Liver Transcriptome Analysis Research Articles

Liver transcriptome analysis reveals PSC-attributed gene set associated with fibrosis progression

BackgroundPrimary Sclerosing Cholangitis (PSC) is a chronic heterogenous cholangiopathy with unknown etiology where chronic inflammation of the bile ducts leads to multifocal biliary strictures and biliary fibrosis with consecutive cirrhosis development. We here aimed to identify a PSC-specific gene signature associated with biliary fibrosis development. MethodsWe performed RNA-sequencing of 47 liver biopsies from people with PSC (n = 16), primary biliary cholangitis (PBC, n = 15), and metabolic dysfunction-associated steatotic liver disease (MASLD, n = 16) with different fibrosis stages to identify a PSC-specific gene signature associated with biliary fibrosis progression. For validation, we compared an external transcriptome data set of liver biopsies from people with PSC (n = 73) with different fibrosis stages (DOI: 10.1002/hep.31488; baseline samples from NCT01672853). ResultsDifferential gene expression analysis of the liver transcriptome from PSC patients with advanced versus early fibrosis revealed 431 genes associated with fibrosis development. Of those, 367 were identified as PSC-associated when compared to PBC or MASLD. Validation against an external data set of 73 liver biopsies from PSC patients with different fibrosis stages led to a condensed set of 150 (out of 367) DEGs. Cell type specificity assignment of those genes by using published single cell RNA-seq data revealed genetic disease drivers expressed by cholangiocytes (e.g. CXCL1, SPP1), fibroblasts, innate and adaptive immune cells while deconvolution along fibrosis progression of the PSC, PBC, MASLD samples highlighted an early involvement of macrophage- and neutrophil-associated genes in PSC fibrosis. ConclusionWe reveal a PSC-attributed gene signature associated with biliary fibrosis development that may enable the identification of potential new biomarkers and therapeutic targets in PSC-related fibrogenesis. IMPACT AND IMPLICATIONSPrimary sclerosing cholangitis (PSC) is an inflammatory liver disease that is characterized by multifocal inflammation of bile ducts and subsequent biliary fibrosis. Herein, we identify a PSC-specific gene set of biliary fibrosis progression attributing to a uniquely complex milieu of different cell types, including innate and adaptive immune cells while neutrophils and macrophages showed an earlier involvement in fibrosis initiation in PSC in contrast to PBC and MASLD. Thus, our unbiased approach lays an important groundwork for further mechanistic studies for research into PSC-specific fibrosis.

Transcriptome analysis of liver and ileum reveals potential regulation of long non-coding RNA in pigs with divergent feed efficiency.

LncRNA plays a significant role in regulating feed efficiency. This study aims to explore the key long non-coding RNAs, associated genes, and pathways in pigs with extreme feed efficiencies. We screened pigs with extremely high and low RFI through a 12-week animal growth trial and then conducted transcriptome analysis on their liver and ileum tissues. We analyzed the differential expressed lncRNAs, miRNAs, and mRNAs through target gene prediction and functional analysis. And we identified key lncRNAs and their potential regulatory genes associated with feed efficiency through the construction of competitive endogenous RNA network. Differentially expressed lncRNAs were pinpointed in the liver, revealing 23 crucial target genes primarily associated with GTP metabolism and glycolipid biosynthesis. In the ileum, a screening identified 92 pivotal target genes, mainly linked to lipid and small molecule metabolism. Moreover, LOC106504303 and LOC102160805 emerged as potentially significant lncRNAs respectively, playing roles in mitochondrial oxidative phosphorylation in the liver, and lipid and cholesterol metabolism in the ileum. The lncRNAs regulate energy metabolism and biosynthesis in the liver, and the digestive absorption capacity in the small intestine, affecting the feed efficiency of pigs.

Targeting S100A9-TLR2 axis controls macrophage NLRP3 inflammasome activation in fatty liver ischemia reperfusion injury

