Ratio Of Liver Weight Research Articles

PSI-21 Limited impact of hypothyroidism on porcine fetal growth during mid to late gestation

Abstract In the fetal pig, both circulating thyroid hormone and growth rate are known to increase throughout gestation; however, the functional association between these coincident factors has not been established. Thus, the objective of this project was to investigate this cause-and-effect relationship by evaluating the impact of induced fetal hypothyroidism on fetal growth during mid to late gestation. To induce fetal hypothyroidism, n = 12 pregnant gilts were orally treated with the goitrogen methimazole (MMI) at a dose of 5 mg/kg/d for 21 d, with n = 3 gilts starting treatment on gestation d 34, 45, 55 and 65. An equivalent group n = 12 of gilts were sham treated for the same periods to produce gestationally age-matched euthyroid control litters (CON). Upon completion of the treatment period, gilts were humanely euthanized, and the resulting populations of n = 174 MMI and n = 166 CON fetuses deeply phenotyped. No meconium-stained fetuses were observed at any time point, and only 5 mummified fetuses were observed (3 CON, 2 MMI), indicating treatment has no effect on fetal viability. Fetal body weight (BW) and the weights of individual organs including thyroid, liver, heart, lung, kidney, spleen, and brain were collected. In addition, fetuses were imaged in both left and right lateral recumbency for subsequent morphometric assessment using a custom analysis pipeline in ImageJ. Image analysis yielded parameters including crown-rump length, girth, brow length, depth at the snout/skull junction, depth at the snout/nose junction, and area under the skull curvature (AUC). Left and right measurements for all morphometric parameters were found to be highly correlated (r2 > 0.9) indicating a repeatable measure using this approach. Statistical analysis of all phenotypic differences was carried out using a linear mixed effect model including gestational age and treatment as fixed effects and gilt as a random effect. A significant increase in both absolute and relative thyroid weights indicated the development of goiter and thus, successful induction of hypothyroidism within the MMI litters. In addition, a significant treatment by time interaction was observed, with 0.014 g and 0.21 g increase at d 55 and 66, respectively, indicating reduced compensatory action within the fetal hypothalamic-pituitary-thyroid axis during this earliest period. Liver weight as a percentage of BW decreased from 6.06% to 2.56% between d 55 and 86 in the CON group but was significantly increased at all time points in response to MMI induced hypothyroidism (P < 0.01). A corresponding increase in brain to liver weight ratio over time was suppressed in MMI fetuses (P < 0.05). While all other phenotypic parameters were significantly altered by gestational age, there was no significant impact of fetal hypothyroidism. Collectively, the results indicate that fetal growth during mid to late gestation is not driven by fetal thyroid hormone.

The effect of sea grapes (Caulerpa racemosa) powder drink on improvement of obesity biomarker in Wistar rats

Obesity has become a global public health issue due to its rapidly increasing prevalence. Sea grapes powder drink (SPD) as a functional food has the potential to become an important biomarker in the improvement of obesity. The biomarkers in obesity can be assessed by Lee’s index and lipid profile. Due to its high antioxidant content, SPD can improve both Lee’s index and lipid profile. The objective of this study was to analyse the effect of SPD on the obesity biomarkers of Wistar rats. In this research, a completely randomized design that involved 24 male rats weighing between 150–250 g was used. Rats were randomly put into six groups. Biomarkers were measured using Lee’s index, lipid profile and the weight ratio of both visceral fat and liver. Results after 21 days of intervention showed a reduction in Lee’s index in the group that was given HFD + SPD 1 g, 1.5 g and 2 g. The visceral fat weight ratio in HFD + SPD 1.5 g and 2 g group significantly decreased. However, it had no effect on the liver weight ratio. Levels of Total Cholesterol (TC), Triglyceride (TG), and Cholesterol-Low Density Lipoprotein (CLDL) in the HFD + SPD 1 g, 1.5 g and 2 g group significantly decreased. The Cholesterol -High Density Lipoprotein (C-HDL) dramatically increased HFD + SPD 2 g group. SPD is effective in improving Lee's index, visceral fat weight ratio and lipid profile but not liver weight ratio. SPD can be used as an alternative therapeutic product in the management of obesity and consequent reduction of its prevalence.

