Hepatic mRNA Research Articles

Ferulic acid inhibits tumor proliferation and attenuates inflammation of hepatic tissues in experimentally induced HCC in rats.

Hepatocellular carcinoma (HCC) is a prevalent form of primary liver cancer with a 5-year survival rate of just 18%. Ferulic acid, a natural compound found in fruits and vegetables such as sweet corn, rice bran, and dong quai, is an encouraging drug known for its diverse positive effects on the body, including anti-inflammatory, anti-apoptotic, and neuroprotective properties. Our study aimed to investigate the potential antitumor effects of ferulic acid to inhibit tumor growth and inflammation of HCC in rats. HCC was induced in rats by administering thioacetamide. Additionally, some rats were given 50 mg/kg of ferulic acid three times a week for 16 weeks. Liver function was assessed by measuring serum alpha-fetoprotein (AFP) and examining hepatic tissue sections stained with hematoxylin/eosin or anti-hypoxia induced factor-1α (HIF-1α). The hepatic mRNA and protein levels of HIF-1α, nuclear factor κB (NFκB), tumor necrosis factor-α (TNF-α), mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3), cMyc, and cyclin D1 were examined. The results showed that ferulic acid increased the rats' survival rate by reducing serum AFP levels and suppressing hepatic nodules. Furthermore, ferulic acid ameliorated the appearance of vacuolated cytoplasm induced by HCC, reduced apoptotic nuclei, and necrotic nodules. Finally, ferulic acid decreased the expression of HIF-1α, NFκB, TNF-α, mTOR, STAT3, cMyc, and cyclin D1. In conclusion, ferulic acid is believed to possess antitumor properties by inhibiting HCC-induced hypoxia through the suppression of HIF-1α expression. Additionally, it helps in reducing the expression of mTOR, STAT3, cMyc, and cyclin D1, thereby slowing down tumor growth. Lastly, ferulic acid reduced hepatic tissue inflammation by downregulating NFκB and TNF-α.

Direct Molecular Action of Taurine on Hepatic Gene Expression Associated with the Amelioration of Hypercholesterolemia in Rats.

Taurine can ameliorate hypercholesterolemia by facilitating cholesterol efflux and increasing cytochrome P450 7A1 (CYP7A1) without clear underlying molecular mechanisms. This study aims to elucidate the molecular action of taurine in diet-induced hypercholesterolemia. Male Wistar rats were fed a high cholesterol diet containing 5% taurine for 14 days. Three-dimensional primary hepatocytes from rats were exposed to 10 mM taurine for 24 h. Transcriptome analyses of both the liver and hepatocytes were performed using DNA microarray. Taurine significantly decreased serum cholesterol levels and increased hepatic CYP7A1 mRNA levels and transcription rates in rats. Taurine altered the expression of seventy-seven genes in the liver, involving lipid, drug, amino acid metabolism, and gluconeogenesis pathways. The small heterodimer partner (SHP), a transcription factor regulated by taurine, was suppressed. "Network analysis" revealed a negative correlation between the SHP and induction of CYP7A1 and cytochrome P450 8B1 (CYP8B1). However, CYP7A1 and CYP8B1 levels were not altered by taurine in 3D-primary hepatocytes. Venn diagram analyses of the transcriptomes in both hepatocytes and the liver indicated a consistent upregulation of organic anion transporting polypeptide 2 (OATP2) and betaine homocysteine methyltransferase (BHMT). Taurine ameliorated hypercholesterolemia in rats fed a high cholesterol diet by directly enhancing the hepatic expression of BHMT and OATP2, which modulated the SHP and induced CYP7A1 and CYP8B1, thereby promoting cholesterol catabolism and lowering blood cholesterol levels.

In-silico trial emulation to predict the cardiovascular protection of new lipid-lowering drugs: an illustration through the design of the SIRIUS programme.

