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Hereditary angioedema is a potentially life-threatening autosomal dominant connology dition, causing attacks of angioedema due to failure to regulate bradykinin. Nearly all cases of hereditary angioedema are caused by mutations in the gene encoding Cl inhibitor, SERPINGl. Cl inhibitor is a multifunctional protein produced in the liver that regulates the kallikrein-kinin system at multiple points. An infant with genetically confirmed hereditary angioedema and low Cl inhibitor levels (but withand out previous episodes of angioedema) underwent liver tranSplantatiOn for biliary atresia, an unrelated condition. Liver transplantation led to normalization of the Cl inhibitor level and function. To our knowledge, this represents the first patient to be potentially cured of hereditary angioedema. [ABSTRACT FROM AUTHOR]

Rationale: In clinical diagnosis of liver injury, which is an important health concern, serum aminotransferase assays have been the go‐to method used worldwide. However, the measurement of serum enzyme activity has limitations, including inadequate disease specificity and enzyme specificity. Methods: With the high selectivity and specificity provided by nano liquid chromatography–tandem mass spectrometry (LC/MS/MS), this work describes a method for the simultaneous determination of six proteins in liver that can be potentially used as biomarkers for liver injury: glutamic‐pyruvic transaminase 1 (GPT1), glutamic oxaloacetic transaminase 1 (GOT1), methionine adenosyl transferase 1A (MAT1A), glutathione peroxidase 1 (GPX1), cytokeratin 18 (KRT18) and apolipoprotein E (APOE). Results: In validation, the method was shown to have good selectivity and sensitivity (limits of detection at pg/mL level). The analytical method revealed that, compared with normal mice, in carbon tetrachloride‐induced acute liver injury mice, liver MAT1A and GPX1 were significantly lower (p < 0.01 and p < 0.05, respectively), KRT18 was significantly higher (p < 0.05) and APOE and GPT1 were marginally significantly lower (p between 0.05 and 0.1). This is the first work reporting the absolute contents of GPT1, GOT1, MAT1A, GPX1 and KRT18 proteins based on LC/MS. Conclusions: The proposed method provides a basis for establishing more specific diagnostic indicators of liver injury. [ABSTRACT FROM AUTHOR]

SUMOylation is an important protein post-translational modification (PTM) process, in which the small ubiquitin-like modifier (SUMO) protein covalently binds to the target protein and regulates stability, subcellular localization, and protein–protein interaction of the target protein. Protein SUMOylation exerts crucial regulatory function in the liver, and its abnormalities are associated with various liver-related disease processes. This review focuses on the biological functions of protein SUMOylation in liver-related diseases in recent years, summarizes the molecular mechanisms of SUMOylation in the replication of hepatitis viruses and the occurrence of hepatocellular carcinoma, and discusses the significance of SUMOylation in liver-related disorders, which is essential for understanding liver biological processes and formulating therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Drug-induced liver injury (DILI) is extremely common in clinical practice and needs to be focused. Anwulignan is a unique lignan monomer of Schisandra Sphenanthera Fructus and is used as the main active ingredient of Wuzhi tablet, which is used for liver protection in clinical practice. In this study, an acute liver injury mouse model induced by acetaminophen and paracetamol (APAP) was used to observe its effects. Materials and Methods: An acute liver injury mouse model was established by intraperitoneally injecting APAP. Mice were divided into blank control (CON) group, APAP model (MOD) group, Anwulignan CON group, and Anwulignan MOD group. Anwulignan (6 mg/kg) or sodium carboxymethylcellulose (10 mL/kg) was intragastrically given to mice once a day, successively for 14 days. On day 14, 250 mg/kg APAP solution (10 mL/kg) or saline was injected intraperitoneally, and 12 h later, the mice were killed. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum of mice were tested. The liver index of mice was calculated, and the pathology of liver injury was evaluated by HE staining in mice. The activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as the content of malondialdehyde (MDA) in the liver tissue were tested. The levels of kelch-like ECH-associated protein 1 (Keap-1), nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), BCL2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), caspase-3 and tumor suppressor protein (P53) mRNAs in the liver tissues of mice were detected by reverse transcription-PCR (RT-PCR), and the expression levels of Keap-1, Nrf2, HO-1, Bax, Bcl-2, caspase-3 and P53 proteins in the liver tissue of mice were detected by Western blot. Results: Anwulignan can alleviate the acute liver injury of mice. The down-regulation of the cyclophosphamide (CYP2E1) expression in the liver tissue of mice to reduce the hepatotoxicity of APAP, and the regulation of Nrf2-ARE signaling pathway-related gene expressions to play an antioxidant role and apoptosis-related gene expressions to inhibit the liver cell apoptosis may be involved in the mechanism through which Anwulignan can exert its effect. Conclusion: Anwulignan can alleviate the liver injury induced by APAP in mice, and this study may provide evidence for researching and developing some drugs and nutraceuticals used for preventing and treating liver injury. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the intervention effect of curcumin on hepatic fibrosis in rodent models through systematic review and meta-analysis, in order to provide meaningful guidance for clinical practice. Methods: A systematic retrieval of relevant studies on curcumin intervention in rats or mice hepatic fibrosis models was conducted, and the data were extracted. The outcome indicators included liver cell structure and function related indicators, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), ratio of albumin to globulin (A/G), total bilirubin (TBIL), bax protein, bcl-2 protein and index of liver, as well as the relevant indicators for evaluating the degree of hepatic fibrosis, such as hyaluronic acid (HA), laminin (LN), type I collagen (Collagen I), type III collagen (Collagen III), type III procollagen (PCIII), type III procollagen amino terminal peptide (PIIINP), type IV collagen (IV-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), α-Smooth muscle actin (α-SMA), hydroxyproline (HYP), platelet derived factor-BB (PDGF-BB), connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1), and oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px). These results were then analyzed by meta-analysis. Studies were evaluated for methodological quality using the syrcle's bias risk tool. Results: A total of 59 studies were included in the meta-analysis, and the results showed that curcumin can reduce the levels of ALT, AST, ALP, TBIL, bax protein, and index of liver in hepatic fibrosis models. It can also reduce HA, LN, Collagen I, Collagen III, PCIII, PIIINP, IV-C, TNF-α, α-SMA, HYP, PDGF-BB, CTGF, TGF-β1 and MDA, and increase the levels of ALB, A/G, SOD, and GSH-Px in the hepatic fibrosis models. However, the effects of curcumin on bcl-2 protein, IL-6 in hepatic fibrosis models and index of liver in mice were not statistically significant. Conclusion: The analysis results indicate that curcumin can reduce liver cell apoptosis by maintaining the stability of liver cell membrane, inhibit the activation and proliferation of hepatic stellate cells by reducing inflammatory response, and alleviate tissue peroxidation damage by clearing oxygen free radicals. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of enzymes in the feed of chickens and the production animals is already well established, given the nutritional and economic benefits that can be achieved without affecting the quality of the final product. Among research efforts, new discoveries are made every day regarding the potential of products developed to provide efficient enzymes as additives in animal diets. Therefore, this study investigated the influence of enzymes produced from the cultivation of Trichoderma reesei in powder and liquid forms on the feeding of broiler chickens from 1 to 21 days of age. The diets were composed of corn and soybean meal, and this study evaluated their effects on performance, digestibility, blood parameters, and the biometry of the digestive system. The enzymes produced, cellulases, affected feed intake, digestibility, and blood electrolyte concentrations were quantified. However, the biometry of the digestive system and analyses of pancreas and liver viscera were not altered, which may indicate normal bird development and the absence of toxicity. In conclusion, Trichoderma reesei cellulases are an interesting option for use in animal diets. The cellulose present in the cell wall of vegetables prevents the greater release of nutrients to the animal. Therefore, the use of the cellulase enzyme is a viable strategy as it is capable of breaking cellulose bonds, releasing nutrients such as glucose, increasing dietary energy, and thus improving the productive performance of birds. Trichoderma reesei is efficient in the production of cellulase, which is produced via submerged fermentation followed by purification, formulation, and drying. Therefore, an experiment was carried out using 240 male broilers of the Cobb-500® lineage to verify the effects resulting from the addition of powdered (500 g/t and 1000 g/t) and liquid (500 mL/t) cellulase over a period of 1 to 21 days. A completely randomized experimental design was used, consisting of four treatments with six replications and ten birds per replication that were housed in an experimental cage. It was observed that performance and digestibility results were significantly different with cellulase supplementation. Also, the relative weight of the large intestine in the period between one and seven days increased when cellulase was added at 1000 g/t. In the period of between eight and 14 days of life, the birds that consumed only the basal diet obtained higher levels of liver protein than those that received the treatments with the addition of the enzyme. However, 15 and 21 days, the consumed feed effect did not occur between thus, it is not conclusive whether hepatotoxicity occurs with the addition of cellulase. For the blood parameters, at 21 days, the diets with added cellulase were not significantly different regarding electrolytes. It was concluded that this cellulase produced by Trichoderma reesei can be included in the animals' diet. [ABSTRACT FROM AUTHOR]

