterol shows marked interindividual variation in response to the replacement of saturated fatty acids (SFAs) with unsaturated fatty acids (UFAs). OBJECTIVES: To demonstrate the efficacy of United Kingdom guidelines for exchanging dietary SFAs for UFAs, to reduce serum LDL cholesterol and other cardiovascular disease (CVD) risk factors, and to identify determinants of the variability in LDL cholesterol response. METHODS: Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2), consumed a higher-SFA/lower-UFA diet for 4 wk, followed by an isoenergetic, lower-SFA/higher-UFA diet for 4 wk (achieved intakes SFA:UFA as % total energy 19.1:14.8 and 8.9:24.5, respectively). Serum LDL cholesterol, CVD risk markers, peripheral blood mononuclear cell (PBMC) gene expression, and dietary intakes were assessed at baseline and the end of each diet. RESULTS: Transition from a higher-SFA/lower-UFA to a lower-SFA/higher-UFA diet significantly reduced fasting blood lipids: LDL cholesterol (-0.50 mmol/L; 95% confidence interval [CI]: -0.58, -0.42), high-density lipoprotein (HDL) cholesterol (-0.11 mmol/L; 95% CI: -0.14, -0.08), and total cholesterol (TC) (-0.65 mmol/L; 95% CI:-0.75, -0.55). The dietary exchange also reduced apolipoprotein (apo)B, TC:HDL cholesterol ratio, non-HDL cholesterol, E-selectin (P < 0.0001), and LDL subfraction composition (cholesterol [LDL-I and LDL-II], apoB100 [LDL-I and LDL-II], and TAG [LDL-II]) (P < 0.01). There was also an increase in plasma biomarkers of cholesterol intestinal absorption (ß-sitosterol, campesterol, cholestanol), and synthesis (desmosterol) (P < 0.0001) and fold change in PBMC LDL-receptor mRNA expression relative to the higher-SFA/lower-UFA diet (P = 0.035). Marked interindividual variation in the change in serum LDL cholesterol response (-1.39 to +0.77 mmol/L) to this dietary exchange was observed, with 33.7% of this variation explained by serum LDL cholesterol before the lower-SFA/higher-UFA diet and reduction in dietary SFA intake (adjusted R2 27% and 6.7%, respectively). APOE genotype was unrelated to serum LDL cholesterol response to SFA. CONCLUSIONS: These findings support the efficacy of United Kingdom SFA dietary guidelines for the overall lowering of serum LDL cholesterol but showed marked variation in LDL cholesterol response. Further identification of the determinants of this variation will facilitate targeting and increasing the efficacy of these guidelines. The RISSCI-1 study was registered with ClinicalTrials.Gov (No. NCT03270527).

A high-resolution 13C NMR approach for profiling fatty acid unsaturation in lipid extracts and in live Caenorhabditiselegans.

Unsaturated fatty acids (UFA) play a crucial role in central cellular processes in animals, including membrane function, development, and disease. Disruptions in UFA homeostasis can contribute to the onset of metabolic, cardiovascular, and neurodegenerative disorders. Consequently, there is a high demand for analytical techniques to study lipid compositions in live cells and multicellular organisms. Conventional analysis of UFA compositions in cells, tissues, and organisms involves solvent extraction procedures coupled with analytical techniques such as gas chromatography, MS and/or NMR spectroscopy. As a nondestructive and nontargeted technique, NMR spectroscopy is uniquely capable of characterizing the chemical profiling of living cells and multicellular organisms. Here, we use NMR spectroscopy to analyze Caenorhabditis elegans, enabling the determination of their lipid compositions and fatty acid unsaturation levels both in cell-free lipid extracts and in vivo. The NMR spectra of lipid extracts from WT and fat-3 mutant C. elegans strains revealed notable differences due to the absence of Δ-6 fatty acid desaturase activity, including the lack of arachidonic and eicosapentaenoic acyl chains. Uniform 13C-isotope labeling and high-resolution 2D solution-state NMR of live worms confirmed these findings, indicating that the signals originated from fast-tumbling lipid molecules within lipid droplets. Overall, this strategy permits the analysis of lipid storage in intact worms and has enough resolution and sensitivity to identify differences between WT and mutant animals with impaired fatty acid desaturation. Our results establish methodological benchmarks for future investigations of fatty acid regulation in live C. elegans using NMR.

Does a High Ratio of Dietary Omega-6/Omega-3 Fatty Acids Increase the Risk of Helicobacter pylori Infection? A Case-Control Study.