TSA attenuates the progression of c-Myc-driven hepatocarcinogenesis by pAKT-ADH4 pathway

Hepatocellular carcinoma (HCC) is the primary malignant tumor of the liver. c-Myc is one of the most common oncogenes in clinical settings, and amplified levels of c-Myc are frequently found in HCC. Histone deacetylase inhibitors (HDACi), such as Trichostatin A (TSA), hold enormous promise for the treatment of HCC. However, the potential and mechanism of TSA in the treatment of c-Myc-induced HCC are unclear. In this study, we investigated the effects of TSA treatment on a c-Myc-induced HCC model in mice. TSA treatment delayed the development of HCC, and liver function indicators such as ALT, AST, liver weight ratio, and spleen weight ratio demonstrated the effectiveness of TSA treatment. Oil red staining further demonstrated that TSA attenuated lipid accumulation in the HCC tissues of mice. Through mRNA sequencing, we identified that TSA mainly affected cell cycle and fatty acid degradation genes, with alcohol dehydrogenase 4 (ADH4) potentially being the core molecular downstream target. QPCR, immunohistochemistry, and western blot analysis revealed that ADH4 expression was repressed by c-Myc and restored after TSA treatment both in vitro and in vivo. Furthermore, we observed that the levels of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration increased after c-Myc transfection in liver cells but decreased after TSA intervention. The levels of phosphorylated protein kinase B (p-AKT) and p-mTOR were identified as targets regulated by TSA, and they governed the ADH4 expression and the downstream regulation of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration. Overall, our study suggests that TSA has a therapeutic effect on c-Myc-induced HCC through the AKT-mTOR-ADH4 pathway. These findings provide valuable insights into the potential treatment of HCC using TSA and shed light on the underlying molecular mechanisms involved.

The role of C5aR1-mediated hepatic macrophage efferocytosis in NASH

Non-alcoholic fatty liver disease (NAFLD) has become the first major chronic liver disease in developed countries. 10–20% of NAFLD patients will progress to non-alcoholic steatohepatitis (NASH), and up to 25% of NASH patients may develop cirrhosis within 10 years. Therefore, it is critical to find key targets that may treat this disease. Here, we identified C5aR1 as a highly-expressed gene in NASH mouse model through analyzing Gene Expression Omnibus (GEO) database and confirmed its higher expression in livers of NASH patients than that of NAFL patients. Meanwhile, we verified its positive correlation with patients’ serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. In vivo and in vitro experiments revealed that knocking down C5aR1 in liver significantly reduced liver weight ratio and serum ALT and AST levels and attenuated inflammatory cell infiltration and cell apoptosis in the liver of NASH mice as well as enhanced the efferocytotic ability of liver macrophages, suggesting that C5aR1 may play a crucial role in the efferocytosis of liver macrophages. Furthermore, we also found that the expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3), caspase-1, IL-1β and other inflammation-related factors in the liver were significantly reduced. Our work demonstrates a potential mechanism of how C5aR1 deficiency protects against diet-induced NASH by coordinating the regulation of inflammatory factors and affecting hepatic macrophage efferocytosis.

Efficacy of epigallocatechin gallate (EGCG) and its underlying mechanism in preventing bisphenol-A-induced metabolic disorders in mice

To investigate the efficacy of epigallocatechin gallate (EGCG) and its underlying mechanism in preventing bisphenol-A-induced metabolic disorders, in this study, a mice model of metabolic disorders induced by BPA was developed to investigate the efficacy and mechanism of EGCG using microbiomes and metabolomics. The results showed that EGCG reduced body weight, liver weight ratio, and triglyceride and total cholesterol levels in mice by decreasing the mRNA expression of genes related to fatty acid synthesis (Elov16) and cholesterol synthesis (CYP4A14) and increasing the mRNA expression of genes related to fatty acid oxidation (Lss) and cholesterol metabolism (Cyp7a1). In addition, EGCG normalized BPA-induced intestinal microbial dysbiosis. Metabolic pathway analysis showed that low-dose EGCG was more effective than high-dose EGCG at affecting the biosynthesis of L-cysteine, glycerophosphorylcholine, and palmitoleic acid. These results provide specific data and a theoretical basis for the risk assessment of BPA and the utilization of EGCG.

Asymmetric growth-limiting development of the female conceptus.