Liver mitochondria play a central role in metabolic adaptations to changing nutritional states, yet their dynamic regulation upon anticipated changes in nutrient availability has remained unaddressed. Here, we found that sensory food perception rapidly induced mitochondrial fragmentation in the liver through protein kinase B/AKT (AKT)–dependent phosphorylation of serine 131 of the mitochondrial fission factor (MFFS131). This response was mediated by activation of hypothalamic pro-opiomelanocortin (POMC)–expressing neurons. A nonphosphorylatable MFFS131G knock-in mutation abrogated AKT-induced mitochondrial fragmentation in vitro. In vivo, MFFS131G knock-in mice displayed altered liver mitochondrial dynamics and impaired insulin-stimulated suppression of hepatic glucose production. Thus, rapid activation of a hypothalamus–liver axis can adapt mitochondrial function to anticipated changes of nutritional state in control of hepatic glucose metabolism. [ABSTRACT FROM AUTHOR]

Background: Considering the expected increase in the elderly population and the growing emphasis on aging-related biomedical research, the demand for aged laboratory animals has surged, challenging established husbandry practices. Our objective was to establish a cost-effective method for environmental enrichment, utilizing the liver as a representative organ to assess potential metabolic changes in response to differing enrichment levels. Methods: We conducted a six-month study involving 24 male Sprague Dawley rats, randomly assigned to four environmental enrichment groups. Two groups were housed in standard cages, while the others were placed in modified rabbit cages. Half of the groups received weekly playtime in an activity focused rat housing unit. We evaluated hormone levels, playtime behavior, and subjective handling experience. Additionally, liver tissue proteomic analysis was performed. Results: Initial corticosterone levels and those after 3 and 6 months showed no significant differences. Yet, testosterone levels were lower in the control group by the end of the study (p = 0.007). We observed 1871 distinct proteins in liver tissue, with 77% being common across groups. In gene ontology analysis, no specific pathways were overexpressed. In semiquantitative analysis, we observed differences in proteins associated in lipid metabolism such as Apolipoprotein A-I and Acyl-CoA 6-desaturase, which were lower in the control group (p = 0.024 and p = 0.009). Rats in the intervention groups with weekly playtime displayed the least amount of reported distress during inspection or upon room entry and were less prone to accepting treats. Removing animals from their enclosure was most effortless for those in the large cage group. Over time, there was a decrease in conflicts among rats that interacted only twice weekly during playpen time. Discussion: In summary, refining husbandry practices for aging rats is both simple and budget-friendly, with no apparent adverse effects on stress levels, animal development, or relevant metabolic changes in the liver. [ABSTRACT FROM AUTHOR]

Simple Summary: Cytochrome P450 2E1 (CYP2E1) is a key enzyme involved in the hepatic metabolism of the major boar taint compound, skatole. Here, we identified single-nucleotide polymorphisms (SNPs) in the promoter region of the CYP2E1 gene that were associated with CYP2E1 mRNA expression, but not with CYP2E1 protein expression. This demonstrates the role of promoter SNPs in the expression of CYP2E1 mRNA and suggests that factors that regulate the translation of CYP2E1 mRNA may also be important in affecting skatole metabolism. Boar taint, an unfavorable odor in the meat of intact male pigs, is caused primarily by the accumulation of two compounds: androstenone and skatole. This multifactorial trait is regulated by numerous dietary, management and genetic factors. At the mechanistic level, there are many genes known to be involved in boar taint metabolism. Cytochrome P450 2E1 (CYP2E1) impacts boar taint through the phase I metabolism of skatole. The aim of this study was to identify single-nucleotide polymorphisms (SNPs) within the CYP2E1 gene promoter and explore their relationship with the expression of CYP2E1 mRNA and protein. Sequencing of the promoter region using pools of genomic DNA identified seven promoter region SNPs at −159, −586, −1693, −1806, −2322, −2369 and −2514 bp upstream of the ATG start site. Genomic DNA was obtained from 65 boars from the three major swine breeds: Duroc, Landrace and Yorkshire, and individual animals were genotyped for the identified SNPs. RNA was isolated from liver tissue and quantitative PCR was performed to measure CYP2E1 gene expression, while levels of CYP2E1 protein in liver were measured by Western blotting. Significant within-breed variation in CYP2E1 protein and mRNA expression was observed, indicating significant differences in gene expression among individuals. However, levels of CYP2E1 mRNA and protein were not significantly correlated. Two SNPs within the promoter were significantly associated with CYP2E1 mRNA expression, but not with protein expression. This study provides evidence of additional mutations affecting the gene expression of CYP2E1 and suggests that factors that affect the differences in translation of CYP2E1 mRNA may also be important in affecting skatole metabolism. [ABSTRACT FROM AUTHOR]

Prior to nuclear export, the hepatitis B virus (HBV) pregenomic RNA may be spliced by the host cell spliceosome to form shorter RNA sequences known as splice variants. Due to deletions in the open reading frames, splice variants may encode novel fusion proteins. Although not essential for HBV replication, the role of splice variants and their novel fusion proteins largely remains unknown. Some splice variants and their encoded novel fusion proteins have been shown to impair or promote wild-type HBV replication in vitro, and although splice variants Sp3 and Sp9 are two of the most common splice variants identified to date, their in vitro replication phenotype and their impact on wild-type HBV replication are unclear. Here, we utilize greater than genomelength Sp3 and Sp9 constructs to investigate their replication phenotype in vitro, and their impact on wild-type HBV replication. We show that Sp3 and Sp9 were incapable of autonomous replication, which was rescued by providing the polymerase and core proteins in trans. Furthermore, we showed that Sp3 had no impact on wild-type HBV replication, whereas Sp9 strongly reduced wild-type HBV replication in co-transfection experiments. Knocking out Sp9 novel precore-surface and core-surface fusion protein partially restored replication, suggesting that these proteins contributed to suppression of wild-type HBV replication, providing further insights into factors regulating HBV replication in vitro. IMPORTANCE The role of hepatitis B virus (HBV) splice variants in HBV replication and pathogenesis currently remains largely unknown. However, HBV splice variants have been associated with the development of hepatocellular carcinoma, suggesting a role in HBV pathogenesis. Several in vitro co-transfection studies have shown that different splice variants have varying impacts on wild-type HBV replication, perhaps contributing to viral persistence. Furthermore, all splice variants are predicted to produce novel fusion proteins. Sp1 hepatitis B splice protein contributes to liver disease progression and apoptosis; however, the function of other HBV splice variant novel fusion proteins remains largely unknown. We show that Sp9 markedly impairs HBV replication in a cell culture co-transfection model, mediated by expression of Sp9 novel fusion proteins. In contrast, Sp3 had no effect on wild-type HBV replication. Together, these studies provide further insights into viral factors contributing to regulation of HBV replication. [ABSTRACT FROM AUTHOR]