Helicobacter pylori infection is the cause of 90% of non-cardia gastric cancer. Several dietary elements have been identified as possible contributors to H. pylori infection and its advancement through various pathways. Based on the anti-inflammatory and anti-microbial effects of a diet low in omega-6 and high in omega-3 polyunsaturated fatty acids (PUFAs), this study aimed to assess the ratio of dietary omega-6 to omega-3 PUFAs and the risk of developing H. pylori. The present case-control study was conducted on 150 cases with H. pylori infection and 302 controls. The omega-6 to omega-3 ratio was calculated using food intake information sourced from a validated food frequency questionnaire. Physical activity and demographic data were collected through a related questionnaire. The association between the odds of H. pylori infection and the omega-6 to omega-3 ratio was evaluated using logistic regression models. A p value < 0.05 was considered statistically significant. The findings revealed that individuals in the third tertile had significantly higher odds of H. pylori (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.30-3.40) in the crude model. Furthermore, even after adjusting the potential confounders including sex, age, body mass index, physical activity, energy intake, alcohol, and smoking status, this association remained significant (fully adjusted model: OR, 2.00; 95% CI, 1.17-3.34). Our study revealed a higher ratio of omega-6 to omega-3 was related to a higher likelihood of H. pylori infection. Therefore, it is advisable to maintain a balanced intake of PUFAs in the diet.

Significance of fatty acids in fish broodstock nutrition.

The nutritional status of broodstock profoundly affects their reproductive performance and offspring survival. Studies on lipids and essential fatty acids in broodstock diets highlight their importance in cell structure, fecundity, fertilization, egg and larval quality, and providing metabolic energy for reproduction. Long-chain polyunsaturated fatty acids (Lc-PUFA) like DHA (22:6 n-3) and EPA (20:5 n-3) are vital for egg and larval development, while arachidonic acid (ARA) produces eicosanoids essential for reproduction. The fatty acid requirements vary by habitat; freshwater fish typically lack ∆12 and ∆15 desaturase enzymes to convert oleic acid into vital polyunsaturated fatty acids like linoleic and linolenic acids but can synthesize linoleic (18:2 n-6) and linolenic (18:3 n-3) into Lc-PUFAs such as EPA, DHA, and ARA through desaturation and elongation, whereas marine teleost cannot. Hence, broodstock feed fatty acid composition must be tailored by incorporating ingredients with a specific fatty acid composition to enhance reproductive performance. This review provides updated information on fatty acid supplementation in broodstock diets to improve reproductive outcomes in commercially important finfish, offering valuable insights for researchers, academicians, hatchery owners, and fish farmers to produce better-quality seeds.

Effects of saturated fatty acid consumption on lipoprotein (a): a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: An inverse relationship between saturated fatty acid (SFA) intake and Lp(a) concentration has been observed; however, there has been no quantification of this effect. OBJECTIVES: The objective was to determine whether SFA consumption alters Lp(a) concentrations among adults without atherosclerotic cardiovascular disease (ASCVD). METHODS: A systematic review and meta-analysis of randomized controlled trials contrasting a lower SFA diet(s) with a higher SFA diet(s) among adults without ASCVD was conducted. PubMed, Cochrane Central Register of Clinical Trials, clinicaltrials.gov, and Web of Science databases and registers were searched through October 2023. The standardized mean difference (SMD) in Lp(a) between diets lower and higher in SFA [percentage of energy (%E)] was determined using random-effects meta-analysis. Analyses were also conducted to examine the effect of replacing SFA with carbohydrates (CHO), monounsaturated (MUFAs), polyunsaturated (PUFAs), or trans fatty acids (TFAs). RESULTS: In total, 6255 publications were identified in the systematic search. Twenty-six publications reporting 27 randomized controlled trials, including 1325 participants and 49 diet comparisons, were included. The mean difference in SFA between lower and higher SFA diets was 7.6%E (3.7%-17.8%E). After lower SFA diets, Lp(a) concentration was higher (SMD: 0.14; 95% confidence interval [CI]: 0.03, 0.24) than after higher SFA diets. Subgroup analyses showed higher Lp(a) following diets where SFA was replaced by CHO (trials = 8; n = 539; SMD: 0.21; 95% CI: 0.02, 0.40) or TFAs (trials = 8; n = 300; SMD: 0.32; 95% CI: 0.17, 0.48). No differences in Lp(a) were observed when MUFA (trials = 16; n = 641; SMD: 0.04; 95% CI: -0.08, 0.16) or PUFA (trials = 8; n = 415; SMD: 0.09; 95% CI: -0.04, 0.22) replaced SFA. CONCLUSIONS: Lower SFA diets modestly increase Lp(a) compared to higher SFA diets among individuals without ASCVD. This effect appeared to be driven by replacement of SFA with CHO or TFA. Research investigating the atherogenicity of diet-induced Lp(a) changes is needed to inform dietary management of lipid/lipoprotein disorders. This trial was registered with PROSPERO as CRD42020154169.