Abstract Liver ischemia reperfusion (IR) injury significantly impacts clinical outcomes by increasing the risk of hepatic dysfunction after liver surgery. Fatty livers are more susceptible to IR stress. Recent studies have demonstrated that S100A9 plays a crucial role in both IR injury and the progression of liver steatosis. Nevertheless, the precise mechanisms underlying these effects remain unclear. In our study, transcriptome analysis of fatty livers subjected to IR insult in mice identified S100A9 as an important mediator. Employing loss-of-function approaches, we investigated the immune regulatory function of S100A9 and its downstream signaling in fatty liver IR injury. As expected, S100A9 emerged as one of the most significantly upregulated genes during the reperfusion stage in fatty livers. Genetic knockdown of S100A9 markedly ameliorated liver pathological damage, evidenced by reduced macrophage/neutrophil infiltration as well as the decreased expression of proinflammatory factors. Transcriptome/functional studies revealed that S100A9 triggered liver inflammatory response via regulating Toll-like receptor 2 (TLR2)/Activating transcription factor 4 (ATF4) signaling. Additionally, TLR2 expression was notably increased in macrophages from ischemic fatty livers. In vitro, recombinant S100A9-stimulated macrophages exhibited the elevated production of proinflammatory factors and TLR2/ATF4 pathway activation. Intriguingly, S100A9 facilitated ATF4 nuclear translocation and enhanced NEK7/NLRP3 inflammasome activation in macrophages. In conclusion, our study identified S100A9 as a key regulator responsible for macrophage NLRP3 inflammasome activation and subsequent inflammatory injury in fatty liver IR process. Targeting TLR2/ATF4 signaling may offer a novel therapeutic strategy for mitigating S100A9-mediated liver injury.

Integrative transcriptomics and lipidomics unravels the amelioration effects of Radix Bupleuri on non-alcoholic fatty liver disease

Ethnopharmacological relevanceRadix Bupleuri (Bupleurum chinense DC.) is the most commonly used traditional Chinese medicine (TCM) for the treatment of liver diseases. While the effects of Radix Bupleuri (BR) on lipid-lowering and liver protection have been established, its role in the development of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet remains unclear. Aim of the studyThe objective of this study was to evaluate the alleviation effects of the active fraction of BR on NAFLD in vivo and to explore the underlying mechanisms through an analysis of liver transcriptome and lipidomics. Materials and methodsThe NAFLD model was established in SD rats by administering a high-fat diet (HFD) for 8 weeks. Subsequently, the NAFLD model rats were continuously gavaged with different polarity fractions of BR (25 g/kg/d) and melatonin (MT) (30 mg/kg/d) for an additional 6 weeks to assess therapeutic effects. The potential mechanism of the low polarity fraction of BR (LBR) in treating NAFLD was investigated through hepatic transcriptome analysis, non-targeted lipidomics, RT-qPCR, protein-protein interaction (PPI) network construction, molecular docking, and Western blotting, aiming to elucidate the underlying mechanisms by which LBR may ameliorate NAFLD. ResultsThese results demonstrated that LBR significantly alleviated the effects of HFD-induced NAFLD, as evidenced by reductions in body weight (BW), liver weight (LW), and epididymal fat weight (EFW) compared to model rats and other polarity fractions of BR. Furthermore, LBR notably down-regulated serum and liver levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while up-regulating high-density lipoprotein cholesterol (HDL-C) in serum. Mechanistically, liver transcriptome analysis indicated that fatty acid metabolism may be a crucial pathway for the improvement of NAFLD following LBR treatment. Lipidomics data suggested that LBR can modulate the metabolic profile in NAFLD rats. Enrichment analysis revealed that glycerophospholipid and glycerolipid metabolism might be key pathways involved in the development of NAFLD. RT-qPCR analysis demonstrated that LBR could regulate the expression of lipid-related genes in these critical pathways. Additionally, Spearman correlation analysis showed a strong relationship between lipid metabolic biomarkers, pathological indices, and lipid-related genes. Moreover, protein-protein interaction (PPI) network and molecular docking analyses identified seven key targets with six ingredients of LBR exhibiting good binding capacity (< -5.0 kcal/mol). Finally, Western blotting analysis indicated that LBR up-regulates the expression levels of PPARα, CPT1, and FABP1 while down-regulating the expression levels of SREBF1 and SCD1, thereby improving metabolism and exerting a lipid-lowering effect. ConclusionIn conclusion, the present research elucidated the lipid-lowering mechanisms of the active fractions of BR. Both BR and LBR presented themselves as promising candidates for the development of novel pharmacological agents targeting NAFLD. LBR effectively ameliorated lipid disturbances associated with HFD-induced NAFLD by modulating the metabolism of fatty acids, cholesterol, glycerolipid, and glycerophospholipids. Consequently, LBR held significant potential for development as an effective lipid-lowering therapeutic.