Inclisiran, an siRNA targeting hepatic PCSK9 mRNA, administered twice-yearly (after initial and 3-month doses), substantially and sustainably reduced LDL-cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a reduced risk of major adverse cardiovascular events (MACE) is not yet established. In-silico trials applying a disease computational model to virtual patients receiving new treatments allow to emulate large scale long term clinical trials. The SIRIUS in-silico trial programme aims to predict the efficacy of inclisiran on CV events in individuals with established atherosclerotic cardiovascular disease (ASCVD). A knowledge-based mechanistic model of ASCVD was built, calibrated, and validated to conduct the SIRIUS programme (NCT05974345) aiming to predict the effect of inclisiran on CV outcomes.The SIRIUS Virtual Population included patients with established ASCVD (previous myocardial infarction (MI), previous ischemic stroke (IS), previous symptomatic lower limb peripheral arterial disease (PAD) defined as either intermittent claudication with ankle-brachial index <0.85, prior peripheral arterial revascularization procedure, or vascular amputation) and fasting LDL-C ≥ 70 mg/dL, despite stable (≥ 4 weeks) well-tolerated lipid lowering therapies.SIRIUS is an in-silico multi-arm trial programme. It follows an idealized crossover design where each virtual patient is its own control, comparing inclisiran to 1) placebo as adjunct to high-intensity statin therapy with or without ezetimibe, 2) ezetimibe as adjunct to high-intensity statin therapy, 3) evolocumab as adjunct to high-intensity statin therapy and ezetimibe.The co-primary efficacy outcomes are based on time to the first occurrence of any component of 3P-MACE (composite of CV death, nonfatal MI or nonfatal IS) and time to occurrence of CV death over 5 years. The SIRIUS in-silico trial programme will provide early insights regarding a potential effect of inclisiran on MACE in ASCVD patients, several years before the availability of the results from ongoing CV outcomes trials (ORION-4 and VICTORION-2-P).

SIRT1 and FOXO1 role on MASLD risk: effects of DHA-rich n-3 PUFA supplementation and exercise in aged obese female mice and in post-menopausal overweight/obese women

Sirtuins 1 (SIRT1) and Forkhead box protein O1 (FOXO1) expression have been associated with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Exercise and/or docosahexaenoic acid (DHA) supplementation have shown beneficial effects on MASLD. The current study aims to assess the relationships between Sirt1, Foxo1 mRNA levels and several MASLD biomarkers, as well as the effects of DHA-rich n-3 PUFA supplementation and/or exercise in the steatotic liver of aged obese female mice, and in peripheral blood mononuclear cells (PBMCs) of postmenopausal women with overweight/obesity. In the liver of 18-month-old mice, Sirt1 levels positively correlated with the expression of genes related to fatty acid oxidation, and negatively correlated with lipogenic and proinflammatory genes. Exercise (long-term treadmill training), especially when combined with DHA, upregulated hepatic Sirt1 mRNA levels. Liver Foxo1 mRNA levels positively associated with hepatic triglycerides (TG) content and the expression of lipogenic and pro-inflammatory genes, while negatively correlated with the lipolytic gene Hsl. In PBMCs of postmenopausal women with overweight/obesity, FOXO1 mRNA expression negatively correlated with the hepatic steatosis index (HSI) and the Zhejiang University index (ZJU). After 16-weeks of DHA-rich PUFA supplementation and/or progressive resistance training (RT), most groups exhibited reduced MASLD biomarkers and risk indexes accompanying with body fat mass reduction, but no significant changes were found between the intervention groups. However, in PBMCs n-3 supplementation upregulated FOXO1 expression, and the RT groups exhibited higher SIRT1 expression. In summary, SIRT1 and FOXO1 could be involved in the beneficial mechanisms of exercise and n-3 PUFA supplementation related to MASLD manifestation.

Comparative assessment of climate resilient potential in four poultry genotypes reared in hot-humid tropical environment: a preliminary evaluation.

The general objective of this study is to comparatively assess the climate-resilient potential of four different poultry genotypes-Giriraja (n = 8), Country chicken (n = 8), Naked neck (n = 8), and Kadaknath (n = 8)-reared in a hot-humid tropical environment. Birds from all genotypes had ad libitum access to feed and water and were exposed to identical environmental temperatures in the experimental shed. Diurnal meteorological data were recorded inside and outside the shed daily. Blood biochemical, hormonal, and endocrine variables were monitored monthly until the birds reached 12 weeks of age. Significant variations (P < 0.01) were observed at different intervals in variables, including total protein, albumin, globulin, triglycerides, and cholesterol. Genotype-specific differences were noted in triglycerides (P < 0.01), albumin (P < 0.01), total protein (P < 0.05), and cholesterol (P < 0.05). Inter-genotype variations (P < 0.05) were also observed in serum cortisol, T3, and T4 levels. Distinct variations (P < 0.05) were also observed during specific intervals, particularly in cortisol and T3 levels. The study of hepatic mRNA expression of HSPs and HSF-1 revealed a significant breed difference (P < 0.05) in the expression pattern of HSP60, HSP70, HSP90, and HSP110, while no difference was observed between genotypes for HSP40 and HSF-1. The study highlights the Naked Neck breed as an exemplar of resilience, showcasing its distinctive ability to maintain homeostasis under heat stress compared to other genotypes. The genetic and physiological insights gained from this investigation offer prospective pathways for aligning sustainable poultry farming with environmental exigencies.