A genome-wide CRISPR screen reveals that antagonism of glutamine metabolism sensitizes head and neck squamous cell carcinoma to ferroptotic cell death.

Glutamine is a conditionally essential amino acid for the growth and survival of rapidly proliferating cancer cells. Many cancers are addicted to glutamine, and as a result, targeting glutamine metabolism has been explored clinically as a therapeutic approach. Glutamine-catalyzing enzymes are highly expressed in primary and metastatic head and neck squamous cell carcinoma (HNSCC). However, the nature of the glutamine-associated pathways in this aggressive cancer type has not been elucidated. Here, we explored the therapeutic potential of a broad glutamine antagonist, DRP-104 (sirpiglenastat), in HNSCC tumors and aimed at shedding light on glutamine-dependent pathways in this disease. We observed a potent antitumoral effect of sirpiglenastat in HPV- and HPV + HNSCC xenografts. We conducted a whole-genome CRISPR screen and metabolomics analyses to identify mechanisms of sensitivity and resistance to glutamine metabolism blockade. These approaches revealed that glutamine metabolism blockade results in the rapid buildup of polyunsaturated fatty acids (PUFAs) via autophagy nutrient-sensing pathways. Finally, our analysis demonstrated that GPX4 mediates the protection of HNSCC cells from accumulating toxic lipid peroxides; hence, glutamine blockade sensitizes HNSCC cells to ferroptosis cell death upon GPX4 inhibition. These findings demonstrate the therapeutic potential of sirpiglenastat in HNSCC and establish a novel link between glutamine metabolism and ferroptosis, which may be uniquely translated into targeted glutamine-ferroptosis combination therapies.

Transcriptome Analysis Reveals the Potential Key Genes in Nutritional Deposition in the Common Carp (Cyprinus carpio).

The common carp (Cyprinus carpio) is one of the most important aquaculture species in China, known for its remarkable adaptability and nutritional profile. However, the specific molecular response mechanisms regulating the nutritional deposition of carp remain inadequately elucidated. This study conducted a comprehensive analysis of muscle nutritional content and transcriptome data from liver and muscle tissues of three distinct carp varieties. The aim was to elucidate the key genes and signaling pathways that regulate muscle nutritional composition in carp. The findings revealed that FFRC carp (FFRC) exhibited significantly higher levels of crude fat, total n-3 polyunsaturated fatty acids, and total n-6 polyunsaturated fatty acids in muscle tissue compared to Ying carp (YC) and Huanghe carp (HC) (p < 0.05). Transcriptomic analyses correlated these elevated levels with a marked upregulation of genes involved in the activation and transportation of fatty acid (fabp7, acsl5, acsbg2) as well as biosynthesis and elongation of long-chain unsaturated fatty acids (elovl2, fads2) within the liver. Furthermore, the flavor amino acid, essential amino acids, and crude protein content in the muscle of HC were significantly higher than in FFRC and YC (p < 0.05). Transcriptomic analyses indicated that this was associated with significant changes in the expression of genes related to amino acid metabolism (asns, alt, ldha, glul, setd, prodh, l3hypdh, hoga1) within their muscle tissue. This research provides a theoretical foundation for the precise modulation of the muscle nutritional composition in carp.

Absence of Causal Relationship Between Levels of Unsaturated Fatty Acids and ADHD: Evidence From Mendelian Randomization Study.