Low polarity fraction of Radix Bupleuri alleviates chronic unpredictable mild stress-induced depression in rats through FXR modulating bile acid homeostasis in liver, gut, and brain

Radix Bupleuri (BR, Bupleurum chinense DC.) is a well-known traditional Chinese medicine (TCM) known for its effects on soothing the liver and alleviating depression, and is widely used in clinical settings to manage depressive symptoms. A dosage of 12.5g crude drug/kg/d of the low-polarity fraction of Radix Bupleuri (LBR) demonstrated effectiveness in treating depression in our previous study. However, the mechanism through which BR ameliorates depression remains unclear. This study aimed to explore the polar fractions of BR and their mechanisms of action in the treatment of depression. Chronic unpredictable mild stress (CUMS) rats were continuously administered BR by oral gavage for 4 weeks. Behavioral and biochemical indicators were evaluated to assess the antidepressant effects of LBR, and transcriptomics was used to explore the relevant pathways. In addition, pseudo-targeted bile acid (BA) metabonomics was used to quantify the BA profiles. Molecular biology techniques have been used to investigate the underlying mechanisms. LBR serves as a more effective active fraction with antidepressant activity. Intervention with LBR, which is characterized by a clearly defined chemical composition, significantly ameliorated depression-like behavior and biochemical indicators in rats subjected to CUMS. Notably, marked improvements were observed in the levels of total bile acids (TBAs) in the blood, liver, and ileum. Mechanistically, liver transcriptome analysis suggested that bile secretion may be a crucial pathway for alleviating depression after LBR treatment. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) BA metabonomics indicated that TCA, β-MCA, γ-MCA, Tβ-MCA, and UDCA in the liver, Tβ-MCA, TCA, βMCA, GHDCA, and GLCA in the ileum, and β-MCA, CA, and DCA in the hippocampus were the potential therapeutic targets. In addition, molecular biology experiments showed that LBR exerts antidepressant effects by regulating the FXR/SHP/CYP7A1 pathway in the liver, the FXR/FGF15/ASBT pathway in the ileum, and the FXR/CREB/BDNF pathway in the hippocampus. In conclusion, LBR attenuated depression by moderating BA homeostasis through FXR and related genes within the liver-gut-brain axis.

PSIV-23 Transcriptomic analysis revealed the mechanisms of resilience and susceptibility to nonalcoholic steatohepatitis in dairy goats under high-concentrate diet

Abstract Liver health is vital for growth and health of ruminants, which can directly affect their performance. High-concentrate diet (HCD) feeding, a common practice to meet the energy requirements for animal production and growth, has been known to induce liver damage, including nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) in ruminants. To date, the regulatory mechanisms of liver metabolic dysfunctions in ruminants induced by HCD are not well defined. To elucidate molecular regulatory mechanisms underlying liver dysfunction in ruminants, we compared liver transcriptome and single-cell transcriptome of dairy goats that had varied responses to the HCD, aiming to underpin the key mechanisms behind resilience and susceptibility to NASH in ruminants. After feeding 30 dairy goats with low-concentrate diet (LCD, n = 15, defined as Con) or high-concentrate diet (HCD, n = 15) for 6 wk, 10 of them developed NASH (defined as NASH), while the other 5 did not showed any NASH symptom (defined as NASH-tolerance, NASH-T) under HCD. Liver tissues were collected to extract RNA. The paired-end RNA-seq library was sequenced with a NovaSeq6000 sequencer (Illumina). Real-time quantitative PCR was conducted to verify the significantly different genes among groups. Liver single-cell transcriptome was performed using 10×Genomics Chromium system. Liver transcriptome analysis revealed that the expression level of genes involved in the interleukin (IL)-17 signaling pathway, including IL-17A (P = 0.035; 0.001), Act1 (P = 0.036; 0.002), FOSB (P = 0.041; 0.048) and IL-1β (P = 0.022; 0.002) in the NASH group were significantly greater than those in the Con and NASH-T groups. Hepatic single-cell RNA sequencing identified seven cell types in the liver, including hepatocytes, macrophages, T cells, endothelial cell, natural killer (NK) cell, hepatic stellate cells (HSCs), B cells. In T cell subset, significantly decreased T helper 17 (TH17) cells and increased regulatory T (Treg) cells were detected in the NASH group compared with Con and NASH-T groups. In TH17 cell, the expression levels of IL-17A (P = 0.004; 0.009) and IL-23R (P = 0.007; 0.01; the surface antibodies of TH17 cells) in NASH group were significantly greater than those in the Con and NASH-T groups. The expression levels of Foxp3 (P &amp;lt; 0.001; 0.013), IL-2R (P &amp;lt; 0.001; 0.001), CTLA-4 (P = 0.005; 0.017) and CD127 (P = 0.004; 0.009; the surface antibodies of Treg cells) in NASH group were significantly less than those in the Con and NASH-T groups. Our results revealed the role of liver immune cells in maintaining tolerance to NASH in dairy goats under HCD, which provides new understanding in pathogenesis of NASH under HCD. Further studies are needed to identify major factors that drive the changes of ratio of TH17/Treg cell.