BACKGROUND: The influence of protein hydrolysate produced from bovine liver protein hydrolysate (LPH) by enzymatic hydrolysis, using Alcalase/Protamex (1:1), on lipid dispersions was investigated. LPH production was optimized to maximize the antioxidant activity (at 45, 50, and 55 °C for 12, 18, and 24 h). Different concentrations of LPHs (1, 3, and 5 mg/g) were added to emulsions and to liposomes. Lipid oxidation level and particle size of the lipid dispersions were monitored for 14 days of storage at 25 °C. RESULTS: Radical scavenging activity and reducing power were the highest at 45 °C after 24 h of hydrolysis. Electrophoresis pattern showed that the antioxidant activity was arising from the peptides with molecular weight around 10 kDa. Lipid oxidation occurred more rapidly in samples without LPH during storage. In emulsions, lower thiobarbituric acid-reactive substance and conjugated diene values were measured with increasing concentrations of LPH at day 14. Accordingly, particle size of the samples containing 5 mg/g of LPH was smaller than those of other groups. Phase separation was observed only in lecithin emulsion without LPH at day 14. The use of LPH in liposome limited the lipid oxidation and maintained the size of the particles independently from the concentration. CONCLUSION: This study highlights the potential applications of animal by-products as natural antioxidants in complex food systems. The results demonstrate that LPH, particularly when hydrolyzed at optimized conditions, can effectively inhibit lipid oxidation. The findings suggest that biphasic systems incorporating LPH have promising prospects for enhancing the stability and quality of food products. [ABSTRACT FROM AUTHOR]

Methionine (Met) rich diet inducing oxidative stress is reported to alter many organs. Proteasome as a regulator of oxidative stress can be targeted. This study was performed to investigate if excessive methionine supplementation causes hepatotoxicity related to proteasome dysfunction under endogenous oxidative stress in rats. Male Wistar albino rats (n = 16) were divided into controls and treated groups. The treated rats (n = 08) received orally l-methionine (1 g/kg/day) for 21 days. Total homocysteine (tHcy), total oxidant status (TOS), total antioxidant status (TAS), hepatic enzymes levels: aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), with total bilirubin (TBil), albumin (Alb), and C-reactive protein (CRP) were determined in plasma by biochemical assays. Liver supernatants were used for malondialdehyde (MDA), protein carbonyls (PC), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), 20S proteasome activities and their subunits expression, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) evaluation by appropriate methods and light microscopy for liver histological examination. Methionine treatment increased homocysteine, TOS, oxidative stress index (OSI), MDA and PC but decreased TAS, GSH, CAT, SOD, GPx with the 20S proteasome activities and their β subunits expression. Liver proteins: AST, ALT, LDH, ALP, TBil and CRP were increased but Alb was decreased. Liver histology was also altered. An increase in liver TNF-α and IL-6 levels were observed. These findings indicated that methionine supplementation associated oxidative stress and proteasome dysfunction, caused hepatotoxicity and inflammation in rat. Further investigations should be to better understand the relation between methionine, oxidative stress, proteasome, and liver injuries. [ABSTRACT FROM AUTHOR]

The current study was performed to investigate the impact of different temperatures and protein levels on the growth performance, proximate composition and digestive and hepatic enzyme activities of Labeo rohita fingerlings. For this purpose, healthy fingerlings (average initial weight of 6.40 ± 0.02 g) were acclimatized for 15 days, then reared at three temperatures (25°C, 30°C and 35°C) and fed three levels of crude protein (25%, 30% and 35% crude protein (CP)) twice daily until satiation for 60 days. The results of the study revealed that the highest growth performance was observed in fish fed 35% protein and reared at 30°C. Similarly, fish reared at 35°C and 25°C water temperature showed comparatively better growth performance in fish fed with 35% protein. Furthermore, a significant enhancement in feed intake was observed with increasing culture temperature and increasing CP levels, but at 25°C, increasing CP levels significantly decreased the feed intake. Sligh variations were also observed in proximate composition in terms of moisture, CP, crude fat (CF) and ash contents in fish fed with different CP levels and reared at different temperatures. The hepatosomatic index and viscerosomatic index decreased significantly with increasing levels of protein and temperature. Amylase activities were significantly reduced with increasing culture temperature at each protein level. Increasing culture temperature did not affected the lipase activities. However, lipase activities were enhanced with increasing CP levels at 25°C and activities decreased with increasing CP levels at 30–35°C. Protease activity was enhanced with increasing temperature and CP levels. Significant increases were also observed in serum total proteins and liver functioning enzymes such as alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase in response to increased temperature, and protein had a reciprocal effect. It is concluded that increasing the CP levels increased the growth performance independent of temperature. However, similar growth performance at 30 CP (30°C) and 35 CP (35°C) indicates that L. rohita requires more protein at higher temperature for optimum growth. [ABSTRACT FROM AUTHOR]

Methylcarbamate (MC), a reaction product between dimethyl dicarbonate and ammonia or ammonium ion, is a potent hepatocarcinogen in F344 rats. Various genotoxicity tests have shown negative results for MC. Although previous studies have described the effects of MC on the liver, including the formation of characteristic basophilic cytoplasmic inclusions (CIs) in hepatocytes, the toxicological significance of CIs and their involvement in hepatocarcinogenesis remain unclear. In the current study, to elucidate the mechanisms of MC hepatocarcinogenesis, we examined hepatotoxicity and genotoxicity after 4 weeks of administration of MC using gpt delta rats with an F344 genetic background as a reporter gene transgenic animal model. Histopathologically, single-cell necrosis, karyomegaly, and the formation of CIs positive for Feulgen staining were observed in hepatocytes at the carcinogenic dose, demonstrating the hepatotoxicity of MC. CIs were also detected as large micronuclei in liver micronucleus tests but not in the bone marrow, suggesting that MC could cause chromosomal instability specifically in the livers of rats. Reporter gene mutation assays demonstrated that MC did not induce mutagenicity even in the liver. Immunofluorescence analyses revealed that CIs exhibited loss of nuclear envelope integrity, increased heterochromatinization, and accumulation of DNA damage. An increase in liver STING protein levels suggested an effect on the cyclic GMP-AMP synthase/stimulator of interferon genes innate immune pathway. Overall, these data demonstrated the possible occurrence of chromothripsis-like chromosomal rearrangements via CIs. Thus, the formation of CIs could be a crucial event in the early stage of MC-induced hepatocarcinogenesis in F344 rats. [ABSTRACT FROM AUTHOR]

Pork liver is a protein-rich offal, generated in large quantities in the meat industry and considered non-allergenic, although not highly appreciated by Western consumers. The recovery of its proteins through a simple and easily scalable process with the purpose of obtaining economical and environmentally friendly techno-functional ingredients might be an alternative for its valorization. Of great interest are protein fractions with good foaming properties that can act as substitutes for other highly allergenic proteins in food formulation. In this study, protein extractions from fresh pork livers were performed using buffer solutions adjusted to different pH (from 4.0 to 8.5), without a subsequent concentration/purification step. The main parameters evaluated were yield and foaming properties of the recovered extracts; their physicochemical characteristics and the SDS-PAGE protein profiles were determined as well. Acceptable extraction yields (> 50% of the total protein) were obtained using buffer solutions adjusted to pH ≥ 4.80, but their foaming properties were poor. By contrast, the extracts recovered using buffers adjusted to pH ≤ 4.75 were capable of forming very voluminous and stable foams, although rather low yields were achieved under these conditions (31.5–36.0% of the total protein). In addition to the profile of solubilized proteins, a low fat and relatively high carbohydrate content in the extracts seem to contribute to their excellent foaming properties. Therefore, protein extracts from fresh pork liver obtained using buffer solutions adjusted to pH 4.0–4.5 (extract pH: 5.3–5.6) could be a real alternative to other protein foaming agents that cause food allergies, in a simple, cost-effective and sustainable way. [ABSTRACT FROM AUTHOR]