OBJECTIVE: Previous research suggests a potential link between unsaturated fatty acids (UFAs) and ADHD, but the causal relationship remains uncertain. This study aims to investigate the causal association between ADHD and UFAs using Mendelian randomization (MR) analysis. METHODS: Summary data from genome-wide association studies were used to estimate the concentration of circulating UFAs, including Monounsaturated Fatty Acids (MUFAs), Polyunsaturated Fatty Acids (PUFAs), Omega-3 PUFAs, Omega-6 PUFAs, Linoleic Acid (LA), and Docosahexaenoic Acid (DHA). Data from the Psychiatric Genomics Consortium, including both childhood and adult ADHD, were respectively used to examine the relationship between genetically predicted UFAs levels and ADHD. Various MR methods, including Inverse-variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier, MR-Egger, weighted median, and weighted mode, were employed to assess heterogeneity and pleiotropy. RESULTS: The IVW revealed only nominal evidence suggesting a potential causal relationship between genetically predicted PUFAs (OR = 0.92, 95% CI [0.85, 0.99], p = .031), Omega-6 PUFAs (OR = 0.90, 95% CI [0.83, 0.98], p = .020), and LA levels (OR = 0.90, 95% CI [0.82, 0.98], p = .021) with childhood ADHD risk. However, after false discovery rate correction, the p-values for PUFAs, Omega-6 PUFAs, and LA levels all exceeded the threshold for significance. For adult ADHD, we did not find any significant associations between the six circulating UFA levels and adult ADHD. CONCLUSION: Our findings do not support a causal relationship between UFAs levels and ADHD. This suggests that UFAs supplements may not be effective in improving ADHD symptoms and importantly, it appears that UFAs levels may not have a long-term effect on ADHD.

Early activation of hepatic stellate cells induces rapid initiation of retinyl ester breakdown while maintaining lecithin:retinol acyltransferase (LRAT) activity.

Lecithin:retinol acyltransferase (LRAT) is the main enzyme producing retinyl esters (REs) in quiescent hepatic stellate cells (HSCs). When cultured on stiff plastic culture plates, quiescent HSCs activate and lose their RE stores in a process similar to that in the liver following tissue damage, leading to fibrosis. Here we validated HSC cultures in soft gels to study RE metabolism in stable quiescent HSCs and investigated RE synthesis and breakdown in activating HSCs. HSCs cultured in a soft gel maintained characteristics of quiescent HSCs, including the size, amount and composition of their characteristic large lipid droplets. Quiescent gel-cultured HSCs maintained high expression levels of Lrat and a RE storing phenotype with low levels of RE breakdown. Newly formed REs are highly enriched in retinyl palmitate (RP), similar to freshly isolated quiescent HSCs, which is associated with high LRAT activity. Comparison of these quiescent gel-cultured HSCs with activated plastic-cultured HSCs showed that although during early activation the total RE levels and RP-enrichment are reduced, levels of RE formation are maintained and mediated by LRAT. Loss of REs was caused by enhanced RE breakdown in activating HSCs. Upon prolonged culturing, activated HSCs have lost their LRAT activity and produce small amounts of REs by DGAT1. This study reveals unexpected dynamics in RE metabolism during early HSC activation, which might be important in liver disease as early stages are reversible. Soft gel cultures provide a promising model to study RE metabolism in quiescent HSCs, allowing detailed molecular investigations on the mechanisms for storage and release.

Pomegranate seeds: a comprehensive review of traditional uses, chemical composition, and pharmacological properties.

Pomegranate seeds (PS) are the dried seeds derived from pomegranate fruit, accounting for approximately 20% of the fruit's total weight, and are a by-product of pomegranate juice extraction. These seeds hold significance in traditional medicine among Uyghurs and Tibetan cultures, featuring diverse clinical applications within traditional Chinese medicine. These applications include management of gastric coldness and acidity, abdominal distension, liver and gallbladder fever, and pediatric enteritis. PS demonstrates properties such as stomach tonicity, qi regulation, analgesia, and anti-inflammatory effects. Extensive research underscores the richness of PS in various phytochemical compounds and metabolites, notably unsaturated fatty acids (particularly linolenic acid and linoleic acid), phenolic compounds tocopherols, proteins, and volatile oils. Notably, among these bioactive compounds, punicic acid (PA), found within PS, demonstrates potential in the prevention and treatment of cancers, diabetes, obesity, and other ailments. Despite extensive literature on pomegranate as a botanical entity, a comprehensive review focusing specifically on the chemical composition and pharmacological effects of PS remains elusive. Therefore, this review aimed to consolidate knowledge regarding the medicinal properties of PS, summarizing its chemical composition, traditional uses, and pharmacological effects in treating various diseases, thereby laying a foundation for the advancement and application of PS in the field of pharmacology.

Association between blood metabolites and basal cell carcinoma risk: a two-sample Mendelian randomization study.