Transcriptome, histology, and enzyme activities analysis of liver in Phoxinus lagowskii to the low temperature stress and recovery

Assessing the response and resilience of fish to low temperatures over different time scales can provide valuable insights into their mechanisms of adaptation to cold conditions. Farmed Amur minnows (Phoxinus lagowskii) frequently encounter low temperatures, especially during winter. However, the specific responses of P. lagowskii to low-temperature stress remain largely unexplored. In this study, we examined serum glucose and cortisol levels, histological changes, enzymes associated with phosphate and carbohydrate metabolism, triglyceride levels, and liver transcriptomics under various conditions: control (CK), short-term cold exposure (6 days, SC), prolonged cold exposure (14 days, PC), and recovery (RY) from cold exposure at 2 °C. Liver vacuolation was observed during short-term cold exposure. Additionally, we analyzed the enzymatic activity related to carbohydrate and lipid metabolism in serum and liver. Liver transcriptomic data revealed that the PPAR signaling pathway and autophagy-related genes were enriched during short-term cold exposure. Carbohydrate metabolism-related pathways, including the AMPK and MAPK signaling pathways, were significantly enriched after prolonged cold exposure. Metabolic pathways such as fat digestion and absorption, glycine, serine, and threonine metabolism, and arginine and proline metabolism were significantly enriched in the recovery group. Rapid warming after prolonged cold stress allowed P. lagowskii to recover quickly. These findings suggest that P. lagowskii has a strong adaptive capacity for energy metabolism during prolonged cold exposure and the ability to recover rapidly from cold stress. A comprehensive examination of the histological, physiological, biochemical, and molecular responses of P. lagowskii to low temperatures is crucial for developing effective strategies for cultivating this species in challenging environments.

Research Note: Integrative analysis of transcriptome and gut microbiome reveals foie gras capacity difference between cage and floor rearing systems

To explore the differences in foie gras performance between geese raised in cages and on the ground, we conducted an integrative analysis of liver transcriptome and gut microbial metagenomes. The results showed extremely significant differences in the liver weight (P < 0.01) and liver lipid accumulation of FRS and CRS groups. The levels of triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) of CRS were significantly higher than those of FRS (P < 0.05). Transcriptome analysis showed that 3,917 upregulated and 1,395 downregulated genes were identified, and lipid metabolism pathway and fatty acid metabolism were significantly enriched. Analysis of cecum microbiota revealed that several inflammation-related bacteria (including Gallibacterium, Escherichia-Shigella, Desulfovibrio, Alistipes, and Fournierella) were enriched in CRS, while beneficial bacteria (including Lactobacillus, Limosilactobacillus, and Ligilactobacillus) were significantly enriched in FRS. In conclusion, CRS was better than FRS in foie gras production, which was more conducive to lipid deposition in the goose liver.

Thyroid hormone receptor beta (THRB) dependent regulation of diurnal hepatic lipid metabolism in adult male mice

Thyroid hormones (THs) are critical regulators of systemic energy metabolism and homeostasis. In the liver, high TH action protects against steatosis by enhancing cholesterol and triglyceride turnover, with thyroid hormone receptor beta (THRB) signaling playing a pivotal role. This study probed the potential interaction between THRB action and another critical regulator of liver energy metabolism, the circadian clock. Liver transcriptome analysis of THRB deficient (THRBKO) mice under normal chow conditions revealed a modest impact of THRB deletion. Temporal transcriptome and lipidome profiling uncovered significant alterations in diurnal metabolic rhythms attributable to THRB deficiency pointing to a pro-steatotic state with elevated levels of cholesterol, tri- and diacylglycerides, and fatty acids. These findings were confirmed by THRB agonization in hepatocytes under steatosis-promoting conditions in vitro. Integration of transcriptome profiles from THRBKO mice and mice with induced high or low TH action identified a subset of TH responsive but THRB insensitive genes implicated in immune processes. In summary, our study reveals a complex time-of-day dependent interaction of different TH-related signals in the regulation of liver physiology indicating an opportunity for chronopharmacological approaches to TH/THRB manipulation in fatty liver diseases.