Sex differences in prenatal growth may contribute to sex-dependent programming effects on postnatal phenotype. We integrated for the first time phenotypic, histomorphological, clinico-chemical, endocrine and gene expression analyses in a single species, the bovine conceptus at mid-gestation. We demonstrate that by mid-gestation, before the onset of accelerated growth, the female conceptus displays asymmetric lower growth compared to males. Female fetuses were smaller with lower ponderal index and organ weights than males. However, their brain:body weight, brain:liver weight and heart:body weight ratios were higher than in males, indicating brain and heart 'sparing'. The female placenta weighed less and had lower volumes of trophoblast and fetal connective tissue than the male placenta. Female umbilical cord vessel diameters were smaller, and female-specific relationships of body weight and brain:liver weight ratios with cord vessel diameters indicated that the umbilico-placental vascular system creates a growth-limiting environment where blood flow is redistributed to protect brain and heart growth. Clinico-chemical indicators of liver perfusion support this female-specific growth-limiting phenotype, while lower insulin-like growth factor 2 (IGF2) gene expression in brain and heart, and lower circulating IGF2, implicate female-specific modulation of key endocrine mediators by nutrient supply. This mode of female development may increase resilience to environmental perturbations in utero and contribute to sex-bias in programming outcomes including susceptibility to non-communicable diseases.

Potency of <i>Clitoria ternatea</i> L. Ethanol Extract Against IFNγ and GLUT4 Protein in Type 2 Diabetes Mellitus Rat Model

Diabetes Mellitus (DM) is a chronic disease caused by genetics, lifestyle, and immunology. Type 2 DM is caused by resistanceto insulin, which causes blood sugar to not be stored in glycogen. Clitoria ternatea L. (Fabaceae) flower contains a lot ofanthocyanins and has long been used in various traditional medicines. They are believed to treat fever, inflammation, anddiabetes. Anthocyanins have antidiabetic, anticancer, anti-inflammatory, and anticancer properties. This study aimed toevaluate anti-DM of Clitoria ternatea L. flower extract (CTE) in DM model rats with parameters such as liver weight ratio,IFNγ, and GLUT4 protein expression in pancreas and femoral muscle. Rats with a streptozotocin-induced (STZ) DM modelwere used to test the effects of oral administration of CTE at doses of 200, 400, and 800 mg/kg BW, glybenclamide (0.45mg/kg BW), and simvastatin (0.9 mg/kg BW). After blood sugar levels were >200 mg/dL, the rats were given various dosesof CTE and tested for protein expression of IFNγ and GLUT4 in femoral muscle by immunohistochemistry (IHC) method.Data analysis used ANOVA and continued with Tukey’s post hoc test. Results showed that CTE could increase liver ratiowhile decreasing IFNγ activation at CTE 400 mg/kg BW and upregulating GLUT4 at 400 mg/kg BW. CTE has an anti-DM activity potential for diabetes mellitus treatment due to its anthocyanin content.

Hepatoprotective effects of aspirin on diethylnitrosamine-induced hepatocellular carcinoma in rats by reducing inflammation levels and PD-L1 expression

Aspirin, as a widely used anti-inflammatory drug, has been shown to exert anti-cancer effects in a variety of cancers. PD-L1 is widely expressed in tumor cells and inhibits anti-tumor immunity. This study aims to clarify whether aspirin exerts its anti-hepatocellular carcinoma (HCC) effect by inhibiting PD-L1 expression. The rat model of HCC was established by drinking 0.01% diethylnitrosamine (DEN), and aspirin was given by gavage. The gross and blood biochemical indexes of rats were analyzed. CD4 and CD8 expression in liver tissues were investigated by immunohistochemistry. CCK8 assay was used to detect the inhibitory effect of aspirin on the proliferation of HCC cells. The regulatory effect of aspirin on PD-L1 expression was analyzed by western blot. As a result, the tumor number and liver weight ratio in the DEN + ASA group were lower than those in the DEN group (P = 0.006, P = 0.046). Compared with the DEN group, the expression of CD4 in the DEN + ASA group was significantly increased, while CD8 was decreased (all P < 0.01). Biochemical indexes showed that there were differences in all indexes between the DEN and control group (P < 0.05). The levels of DBIL, ALP, and TT in the DEN + ASA group were lower than those in the DEN group (P = 0.038, P = 0.042, P = 0.031). In the DEN group, there was an obvious fibrous capsule around the tumor, and the portal vein was dilated. The pathological changes were mild in the DEN + ASA group. Compared with the DEN group, the expression of PD-L1 in liver tissue of the DEN + ASA group was decreased (P = 0.0495). Cytological experiments further showed that aspirin could inhibit the proliferation and PD-L1 expression in Hep G2 and Hep 3B cells. In conclusion, aspirin can inhibit the proliferation of HCC cells and reduce tumor burden by reducing inflammation and targeting PD-L1.

Isolinderalactone Resistance to the Liver Injury Induced by Oxaliplatin in Rats through Inhibiting IL-6/STAT3 Signal Pathway.