Hepatitis E represents an emerging zoonotic disease caused by the Hepatitis E virus (HEV), for which the main route of transmission is foodborne. In particular, infection in humans has been associated with the consumption of contaminated undercooked meat of pig origin. The aim of this study was to apply comparative proteomics to determine if porcine liver protein profiles could be used to distinguish between pigs seropositive and seronegative for HEV. Preliminarily, an ELISA was used to evaluate the presence of anti-HEV antibodies in the blood serum of 136 animals sent to slaughter. Among the analyzed samples, a seroprevalence of 72.8% was estimated, and it was also possible to identify 10 animals, 5 positive and 5 negative, coming from the same farm. This condition created the basis for the quantitative proteomics comparison between homogeneous animals, in which only the contact with HEV should represent the discriminating factor. The analysis of the proteome in all samples of liver exudate led to the identification of 554 proteins differentially expressed between the two experimental groups, with 293 proteins having greater abundance in positive samples and 261 more represented in negative exudates. The pathway enrichment analysis allowed us to highlight the effect of the interaction between HEV and the host biological system in inducing the potential enrichment of 69 pathways. Among these, carbon metabolism stands out with the involvement of 41 proteins, which were subjected to interactomic analysis. This approach allowed us to focus our attention on three enzymes involved in glycolysis: glucose-6-phosphate isomerase (GPI), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and fructose-bisphosphate aldolase A (ALDOA). It therefore appears that infection with HEV induced a strengthening of the process, which involves the breakdown of glucose to obtain energy and carbon residues useful for the virus's survival. In conclusion, the label-free LC-MS/MS approach showed effectiveness in highlighting the main differences induced on the porcine liver proteome by the interaction with HEV, providing crucial information in identifying a viral signature on the host metabolism. [ABSTRACT FROM AUTHOR]

Circadian rhythm disturbances caused by anaesthesia may be one of the important reasons of many disturbances following surgery. The effects of 6% desflurane on suprachiasmatic nucleus (SCN), liver, and pancreas PER2, CRY1, BMAL, and CLOCK circadian protein levels and serum concentrations of glucose, melatonin, cortisol 24 h following the administration of anaesthesia were determined in this study. 10-12-weekold Wistar albino male rats (n=12) were divided into two groups. Control group (C) was not exposed to desflurane, while the anaesthesia group (D) received desflurane at 6% concentration for 6 h between 07.00 and 13.00 a.m. and was euthanized 24 h after anaesthesia. Tissue samples were collected from both groups at the same time of the day (07.00 a.m.). Serum glucose, melatonin, cortisol and SCN, liver, pancreas CLOCK, BMAL1, PER2, CRY1 levels were determined using commercial kits. CLOCK and PER2 protein levels in SCN and BMAL1 protein concentration in liver decreased, while liver PER2 protein level increased at the 24th h following anaesthesia. Pancreas BMAL1, CLOCK, PER2, CRY1 protein levels were not affected by the anaesthesia protocol applied. No statistically significant alteration was observed in plasma glucose, cortisol and melatonin concentrations. Our findings show that, the circadian clock rhythm in SCN and liver are still affected at the 24th h following exposure to desflurane. [ABSTRACT FROM AUTHOR]

The blackfin snook, Centropomus medius, is a valuable fish in American and Mexican markets, mainly from catches. Nonetheless, information and studies about the biology of this species still need to be made available; thus, its aquaculture should be developed. This study aimed to describe the seasonal changes of proximate composition during a reproductive cycle of C. medius, analyzing differences between tissues and their changes related to the reproductive process. The snook specimens were collected in Magdalena Bay, Baja California Sur, Mexico, and measured every month from September 2001 to November 2002. Liver, gonads, muscle tissue, and intraperitoneal fat (IPF) were sampled and weighed. The gonadosomatic index (GSI), hepatosomatic index (HSI), IPF ratio, and condition factor index (K) were calculated. The biochemical composition was analyzed in the gonad, liver, and muscle. The reproductive period (RP) of wild C. medius in Baja California Sur, Mexico, was from June to December. The spawning period was recorded at summer temperature (25-30°C) and photoperiod (>13 h daylight) starting in September. High GSI values (gonad development), low HSI values (lipid reserve mobilization), low IPF, and low K ratio were related to elevated temperatures. Moreover, variations were observed in protein, total lipid, triglycerides, and glycogen content in muscle, liver, and gonad according to the reproductive phase. A positive correlation was demonstrated between protein contents in muscle, gonad, and K, with lower concentrations during RP, while liver protein composition showed an opposite pattern. Lipids were mainly present in the liver, and the concentration decreased during RP while muscle increased. The results obtained in this study show differences in the proximate analyses in the liver, muscle, and gonads throughout the year concerning different phases of the reproductive cycle, indicating a great dependence of this process on the mobilization of reserves during C. medius reproduction. Therefore, understanding the feeding requirements to pursue the management of this species in captivity for aquaculture development is greatly important. [ABSTRACT FROM AUTHOR]

Supplementing minerals beyond dietary requirements can increase the risk of toxicity and mineral excretion, making the selection of more bioavailable sources crucial. Thus, this work aimed to use metalloproteomics tools to investigate possible alterations in the hepatic proteome of broilers fed with diets containing two sources (sulfate and hydroxychloride) and two levels of copper (15 and 150 ppm) and manganese (80 and 120 ppm), totaling four treatments: low Cu/Mn SO4, high Cu/Mn SO4, low Cu/Mn (OH)Cl and high Cu/Mn (OH)Cl. The difference in abundance of protein spots and copper and manganese concentrations in liver and protein pellets were analyzed by analysis of variance with significance level of 5%. The Cu and Mn concentrations determined in liver and protein pellets suggested greater bioavailability of hydroxychloride sources. We identified 19 Cu-associated proteins spots, 10 Mn-associated protein spots, and 5 Cu and/or Mn-associated protein spots simultaneously. The analysis also indicated the induction of heat shock proteins and detoxification proteins in broilers fed with high levels of copper and manganese, suggesting the involvement of these proteins in metal tolerance and stress. [ABSTRACT FROM AUTHOR]

N- and O-glycosylation modifications of proteins are closely linked to the onset and development of many diseases and have gained widespread attention as potential targets for therapy and diagnosis. However, the low abundance and low ionization efficiency of glycopeptides as well as the high heterogeneity make glycosylation analysis challenging. Here, an enrichment strategy, using Knoevenagel copolymers modified with polydopamine–adenosine (denoted as PDA–ADE@KCP), was firstly proposed for simultaneous enrichment of N- and O-glycopeptides through the synergistic effects of hydrophilic and electrostatic interactions. The adjustable charged surface and hydrophilic properties endow the material with the capability to achieve effective enrichment of intact N- and O-glycopeptides. The experimental results exhibited excellent selectivity (1 : 5000) and sensitivity (0.1 fmol μL−1) of the prepared material for N-glycopeptides from standard protein digest samples. Moreover, it was further applied to simultaneous capturing of N- and O-glycopeptides from mouse liver protein digests. Compared to the commercially available zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) material, the number of glycoproteins corresponding to all N- and O-glycopeptides enriched with PDA–ADE@KCP was much more than that with ZIC-HILIC. Furthermore, PDA–ADE@KCP captured more O-glycopeptides than ZIC-HILIC, revealing its superior performance in O-glycopeptide enrichment. All these results indicated that the strategy holds immense potential in characterizing N- and O-intact glycopeptides in the field of proteomics. [ABSTRACT FROM AUTHOR]

This study investigated the effects of varying doses of dietary aflatoxin B1 (AFB1) on the growth, intestinal health, and muscle quality of hybrid grouper. Four diets with varying AFB1 concentrations (0, 30, 445, and 2,230 μg kg−1) were used. Elevating AFB1 concentrations led to a decline in growth indexes, specifically the weight gain rate and the specific growth rate, although the survival rate remained unchanged. Morphological indicators showed a dose-dependent decline with AFB1 exposure. Intestinal MDA content and hindgut reactive oxygen species (ROS) levels increased, while antioxidant indexes and digestive enzymes decreased with higher AFB1 levels. AFB1 negatively influenced hindgut tight junction protein and antioxidant-related gene expression while promoting inflammation-related gene expression. The presence of AFB1 in the experiment led to a decrease in beneficial intestinal bacteria, such as Prevotella, and an increase in harmful intestinal bacteria, such as Prevotellaceae_NK3B31_group. Muscle lipid and unsaturated fatty acid content significantly decreased, while muscle protein and liver AFB1 content increased dramatically with higher AFB1 concentrations. AFB1 caused myofibrillar cleavage and myofilament damage, leading to increased spaces between muscle fibers. In conclusion, diets with AFB1 levels exceeding 30 μg kg−1 inhibited hybrid grouper growth, while levels surpassing 445 μg kg−1 resulted in hindgut ROS accumulation, inflammation, elevated intestinal permeability, reduced digestive enzyme activity, and compromised muscle quality. [ABSTRACT FROM AUTHOR]

