Fatty Acid Regulation Research Articles

Effect of Bacillus amyloliquefaciens supplementation on intramuscular fat accumulation and meat quality in finishing pigs.

This study evaluated the potential of Bacillus amyloliquefaciens to improve growth performance and meat quality in finishing pigs. Thirty-two female Landrace × Duroc pigs, 21 weeks old with initial body weight 77.45±3.29 kg, were divided into two groups: a control group (basal diet) and a probiotic group (basal diet with Bacillus amyloliquefaciens at 1×109 CFU/kg). Body weight and average daily gain (ADG) were recorded at the start and at fortnight intervals for a 56-d feeding trial. At the end of the experiment, carcass traits, meat quality and intramuscular fat related gene expression of longissimus dorsi muscle were analyzed. The probiotic group showed significantly higher final body weight and D0-D56 ADG (p < 0.05). Additionally, the probiotic group had greater carcass weight, back fat thickness and marbling score (p < 0.05), while the lean meat percentage remained unchanged. Meat quality analysis revealed that the probiotic group had a higher b* value (5.47) (p < 0.05), and a lower shear value (p < 0.001), but there was no effect on the a* value and water holding capacity. Moreover, probiotic treatment increased the gene expression of fatty acid uptake and regulator, such as LPL, CD36, and SLC27A1 (p < 0.05). Our findings suggest that the supplementation of Bacillus amyloliquefaciens not only enhanced growth performance and carcass weight in finishing pigs, but also improved marbling and tenderness in the longissimus dorsi muscle through the up-regulation of lipogenic-genes related to fat accumulation. This indicates its potential as feed additive to enhance pork quality.

Polymorphisms of PRKAA1 and FABP4 genes and their association with feed efficiency in Hu sheep

Feed efficiency (FE) is an important economic trait in the sheep industry, influenced by biological processes such as digestion and metabolism. PRKAA1 gene participates in the synthesis and oxidation of fatty acids; the FABP4 gene is closely associated with intracellular fatty acid regulation. In this study, we use Sanger sequencing, KASPar genotyping, and qRT-PCR to investigate the association between variations in PRKAA1 and FABP4 genes and feed efficiency in Hu sheep, the expression patterns of PRKAA1 and FABP4 genes in different tissues, as well as the differences in expression of different genotypes in tail fat. The association analysis results indicated that PRKAA1 gene g.35431965 C > T locus and FABP4 gene g.62829807 C > T locus were significantly associated with the feed conversion ratio (FCR) of Hu sheep aged 80–180 days, with the dominant genotypes being CC and CC, respectively. Simultaneously, there existed notable disparities among various genotype combinations. The qRT-PCR results showed PRKAA1 and FABP4 genes were widely expressed in ten tissues, of which the PRKAA1 gene was lower expression level in rumen and lung, FABP4 gene was significantly highest expression in the tail fat than the other tissues; the expression of two different genotypes in tail fat also exhibits significant differences (P ≤ 0.05). Therefore, these findings suggested that the variation of PRKAA1 and FABP4 genes might be used as novel genetic marker for improving feed efficiency in sheep.

PSVII-1 Widespread allele-specific expression across tissues and cells of the chicken genome