Oxaliplatin (OXA) is easy to cause sinusoidal obstruction syndrome (SOS), leading to liver injury. Isolinderalactone (ILL), one of the main components of Lindera aggregate, has been reported to have a preservative effect on the liver. However, it is unclear whether ILL has a therapeutic effect on liver injury caused by OXA or not. This study aims to determine the effect of ILL on the prevention and treatment of OXA liver injury and to provide a basis for the chemotherapy of gastrointestinal tumors. Intraperitoneal injection of folinic acid, 5-fluorouracil, and OXA was administered on the SOS rat model for 7 weeks. The indexes of liver function were measured by biochemical kit. The ratio of liver weight to body weight was calculated. The pathological analysis of the liver was scored with the SOS scoring standard, fibrosis was evaluated with a four-point scale. The expression of inflammation factors was detected by Real-Time PCR, and the related indexes of IL-6/STAT3 were examined by Western blot analysis. ILL down-regulated the portal vein pressure and alleviated the abnormal liver function of SOS rats and improved the liver lesions. ILL inhibited the SOS by inhibiting IL-6/STAT3. ILL resistance to liver injury through inhibiting IL-6/STAT3 signal pathway.

Liver regeneration after portal vein embolization: comparison between absolute ethanol and N-butyl-cyanoacrylate in an in vivo rat model.

To compare the effects of absolute ethanol (ethanol) and N-butyl-cyanoacrylate (NBCA) on non-embolized liver lobe regeneration in a rat model. Twenty-seven Sprague-Dawley rats underwent portal vein embolization (PVE) using ethanol:lipiodol, 1:1 (ethanol group, n = 11, 40.74%), NBCA:lipiodol, 1:1 (NBCA group, n = 11, 40.74%), or sham treatment (sham group, n = 5, 18.52%). The non-embolized and embolized lobe-to-whole liver weight ratios 14 days after PVE were compared among the groups (n = 5, 18.52%). The expressions of CD68 and Ki-67 and embolized-lobe necrotic area percentages one day after PVE were compared between the ethanol (n = 3, 11.11%) and NBCA (n = 3, 11.11%) groups. The non-embolized lobe-to-whole liver weight ratio after PVE was significantly higher in the NBCA group (n = 5, 33.33%) than in the ethanol group (n = 5, 33.33%) (84.28% ± 1.53% vs. 76.88% ± 4.12%, P = 0.029). The embolized lobe-to-whole liver weight ratio after PVE was significantly lower in the NBCA group than in the ethanol group (15.72% ± 1.53% vs. 23.12% ± 4.12%, P = 0.029). The proportions of CD68- and Ki-67-positive cells in the non-embolized lobe after PVE were significantly higher in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [60 (48-79) vs. 55 (37-70), P = 0.003; 1 (0-2) vs. 1 (0-2), P = 0.004]. The embolized-lobe necrotic area percentage after PVE was significantly larger in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [29.46 (12.56-83.90%) vs. 16.34 (3.22-32.0%), P < 0.001]. PVE with NBCA induced a larger necrotic area in the embolized lobe and promoted greater non-embolized liver lobe regeneration compared with PVE with ethanol.

CORRECTION OF DAPSONE-INDUCED CHANGES IN LIVER FUNCTIONS BY EXTRACT OF LICORICE ROOTS NAKED

Relevance. To date, much attention is paid to an important aspect of pharmacotherapy aimed at improving the safety of drugs used in various diseases, as well as the search for means of correcting complications that have arisen as a result of the therapy. Antimicrobials occupy one of the leading places in the development of drug disorders on the part of various systems and organs, including the liver. In this regard, it is necessary to use means that correct functional disorders and improve metabolic processes in the liver. Licorice extract (Glycyrrhiza glabra) can be considered as such a remedy. The aim of the study was to evaluate the effect of licorice extract on dapsone–induced changes in liver function. Material and methods. All studies were conducted on non-linear white male rats (7 months) weighing 410.0 ± 20.0. The animals in the experiment were divided into groups (n=10): "control" - received purified intragastric water; "dapsone" – rats receiving intragastric dapsone (Novartis; Switzerland) once at a dose of 25 mg/kg for 30 days; "dapsone+licorice" – rats receiving oral dapsone in in the same mode and extract of licorice roots naked at a dose of 50 mg / kg intragastrically 1 time a day for 30 days. After the animals were removed from the experiment, the development of toxic liver damage and the degree of its correction were evaluated by determining the liver weight coefficient, the activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, total protein, albumin, total bilirubin. Results. An analysis of the biochemical parameters of experimental animals with the use of licorice root extract under conditions of dapsone admin-istration for 30 days showed a decrease in the weight coefficient of the liver, levels of total protein and albumin, as well as a significant increase in transaminase activity, an increase in the level of bilirubin. Conclusion. The results obtained with the use of licorice root extract indicate the presence of hepatoprotective properties, manifested by correction of violations by biochemical parameters (reduced liver weight ratio, total protein and albumin levels, as well as significantly increased transaminase activity and increased bilirubin levels), indicating the development of hepatocellular disorders under the conditions of course administration of dapsone.