Background and Aim: Liver injury results in the production of free radicals that can lead to hepatocytic degeneration, cirrhosis, and hepatocellular carcinoma (HCC). Liver-fatty acid-binding protein (L-FABP) is highly expressed in hepatocytes and is a key regulator of hepatic lipid metabolism and antioxidant characteristics. Interestingly, the increase in L-FABP expression could be used as a novel marker of liver injury. Therefore, this study aimed to use immunohistochemical techniques to investigate the expression of L-FABP in dogs with liver injury compared with dogs with non-pathological liver. Materials and Methods: Liver tissue samples were collected from dog biopsy specimens at the Veterinary Diagnostic Laboratory at the Faculty of Veterinary Medicine, Chiang Mai University. The tissues were prepared for immunohistochemistry and the expression and localization of L-FABP were investigated using one-way analysis of variance. Results: Immunohistochemical analysis showed that L-FABP was strongly expressed in the hepatocytes of dogs with lipidosis and HCC when compared with that in normal liver. Semi-quantitative immunohistochemistry evaluation showed the percentage of protein expression of L-FABP 0.023 ± 0.027 in the non-pathological liver. The percentage of L-FABP protein expression in lipidosis and HCC was found to be 8.517 ± 1.059 and 17.371 ± 4.026, respectively. Conclusion: L-FABP expression in dogs with liver injuries was significantly higher than that in dogs with non-pathological liver injury (p = 0.05). These results suggest that L-FABP has the potential as a novel marker for specific diagnosis and prognosis of dogs with liver injury. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common gastrointestinal malignancies, characterized by insidious onset and high propensity for metastasis and recurrence. Apart from surgical resection, there are no effective curative methods for HCC in recent years, due to resistance to radiotherapy and chemotherapy. Heat shock proteins (HSP) play a crucial role in maintaining cellular homeostasis and normal organism development as molecular chaperones for intracellular proteins. Both basic research and clinical data have shown that HSPs are crucial participants in the HCC microenvironment, as well as the occurrence, development, metastasis, and resistance to radiotherapy and chemotherapy in various malignancies, particularly liver cancer. This review aims to discuss the molecular mechanisms and potential clinical value of HSPs in HCC, which may provide new insights for HSP-based therapeutic interventions for HCC. [Display omitted] • Heat shock proteins (HSP) plays an important role in the tumor microenvironment of Hepatocellular carcinoma. • In highly suspicious cases, HSP helps in differential diagnosis. • HSP related inhibitors and HSP based tumor vaccines have broad prospects in the treatment of HCC. [ABSTRACT FROM AUTHOR]

The effects of plant protein sources (PPSs) on the health of the liver and intestine of the largemouth bass, Micropterus salmoides, were compared to verify the potential damaging effects of dietary fiber (DF). A diet containing 55% fish meal (FM) was used as the control. The test diets contained 25% soybean meal (SBM), rapeseed meal (RSM), cottonseed meal, or peanut meal, and the FM content was decreased to 30%. The protein and lipid contents of these five diets were balanced by casein and oil. Fish were raised for 8 weeks. The fish fed the diet containing PPS showed a trend of decreasing growth and apparent digestibility coefficients. The contents of total bile acid, lipid, and collagen in the liver were increased, and the mRNA expression levels of genes encoding inflammatory factors and enzymes involved in de novo fatty acid synthesis and bile acid synthesis were upregulated. Both the lipid and collagen contents in the liver were positively correlated with the DF content in the diet significantly. Morphology and histology showed reduced liver size, hepatic steatosis, and fibrosis in fish fed diets containing PPS. The lowest hepatosomatic index was observed in fish fed the SBM diet, and the most severe damage was observed in fish fed the RSM diet. No obvious histological abnormalities were observed in the hindgut. The bile acid profile in the liver could be used to distinguish the types of PPS very well by Fisher discriminant analysis. These results indicated that 25% of each of the four PPSs in the diet exceeded the tolerance range of largemouth bass and caused liver damage, which might be mediated by bile acid. DF in PPS might be an important agent contributing to liver damage. [ABSTRACT FROM AUTHOR]

Integrative studies are lacking on the responses of digestive enzymes and energy reserves in conjunction with morphological traits at distinct postprandial times in marine estuarine‐dependent flatfishes of ecological and economic importance, such as Paralichthys orbignyanus. We determined total weight (TW), hepato‐somatic index (IH), activities of digestive enzymes in the intestine, and the concentration of energy reserves in the liver and the muscle at 0, 24, 72, and 360 h after feeding in juveniles of P. orbignyanus. Amylase activity decreased at 72 h (about 30%). Maltase, sucrose, and lipase activities reached peak at 24 h (67%, 600%, and 35%, respectively). Trypsin and aminopeptidase‐N activities at 24 and 72 h, respectively, were lower than those at t = 0 (53% and 30%). A peak increase in the concentration of glycogen and triglycerides in the liver (24 h) (86% and 89%, respectively) occurred. In muscle, glycogen and triglyceride concentrations were unchanged at 24 h and higher at 72 and 360 h (100% and 60%). No changes were found in TW, IH, free glucose in the liver and muscle, and protein in the liver. The protein concentration in the muscle sharply increased at 24 and 360 h after feeding (60%). The results indicate a distinct and specific response of central components of carbohydrate, lipid, and protein metabolism that could be adjustments at the biochemical level upon periods of irregular feeding and even of long‐term food deprivation inside coastal lagoons or estuaries. The distinct responses of digestive enzymes in the intestine and energy reserves in the liver and muscle suggest the differential modulation of tissue‐specific anabolic and catabolic pathways that would allow the maintenance of physical conditions. [ABSTRACT FROM AUTHOR]

LECT2 is not a routine diagnostic marker for any disease, but it has been associated with many pathologies, including systemic amyloidosis, rheumatoid arthritis, diabetes, atherosclerosis, and metabolic syndrome. With human aortic sections (n = 22) and sera from geriatric subjects (n = 79), we analyzed the relationships that could be observed between this protein and other parameters related to metabolic diseases. As a result, we observed a relatively high (r~0.8, p < 0.05) positive correlation between SRA and LECT2 and a negative correlation between EGFR and LECT2 (r~−0.4, p < 0.05). We observed LECT2 expression in macrophages, myocytes, and other aortic cells, with a tendency to be overexpressed in developed atherosclerotic plaques. We conclude that LECT2 exerts its chemotactic effects not only as a protein synthesized in the liver and secreted and circulating in the blood but also as a locally expressed protein within atherosclerotic plaque development. The LECT2-EGFR correlation suggests an association of this protein with loss of normal renal function. This fact can be associated with LECT2 amyloidosis, although it should be verified whether in the geriatric population there is indeed a widespread accumulation of LECT2 with the progression of aging or whether it is rather a marker of general deterioration of renal function. [ABSTRACT FROM AUTHOR]