IL-10 Enhances the Inhibitory Effect of Adipose-Derived Stromal Cells on Insulin Resistance/Liver Gluconeogenesis by Treg Cell Induction.

The modulation of cellular phenotypes within adipose tissue provides a potential means for therapeutic intervention for diabetes. Endogenous interleukin-10 (IL-10) protects against diet-induced insulin resistance. We examined the effects and mechanisms of action of IL-10-treated adipose-derived stromal cells on diabetes-induced insulin resistance and liver gluconeogenesis. We harvested stromal vascular fractions (SVFs) from the adipose tissue of diabetic (Leprdb/db) mice and treated them with IL-10 in vitro. SVFs treated with 10 or 100 ng of IL-10 were injected into the inguinal adipose tissue of Leprdb/db mice. IL-10 treatment suppressed the mRNA expression of IL-6, IL-33, CCL2, TNF-α, and IL-1β. Additionally, it suppressed the protein expression of IL-6, pmTOR, pJNK, and pNF-κB but enhanced Foxp3 mRNA expression in SVFs from diabetic mice. Meanwhile, IL-10 treatment repressed CCL2 and PDGFRα expression in adipose tissue macrophages (ATMs) and IL-6 expression in non-ATMs but increased the Foxp3 and IL-10 mRNA expression of ATMs from diabetic mice. Injection of IL-10-treated SVFs decreased the IL-6, IL-33, CCL2, IL-1β, and CCL2 but enhanced the Foxp3 and IL-10 mRNA expression of adipose tissue from Leprdb/db mice. Furthermore, injection of IL-10-treated SVFs increased CD4+ regulatory T cells (Tregs) in SVFs and adipose IL-10 levels and suppressed plasma adiponectin levels and DPP4 activity in diabetic mice. Injection of IL-10-treated SVFs decreased hepatic G6PC and PCK1 mRNA expression and increased Akt activation, STAT3 phosphorylation in the liver, and glucose tolerance in diabetic mice. Our data suggest that IL-10 treatment decreases inflammation in adipose SVFs of diabetic mice. Injection of IL-10-treated SVFs into the adipose tissue decreased diabetes-induced gluconeogenesis gene expression, DPP4 activity, and insulin resistance by enhancing Treg cells in diabetic mice. These data suggest that IL-10-treated adipose stromal vascular cells could be a promising therapeutic strategy for diabetes mellitus.

Dietary medium-chain fatty acids reduce hepatic fat accumulation via activation of a CREBH-FGF21 axis

ObjectiveDietary medium-chain fatty acids (MCFAs), characterized by chain lengths of 8–12 carbon atoms, have been proposed to have beneficial effects on glucose and lipid metabolism, yet the underlying mechanisms remain elusive. We hypothesized that MCFA intake benefits metabolic health by inducing the release of hormone-like factors. MethodsThe effects of chow diet, high-fat diet rich in long-chain fatty acids (LCFA HFD) fed ad libitum or pair-fed to a high-fat diet rich in MCFA (MCFA HFD) on glycemia, hepatic gene expression, circulating fibroblast growth factor 21 (FGF21), and liver fat content in both wildtype and Fgf21 knockout mice were investigated. The impact of a single oral dose of an MCFA-rich oil on circulating FGF21 and hepatic Fgf21 mRNA expression was assessed. In flag-tagged Crebh knockin mice and liver-specific Crebh knockout mice, fed LCFA HFD or MCFA HFD, active hepatic CREBH and hepatic Fgf21 mRNA abundance were determined, respectively. ResultsMCFA HFD improves glucose tolerance, enhances glucose clearance into brown adipose tissue, and prevents high-fat diet-induced hepatic steatosis in wildtype mice. These benefits are associated with increased liver expression of CREBH target genes (Apoa4 and Apoc2), including Fgf21. Both acute and chronic intake of dietary MCFAs elevate circulating FGF21. Augmented hepatic Fgf21 mRNA following MCFA HFD intake is accompanied by higher levels of active hepatic CREBH; and MCFA-induced hepatic Fgf21 expression is blocked in mice lacking Crebh. Notably, while feeding male and female Fgf21 wildtype mice MCFA HFD results in reduced liver triacylglycerol (TG) levels, this liver TG-lowering effect is blunted in Fgf21 knockout mice fed MCFA HFD. The reduction in liver TG levels observed with MCFA HFD was independent of weight loss. ConclusionsDietary MCFAs reduce liver fat accumulation via activation of a CREBH-FGF21 signaling axis.

Hepatic GDP-fucose transporter SLC35C1 attenuates cholestatic liver injury and inflammation by inducing CEACAM1 N153 fucosylation.