CS27109, A Selective Thyroid Hormone Receptor-β Agonist Alleviates Metabolic-Associated Fatty Liver Disease in Murine Models.

Thyroid hormone receptor-β (THR-β) agonists play crucial roles in dyslipidemia and metabolic associated fatty liver disease (MAFLD). We developed a novel oral and liver-targeted THR-β agonist, CS27109, and evaluated its efficacy in the treatment of metabolic disorders. We evaluated in vitro and in vivo efficacy and/or safety of CS27109 along with MGL3196 (a phase III THR-β agonist). CS27109 showed pronounced activity and selectivity to THR-β and favorable PK properties, which was equivalent to MGL3196. In the hamster model, animals treated with a high dose of CS27109 showed equivalent reductions in serum TC and LDL-c with groups treated with MGL3196. In the rat model, CS27109 and MGL3196 reduced serum ALT, TC, TG, LDL-c, liver weight ratio, and liver steatosis. CS27109 simultaneously decreased liver TG and TC, and MGL3196 additionally reduced AST. In the mouse model, CS27109 dose-dependently reduced serum AST, ALT, liver inflammation, and NAS score, and also downregulated TC, LDL-c, liver steatosis, and fibrosis, but not in a dose-dependent manner. MGL3196 revealed an equivalent effect with CS27109 in that model. CS27109 also exhibited tolerable toxicity to the heart. CS27109 shows comparative in vitro and in vivo efficacy with MGL3196, suggesting its potential therapeutic application in the treatment of MAFLD such as dyslipidemia and steatohepatitis.

The PPARα/CYP4A14 bile acid pathway is associated with lipid metabolism disorders caused by low birth weight with high-fat diet.

To investigate possible mechanisms underlying the greater susceptibility of lipid metabolism disorders in low birth weight (LBW) mice fed with high-fat diets (HFDs). LBW mice model was established by using the pregnancy malnutrition method. Male pups were selected from LBW and normal-birth weight (NBW) offspring at random. After 3 weeks of weaning, all offspring mice were fed with HFD. Serum triglycerides (TGs), cholesterol (TC), low density lipoprotein (LDL-C), total bile acid (TAB), non-esterified fatty acid (NEFA), and mice fecal bile acid profiles were measured. Lipid deposition in liver sections was visualized by Oil Red O staining. The weight ratio of liver, muscle, and adiposity was calculated. Tandem mass tag (TMT) combined with LC-MS/MS was used to determine the differentially expressed proteins (DEPs) of liver tissue in two groups. Bioinformatics was used for further analysis of DEPs to screen key target proteins, and then Western Blot (WB) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to validate the expressions of DEPs. LBW mice fed with HFD showed more severe lipid metabolism disorders in the childhood. In contrast to the NBW group, the serum bile acids and fecal ω-muricholic acid (ω-MCA) levels in the LBW group were significantly lower. LC-MS/MS analysis showed that downregulated proteins were associated with lipid metabolism, and further analysis found that these proteins are mainly concentrated in peroxisome proliferation-activated receptor (PPAR) and primary bile acid synthesis signaling pathways and are involved in cellular processes and metabolic processes through binding and catalytic functions. Bioinformatics analysis indicated that the level of Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1), PPARα, key factors of cholesterol metabolism and bile acid synthesis, as well as downstream molecules Cytochrome P450 Family 4 Subfamily A Member 14 (CYP4A14), and Acyl-Coenzyme A Oxidase 2 (ACOX2) are markedly different in the liver of LBW individuals fed with HFD, and confirmed by WB and RT-qPCR. LBW mice are more prone to dyslipidemia probably due to downregulated bile acid metabolism-related PPARα/CYP4A14 pathway, resulting in insufficient metabolism of cholesterol to bile acids, which, in turn, leads to elevated blood cholesterol.