Abstract Chickens are a valuable livestock species, providing an affordable and nutritious food source worldwide through eggs and meat. Additionally, chickens are extensively used in scientific research as model organisms in virology, immunology, epigenetics, development, and conservation biology. Considering this, there are increasing efforts to deepen our understanding of their genome complexity, such as efforts by the Functional Annotation of Animal Genomes (FAANG) Consortium. Toward this goal, we are working to contribute to the annotation of the chicken transcriptome. Allele-specific expression (ASE) is an imbalance of allelic gene expression often driven by genetic and epigenetic changes in cis-regulatory regions. We, therefore, aimed to determine allelic imbalances in gene expression across 20 tissues and cells to shed light on mechanisms regulating gene expression. Using replicate paired-end (PE) RNA-seq samples, we identified around 7 million variants across 20 tissues and cells (e.g., reproductive tissues, intestine tissues, muscle, and immune tissues and cells). We applied quality control measures and filtered out monoallelic and homozygous variants. After that, we calculated read counts per allele to determine allelic expression. We found 365,894 significant ASE SNPs and 11,530 ASE genes in at least one tissue or cell type (FDR ≤ 0.05). We discovered that ASE SNPs are widely distributed throughout the chicken genome, and ASE SNPs and ASE genes showed a varied distribution across tissues and cells. Primary macrophage exhibited the most abundant, while the pectoralis major (breast muscle) had the lowest ASE genes and ASE SNPs, ranging from 7,592 to 32,505 ASE SNPs and 773 to 2,387 ASE genes. Our findings reveal several important pathways affected by allelic imbalance of expression. These pathways included fatty acid biosynthesis and regulation, cell proliferation and differentiation, cell metabolism, adipocytokine signaling, proteolysis and autophagy, and focal adhesion. In summary, our study provides insight into relevant biological processes critical to chickens and can contribute to improving genome annotation, helping to expand the transcriptomic reference source.

Identification of candidate genes and genomic prediction of soybean fatty acid components in two soybean populations.

Soybean, a source of plant-derived lipids, contains an array of fatty acids essential for health. A comprehensive understanding of the fatty acid profiles in soybean is crucial for enhancing soybean cultivars and augmenting their qualitative attributes. Here, 180 F10 generation recombinant inbred lines (RILs), derived from the cross-breeding of the cultivated soybean variety 'Jidou 12' and the wild soybean 'Y9,' were used as primary experimental subjects. Using inclusive composite interval mapping (ICIM), this study undertook a quantitative trait locus (QTL) analysis on five distinct fatty acid components in the RIL population from 2019 to 2021. Concurrently, a genome-wide association study (GWAS) was conducted on 290 samples from a genetically diverse natural population to scrutinize the five fatty acid components during the same timeframe, thereby aiming to identify loci closely associated with fatty acid profiles. In addition, haplotype analysis and the Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed to predict candidate genes. The QTL analysis elucidated 23 stable QTLs intricately associated with the five fatty acid components, exhibiting phenotypic contribution rates ranging from 2.78% to 25.37%. In addition, GWAS of the natural population unveiled 102 significant loci associated with these fatty acid components. The haplotype analysis of the colocalized loci revealed that Glyma.06G221400 on chromosome 6 exhibited a significant correlation with stearic acid content, with Hap1 showing a markedly elevated stearic acid level compared with Hap2 and Hap3. Similarly, Glyma.12G075100 on chromosome 12 was significantly associated with the contents of oleic, linoleic, and linolenic acids, suggesting its involvement in fatty acid biosynthesis. In the natural population, candidate genes associated with the contents of palmitic and linolenic acids were predominantly from the fatty acid metabolic pathway, indicating their potential role as pivotal genes in the critical steps of fatty acid metabolism. Furthermore, genomic selection (GS) for fatty acid components was conducted using ridge regression best linear unbiased prediction based on both random single nucleotide polymorphisms (SNPs) and SNPs significantly associated with fatty acid components identified by GWAS. GS accuracy was contingent upon the SNP set used. Notably, GS efficiency was enhanced when using SNPs derived from QTL mapping analysis and GWAS compared with random SNPs, and reached a plateau when the number of SNP markers exceeded 3,000. This study thus indicates that Glyma.06G221400 and Glyma.12G075100 are genes integral to the synthesis and regulatory mechanisms of fatty acids. It provides insights into the complex biosynthesis and regulation of fatty acids, with significant implications for the directed improvement of soybean oil quality and the selection of superior soybean varieties. The SNP markers delineated in this study can be instrumental in establishing an efficacious pipeline for marker-assisted selection and GS aimed at improving soybean fatty acid components.