Inflammatory response is crucial for bile acid (BA)-induced cholestatic liver injury, but molecular mechanisms remain to be elucidated. Solute Carrier Family 35 Member C1 (SLC35C1) can transport GDP-fucose into the Golgi to facilitate protein glycosylation. Its mutation leads to the deficiency of leukocyte adhesion and enhances inflammation in humans. However, little is known about its role in liver diseases. Hepatic SLC35C1 mRNA transcripts and protein expression were significantly increased in patients with obstructive cholestasis (OC) and mouse models of cholestasis. Immunofluorescence revealed that the upregulated SLC35C1 expression mainly occurred in hepatocytes. Liver-specific ablation of Slc35c1 (Slc35c1 cKO) significantly aggravated liver injury in mouse models of cholestasis induced by bile duct ligation and 1% cholic acid-feeding, evidenced by increased liver necrosis, inflammation, fibrosis, and bile ductular proliferation. The Slc35c1 cKO increased hepatic chemokine Ccl2 and Cxcl2 expression and T-cell, neutrophil and F4/80 macrophage infiltration, but did not affect the levels of serum and liver BA in mouse models of cholestasis. LC-MS/MS analysis revealed that hepatic Slc35c1 deficiency substantially reduced the fucosylation of cell-cell adhesion protein CEACAM1 at N153. Mechanistically, cholestatic levels of conjugated BAs stimulated SLC35C1 expression by activating the STAT3 signaling to facilitate CEACAM1 fucosylation at N153, and deficiency in the fucosylation of CEACAM1 at N135 enhanced the BA-stimulated CCL2 and CXCL2 mRNA expression in primary mouse hepatocytes and PLC/PRF/5-ASBT cells. Elevated hepatic SLC35C1 expression attenuates cholestatic liver injury by enhancing CEACAM1 fucosylation to suppress CCL2 and CXCL2 expression and liver inflammation.

Molecular targets of PXR-dependent ethanol-induced hepatotoxicity in female mice

The pregnane X receptor (PXR, NR1I2), a xenobiotic-sensing nuclear receptor signaling potentiates ethanol (EtOH)-induced hepatotoxicity in male mice, however, how PXR signaling modulates EtOH-induced hepatotoxicity in female mice is unknown. Wild type (WT) and Pxr-null mice received 5 % EtOH-containing diets or paired-fed control diets for 8 weeks followed by assessment of liver injury, EtOH elimination rates, histology, and changes in gene and protein expression; microarray and bioinformatic analyses were also employed to identify PXR targets in chronic EtOH-induced hepatotoxicity. In WT females, EtOH ingestion significantly increased serum ethanol and alanine aminotransferase (ALT) levels, hepatic Pxr mRNA, constitutive androstane receptor activation, Cyp2b10 mRNA and protein, oxidative stress, endoplasmic stress (phospho-elF2α) and pro-apoptotic (Bax) protein expression. Unexpectedly, EtOH-fed female Pxr-null mice displayed increased EtOH elimination and elevated levels of hepatic acetaldehyde detoxifying aldehyde dehydrogenase 1a1 (Aldh1a1) mRNA and protein, EtOH-metabolizing alcohol dehydrogenase 1 (ADH1), and lipid suppressing microsomal triglyceride transport protein (MTP) protein, aldo–keto reductase 1b7 (Akr1b7) and Cyp2a5 mRNA, but suppressed CYP2B10 protein levels, with evidence of protection against chronic EtOH-induced oxidative stress and hepatotoxicity. While liver injury was not different between the two WT sexes, female sex may suppress EtOH-induced macrovesicular steatosis in the liver. Several genes and pathways important in retinol and steroid hormone biosynthesis, chemical carcinogenesis, and arachidonic acid metabolism were upregulated by EtOH in a PXR-dependent manner in both sexes. Together, these data establish that female Pxr-null mice are resistant to chronic EtOH-induced hepatotoxicity and unravel the PXR-dependent and −independent mechanisms that contribute to EtOH-induced hepatotoxicity.

Hepatic glucokinase regulatory protein and carbohydrate response element binding protein attenuation reduce de novo lipogenesis but do not mitigate intrahepatic triglyceride accumulation in Aldob deficiency