Mettl14 mutation restrains liver regeneration by attenuating mitogens derived from non-parenchymal liver cells

Liver regeneration is a well-known systemic homeostatic phenomenon. The N6-methyladenosine (m6A) modification pathway has been associated with liver regeneration and hepatocellular carcinoma. m6A methyltransferases, such as methyltransferase 3 (METTL3) and methyltransferase 14 (METTL14), are involved in the hepatocyte-specific-regenerative pathway. To illustrate the role of METTL14, secreted from non-parenchymal liver cells, in the initiation phase of liver regeneration, we performed 70% partial hepatectomy (PH) in Mettl14 heterozygous (HET) and wild-type (WT) mice. Next, we analyzed the ratio of liver weight to body weight and the expression of mitogenic stimulators derived from non-parenchymal liver cells. Furthermore, we evaluated the expression of cell cycle-related genes and the hepatocyte proliferation rate via MKI67-immunostaining. During regeneration after PH, the weight ratio was lower in Mettl14 HET mice compared to WT mice. The expressions of hepatocyte growth factor (HGF) and tumor necrosis factor (TNF)-α, mitogens derived from non-parenchymal liver cells that stimulate the cell cycle, as well as the expressions of cyclin B1 and D1, which regulate the cell cycle, and the number of MKI67-positive cells, which indicate proliferative hepatocyte in the late G1-M phase, were significantly reduced in Mettl14 HET mice 72 h after PH. Our findings demonstrate that global Mettl14 mutation may interrupt the homeostasis of liver regeneration after an acute injury like PH by restraining certain mitogens, such as HGF and TNF-α, derived from sinusoidal endothelial cells, stellate cells, and Kupffer cells. These results provide new insights into the role of METTL14 in the clinical treatment strategies of liver disease. [BMB Reports 2022; 55(12): 633-638].

Cholesterol-lowering effects and safety assessment of Lactobacillus spp. in vivo and in vitro testing for human use as probiotic from the dairy product in Egypt

BackgroundThe toxicity profile of lactobacilli may be strain dependent, so it should be considered for safe utilization of probiotics. Further, in vivo studies are necessary to evaluate their safety. ResultThe ability of various probiotic strains to hydrolyze bile salts has been confirmed without noticeable hemolytic activity. Results revealed the presence of α-glucosidase, β-glucosidase, α-galactosidase, and β-galactosidase activity in all investigated isolates, while none of the isolates produced the carcinogenic enzyme β-glucuronidase. The probiotic strains exhibited remarkable cholesterol-lowering impact. Also, we found no evidence of chronic toxicity under the experimental conditions based on gross pathological examination of the viscera and study of the spleen and liver weight ratios. These findings indicated that the investigated strains, either alone or combined with their metabolites, had no obvious adverse effect on the mice’s general health status. ConclusionThere is prove that the investigated probiotic strains are safe to be utilized for enhancing of the growth performance and are free of adverse side effects.

312.8: What Is the Risk Factor of Graft Mortality in Patients Who Underwent Simultaneous Splenectomy During Living Donor Liver Transplantation?

Introduction: Splenectomy is performed in living donor liver transplantation (LDLT) for portal flow modulation. The aim of this study was to identify the risk factor of 6-month graft mortality in patients who underwent splenectomy in LDLT. Methods: Data from 441 adult patients who underwent simultaneous splenectomy during primary LDLT were collected retrospectively. Risk factors of 6-month graft mortality were investigated. Results: Mean recipient age was 55 years. Mean donor age was 38.7 years. Two hundred and five patients (46.5%) received left lobe graft. Mean graft weight (GW)-standard liver weight ratio was 41.5% and GW-recipient weight ratio was 0.79%. Six-month graft survival rate after LDLT in 441 patients was 93.8%, which was significantly better compared to patients without simultaneous splenectomy or splenic artery ligation (83.9%, p<0.0001). Univariate analysis revealed the following risk factors for 6-month graft mortality in patients with splenectomy: neutrophil-lymphocyte ratio > 4, acute liver failure, hospitalized before LDLT, donor > 60 years of age, MELD score > 22, pre-LDLT platelet < 40, 000/mm3, portal vein pressure when LDLT finished (PVP) > 20 mmHg. Multivariate analysis identified that donor > 60 years of age (Hazard ratio=4.50, p=0.049), pre-LDLT platelet < 40, 000/mm3 (Hazard ratio=2.58, p=0.03), and PVP > 20 mmHg (Hazard ratio=7.46, p<0.001) were the independent risk factors of 6-month graft mortality after LDLT.Conclusion: Splenectomy in LDLT improves survival rate after LDLT. Careful attention is needed for patients with platelet < 40, 000/mm3, PVP > 20 mmHg, and received graft from donor > 60 years of age.