Multi-omics integrated analysis reveals the physiological response of large yellow croaker (Larimichthys crocea) to starvation and refeeding during overwintering

This study aimed to investigate the physiological response to starvation and refeeding during the overwintering period of large yellow croaker (Larimichthys crocea) using physiological and biochemical assays, microbiomics and transcriptomics. Fish were sampled at the beginning of starvation (Fa0 group), after 8 weeks (Fa8 group), after 16 weeks (Fa16 group), and after 8 weeks of refeeding (Fe group). Results indicated that compared to the Fa0 group, the viscerosomatic index (VSI) and intestinal digestive enzyme activities (trypsin, lipase, and amylase) significantly decreased in the Fa8 and Fa16 groups (P < 0.05), but these indicators recovered in the Fe group. Prolonged starvation significantly reduced triglyceride (TG) levels in both serum and liver, but these levels rebounded after 8 weeks of refeeding. Chronic starvation also led to a notable increase in serum low-density lipoprotein (LDL) levels, accompanied by a significant decrease in liver LDL content. As the duration of starvation increasing, the antioxidant and immune capabilities in the serum total antioxidant capacity (T-AOC), superoxide dismutase (SOD), lysozyme (LZM), alkaline phosphatase (AKP), acid phosphatase (ACP) significantly enhanced (P < 0.05), and these indicators significantly declined in the Fe group (P < 0.05). Intestinal flora analysis showed that the Alpha diversity gradually decreased with the prolongation of starvation but recovered after 8 weeks of refeeding, with the abundance of Akkermansia muciniphila significantly increasing (P < 0.05) in the Fa16 group compared to the other groups. Liver transcriptomic analysis revealed that upregulated genes enriched in pathways such as "Ribosome biogenesis in eukaryotes", "Proteasome", "RNA transport", "Biosynthesis of unsaturated fatty acids", "Fatty acid metabolism", "Fatty acid degradation", and "PPAR signaling pathway" (P < 0.05), while downregulated genes significantly enriched in "metabolic pathways" (P < 0.05) in the Fa16 group. Genes related to immune responses were significantly downregulated (P < 0.05) in the Fe group. The correlation analysis of intestinal flora and transcriptome revealed LOC104925398 (complement C3-like) and LOC113745439 (heat shock 70 kDa protein) exhibited significant positive correlations with Levilactobacillus brevis, unclassified Lachnoclostridium, Escherichia coli, and Akkermansia muciniphila (P < 0.05). In conclusion, prolonged starvation was more advantageous to the safe overwintering of large yellow croaker. Our study revealed the physiological response of large yellow croaker to starvation and refeeding during the overwintering period, providing a theoretical foundation for the formulation of safe overwintering strategies.

Maternal α-casein deficiency extends the lifespan of offspring and programmes their body composition.

Early nutrition has significant effects on physiological outcomes during adult life. We have analysed the effect of maternal α-casein (CSN1S1) deficiency on the physiological fate of dams and their offspring. α-casein deficiency reduces maternal milk protein concentration by more than 50% and attenuates the growth of pups to 27% (p < 0.001) of controls at the point of weaning. This is associated with a permanent reduction in adult body weight (- 31% at 25weeks). Offspring nursed by α-casein deficient dams showed a significantly increased lifespan (+ 20%, χ2: 10.6; p = 0.001). Liver transcriptome analysis of offspring nursed by α-casein deficient dams at weaning revealed gene expression patterns similar to those found in dwarf mice (reduced expression of somatotropic axis signalling genes, increased expression of xenobiotic metabolism genes). In adult mice, the expression of somatotropic axis genes returned to control levels. This demonstrates that, in contrast to dwarf mice, attenuation of the GH-IGF signalling axis in offspring nursed by α-casein deficient dams is transient, while the changes in body size and lifespan are permanent. Offspring nursed by α-casein deficient dams showed permanent changes in body composition. Absolute and relative adipose tissue weights (p < 0.05), the percentage of body fat (p < 0.001) as well as adipocyte size in epididymal white adipose tissue are all reduced. Serum leptin levels were 25% of those found in control mice (p < 0.001). Liver lipid content and lipid composition were significantly altered in response to postnatal nutrition. This demonstrates the nutrition in early life programmes adult lipid metabolism, body composition and lifespan.

Gut microbiota dysbiosis links chronic apical periodontitis to liver fibrosis in nonalcoholic fatty liver disease: Insights from a mouse model.