ObjectiveStable isotope studies have shown that hepatic de novo lipogenesis (DNL) plays an important role in the pathogenesis of intrahepatic lipid (IHL) deposition. Furthermore, previous research has demonstrated that fructose 1-phosphate (F1P) not only serves as a substrate for DNL, but also acts as a signalling metabolite that stimulates DNL from glucose. The aim of this study was to elucidate the mediators of F1P-stimulated DNL, with special focus on two key regulators of intrahepatic glucose metabolism, i.e., glucokinase regulatory protein (GKRP) and carbohydrate response element binding protein (ChREBP). MethodsAldolase B deficient mice (Aldob−/−), characterized by hepatocellular F1P accumulation, enhanced DNL, and hepatic steatosis, were either crossed with GKRP deficient mice (Gckr−/−) or treated with short hairpin RNAs directed against hepatic ChREBP. ResultsAldob−/− mice showed higher rates of de novo palmitate synthesis from glucose when compared to wildtype mice (p < 0.001). Gckr knockout reduced de novo palmitate synthesis in Aldob−/− mice (p = 0.017), without affecting the hepatic mRNA expression of enzymes involved in DNL. In contrast, hepatic ChREBP knockdown normalized the hepatic mRNA expression levels of enzymes involved in DNL and reduced fractional DNL in Aldob−/− mice (p < 0.05). Of interest, despite downregulation of DNL in response to Gckr and ChREBP attenuation, no reduction in intrahepatic triglyceride levels was observed. ConclusionsBoth GKRP and ChREBP mediate F1P-stimulated DNL in aldolase B deficient mice. Further studies are needed to unravel the role of GKRP and hepatic ChREBP in regulating IHL accumulation in aldolase B deficiency.

Effects of rumen-bypass protein supplement on growth performance, hepatic mitochondrial protein complexes, and hepatic immune gene expression of beef steers with divergent residual feed intake.

We investigated the impact of a rumen-bypass protein (RBP) supplement on growth performance, plasma and urinary N (UN) concentration, hepatic mitochondrial protein complexes, and hepatic mRNA expression of immune genes of beef steers with negative or positive residual feed intake (RFI) phenotype. Forty crossbred beef steers with an average body weight (BW) of 492 ± 36 kg were subjected to a generalized randomized block design over a 42-day experimental period. This study followed a 2 × 2 factorial arrangement of treatments. The factors evaluated were: 1) RFI classification (low-RFI (-2.12 kg/d) vs. high-RFI (2.02 kg/d), and 2) rumen-bypass protein supplement: RBP supplement (RBP; 227 g/steer/d) vs. control diet (CON; 0 g/d), resulting in four distinct treatments: LRFI-CON (n = 10), LRFI-RBP (n = 10), HRFI-CON (n = 10), and HRFI-RBP (n = 10). The RBP supplement (84% crude protein) is a mixture of hydrolyzed feather meal, porcine blood meal, and DL-methionine hydroxy analogue. The beef steers were stratified by BW, randomly assigned to treatments, and housed in four pens (1 treatment/pen) equipped with two GrowSafe feed bunks each to measure individual dry mater intake (DMI). Body weight was measured every 7 d. Liver tissue samples were collected on d 42 from all the beef steers. These samples were used for mRNA expression analysis of 16 immune-related genes and for evaluating the mitochondrial protein complexes I - V. No significant effects due to RBP supplementation or RFI × RBP interactions (P > 0.05) were observed for average daily gain (ADG) and DMI. However, compared to high-RFI steers, low-RFI steers showed a trend towards reduced DMI (12.9 vs. 13.6 kg/d; P = 0.07) but ADG was similar for the two RFI groups. Regardless of RFI status, supplemental RBP increased blood urea nitrogen (BUN) (P = 0.01), with a lower BUN concentration in low-RFI steers compared to high-RFI ones. A tendency for interaction (P = 0.07) between RFI and RBP was detected for the UN concentrations; feeding the dietary RBP increased the UN concentration in high-RFI beef steers (209 vs. 124 mM), whereas the concentration was lower than that of the CON group for low-RFI beef steers (86 vs. 131 mM). Interactions of RBP and RFI were observed (P ≤ 0.05) for mitochondrial activities of complexes IV, V, and mRNA expressions of some immune genes such as TLR2, TLR3, and IL23A. In conclusion, while RBP supplementation did not alter growth performance, its observed effects on hepatic immune gene expression, mitochondrial protein complexes, BUN, and UN depended on the beef steers' RFI phenotype. Therefore, the RFI status of beef steers should be considered in future studies evaluating the effects of dietary protein supplements.

Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty Liver

The antidiabetic drug metformin has a wide range of metabolic effects and may also reduce the risk of obesity-related diseases. The aim of the current study was to investigate if metformin could counteract meldonium-induced fatty liver. Four groups of male C57BL/6J mice were fed a low-fat control diet, or low-fat diets supplemented with metformin, meldonium, or metformin and meldonium for three weeks. Meldonium treatment led to 5.2-fold higher hepatic triacylglycerol (TAG) levels compared to control, and metformin lowered the meldonium-induced lipid accumulation insignificantly by 21%. Mice treated with metformin and meldonium demonstrated significantly lower weight gain, visceral adipose tissue weight and plasma levels of TAG compared to meldonium alone. The hepatic mRNA level of carnitine palmitoyl transferase 1 was increased 2-fold with combined meldonium and metformin treatment compared to meldonium treatment (p &lt; 0.001). Increased hepatic expression of genes involved in fatty acid oxidation and lipid transport was observed in the combination group compared to control, and increased gene expression of the mitochondrial uncoupling protein UCP2 was observed compared to the meldonium group. In addition, the product of fatty acid oxidation, acetylcarnitine, increased in plasma in metformin-treated mice. Altogether, metformin treatment influenced hepatic lipid metabolism and lowered plasma TAG in meldonium-induced fatty liver in mice.

Acute ultraviolet B irradiation increases cholesterol and decreases Cyp7a1 expression in the liver of female mice.

Recent studies have demonstrated that ultraviolet B (UVB) irradiation impacts both skin and hepatic functions. In this study, we investigated the effects of UVB irradiation on cholesterol metabolism in the liver. Hairless mice were exposed to UVB (1.6 J/cm2) irradiation. Dorsal skin and liver samples were collected 24 h after exposure. Total RNA was extracted from the skin and liver tissues, and used for DNA microarray analysis and real-time polymerase chain reaction (PCR). Hepatic mRNA expression of Cyp7a1 revealed a 4.4-fold decrease in the UVB (+) group compared to that in the UVB (-) group. No differences were observed in the expression of the other genes related to cholesterol metabolism. Additionally, the level of hepatic total cholesterol in the UVB (+) group was significantly higher than in the UVB (-) group. These findings suggest that acute UVB irradiation increases total cholesterol levels and decreases Cyp7a1 expression in the liver.

Association between rat decompression sickness resistance, transthyretin single nucleotide polymorphism, and expression: A pilot study.

Decompression sickness (DCS) is a systemic syndrome that can occur after an environmental pressure reduction. Previously, we showed that the plasmatic tetrameric form of transthyretin (TTR) nearly disappeared in rats suffering DCS but not in asymptomatic ones. In this pilot study, we assessed whether the resistance to DCS could be associated with polymorphism of the gene of TTR. For this study, Sanger sequencing was performed on purified PCR products from the liver of 14-week-old male and female standard and DCS-resistant rats (n = 5 per group). Hepatic TTR mRNA expression was assessed by RT-qPCR in 18-19 week-old male and female standard and resistant rats (n = 6 per group). There is a synonymous single nucleotide polymorphism (SNP) on the third base of codon 46 (c.138 C > T). The thymine allele was present in 90% and 100% of males and females standard, respectively. However, this allele is present in only 30% of DCS-resistant males and females (p = 0.0002301). In the liver, there is a significant effect of the resistance to DCS (p = 0.043) and sex (p = 0.047) on TTR expression. Levels of TTR mRNA were lower in DCS-resistant animals. To conclude, DCS resistance might be associated with a SNP and a lower expression of TTR.

Effects of dietary fish oil replacement with rice bran oil on growth performance, serum biochemical index, antioxidant capacity, lipid metabolism and inflammatory response of large yellow croaker (Larimichthys crocea) juveniles

Fish oil (FO) replacement has become a top priority with the increasing growth of aquaculture and the decline of FO production. Dietary rice bran oil (RBO) has been marked with good application prospects and development potential in humans and terrestrial animals. Hence, this study was geared towards ascertaining the effects of replacing dietary FO with RBO in fish feeds. In this study, a 74-day feeding trial was conducted with large yellow croaker (Larimichthys crocea) juveniles to ascertain the effects of dietary FO replaced by different levels (0%, 25%, 50%, 75% and 100%) of RBO. Each diet was randomly fed to triplicate groups of large yellow croaker juveniles (120 fish per group) with an initial mean body weight of 13.02 ± 0.02 g. Fish fed with dietary RBO 25% showed significantly higher final body weight, weight gain rate, specific growth rate, and feed intake compared to other treatments. Also, fish fed diets with RBO showed significantly higher antioxidant capacity compared to the control. Interestingly, fish fed with RBO 25% diet showed a significantly improved serum lipid profile when compared to the control. Moreover, the hepatic mRNA expression of sterol regulatory element-binding protein-1 (srebp-1), and fatty acid synthase (fas) was significantly upregulated in RBO 25% replacement, while peroxisome proliferator-activated receptor α (pparα), was significantly suppressed in fish fed RBO 100% compared to the control. Furthermore, fish fed RBO 100% had significantly increased Interleukin-1β (il-1β), Tumour necrosis factor-α (tnf-α), and Interferon-γ (ifn-γ), and significantly decreased transcript levels of Interleukin-10 (il-10). Therefore, the results of the present study showed that RBO could promote the performance of large yellow croaker juveniles, by improving the growth indexes, serum biochemical properties, antioxidant capacity, and alleviating liver inflammation.