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.

SNHG1: Redefining the Landscape of Hepatocellular Carcinoma through Long Noncoding RNAs.

Hepatocellular carcinoma (HCC) represents a global health concern, ranking as the sixth most common malignancy worldwide and the third leading cause of cancer-related mortality. Despite advances in research, the diagnosis and prognosis of such malignancy remain challenging. Alpha-fetoprotein, the current serum biomarker used in the management of HCC, has limited sensitivity and specificity, making early detection and effective management more difficult. Thus, new management approaches in diagnosis and prognosis are needed to improve the outcome and survival of HCC patients. SNHG1 is a long noncoding RNA mainly expressed in the cell and cytoplasm of cells and is consistently upregulated in tissues and cell lines of HCC, where it acts as an important regulator of various processes: modulation of p53 activity, sponging of microRNAs with consequent upregulation of their target mRNAs, regulation of fatty acid, iron and glucose metabolism, and interaction with immune cells. The deregulation of these processes results in abnormal cell division, angiogenesis, and apoptosis, thus promoting various aspects of tumorigenesis, including proliferation, invasion, and migration of cells. Clinically, a higher expression of SNHG1 predicts poorer clinical outcomes by significantly correlating with bigger, less differentiated, and more aggressive tumors, more advanced disease stages, and lower overall survival in HCC patients. This article comprehensively summarizes the current understanding of the multifaceted roles of SNHG1 in the pathogenesis of HCC, while also highlighting its clinicopathological correlations, therefore concluding that it has potential as a biomarker in HCC diagnosis and prognosis.

Bringing Cerium Oxysulfate Clusters into Nanozymes by Saturated Fatty Acid Regulation for Oxidase-like Activity

Bringing Cerium Oxysulfate Clusters into Nanozymes by Saturated Fatty Acid Regulation for Oxidase-like Activity

An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer

BackgroundIrinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study.ObjectiveThis study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism.MethodsThe orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics.ResultsIn vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism.ConclusionThe optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.

A novel phosphodiesterase inhibitor for the treatment of chronic liver injury and metabolic diseases.

Chronic liver disease (CLD) leads to approximately two million deaths annually. Cyclic adenosine monophosphate (cAMP) signaling has long been studied in liver injury, particularly in the regulation of fatty acid (FA) β-oxidation and pro-inflammatory polarization of tissue-resident lymphocytes. Phosphodiesterase 4B (PDE4B) inhibition has been explored as a therapeutic modality, but these drugs have had limited success and are known to cause significant adverse effects. The PDE4 inhibitor 2-(4-([2-(5-Chlorothiophen-2-yl)-5-ethyl-6-methylpyrimidin-4-yl]amino)phenyl)acetic acid) (known as A-33) has yet to be explored for the treatment of metabolic diseases. Herein, we evaluated the efficacy of A-33 in the treatment of animal models of alcohol-associated liver disease (ALD) and steatotic liver disease (SLD). We demonstrated that A-33 effectively ameliorated the signs and symptoms of CLD, resulting in significant decreases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, decreased overall fat and collagen deposition in the liver, decreased intrahepatic triglyceride (TG) concentrations, and normalized expression of genes related to β-oxidation of fatty acids, inflammation, and extracellular matrix (ECM) deposition. We also designed and synthesized a novel analog of A-33, termed MDL3, which inhibited both PDE4B and PDE5A and was more effective in ameliorating pathophysiological signs and symptoms of liver injury and inflammation. In addition, MDL3 re-sensitized obese mice to glucose and significantly inhibited the pathological remodeling of adipose tissue, which was not observed with A-33 administration. In conclusion, we synthesized and demonstrated that MDL3, a novel PDE4B and PDE5A inhibitor, presents a promising avenue of exploration for treating CLD.