In this study, we investigated the systemic implications of chronic apical periodontitis (CAP). CAP may contribute to the nonalcoholic fatty liver disease (NAFLD) progression through the gut microbiota and its metabolites, which are related to the degree of fibrosis. Sixteen 7-week-old male apolipoprotein E knockout (apoE-/-) mice were randomly divided into two groups: the CAP and Con groups. A CAP model was established by sealing the first- and second-maxillary molars with bacterium-containing cotton balls. Apical lesions were evaluated by micro-CT. Histological evaluations of NAFLD were performed using second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) assays. Additionally, we comprehensively analyzed the gut microbiota using 16S rRNA gene sequencing and explored metabolic profiles by liquid chromatography-mass spectrometry (LC-MS). Immunofluorescence analysis was used to examine the impact of CAP on tight junction proteins and mucin expression. Transcriptome assays have elucidated gene expression alterations in liver tissues. Micro-CT scans revealed an evident periapical bone loss in the CAP group, and the total collagen percentage was increased (Con, 0.0361 ± 0.00510%, CAP, 0.0589 ± 0.00731%, p < .05). 16S rRNA sequencing revealed reduced diversity and distinct taxonomic enrichment in the CAP group. Metabolomic assessments revealed that differentially enriched metabolites, including D-galactosamine, were enriched and that 16-hydroxyhexadecanoic acid and 3-methylindole were depleted in the CAP group. Immunofluorescence analyses revealed disruptions in tight junction proteins and mucin production, indicating intestinal barrier integrity disruption. Liver transcriptome analysis revealed upregulation of Lpin-1 expression in the CAP group. This study provides comprehensive evidence of the systemic effects of CAP on liver fibrosis in NAFLD patients by elucidating alterations in the gut microbiota composition and metabolism.

Transcriptome analysis of avian livers reveals different molecular changes to three urban pollutants: Soot, artificial light at night and noise

Identifying key molecular pathways and genes involved in the response to urban pollutants is an important step in furthering our understanding of the impact of urbanisation on wildlife. The expansion of urban habitats and the associated human-introduced environmental changes are considered a global threat to the health and persistence of humans and wildlife. The present study experimentally investigates how short-term exposure to three urban-related pollutants -soot, artificial light at night (ALAN) and traffic noise-affects transcriptome-wide gene expression in livers from captive female zebra finches (Taeniopygia guttata). Compared to unexposed controls, 17, 52, and 28 genes were differentially expressed in soot, ALAN and noise-exposed birds, respectively. In soot-exposed birds, the enriched gene ontology (GO) terms were associated with a suppressed immune system such as interferon regulating genes (IRGs) and responses to external stimuli. For ALAN-exposed birds, enriched GO terms were instead based on downregulated genes associated with detoxification, redox, hormonal-, and metabolic processes. Noise exposure resulted in downregulation of genes associated with the GO terms: cellular responses to substances, catabolic and cytokine responses. Among the individually differentially expressed genes (DEGs), soot led to an increased expression of genes related to tumour progression. Likewise, ALAN revealed an upregulation of multiple genes linked to different cancer types. Both sensory pollutants (ALAN and noise) led to increased expression of genes linked to neuronal function. Interestingly, noise caused upregulation of genes associated with serotonin regulation and function (SLC6A4 and HTR7), which previous studies have shown to be under selection in urban birds. These outcomes indicate that short-term exposure to the three urban pollutants perturbate the liver transcriptome, but most often in different ways, which highlights future studies of multiple-stress exposure and their interactive effects, along with their long-term impacts for urban-dwelling wildlife.

Green Light Mitigates Cyclic Chronic Heat-Stress-Induced Liver Oxidative Stress and Inflammation via NF-κB Pathway Inhibition in Geese.

Heat stress (HS) induces various physiological disorders in poultry, negatively impacting feed intake, feed efficiency, and growth performance. Considering the documented anti-stress and growth-promoting benefits of monochromatic green light in poultry, we aimed to investigate its effects on cyclic chronic HS-induced oxidative stress (OS) and inflammation in geese. We established three treatment groups-geese exposed to white light (W), white light with HS treatment (WH), and green light with HS treatment (GH)-treated over a six-week period with daily HS sessions. The results revealed that cyclic chronic HS induced liver OS and inflammation, leading to hepatocellular injury and reduced growth performance and feed intake. In comparison, the growth performance of geese under green light significantly improved. Additionally, liver index, serum, liver malondialdehyde (MDA), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α) levels were reduced. Serum total antioxidant capacity (T-AOC), liver catalase (CAT), and superoxide dismutase (SOD) activity were enhanced, reducing hepatic OS and inflammation. Liver transcriptomic analysis indicated that green light alleviates cyclic chronic HS-induced liver injury and promotes geese growth performance by suppressing NF-κB pathway activation.