Supplementation of Saccharomycopsis fibuligera nucleotides in soybean-based diets enhanced growth, intestinal health, and reduced inflammatory responses of turbot juveniles (Scophthalmus maximus L.)

In this study, Saccharomycopsis fibuligera nucleotides (SFN) were extracted for exploring the influence on growth, inflammatory response and intestinal health level in turbot juveniles (initial weight 7.16 ± 0.01 g) for 10 weeks. Five isonitrogenous and isolipidic experimental feeds were formulated to include fishmeal-based diet (FM) that contained no SFN, while the other four soybean meal-based diet (SBM), that replaced 30 % FM, contained 0.25, 0.5 or 0.75 % SFN hereafter referred to as SBM0.25, SBM0.5 and SBM0.75, respectively. The feed efficiency exhibited a significantly quadratic or linear increase with the increase of SFN intake and the values reached the peak in the SBM0.5 treatment (P < 0.05). With the increase of SFN supplementation, the specific growth rate presented a significantly linear increase tendency (P < 0.05), and reached a peak in the SBM0.5 treatment. The hepatic antioxidant ability of turbot juveniles was significantly linear or quadratic promoted with dietary SFN supplementation in SBM-based diets (P < 0.05). Moreover, activities of plasma transaminases and γ-glutamyl transpeptidase of turbots showed significantly linear and quadratic decreasing trends with the SFN supplementation increasing (P < 0.05). The hepatic pro-inflammatory factor mRNA expressions were significantly linear or quadratic down-regulated and the anti-inflammatory factor mRNA expression was significantly linear and quadratic up-regulated with the SFN supplementation increasing (P < 0.05). Moreover, the height of villi and microvilli, the thickness of the muscularis and the tight junction proteins mRNA expression level exhibited significantly linear or quadratic increasing trends with the increasing dietary SFN supplementation (P < 0.05). The relative abundance of Lactobacillus plantarum of hindgut was significantly higher of fish fed the SBM0.75 diet compared with the SBM treatment. In conclusion, SFN supplementation was beneficial to the growth and health level of turbot juveniles, the appropriate amount of SFN supplemented was above 0.5 % in this study.

Elevated IRF9 raised cell apoptosis and tissue damages through suppressing SIRT1 in hyperlipidemia acute pancreatitis with liver injury

BackgroundHyperlipidemia is a vital etiology of acute pancreatitis (AP), 12 to 20% of which have a history of hyperlipidemia. Multiple organ failure is the major cause of the high mortality rate of AP. Liver injury has been discovered in 80% of AP patients. The relationship and role of IRF9 and SIRT1 have not been presented in AP and hyperlipidemia AP (HLAP) with liver injury. This investigation was designed to explore the function and relationship of IRF9 and SIRT1.MethodsHLAP model in vivo was performed by feeding high-fat forage and induced by peritoneal injection with 20% L-arginine. The severity of pancreas and liver tissues was assessed. Cell apoptosis in the liver was determined by the TUNEL experiment. IRF9, SIRT1, p53, and acetylated p53 (Ac-p53) expression levels in liver tissues were detected by qRT-PCR and Western blot. The association of IRF9 expression with SIRT1 levels was evaluated. The relevance of triglyceride level to tissue damage was analyzed.ResultsOur observation exhibited more distinct liver damage, a large number of hepatic cell apoptosis, marked raised IRF9, Ac-p53, and sharply dropped SIRT1 in the AP and HLAP groups. Compared with other groups, HLAP showed the most significant changes in liver injury, hepatic cell apoptosis, protein, and mRNA levels. The declined expression of SIRT1 was correlated with the elevated expression of IRF9. The damage of the pancreas and liver exacerbated with the increase in triglyceride levels.ConclusionElevated IRF9 in pancreatitis with liver injury raised cell apoptosis and tissue damage by decreasing SIRT1 expression.