Сучасний стан законодавчого регулювання вмісту транс-ізомерів жирних кислот у харчових продуктах в Україні та світі (огляд літератури)

Abstract. The influence of fats and oils on human health is in constant attention of leading experts in the field of public health, of both national and international institutions. This is especially true concerning industrially obtained trans fats and their regulation. Currently, in Ukraine, the requirements for the content of trans fatty acids in food products are regulated by documents of two levels. Firstly, the requirements for the content of trans fatty acids in certain types of oil and fat products are set out in the national standards (DSTU), which are do not cover the entire range of fat-containing products. Secondly, a norm on limiting the amount of trans fatty acids in food products was adopted in Section V of the Order of the Ministry of Health of Ukraine dated July 16, 2020 No. 1613 “On Approval of the Rules for Adding Vitamins, Mineral Substances and Certain Other Substances to Food Products”, which is harmonized with European legislation, but this norm will be valid only three years after the entry of this order into force in 2023. Aim. To review the scientific literature on the effects of trans fats on human health. To study and generalize the approaches to limiting the consumption of trans fatty acids in different countries of Europe and world. To compare international and Ukrainian legislation on the regulation of trans fatty acids in food products. Materials and Methods. The article uses information based on the materials of FAO/WHO experts, on legislation regulating trans fatty acids in food products, as well as on publications of foreign and Ukrainian scientists. The results of our own studies of the content of trans fats in some foods were compared with data obtained in other countries. Results and Conclusions. Summarizing the results of numerous studies convincingly prove the relationship between the consumption of industrial trans fats with the risk of occurrence or exacerbation of existing nutritional diseases. Best practice policies to eliminate industrially produced trans fatty acids from national food stocks have been introduced in more than forty countries around the world. In Ukraine, food restrictions on the amount of trans fatty acids, which are not trans fatty acids naturally found in fats of animal origin, at a level of no more than 2 %, came into force in September 2023. In this regard, we consider it necessary to apply large-scale educational campaigns of a high scientific level in the media regarding the harmful effects of trans fats on the biological systems of the human body. In addition, we recommend the introduction of state programs in the field of dietary regulation into the practice of general educational institutions, contributing to a conscious and responsible approach to the transition to a healthy diet, which will contribute to a gradual increase in the life expectancy of the population of our country. Keywords: trans fatty acid isomers, public health, harmonization, review.

Multi-omic analysis reveals that Bacillus licheniformis enhances pekin ducks growth performance via lipid metabolism regulation.

Introduction: Bacillus licheniformis (B.licheniformis) was widely used in poultry feeds. However, it is still unclear about how B.licheniformis regulates the growth and development of Pekin ducks. Methods: The experiment was designed to clarify the effect and molecular mechanism of B. licheniformis on the lipid metabolism and developmental growth of Pekin ducks through multiomics analysis, including transcriptomic and metabolomic analyses. Results: The results showed that compared with the control group, the addition of 400 mg/kg B. licheniformis could significantly increase the body weight of Pekin ducks and the content of triglyceride (p < 0.05), at the same time, the addition of B. licheniformis could affect the lipid metabolism of liver in Pekin ducks, and the addition of 400 mg/kg B. licheniformis could significantly increase the content of lipoprotein lipase in liver of Pekin ducks. Transcriptomic analysis revealed that the addition of B. licheniformis primarily impacted fatty acid and glutathione, amino acid metabolism, fatty acid degradation, as well as biosynthesis and elongation of unsaturated fatty acids. Metabolomic analysis indicated that B. licheniformis primarily affected the regulation of glycerol phospholipids, fatty acids, and glycerol metabolites. Multiomics analysis demonstrated that the addition of B. licheniformis to the diet of Pekin ducks enhanced the regulation of enzymes involved in fat synthesis via the PPAR signaling pathway, actively participating in fat synthesis and fatty acid transport. Discussion: We found that B. licheniformis effectively influences fat content and lipid metabolism by modulating lipid metabolism-associated enzymes in the liver. Ultimately, this study contributes to our understanding of how B. licheniformis can improve the growth performance of Pekin ducks, particularly in terms of fat deposition, thereby providing a theoretical foundation for its practical application. Conclusion: B. licheniformis can increase the regulation of enzymes related to fat synthesis through PPAR signal pathway, and actively participate in liver fat synthesis and fatty acid transport, thus changing the lipid metabolism of Pekin ducks, mainly in the regulation of glycerol phospholipids, fatty acids and glycerol lipid metabolites.