Lipidomic and transcriptomic profiles provide new insights into the triacylglycerol and glucose handling capacities of the Arctic fox.

The Arctic fox (Vulpes lagopus) is a species indigenous to the Arctic and has developed unique lipid metabolism, but the mechanisms remain unclear. Here, the significantly increased body weight of Arctic foxes was consistent with the significantly increased serum very-low-density lipoprotein (VLDL), and the 40% crude fat diet further increased the Arctic fox body weight. The enhanced body weight gain stems primarily from increased subcutaneous adipose tissue accumulation. The adipose triacylglycerol and phosphatidylethanolamine were significantly greater in Arctic foxes. The adipose fatty-acid synthase content was significantly lower in Arctic foxes, highlighting the main role of exogenous fatty-acids in fat accumulation. Considering the same diet, liver-derived fat dominates adipose expansion in Arctic foxes. Liver transcriptome analysis revealed greater fat and VLDL synthesis in Arctic foxes, consistent with the greater VLDL. Glucose homeostasis wasn't impacted in Arctic foxes. And the free fatty-acids in adipose, which promote insulin resistance, also did not differ between groups. However, the hepatic glycogen was greater in Arctic foxes and transcriptome analysis revealed upregulated glycogen synthesis, improving glucose homeostasis. These results suggest that the superior fat accumulation capacity and distinct characteristics of hepatic and adipose lipid and glucose metabolism facilitate glucose homeostasis and massive fat accumulation in Arctic foxes.

Combined toxic effects of fluxapyroxad and multi-walled carbon nanotubes in Xenopus laevis larvae

Carbon nanomaterials rarely exist in isolation in the natural environment, and their combined effects cannot be ignored. Multi-walled carbon nanotubes (MWCNTs) have shown tremendous potential applications in diverse fields, including pollution remediation, biomedicine, energy, and smart agriculture. However, the combined toxicities of MWCNTs and pesticides on non-target organisms, particularly amphibians, are often overlooked. Fluxapyroxad (FLX), a significant succinate dehydrogenase inhibitor fungicide, has been extensively utilized for the protection of food and cash crops and control of fungi. This raises the possibility of coexistence of MWCNTs and FLX. The objective of this study was to explore the individual and combined toxic effects of FLX and MWCNTs on the early life stages of Xenopus laevis. Embryos were exposed to varying concentrations of FLX (0, 5, and 50 μg/L) either alone or in combination with MWCNTs (100 μg/L) for a duration of 17 days. The findings indicated that co-exposure to FLX and MWCNTs worsened the inhibition of growth, liver damage, and dysregulation of enzymatic activity in tadpoles. Liver transcriptomic analysis further revealed that the presence of MWCNTs exacerbated the disturbances in glucose and lipid metabolism caused by FLX. Additionally, the combined exposure groups exhibited amplified alterations in the composition and function of the gut microflora. Our study suggests that it is imperative to pay greater attention to the agricultural applications, management and ecological risks of MWCNTs in the future, considering MWCNTs may significantly enhance the toxicity of FLX.

The gene IFIT1 is associated with dietary copper‐induced yellow fat disease in sheep

AbstractIn the process of rapid fattening and rearing of meat sheep, yellow fat disease of sheep occurs frequently. This study aims to investigate the preliminary pathogenesis of yellow fat disease in sheep. Eighteen healthy sheep (4–5 months old, 34 ± 1 kg) were selected and randomly divided into three groups: the 10 ppm copper group, the 50 ppm copper group, and the 100 ppm copper group. At the end of the experiment, blood, liver, kidney, and adipose tissue samples were taken from all sheep, and measurements of each index were taken. 50 and 100 ppm copper supplementation in the diets did not significantly affect average daily gain, total cholesterol (TC), triglyceride (TG) and sorbitol dehydrogenase in sheep but significantly increased the effects on gamma‐glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase enzyme activities in the liver and increased the accumulation of copper in the liver. 50 and 100 ppm copper supplementation to the feed caused different levels of pathological damage to the liver, the kidney, and fat and significantly affected the brightness, redness, and yellowness of the carcass fat. Sheep in the 50 ppm copper group did not show significant clinical symptoms of yellow fat disease in the later period of the experiment, but those in the 100 ppm copper group showed significant clinical symptoms of yellow fat disease. Transcriptome analysis of sheep livers showed differential genes associated with yellow fat disease, and GO and KEGG analyses associated with yellow fat disease were performed, and further correlation analysis found that the occurrence of copper‐induced yellow fat disease may be closely related to gene IFIT1.