Background: Constitutive photomorphogenic protein 1 (COP1) plays a pivotal role in the development and progression of several human cancers and is reported to be upregulated in liver cancer. However, the role of COP1 in human liver cancer is unclear. Methods: We analyzed the COP1 expression in normal liver and liver cancer tissue samples using western blot and immunohistochemical analysis. We overexpressed and silenced COP1 in HepG2 and Huh7 cells and analyzed the effect on liver cancer cell proliferation. Additionally, COP1 was used as a bait to screen COP1-interacting proteins in a human cDNA library in a yeast two-hybrid screen and the results were confirmed with co-immunoprecipitation (co-IP) assays. Moreover, immunofluorescence staining was performed to assess co-localization. The protein levels of COP1 and mIL1RAcP were determined in clinical samples. Results: COP1 was upregulated in liver cancer samples compared to that in normal tissue samples. COP1 overexpression promoted proliferation of liver cancer cells, while COP1 knockdown exerted the opposite effect. Yeast two-hybrid screen identified interleukin-1 receptor accessory protein (IL1RAP) as a potential COP1-interacting protein. Co-IP assays further confirmed that COP1 interacts with both preIL1RAP and membrane-bound form of IL1RAP (mIL1RAP). Furthermore, COP1 upregulated mIL1RAP protein levels and promoted nuclear translocation and activation of the nuclear factor kappa B (NF-κB) (p50/p65) dimer. Additionally, we demonstrated that COP1 regulated mIL1RAP expression through K63-linked polyubiquitination, suggesting that COP1 plays a role in stabilizing mIL1RAP. Finally, the protein levels of COP1 and mIL1RAcP were found to be positively correlated in clinical samples. Conclusion: COP1 regulates IL1RAP, which in turn results in activation of the NF-κB signaling. Our findings suggest that the COP1/IL1RAP/NF-κB axis promotes proliferation of liver cancer cells and is a potential target for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the protective effects of usnic acid and alpha lipoic acid on changes in cellular mitogenic activity proteins in serum, liver, and kidney tissue of rats with cadmium toxicity. Cadmium (Cd) amounts in samples taken from serum, liver and kidney tissues, and Mitogen Activity Protein Kinases (MAPK), Guanosine Triphosphatase (GTPase), Nuclear Factor Kappa-B P65 (NFκBp65) and Nuclear Factor Kappa-B (NFκB) in cell and mitogenic activity proteins in liver and kidney tissues changes were evaluated. The levels of Cd in liver and kidney tissues increased significantly compared to control, whereas liver Cd levels of usnic acid (UA) group decreased. MAPK activity in liver tissues of alpha lipoic acid (ALA) group showed a statistically significant decrease compared to other groups. In contrast, liver tissues of UA group showed a significant increase compared to all other groups. Renal tissue GTPase level decreased significantly in the control group compared to the other groups, while GTPase level was increased dramatically in UA group compared to all other groups. When the levels of NF-κBp65 protein in liver tissue were compared to control, Cd increased significantly. In contrast, comparison of Cd group to UA + Cd and ALA + Cd groups showed a significant decrease in NF-κBp65 levels. Application of ALA in Cd toxicity significantly increased liver tissue NF-κB levels and decreased renal tissue NF-κB levels. In conclusion, it was determined that UA and ALA have protective effects on Cd-induced liver toxicity in rats. In contrast, UA and ALA did not have a protective effect on renal tissue. [ABSTRACT FROM AUTHOR]

Alternanthera sessilis is a plant native to wetlands that is commonly known in the Philippines as "bunga-bunga" (Tagalog). Currently, A. sessilis is available as a natural product that can combat anemia in the Philippines. Anemia, together with diabetes, is one of the complications experienced during pregnancy. This study aimed to identify the safety of A. sessilis as a supplement for pregnant mothers by testing its embryotoxic and possible teratogenic effects in pregnant mice. The experimental design consisted of supplementation of 7.3 mg/mL (low) and 73 mg/mL (high) A. sessilis to pregnant dams compared with 10,000 IU/kg of isotretinoin (positive control), soybean oil (vehicle control), and distilled water (negative control group). Reproductive parameters, histological parameters, and gene expression pattern changes were observed in the embryos of pregnant dams. Dams and embryos in the isotretinoin group had reduced reproductive performance and induced teratogenicity. Administration of a low dose (7.3 mg/mL) of A. sessilis capsule showed no significant changes in the reproductive performance of dams and embryo development (E11.5). Although not significant, a higher dose (73 mg/mL) of A. sessilis resulted in a slight reduction in reproductive performance and embryo growth when compared with the negative control group. According to the immunohistochemistry results, the high-dose group of A. sessilis had a significant increase in the expression of BCL-2 anti-apoptotic protein in the embryonic liver (E11.5) when compared with the negative control group and the isotretinoin group. The findings in this study suggest that the use of A. sessilis as a supplement at a low dose can be beneficial during pregnancy. [ABSTRACT FROM AUTHOR]

Excessive production of transforming growth factor β1 (TGF-β1) in activated hepatic stellate cells (aHSCs) promotes liver fibrosis by activating the TGF-β1/Smad signaling pathway. Thus, specifically inhibiting the pro-fibrotic activity of TGF-β1 in aHSCs is an ideal strategy for treating liver fibrosis. Overexpression of platelet-derived growth factor β receptor (PDGFβR) has been demonstrated on the surface of aHSCs relative to normal cells in liver fibrosis. Interferon-gamma peptidomimetic (mIFNγ) and truncated TGF-β receptor type II (tTβRII) inhibit the TGF-β1/Smad signaling pathway by different mechanisms. In this study, we designed a chimeric protein by the conjugation of (1) mIFNγ and tTβRII coupled via plasma protease-cleavable linker sequences (FNPKTP) to (2) PDGFβR-recognizing peptide (BiPPB), namely BiPPB-mIFNγ-tTβRII. This novel protein BiPPB-mIFNγ-tTβRII was effectively prepared using Escherichia coli expression system. The active components BiPPB-mIFNγ and tTβRII were slowly released from BiPPB-mIFNγ-tTβRII by hydrolysis using the plasma protease thrombin in vitro. Moreover, BiPPB-mIFNγ-tTβRII highly targeted to fibrotic liver tissues, markedly ameliorated liver morphology and fibrotic responses in chronic liver fibrosis mice by both inhibiting the phosphorylation of Smad2/3 and inducing the expression of Smad7. Meanwhile, BiPPB-mIFNγ-tTβRII markedly reduced the deposition of collagen fibrils and expression of fibrosis-related proteins in acute liver fibrosis mice. Furthermore, BiPPB-mIFNγ-tTβRII showed a good safety performance in both liver fibrosis mice. Taken together, BiPPB-mIFNγ-tTβRII improved the in vivo anti-liver fibrotic activity due to its high fibrotic liver-targeting potential and the dual inhibition of the TGF-β1/Smad signaling pathway, which may be a potential candidate for targeting therapy on liver fibrosis. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "WRH-2412 alleviates the progression of hepatocellular carcinoma through regulation of TGF-β/β-catenin/α-SMA pathway." The correction addresses the inclusion of incorrect figures in the previously published version of the article. The correct versions of the figures are provided, including graphs and photos that depict the chemical structure of WRH-2412, the effect of WRH-2412 on survival rate and AFP serum levels in HCC rats, the effect of WRH-2412 on serum liver markers levels, representative images of hepatic sections stained with H/E, the effect of WRH-2412 on TGF-β protein levels and liver sections stained with anti-TGF-β antibody, the effect of WRH-2412 on hepatic protein levels of E-cadherin, β-catenin, and SMAD4, and the effect of WRH-2412 on vascular invasion markers. The authors take no responsibility for the errors, and the online version of the article has been corrected. [Extracted from the article]

Background: Andrographolide (Andro) is a diterpenoid derived from Andrographis paniculate, which has anti-inflammatory, antibacterial, antiviral and hepatoprotective activities. Gram-negative bacterial infections can cause varying degrees of liver injury in chickens, although Andro has been shown to have a protective effect on the liver, its underlying mechanism of action and effects on liver proteins are not known. Methods: The toxicity of Andro on the viability of leghorn male hepatoma (LMH) cells at different concentrations and times was analyzed by CCK-8 assays. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in the culture supernatants were measured using an automatic biochemical analyzer to evaluate the protective effect of androscopolide on LPS-induced injury of LMH cells. Subsequently, TMT proteomics analysis were performed on the negative control group (NC group), LPS, and LPS-Andro groups, and bioinformatics analysis was performed on the differentially expressed proteins (DEPs). Results: It was found that Andro reduced ALT and AST levels in the cell supernatant and alleviated LPS-induced injury in LMH cells. Proteomic analysis identified 50 and 166 differentially expressed proteins in the LPS vs. NC group and LPS-Andro vs. LPS group, respectively. Andro may be involved in steroid metabolic processes, negative regulation of MAPK cascade, oxidative stress, and other processes to protect against LPS-induced liver injury. Conclusions: Andro protects against LPS-induced liver injury, HMGCS1, HMGCR, FDPS, PBK, CAV1, PRDX1, PRDX4, and PRDX6, which were identified by differential proteomics, may be the targets of Andro. Our study may provide new theoretical support for Andro protection against liver injury. [ABSTRACT FROM AUTHOR]