Xinbao Pill ameliorates heart failure via regulating the SGLT1/AMPK/PPARα axis to improve myocardial fatty acid energy metabolism

BackgroundHeart failure (HF) is characterized by a disorder of cardiomyocyte energy metabolism. Xinbao Pill (XBW), a traditional Chinese medicine formulation integrating “Liushen Pill” and “Shenfu Decoction,” has been approved by China Food and Drug Administration for the treatment of HF for many years. The present study reveals a novel mechanism of XBW in HF through modulation of cardiac energy metabolism.Methods In vivo, XBW (60, 90, 120 mg/kg/d) and fenofibrate (100 mg/kg/d) were treated for six weeks in Sprague–Dawley rats that were stimulated by isoproterenol to induce HF. Cardiac function parameters were measured by echocardiography, and cardiac pathological changes were assessed using H&E, Masson, and WGA staining. In vitro, primary cultured neonatal rat cardiomyocytes (NRCMs) were induced by isoproterenol to investigate the effects of XBW on myocardial cell damage, mitochondrial function and fatty acid energy metabolism. The involvement of the SGLT1/AMPK/PPARα signalling axis was investigated.ResultsIn both in vitro and in vivo models of ISO-induced HF, XBW significantly ameliorated cardiac hypertrophy cardiac fibrosis, and improved cardiac function. Significantly, XBW improved cardiac fatty acid metabolism and mitigated mitochondrial damage. Mechanistically, XBW effectively suppressed the expression of SGLT1 protein while upregulating the phosphorylation level of AMPK, ultimately facilitating the nuclear translocation of PPARα and enhancing its transcriptional activity. Knockdown of SGLT1 further enhanced cardiac energy metabolism by XBW, while overexpression of SGLT1 reversed the cardio-protective effect of XBW, highlighting that SGLT1 is probably a critical target of XBW in the regulation of cardiac fatty acid metabolism.ConclusionsXBW improves cardiac fatty acid energy metabolism to alleviate HF via SGLT1/AMPK/PPARα signalling axis.

Influences of Cluster Thinning on Fatty Acids and Green Leaf Volatiles in the Production of Cabernet Sauvignon Grapes and Wines in the Northwest of China.

Cluster thinning has been widely applied in yield management and its effect on green leaf volatiles (GLVs) in wines has seldom been studied. GLVs are important flavor compositions for grapes and wines. This work aimed to investigate the impact of cluster thinning on these volatiles and their precursors in grapes and wines. Severe cluster thinning (CT1) and medium cluster thinning (CT2) were performed on Cabernet Sauvignon (Vitis vinifera L.) vines in two sites (G-farm and Y-farm) from Xinjiang province in the Northwest of China. The impact of cluster thinning treatments on the accumulation of GLVs and their precursors, long chain fatty acids (LCFAs) of grape berries and C6 volatiles, in resulting wines was investigated. Multivariate analysis showed that cluster thinning treatments induced significant changes in fruit and wine composition in both farms. In Y-farm, medium cluster thinning (CT2) significantly increased the average cluster weight of harvested berries. Additionally, both cluster thinning treatments (CT1 and CT2) increased fatty acids in harvested berries and CT2 led to an increase in C6 esters and a decrease in C6 alcohols in the wines of Y-farm under the warmer and drier 2012 vintage. However, the effect of cluster thinning was likely negative in G-farm due to its wetter soil and excessive organic matter. The treatments may be applicable for local grape growers to improve viticultural practices for the more balanced vegetative and reproductive growth of Cabernet Sauvignon grapevines. This work also provided further knowledge on the regulation of fatty acids and the derived C6 volatiles through the lipoxygenase (LOX) pathway.