동물복지를 고려한 점등시간이 육계 병아리의 성장 능력 및 혈액 성상에 미치는 영향

This study was conducted to investigate the effect of three different photoperiods on growth performance, blood properties, and stress indicators in broiler chicks between 1-7 days after hatching. Two hundred and fifty-two 1-day-old male broiler chicks (57.0±0.12 g) were divided into three treatments, with 4 replicates per treatment and 22 birds per replicate subjected to three different photoperiods of 24L, 22L/2D and 18L/6D. A light-emitting diode bulb served as the light source, with an illuminance of 30 lx. As an experimental diet, a commercial feed based on a corn-soybean meal, with 22% CP and 3,150 kcal/kg ME diet, and water were fed <i>ad libitum</i>. Body weight gain, feed conversion ratio, and liver weight ratio showed a statistically significant difference between the 18L/6D and 24L treatments (<i>P</i>&lt;0.05), but with no significant difference between the 22L/2D treatment and either the 24L or 18L/6D treatment. The breast meat ratio was 5.59% in the 18L/6D treatment group, which was lower than that of other treatment groups (<i>P</i>&lt;0.05). The triglyceride levels were highest (<i>P</i>&lt;0.05) in the 18L/6D treatment among treatments, but alanine aminotransferase levels were significantly higher (<i>P</i>&lt;0.05) in the 22L/2D treatment than in the 24L treatment. Levels of cytokines, i.e., Interleukin-6 and Tumor Necrosis Factor-α did not show a significant difference among the treatments, but corticosterone content was significantly higher (<i>P</i>&lt;0.05) in the 24L treatment than in the 18L/6D treatment. In conclusion, 22 hours of lighting is appropriate between 1~7 days after hatching, considering growth performance and the overall health of broiler chicks.

Dietary Supplemental Chromium Yeast Improved the Antioxidant Capacity, Immunity and Liver Health in Broilers under High Stocking Density.

Simple SummaryHigh stocking density can reduce the health status of broilers. Organic chromium can promote growth, immunity, antioxidant activity and alleviate stress. This study investigated the effects of different levels of yeast chromium on growth performance, organ index, antioxidant capacity, immune performance and histopathology of broilers under high stocking density and suggested that the optimal yeast chromium supplementation for antioxidant capacity was 425.00–665.00 µg Cr/kg; the optimal yeast chromium supplementation for immunity was 319.30–961.00 µg Cr/kg; and the optimal yeast chromium supplementation of liver health was 800.00–1531.60 µg Cr/kg.This study was conducted to investigate the effects of different levels of yeast chromium on growth performance, organ index, antioxidant capacity, immune performance and liver health of broilers under high stocking density. A total of 684 1-day-old Arbor Acres broilers were selected and fed a common diet from 1 to 22 days of age. At the end of 22 days, broilers with similar weight were randomly divided into six treatments, with six replications in each treatment. The broilers in control groups were fed with a control diet and raised at low stocking density of broilers (14 broilers/m2, LSD) and high stocking density (20 broilers/m2, HSD). The broilers in treatment groups were fed with diets supplemented with 200, 400, 800 and 1600 µg Cr/kg chromium yeast (Cr-yeast) under HSD, respectively. The experimental period was 23~42 days. Compared with the LSD group, the HSD group significantly decreased the liver index (ratio of liver weight to live weight of broilers) of broilers (p < 0.05), the HSD group significantly increased the content of corticosterone (CORT) and the activities of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and decreased the prealbumin (PA) level in the serum (p < 0.05). HSD decreased the total antioxidant capacity (T-AOC) contents in the serum, liver and breast, serum glutathione peroxidase (GSH-Px) activities, breast total superoxide dismutase (T-SOD) activities and liver catalase (CAT) activities of broilers (p < 0.05). The HSD group significantly increased the total histopathological score (p < 0.05). Compared with the HSD group, adding 200, 400, and 1600 Cr-yeast significantly increased the liver index of broilers (p < 0.05), all HSD + Cr-yeast groups decreased the ALT activities (p < 0.05), and the HSD + 800 group significantly decreased the CORT contents and the ALP activities of the serum (p < 0.05); the HSD + 400, 800 and 1600 groups increased the PA contents of the serum (p < 0.05); HSD + 800 group significantly reduced the tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β) contents of the serum (p < 0.05); moreover, the HSD + 400 group increased the GSH-Px activities of the serum (p < 0.05), the T-AOC and the T-SOD activities of the breast (p < 0.05) and the T-AOC and CAT activities of the liver (p < 0.05). Adding 800 Cr-yeast significantly decreased the total histopathological score (degree of hepatocyte edema and inflammatory cell infiltration) under HSD (p < 0.05). In summary, Cr-yeast can improve the antioxidant capacity and immune traits, and liver health of broilers under HSD. Based on the results of the linear regression analysis, the optimal supplementation of Cr-yeast in antioxidant capacity, immunity ability and liver health were at the range of 425.00–665.00, 319.30–961.00, and 800.00–1531.60 µg Cr/kg, respectively.