Light perception and related alternation of physiological performance in spotted knifejaw Oplegnathus punctatus

Light is one of the main environmental factors that affects the behavior and physiology of fish. In the present study, the behavioral responses, retinal histology, hematological parameters (white blood cell [WBC], red blood cell [RBC], hemoglobin [Hb] hematocrit [Hct]), hepatic antioxidant enzyme (superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSH-Px]) activity, aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) activities, malondialdehyde (MDA) content, histological alterations, apoptosis, and stress-related gene expression (hsp70, hsp90a, hsp90b) of spotted knifejaw were investigated under different light colors. The results showed that the residence time of spotted knifejaw plants significantly decreased under red and blue light stimuli but significantly increased under green light. Moreover, a positive and negative phototaxis of the spotted knifejaw under green and red lights was observed. However, retinal structure (relative thickness, cell number, and size) remained unchanged after red and green light treatment for 12 h. WBC and RBC numbers, Hb and Hct contents, hepatic SOD, CAT, GSH-Px, ALT and AST activities, and MDA levels were significantly increased after red and green light treatment for 12 h. Moreover, red and green light treatment caused hepatocyte vacuolization and nuclear migration and significantly increased the percentage of apoptotic cells. Hepatic hsp70, hsp90a, and hsp90b mRNA levels were significantly upregulated under red and green stimuli. Furthermore, the values of the above parameters under red light treatment were significantly greater than those under green light treatment. The aforementioned parameters nearly recovered to normal levels after the fish returned to normal light for 12 h. In conclusion, in spotted knifejaw, green light promoted attraction and red light avoidance, while red light could induce a more sensitive physiological response than green light. These findings expand the current knowledge on light perception and aid in the management of spotted knifejaw in captivity.

Artemisia argyi ethanol extract ameliorates nonalcoholic steatohepatitis-induced liver fibrosis by modulating gut microbiota and hepatic signaling

Ethnopharmacological relevanceArtemisia argyi (AA), a herbal medicine traditionally used in Asian countries, to treat inflammatory conditions such as eczema, dermatitis, arthritis, allergic asthma and colitis. However, the mechanism of action of this plant with regard to hepatitis and other liver-related diseases is still unclear. AimThis study aimed to investigate the effects of AA ethanol extract on NASH-related fibrosis and gut microbiota in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced mouse model. MethodsMale C57BL/6J mice were fed CDAHFD, with or without AA ethanol extract treatment. Biochemical markers, lipid profiles, hepatic mRNA expression levels of key genes, and the fibrosis area were assessed. In vitro, TGF-β-stimulated human hepatic stellate LX-2 cells and mouse primary hepatic stellate cells (mHSCs) were used to elucidate the effects of AA ethanol extract on fibrosis and steatosis. 16S rRNA sequencing, QIIME2, and PICRUST2 were employed to analyze gut microbial diversity, composition, and functional pathways. ResultsTreatment with the AA ethanol extract improved plasma and liver lipid profiles, modulated hepatic mRNA expression levels of antioxidant, lipolytic, and fibrosis-related genes, and significantly reduced CDAHFD-induced hepatic fibrosis. Gut microbiota analysis revealed a marked decrease in Acetivibrio ethanolgignens abundance upon treatment with the AA ethanol extract, and its functional pathways were significantly correlated with NASH/fibrosis markers. The AA ethanol extract and its active components (jaceosidin, eupatilin, and chlorogenic acid) inhibited fibrosis-related markers in LX-2 and mHSC. ConclusionThe AA ethanol extract exerted therapeutic effects on CDAHFD-induced liver disease by modulating NASH/fibrosis-related factors and gut microbiota composition. Notably, AA treatment reduced the abundance of the potentially profibrotic bacterium (A. ethanolgignens). These findings suggest that AA is a promising candidate for treating NASH-induced fibrosis.

Comparative assessment of growth performance, heat resistance and carcass traits in four poultry genotypes reared in hot-humid tropical environment.

This study investigated the impact of heat stress on growth and carcass traits in four poultry genotypes-Giriraja, Country chicken, Naked Neck and Kadaknath reared in a hot and humid tropical environment. Birds from all genotypes had ad libitum access to feed and water while being challenged with consistently high environmental temperatures in the experimental shed. Daily diurnal meteorological data were recorded inside and outside the shed. The study specifically examined growth variables and carcass characteristics. Significant differences (p < 0.01) were observed in body weight and average daily gain at various intervals. Notably, feed intake showed significant differences (p < 0.01) across weeks, indicating interactions between genotypes and time intervals. The feed conversion ratio (FCR) varied significantly (p < 0.01), with the highest FCR recorded in the Kadaknath breed. Livability percentages were similar across groups, except for Giriraja, which had significantly lower livability (p < 0.01). Carcass traits, including dressing, wings, feathers and giblet percentages, showed significant differences among genotypes (p < 0.01). Hepatic mRNA expression of growth-related genes revealed numerical variations, with Naked Neck displaying the highest (p < 0.05) fold change in IGF-1 expression compared to other genotypes. The study recognized in the Naked Neck genotype to possess higher resilience in maintaining homoeostasis and uncompromised growth under heat stress, providing valuable insights for sustainable poultry farming in challenging environmental conditions.