Ziyuglycoside II attenuated OVX mice bone loss via inflammatory responses and regulation of gut microbiota and SCFAs

Background and purposeOsteoporosis (OP) is a frequent clinical problem for the elderly. Traditional Chinese Medicine (TCM) has achieved beneficial results in the treatment of OP. Ziyuglycoside II (ZGS II) is a major active compound of Sanguisorba officinalis L. that has shown anti-inflammation and antioxidation properties, but little information concerning its anti-OP potential is available. Our research aims to investigate the mechanism of ZGS II in ameliorating bone loss by inflammatory responses and regulation of gut microbiota and short chain fatty acids (SCFAs) in ovariectomized (OVX) mice. MethodsWe predicted the mode of ZGS II action on OP through network pharmacology and molecular docking, and an OVX mouse model was employed to validate its anti-OP efficacy. Then we analyzed its impact on bone microstructure, the levels of inflammatory cytokines and pain mediators in serum, inflammation in colon, intestinal barrier, gut microbiota composition and SCFAs in feces. ResultsNetwork pharmacology identified 55 intersecting targets of ZGS II related to OP. Of these, we predicted IGF1 may be the core target, which was successfully docked with ZGS II and showed excellent binding ability. Our in vivo results showed that ZGS II alleviated bone loss in OVX mice, attenuated systemic inflammation, enhanced intestinal barrier, reduced the pain threshold, modulated the abundance of gut microbiota involving norank_f__Muribaculaceae and Dubosiella, and increased the content of acetic acid and propanoic acid in SCFAs. ConclusionsOur data indicated that ZGS II attenuated bone loss in OVX mice by relieving inflammation and regulating gut microbiota and SCFAs.

Abstract LB006: Cell marker-based classification of TNBC subtypes and patient outcomes

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive BC subtype characterized by significant molecular and clinical heterogeneity, influenced by genetic, phenotypic, and environmental factors, as well as interactions of the tumor with its surrounding milieu. In the recent past, gene expression-based subtyping methods have provided a functional understanding for the observed molecular diversity/heterogeneity. In this study, we propose an approach to reclassifying TNBC while considering the cellular heterogeneity of the tumor as well as the tumor milieu. Methods: RNA-Sequencing data for TNBC cohort of 250 diverse women [European (EA, self-reported race, SRR): 114 and African (AA, SRR): 136)], was obtained from our collaborators at LSUHSC. 38/250 were labeled ERhi via IHC but histologically confirmed to be TNBC patients. We utilized 261 breast specific cell type markers to classify our cohort via hierarchical (HC) and consensus (CC) clustering. Differentially expressed genes (DEGs) were identified at p-adj ≤ 0.05. Endotype specific networks were generated using protein-protein interactions, DEGs, and genes regulated by transcription factor. Survival was assessed via log-rank tests. Genetic admixture was performed on 227/250 patients using method described by Pakstis, A. J. et al. Results: We identified three distinct mechanistic subtypes (endotype, CC1-3) containing nine distinct groups (HC1-9), revealing substantial heterogeneity in cell-type and tissue-state within TNBC. Each subtype exhibited unique biomarkers, reflecting diverse immune, extracellular matrix, adipogenesis, and inflammatory signatures. Endotype specific networks revealed patients in CC1 exhibited upregulation of CD8 T cell activation, interferon and interleukin markers, while CC2 showed upregulation of extracellular matrix genes, and CC3, the subtype containing ERhi patients, showed upregulation of fatty acid regulation, hormone sensitivity, and pro-inflammatory genes. Survival analysis demonstrated favorable outcomes for CC1 and less favorable outcomes for CC2. Additionally, SRR-inferred survival differences highlighted poorer outcomes for CC2 groups. We found SRR-inferred prognostic biomarkers such as TTC6, ANKRD30A, and KRT86 associated with distinct prognostic profiles in CC2. Genetic admixture showed a comparable distribution of SRR and genetic ancestry across subtypes. We developed a user-friendly Shiny App for our subtyping method and validated it using TCGA TNBC data. Conclusion: TNBC subtyping using cellular heterogeneity of biopsied samples provides a mechanistic approach to patient classification. Subtype-specific mechanisms suggest tailored therapeutic strategies and provide survival outcomes specific to each subtype. Our method can be applied to other cohorts using the application developed in this work. Citation Format: Zahra Mesrizadeh, Kavitha Mukund, Fokrul Hossain, Jovanny Zabaleta, Denise Danos, Luis Del Valle, Xiao-Cheng Wu, Chindo Hicks, Yuan Chun Ding, Augusto Ochoa, Lucio Miele, Victoria L. Seewaldt, Shankar Subramaniam. Cell marker-based classification of TNBC subtypes and patient outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB006.