Harmful algal bloom toxin microcystin has been associated with metabolic dysfunction-associated steatotic liver disease (MASLD) progression and hepatocellular carcinoma, though the mechanisms remain unclear. Using an established mouse model of MASLD, we show that the NLRP3–Hsp70–TLR4 axis drives in part the inflammation of the liver lobule that results in the progression of MASLD to metabolic dysfunction-associated steatohepatitis (MASH). Results showed that mice deficient in NLRP3 exhibited decreased MASH pathology, blocked Hsp70 expression, and co-binding with NLRP3, a crucial protein component of the liver inflammasome. Hsp70, both in the liver lobule and extracellularly released in the liver vasculature, acted as a ligand to TLR4 in the liver, primarily in hepatocytes to activate the NF-κB pathway, ultimately leading to hepatic cell death and necroptosis, a crucial pathology of MASH progression. The above studies show a novel insight into an inflammasome-triggered Hsp70-mediated inflammation that may have broader implications in MASLD pathology. MASLD to MASH progression often requires multiple hits. One of the mediators of progressive MASLD is environmental toxins. In this research report, we show for the first time a novel mechanism where microcystin-LR, an environmental toxin, advances MASLD to MASH by triggering the release of Hsp70 as a DAMP to activate TLR4-induced inflammation in the liver. [ABSTRACT FROM AUTHOR]

Each tissue has a dominant set of functional proteins required to mediate tissue-specific functions. Epigenetic modifications, transcription, and translational efficiency control tissue-dominant protein production. However, the coordination of these regulatory mechanisms to achieve such tissue-specific protein production remains unclear. Here, we analyzed the DNA methylome, transcriptome, and proteome in mouse liver and skeletal muscle. We found that DNA hypomethylation at promoter regions is globally associated with liver-dominant or skeletal muscle-dominant functional protein production within each tissue, as well as with genes encoding proteins involved in ubiquitous functions in both tissues. Thus, genes encoding liver-dominant proteins, such as those involved in glycolysis or gluconeogenesis, the urea cycle, complement and coagulation systems, enzymes of tryptophan metabolism, and cytochrome P450-related metabolism, were hypomethylated in the liver, whereas those encoding-skeletal muscle-dominant proteins, such as those involved in sarcomere organization, were hypomethylated in the skeletal muscle. Thus, DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins. [ABSTRACT FROM AUTHOR]

This document is a summary of a special issue of the journal Viruses titled "Hepatitis B Virus: New Breakthroughs to Conquer an Ancient Disease." The special issue focuses on various aspects of hepatitis B, including its biology, transmission, replication, pathogenesis, potential cure, and implementation of optimal care. The articles highlight the need for a multidisciplinary approach to address the effects of HBV-associated disease and its psychosocial impacts. Topics covered include the role of viral proteins in liver disease, potential pathways for cancer induction, the impact of comorbidities on pathogenesis, and strategies for expanding care and vaccination coverage. The goal of the special issue is to contribute to the understanding of hepatitis B and work towards its elimination as a public health threat. [Extracted from the article]

Background: Andrographolide (Andro) is a diterpenoid derived from Andrographis paniculate, which has anti-inflammatory, antibacterial, antiviral and hepatoprotective activities. Gram-negative bacterial infections can cause varying degrees of liver injury in chickens, although Andro has been shown to have a protective effect on the liver, its underlying mechanism of action and effects on liver proteins are not known. Methods: The toxicity of Andro on the viability of leghorn male hepatoma (LMH) cells at different concentrations and times was analyzed by CCK-8 assays. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in the culture supernatants were measured using an automatic biochemical analyzer to evaluate the protective effect of androscopolide on LPS-induced injury of LMH cells. Subsequently, TMT proteomics analysis were performed on the negative control group (NC group), LPS, and LPS-Andro groups, and bioinformatics analysis was performed on the differentially expressed proteins (DEPs). Results: It was found that Andro reduced ALT and AST levels in the cell supernatant and alleviated LPS-induced injury in LMH cells. Proteomic analysis identified 50 and 166 differentially expressed proteins in the LPS vs. NC group and LPS-Andro vs. LPS group, respectively. Andro may be involved in steroid metabolic processes, negative regulation of MAPK cascade, oxidative stress, and other processes to protect against LPS-induced liver injury. Conclusions: Andro protects against LPS-induced liver injury, HMGCS1, HMGCR, FDPS, PBK, CAV1, PRDX1, PRDX4, and PRDX6, which were identified by differential proteomics, may be the targets of Andro. Our study may provide new theoretical support for Andro protection against liver injury. [ABSTRACT FROM AUTHOR]

Suaeda vermiculata Forssk. ex JF Gmel. (SV), a traditional known plant, has shown in vitro cytotoxic activity against HepG2 and HepG-2/ADR (doxorubicin-resistant cells) liver cell carcinoma cell lines, as well as hepatoprotection against paracetamol and carbon tetrachloride (CCl4)-induced liver injury. The current study evaluated the protective effect of SV, administered against N-diethylnitrosamine (NDEA)-induced HCC in rats. The possible modulatory effect of SV on the PI3K/HIF-1α/c-MYC/iNOS pathway was investigated. Sixty male adult albino rats (200 ± 10 g) were equally classified into five groups. Group I served as a control; Group 2 (SV control group) received SV (p.o., 200 mg/kg body weight); Group 3 (NDEA-administered rats) received freshly prepared NDEA solution (100 mg/L); and Groups 4 and 5 received simultaneously, for 16 weeks, NDEA + SV extract (100 and 200 mg/kg, orally). NDEA-treated rats displayed significant increases in serum levels of AFP, CEA, PI3K, malondialdehyde (MDA), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGFR), with increased liver tissue protein expression of fibrinogen concomitant and significantly decreased concentrations of antioxidant parameters (catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH)) in comparison to normal rats. On the flip side, AFP, CEA, PI3K, MDA, EGFR, and VEGFR serum levels were significantly reduced in rats that received NDEA with SV, both at low (SV LD) and high (SV HD) doses, accompanied by significant improvements in antioxidant parameters compared to the NDEA-treated group. Conclusions: SV possesses a significant hepatoprotective effect against NDEA-induced HCC via inhibiting the PI3K/HIF-1α/c-MYC/iNOS pathway, suggesting that SV could be a promising hepatocellular carcinoma treatment. [ABSTRACT FROM AUTHOR]

Cytochromes P450 (CYPs or P450s) are important enzymes for drug metabolism. Tree shrews are non-primate animal species used in various fields of biomedical research, including infection (especially hepatitis viruses), depression, and myopia. A recent tree shrew genome analysis indicated that the sequences and the numbers of P450 genes are similar to those of humans; however, P450s have not been adequately identified and analysed in this species. In this study, a novel CYP2E1 was isolated from tree shrew liver and was characterised in comparison with human, dog, and pig CYP2E1. Tree shrew CYP2E1 and human CYP2E1 showed high amino acid sequence identity (83%) and were closely related in a phylogenetic tree. Gene and genome structures of CYP2E1 were generally similar in humans, dogs, pigs, and tree shrews. Tissue expression patterns showed that tree shrew CYP2E1 mRNA was predominantly expressed in liver, just as for dog and pig CYP2E1 mRNAs. In tree shrews, recombinant CYP2E1 protein and liver microsomes metabolised chlorzoxazone and p-nitrophenol, probe substrates of human CYP2E1, just as they do in dogs and pigs. These results suggest that tree shrew CYP2E1 encodes a functional drug-metabolising enzyme that plays a role in the liver, similar to human CYP2E1. [ABSTRACT FROM AUTHOR]