Antioxidative Potential and Ameliorative Effects of Rice Bran Fermented with Lactobacillus against High-Fat Diet-Induced Oxidative Stress in Mice.

Rice bran is an important byproduct of the rice polishing process, rich in nutrients, but it is underutilized and often used as feed or discarded, resulting in a huge amount of waste. In this study, rice bran was fermented by Lactobacillus fermentum MF423 to obtain a product with high antioxidant activity. First, a reliable and efficient method for assessing the antioxidant capacity of the fermentation products was established using high-performance liquid chromatography (HPLC), which ensured the consistency of the batch fermentation. The fermented rice bran product (FLRB) exhibited significant antioxidant activity in cells, C. elegans, and hyperlipidemic mice. Transcriptome analysis of mouse livers showed that the expression of plin5 was upregulated in diabetic mice administered FLRB, thereby preventing the excessive production of free fatty acids (FFAs) and the subsequent generation of large amounts of reactive oxygen species (ROS). These studies lay the foundation for the application of rice bran fermentation products.

Wogonin mitigates acetaminophen-induced liver injury in mice through inhibition of the PI3K/AKT signaling pathway

Ethnopharmacological relevanceScutellaria baicalensis Georgi (SBG), a widely used traditional Chinese medicine, exhibits anti-inflammatory and antioxidant properties. Wogonin is one of the primary bioactive components of SBG. Acetaminophen (APAP)-induced liver injury (AILI) represents a prevalent form of drug-induced liver damage and is primarily driven by inflammatory responses and oxidative stress. Aim of studyTo investigate the therapeutic effects of Wogonin on AILI and the underlying mechanisms. Materials and methodsC57BL/6 J mice were pre-treated with Wogonin (1, 2.5, and 5 mg/kg bodyweight) for 3 days, followed by treatment with APAP (300 mg/kg bodyweight). The serum and liver tissue samples were collected at 24 h post-APAP treatment. Bone marrow-derived macrophages and RAW264.7 cells were cultured and pre-treated with Wogonin (5, 10, and 20 μM) for 30 min, followed by stimulation with lipopolysaccharide (LPS; 100 ng/mL) for 3 h. To examine the role of the PI3K/AKT signaling pathway in the therapeutic effect of Wogonin on AILI, mice and cells were treated with LY294002 (a PI3K inhibitor) and MK2206 (an AKT inhibitor). ResultsWogonin pre-treatment dose-dependently alleviated AILI in mice. Additionally, Wogonin suppressed oxidative stress and inflammatory responses. Liver transcriptome analysis indicated that Wogonin primarily regulates immune function and cytokines in AILI. Wogonin suppressed inflammatory responses of macrophages by inhibiting the PI3K/AKT signaling pathway. Consistently, Wogonin exerted therapeutic effects on AILI in mice through the PI3K/AKT signaling pathway. ConclusionsWogonin alleviated AILI and APAP-induced hepatotoxicity in mice through the PI3K/AKT signaling pathway.

Synergistic detoxification efficiency and mechanism of triclocarban degradation by a bacterial consortium in the liver-gut-microbiota axis of zebrafish (Danio rerio)

Triclocarban (TCC), an emerging organic contaminant, poses a potential threat to human health with long-term exposure. Here, Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 were utilized to degrade TCC at environmental related concentrations for enhancing TCC biodegradation and investigating whether the toxicity of intermediate metabolites is lower than that of the parent compound. The results demonstrated that the bacterial consortium could degrade TCC by 82.0% within 7 days. The calculated 96 h LC50 for TCC, as well as its main degradation product 3,4-Dichloroaniline (DCA) were 0.134 mg/L and 1.318 mg/L respectively. Biodegradation also alleviated histopathological lesions induced by TCC in zebrafish liver and gut tissues. Liver transcriptome analysis revealed that biodegradation weakened differential expression of genes involved in disrupted immune regulation and lipid metabolism caused by TCC, verified through RT-qPCR analysis and measurement of related enzyme activities and protein contents. 16 S rRNA sequencing indicated that exposure to TCC led to gut microbial dysbiosis, which was efficiently improved through TCC biodegradation, resulting in decreased relative abundances of major pathogens. Overall, this study evaluated potential environmental risks associated with biodegradation of TCC and explored possible biodetoxification mechanisms, providing a theoretical foundation for efficient and harmless bioremediation of environmental pollutants.