Background: Circulating metabolites, which play a crucial role in our health, have been reported to be disordered in basal cell carcinoma (BCC). Despite these findings, evidence is still lacking to determine whether these metabolites directly promote or prevent BCC's progression. Therefore, our study aims to examine the potential effects of circulating metabolites on BCC progression. Material and methods: We conducted a two-sample Mendelian randomization (MR) analysis using data from two separate genome-wide association studies (GWAS). The primary study included data for 123 blood metabolites from a GWAS with 25,000 Finnish individuals, while the secondary study had data for 249 blood metabolites from a GWAS with 114,000 UK Biobank participants.GWAS data for BCC were obtained from the UK Biobank for the primary analysis and the FinnGen consortium for the secondary analysis. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. Results: In the primary analysis, significant causal relationships were found between six metabolic traits and BCC with the inverse variance weighted (IVW) method after multiple testing [P < 4 × 10-4 (0.05/123)]. Four metabolic traits were discovered to be significantly linked with BCC in the secondary analysis, with a significance level of P < 2 × 10-4 (0.05/249). We found that all the significant traits are linked to Polyunsaturated Fatty Acids (PUFAs) and their degree of unsaturation. Conclusion: Our research has revealed a direct link between the susceptibility of BCC and Polyunsaturated Fatty Acids and their degree of unsaturation. This discovery implies screening and prevention of BCC.

Protective effect of unsaturated fatty acids on cognitive impairment in CKD patients: Results from the National Health and Nutrition Examination Survey (2011-2014).

BACKGROUND: It is still unknown whether unsaturated fatty acids (UFA) have the same effect on preventing cognitive impairment in chronic kidney disease (CKD) patients as in healthy people. OBJECTIVE: To investigate the protective effect of dietary UFA intake and proportion on cognitive impairment in patients with CKD. METHODS: We extracted data from the National Health and Nutrition Examination Survey (NHANES, 2011-2014) on participants with a previous diagnosis of CKD and at least one complete cognitive assessment (Consortium to Establish a Registry for Alzheimer's Disease test, Animal Fluency Test and Digit Symbol Substitution Test). We used the lower quartile of the total scores of these three tests as the cut-off point, and divided the participants into two groups of normal cognitive performance and low cognitive performance to extract participants' intake of various UFA from the NHANES dietary module. The data were weighted using weighting parameters included in NHANES, and logistics regression and restricted cubic spline were used to analyze the protective effect of UFA intake on cognitive impairment in CKD participants. RESULTS: We found that participants with low cognitive performance all had significantly lower intakes of total monounsaturated fatty acids, total polyunsaturated fatty acids, ω-3 UFA, ω-6 UFA and ω-9 UFA than participants with normal cognitive performance (p< 0.05), and the ω-6 UFA and ω-9 UFA had the most significant protective effects on cognitive impairment of participants. We also discovered that oleic and linoleic acids play important roles in protecting against cognitive impairment in CKD participants. The protective effect of oleic acid, but not linoleic acid, on cognitive impairment showed a nonlinear relationship. The changes in the proportion of monounsaturated fatty acids to polyunsaturated fatty acids, ω-6 UFA to ω-3 UFA, and oleic acid to linoleic acid did not affect the risk of cognitive impairment in CKD participants. CONCLUSIONS: UFA can reduce the risk of cognitive impairment in CKD patients, especially oleic acid and linoleic acid have a more obvious protective effect on cognitive impairment in patients with CKD. Among them, the protective effect of linoleic acid on cognitive impairment was continuously enhanced with the increase of intake, indicating that linoleic acid may be the most important UFA to reduce cognitive impairment in CKD patients.