Dynamic palmitoylation of STX11 controls injury-induced fatty acid uptake to promote muscle regeneration

Different types of cells uptake fatty acids in response to different stimuli or physiological conditions; however, little is known about context-specific regulation of fatty acid uptake. Here, we show that muscle injury induces fatty acid uptake in muscle stem cells (MuSCs) to promote their proliferation and muscle regeneration. In humans and mice, fatty acids are mobilized after muscle injury. Through CD36, fatty acids function as both fuels and growth signals to promote MuSC proliferation. Mechanistically, injury triggers the translocation of CD36 in MuSCs, which relies on dynamic palmitoylation of STX11. Palmitoylation facilitates the formation of STX11/SNAP23/VAMP4 SANRE complex, which stimulates the fusion of CD36- and STX11-containing vesicles. Restricting fatty acid supply, blocking fatty acid uptake, or inhibiting STX11 palmitoylation attenuates muscle regeneration in mice. Our studies have identified a critical role of fatty acids in muscle regeneration and shed light on context-specific regulation of fatty acid sensing and uptake.

Global trends and collaborative networks in gut microbiota-insulin resistance research: a comprehensive bibliometric analysis (2000-2024).

The human gut microbiota plays a crucial role in maintaining metabolic health, with substantial evidence linking its composition to insulin resistance. This study aims to analyze the global scholarly contributions on the relationship between intestinal microbiota and insulin resistance from 2000 to 2024. A bibliometric analysis was conducted using data from Scopus and Web of Science Core Collection. The search strategy included terms related to "Gastrointestinal Microbiome" and "Insulin Resistance" in the title or abstract. The analysis of 1,884 relevant studies from 510 sources was conducted, revealing a mean citation of 51.36 per manuscript and a remarkable annual growth rate of 22.08%. The findings highlight the significant role of gut microbiota in insulin resistance, corroborating prior studies that emphasize its influence on metabolic disorders. The literature review of the current study showed key mechanisms include the regulation of short-chain fatty acids (SCFAs) and gut hormones, which are critical for glucose metabolism and inflammation regulation. The analysis also identifies "Food and Function" as the most productive journal and Nieuwdorp M. as a leading author, underscoring the collaborative nature of this research area. The consistent increase in publications in the field of gut microbiota and insulin resistance indicates growing recognition of the gut microbiota's therapeutic potential in treating insulin resistance and related metabolic disorders. Future research should focus on standardizing methodologies and conducting large-scale clinical trials to fully realize these therapeutic possibilities.

Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids

Baicalin is a small molecule medication used to treat hepatitis. Our research group discovered that administering baicalin orally to mice following fecal microbiota transplantation from patients resistant to ICIs supported anti-PD-1 activity. However, the precise mechanisms behind this effect are presently unknown. In this present study, ATB-treated C57BL/6 J mice received FMT from patients with advanced NSCLC amenable to αPD-1. Additionally, subcutaneous LLC cells were injected into the mice. Baicalin oral gavage and αPD-1 injection were administered to the mice on days 3 and 9 after tumour inoculation. 16 S rRNA, metabolomics, and flow cytometry were utilized to clarify the mechanisms of baicalin's relief of immunosuppression. The results indicated that oral administration of baicalin enriched bacteria such as Akkermansia and Clostridia_UCG-014, resulted in an increase in SCFAs, which improved the ratio of PD-1+ (CD8+ T cell/Treg) and promoted the levels of IFN-γ+ CD8+ T cells and TNF-α+ CD8+ T cells within the tumour microenvironment. In conclusion, baicalin regulates the metabolites of the gut microbiota to improve the PD-1+ (CD8+ T cell/Treg) balance and circumvent anti-PD-1 resistance. This is achieved through the regulation of short-chain fatty acids.

Sesamin inhibits RANKL-induced osteoclastogenesis and attenuates LPS-induced osteolysis via suppression of ERK and NF-κB signalling pathways.

Infection by bacterial products in the implant and endotoxin introduced by wear particles activate immune cells, enhance pro-inflammatory cytokines production, and ultimately promote osteoclast recruitment and activity. These factors are known to play an important role in osteolysis as well as potential targets for the treatment of osteolysis. Sesamin has been shown to have a variety of biological functions, such as inhibiting inflammation, anti-tumour and involvement in the regulation of fatty acid and cholesterol metabolism. However, the therapeutic effect of sesamin on osteolysis and its mechanism remain unclear. Present studies shown that in the condition of invitro, sesamin could inhibit osteoclastogenesis and bone resorption, as well as suppressing the expression of osteoclast-specific genes. Further studies on the mechanism suggest that the effect of sesamin on human osteoclasts was mediated by blocking the ERK and NF-κB signalling pathways. Besides, sesamin was found to be effective in treating LPS-induced osteolysis by decreasing the production of pro-inflammatory cytokines and inhibiting osteoclastogenesis invivo. Sesamin was non-toxic to heart, liver, kidney, lung and spleen. Therefore, sesamin is a promising phytochemical agent for the therapy of osteolysis-related diseases caused by inflammation and excessive osteoclast activation.

Genome-Wide Association and Pathway Analysis of Carcass and Meat Quality Traits in Karachai Young Goats.

Goats with diverse economic phenotypic traits play an important role in animal husbandry. However, the genetic mechanisms underlying complex phenotypic traits are unclear in goats. Genomic studies of variations provided a lens to identify functional genes. The work aimed to search for candidate genes related to body measurements and body weight of Karachai goats and develop an experimental PCR-RV test system for genotyping significant SNPs. Comparison of GWAS results for ages 4 and 8 months revealed 58 common SNPs for significant genotypes. 11 common SNPs were identified for body weight, 4 SNPs-for group of traits withers height, rump height, body length, 2 SNPs-for withers height and rump height, 1 SNP-for body length and chest depth. Structural annotation of genomic regions covering a window of ±0.20 Mb showed the presence of 288 genes; 52 of them had the described functions in accordance with gene ontology. The main molecular functions of proteins encoded by these genes are the regulation of transcription, cell proliferation, angiogenesis, body growth, fatty acid and lipid metabolism, nervous system development, and spermatogenesis. SNPs common to body weight and localized within a window of ±200 kb from the structural genes CRADD, HMGA2, MSRB3, FUT8, MAX, and RAB15 were selected to create a test system. The study of meat productivity after slaughter and chemical analysis of muscle tissue in Karachai goats at the age of 8 months of different genotypes according to the identified SNPs revealed that rs268269710 is the most promising for further research and use in breeding. The GG genotype is associated with a larger live weight of animals, a larger carcass yield, the content of the boneless part in it, and the ratio of protein and adipose tissue in meat preferred for dietary nutrition. These results will contribute to the genetic improvement of Karachai goats.