Polyhalogenated carbazoles induce hepatic metabolic disorders in mice via alteration in gut microbiota

Polyhalogenated carbazoles (PHCZs) have been widely accepted as emerging pollutants, whereas their ecological and health risks remain uncertain. Herein, female and male Sprague-Dawley (SD) mice were treated with four typical PHCZs to investigate their negative consequences, along with alternations in gut microbiota to indicate underlying mechanisms. In female mice, the relative liver weight ratio increased after four PHCZs exposure; 2-bromocarbazole (2-BCZ) increased urine glucose level; 3-bromocarbazole (3-BCZ) decreased the glucose and total cholesterol levels; 3,6-dichlorocarbazole (3,6-DCCZ) decreased glucose level. The only disturbed biochemical index in male mice was the promoted alkaline phosphatase (ALP) level by 3,6-DCCZ. We also found that the differential blood biochemical indices were correlated with gut microbiota. 3-BCZ and 3,6-DCCZ altered Bacteroidetes and Proteobacteria phyla in female and male mice, which were correlated with metabolic disorders. Our findings demonstrated the correlation between PHCZs induced potential hepatotoxicity and metabolic disorders may be due to their dioxin-like potentials and endocrine disrupting activities, and the gender differences might result from their estrogenic activities. Overall, data presented here can help to evaluate the ecological and health risks of PHCZs and reveal the underlying mechanisms.

Inhibiting TET1 alleviates non‐alcoholic liver disease progression by targeting lipid metabolic pathways.

Background &amp; AimNon‐alcoholic fatty liver disease (NAFLD) affects more than one‐quarter of adults worldwide, with 60% in diabetic patients and 90% in obese people. Epigenetic modifications are highly associated with NAFLD development. It has been reported that the 5‐hydroxymethylcytosine (5hmC) epigenetic modification and its catalyzing enzymes, the Ten‐eleven translocation (TET) family dioxygenases, are involved in NAFLD progression. However, it remains unclear how the TET family enzymes participate in NAFLD development. The current study was aimed to clarify the involvement of TET family proteins in NAFLD.MethodsGenetic TET1 knockout mice were generated and challenged with a high fat diet (HFD) for 16 weeks. Liver and serum lipid contents were analyzed by biochemical assays. To determine liver injuries, histological staining and liver functional assays were used. Immunoblotting and RNA sequencing were adopted for the study of molecular mechanisms associated with TET‐mediated NAFLD.ResultsThe HFD challenge led to significant down‐regulation of TET1 and TET3 in male mice, but a greater extent in TET1. Thus, TET1 knockout (KO) male mice were generated to evaluate how TET1 KO impacts NAFLD development. TET1 KO decreased mouse body weight without affecting the ratio of liver weight over body weight and fat weight over body weight, suggesting that TET1 KO may not significantly impact the development of liver and adipose tissue. Unexpectedly, TET1 KO substantially suppressed HFD‐induced steatosis and liver injuries.Mechanism studies revealed that the TET1‐mediated fatty liver development is not related to food/water consumption and fed glucose levels. Although the crucial metabolic regulators, including Akt and AMPK/LKB1 signaling pathways, are highly disrupted by the HFD feeding, no differences between TET1 wild‐type and KO mice were found. Interestingly, serum cholesterol, hepatic triglyceride, and cholesterol were substantially decreased in TET1 KO mice. The RNA sequencing results illustrated significant down‐regulation of those genes involved in lipid, fatty acid, and cellular lipid metabolic processes in TET1 KO mice. With further bioinformatics analysis, it was found that substantial down‐regulation of PPARγ, CD36, and ABCG1 in TET1 KO mice may contribute to the alleviation of NAFLD progression. The functions of PPARγ, CD36, and ABCG1 are highly associated with fatty acid synthesis, uptake, and cholesterol synthesis and efflux, respectively, thus supporting the role of TET1 in NAFLD development through targeting lipid metabolic pathways.ConclusionWe demonstrated that TET1 down‐regulation plays a protective role in NAFLD progression by targeting lipid metabolism.