Association between Unsaturated Fatty Acid-Type Diet and Systemic Lupus Erythematosus: A Systematic Review with Meta-Analyses.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects multiple organ systems, with a higher prevalence among women in their reproductive years. The disease's multifactorial etiology involves genetic, environmental, and hormonal components. Recent studies have highlighted the potential impact of dietary factors, particularly unsaturated fatty acids, on the modulation of SLE due to their anti-inflammatory properties. This meta-analysis aims to evaluate the association between unsaturated fatty acid consumption and the risk, progression, and clinical manifestations of SLE, providing evidence-based guidance for dietary management. METHODS: We conducted a comprehensive search across major medical databases up to January 2024, focusing on studies that examined the intake of unsaturated fatty acids and the impact of such intake on SLE. Using the PICOS (population, intervention, comparator, outcomes, study design) framework, we included randomized controlled trials and case-control studies, assessing outcomes such as SLE activity, measured by SLE Disease Activity Index (SLEDAI) or the British Isles Lupus Assessment Group (BILAG) index, inflammation biomarkers. Studies were analyzed using either a fixed- or random-effects model based on heterogeneity (I2 statistic), with sensitivity analyses performed to assess the robustness of the findings. RESULTS: Our search included 10 studies, encompassing a wide variety of designs and populations. The meta-analysis showed that a diet rich in unsaturated fatty acids is significantly associated with a reduction in SLEDAI scores (pooled SMD) of -0.36, 95% CI: -0.61 to -0.11, p = 0.007, indicating a beneficial effect on disease activity. Additionally, we found that unsaturated fatty acid intake has a significant impact on HDL levels, suggesting a positive effect on lipid profiles. However, no significant effects were observed on levels of the inflammatory marker IL-6 or other lipid components (LDL and cholesterol). With minimal heterogeneity among studies (I2 ≤ 15%), sensitivity analysis confirmed the stability and reliability of these results, highlighting the potential role of unsaturated fatty acids in SLE management. CONCLUSIONS: This meta-analysis suggests that dietary intake of unsaturated fatty acids may play a positive role in reducing SLE activity and may significantly affect HDL levels without having significant effects on inflammation markers or other lipid profiles. These findings support the inclusion of unsaturated fatty acids in the dietary management of SLE patients, although further research is required to refine dietary recommendations and explore the mechanisms underlying these associations.

Proteome Analysis Related to Unsaturated Fatty Acid Synthesis by Interfering with Bovine Adipocyte ACSL1 Gene.

Unsaturated fatty acids (UFAs) in beef play a vital role in promoting human health. Long-chain fatty acyl-CoA synthase 1 (ACSL1) is a crucial gene for UFA synthesis in bovine adipocytes. To investigate the protein expression profile during UFA synthesis, we performed a proteomic analysis of bovine adipocytes by RNA interference and non-interference with ACSL1 using label-free techniques. A total of 3558 proteins were identified in both the NC and si-treated groups, of which 1428 were differentially expressed proteins (DEPs; fold change ≥ 1.2 or ≤ 0.83 and p-value < 0.05). The enrichment analysis of the DEPs revealed signaling pathways related to UFA synthesis or metabolism, including cAMP, oxytocin, fatty acid degradation, glycerol metabolism, insulin, and the regulation of lipolysis in adipocytes (p-value < 0.05). Furthermore, based on the enrichment analysis of the DEPs, we screened 50 DEPs that potentially influence the synthesis of UFAs and constructed an interaction network. Moreover, by integrating our previously published transcriptome data, this study established a regulatory network involving differentially expressed long non-coding RNAs (DELs), highlighting 21 DEPs and 13 DELs as key genes involved in UFA synthesis. These findings present potential candidate genes for further investigation into the molecular mechanisms underlying UFA synthesis in bovines, thereby offering insights to enhance the quality of beef and contribute to consumer health in future studies.

Association between circulating levels of unsaturated fatty acids and risk for prediabetes in the NHANES 2003-2004 and 2011-2012.

AIMS: This study aimed to investigate the association between serum levels of common and uncommon unsaturated fatty acids and prediabetes risk. METHODS: Data were collected from the National Health and Nutrition Examination Survey for 2003-2004 and 2011-2012. Weighted proportional and multivariate logistic regression analyses were performed to assess the association of serum PUFAs and MUFAs with prediabetes risk after adjusting for potential confounders. RESULTS: A total of 3575 individuals were enrolled in this study. Serum levels of PUFAs EPA (20:5 n3) and GLA (18:3 n6) were associated with increased prediabetes risk (EPA (20:5 n3): OR = 1.878, 95% CI: 1.177-2.996, Ptrend = 0.002; GLA (18:3 n6): 1.702, 95% CI: 1.140-2.541, Ptrend = 0.016). The MUFAs PA (16:1 n7) and EA (20:1 n9) were associated with the risk of prediabetes (OR in quintile5: PA (16:1 n7): 1.780, 95% CI: 1.056-3.001, Ptrend = 0.003; EA (20:1 n9): 0.587, 95% CI: 0.347-0.994, Ptrend = 0.010). Moreover, nonlinear analysis revealed that serum levels of EPA (20:5 n3) and EA (20:1 n-9) were nonlinearly associated with prediabetes risk. CONCLUSION: Some serum n-3 PUFAs are positively associated with prediabetes, several serum n-6 PUFAs are inversely associated with prediabetes. Regulating individual serum USFA levels may help prevent prediabetes, thereby providing evidence for clinical and nutritional practices.