Inosine 5′-monophoaphate (IMP) is a food additive that promotes serious lipohyperplasia in the liver of C57/KsJ-db/db (db/db) mice. Thus, IMP taken orally by healthy mice might also damage their health. To date, how IMP affects health after being taken by healthy animals is still unclear. Therefore, we investigated the health of C57BL/6J mice affected by IMP intake. Our data revealed that C57BL/6J mice administered 255 μM IMP daily via oral gavage for 4 months caused hyperlipidemia and an increase in body fat rate. The expressions of acetyl-CoA carboxylase 1 (ACC1) and phosphorylated acetyl-CoA carboxylase 2 (ACC2) in hepatocytes increased though the administration of IMP, promoting the phosphorylation of adenosine 5′-monophosphate-activated protein kinase (AMPK). The conversion of acetyl-CoA into triglycerides (TGs) was promoted by ACC1. These TGs were transported from the hepatocytes to avoid the development of non-alcoholic fatty liver disease (NAFLD), causing a deficiency of acetyl-CoA in the liver, and then, the increased phosphorylated ACC2 promoted the cytoplasm fatty acids entering the mitochondria and conversion into acetyl-CoA through the fatty acid β-oxidation pathway, causing a deficiency in fatty acids. Therefore, the liver showed enhanced absorption of exogenous fatty acids, which were converted into TGs, causing lipohyperplasia. In conclusion, an excessive IMP intake promotes metabolic dysfunction in adipose tissue. [ABSTRACT FROM AUTHOR]

We aimed to investigate the protective effect of FTY‐720 on liver injury and explore its potential mechanism in diabetic mice. The diabetic mouse model was induced with streptozotocin and FTY‐720 was administered for 12 weeks. We assayed biocharacters and liver function and used histopathology staining to evaluate the protective effects of FTY‐720 against diabetic liver injury. Levels of oxidative stress and inflammation in the liver were observed. mRNA and protein levels of essential enzymes for glucose metabolism were quantified in the liver and the protein expression of TLR4, HIF1α and NF‐κB was determined. In vivo results revealed that FTY‐720 significantly lowered blood glucose and lipids and improved liver function and alleviated liver fibrosis in diabetic mice. FTY‐720 reduced oxidative stress and inflammation, with the increased catalase activity and reduced levels of malondialdehyde, myeloperoxidase, IL‐1β, IL‐6, TNF‐α, TGF‐β, and MCP1. Furthermore, FTY‐720 modulated glucose metabolism in liver and elevated the ATP production, showing the promotion of glycogenesis and glycolysis and inhibition of gluconeogenesis. Moreover, FTY‐720 inhibited the expression of TLR4 and HIF1α, contributing to restoration of liver function. In conclusion, FTY‐720 ameliorates diabetes‐induced liver injury and improves glucose homeostasis by inhibiting oxidative stress and inflammation and may be a promise drug for treatment of liver disease. [ABSTRACT FROM AUTHOR]

The liver and ovary perform a vital role in egg production in hens. In the later laying period, the egg-laying capacity of female hens, particularly that of local breeds, declines significantly. Hence, it is essential to study the features and conditions of the ovary and liver during this period. In this research, we characterized the proteins and metabolites in the liver and ovary of 55-week-old Guangyuan gray chickens (Group G) and Hy-Line gray chickens (Group H) by using liquid chromatography chip/electrospray ionization quadruple time-of-flight/mass spectroscopy (LC-MS/MS). In total, 139 differentially expressed proteins (DEPs) and 186 differential metabolites (DMs) were identified in the liver, and 139 DEPs and 36 DMs were identified in the ovary. The upregulated DEPs and DMs in both the liver and ovary of Group G were primarily enriched in pathways involved in amino acid and carbohydrate metabolism. This suggests that energy metabolism was highly active in the Guangyuan gray chickens. In contrast, the upregulated DEPs and DMs in Group H were mainly enriched in pathways associated with lipid metabolism, which may explain the higher egg production and the higher fatty liver rate in Hy-Line gray hens in the later laying period. Additionally, it was found that the unique protein s-(hydroxymethyl) glutathione dehydrogenase (ADH4) in Group G was implicated in functions such as fatty acid degradation, glycolysis, and pyruvate metabolism, whereas the unique proteins, steroid sulfatase (STS), glucosylceramidase (LOC107050229), and phospholipase A2 Group XV (PLA2G15), in Group H were involved in the metabolism of steroid hormones and glycerol phosphate. In conclusion, variations in how carbohydrates, lipids, and amino acids are processed in the liver and ovary of local breeds of chicken and commercial hens towards the end of their laying period could explain the disparities in their egg production abilities. [ABSTRACT FROM AUTHOR]

Objective: To investigate the influence of salidroside (Sal) on liver injury in nude mice with colon cancer SW480 cells by regulating adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (m TOR)/Unc51-like kinase 1 (ULK1) signaling pathway. Methods: Liver metastasis nude mice model was established by subcutaneous injection of SW480 cell suspension, and the nude mice after modeling were randomly grouped into model group, low-dose Sal (Sal-L, 50 mg/kg Sal) group, medium-dose Sal (Sal-M, 100 mg/kg Sal) group, high-dose Sal (Sal-H, 200 mg/kg Sal) group, Sal-H+AMPK inhibitor (Compound C, 200mg/kg Sal+10 mg/kg Compound C) group, and nude mice not inoculated with SW480 cell suspension were performed as the control group. Blood was collected from the abdominal aorta, the serum levels of alanine aminotransferase (AST) and aspartate aminotransferase (ALT) in nude mice were observed. The nude mice were sacrificed, and the number of liver metastases and liver quality were detected. HE staining was used to observe the pathological changes of liver tissue. The expression levels of AMPK, m TOR and ULK1 m RNA in liver tissue were detected by qRT-PCR. Western blot was used to detect the expression of autophagy (Beclin1, p62) proteins and pathway-related proteins in liver tissue. Results: Compared with the control group, liver metastases appeared in the nude mice of the model group, the liver weight, levels of AST and ALT, the m TORm RNA,ULK1 m RNA, and the expression of p62 were obviously increased (P＜0. 05). The m RNA and protein expressions of Beclin1 and AMPK were obviously decreased (P＜0. 05). Compared with the model group, the number of liver metastases, liver weight, levels of AST and ALT, the m TORm RNA,ULK1 m RNA, and the expression of p62in the Sal-L, Sal-M, and Sal-H groups were obviously decreased (P＜0. 05). The m RNA and protein expressions of Beclin1 and AMPK were obviously increased (P＜0. 05). Compared with the Sal-H group, the number of liver metastases, liver weight, levels of AST and ALT, the m TORm RNA,ULK1 m RNA, and the expression of p62 in the Sal-H+Compound C group were obviously increased (P＜0. 05). The m RNA and protein expressions of Beclin1 and AMPK were obviously decreased (P＜0. 05). Conclusion: Sal can protect the liver of nude mice by reducing the formation of liver metastases in nude mice, and its mechanism may be related to the activation of AMPK/m TOR/ULK1 signaling pathway, and the promotion of liver autophagy. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are nanoscale particles that facilitate intercellular communication. They are regarded as a promising natural drug delivery system for transporting and delivering bioactive macromolecules to target cells. Recently, researchers have engineered EVs with FKBP12/FRB heterodimerization domains that interact with rapamycin to load and deliver exogenous proteins for both in vitro and in vivo applications. In this study, we examined the tissue distribution of EVs using near‐infrared fluorescent imaging. We evaluated the effectiveness of EV‐mediated delivery of Cre recombinase specifically to hepatocytes in the livers of Ai9 Cre‐loxP reporter mice. Intravenous injection resulted in more efficient Cre protein delivery to the liver than intraperitoneal injections. Depleting liver‐resident macrophages with clodronate‐encapsulated liposome pre‐treatment did not enhance EV‐mediated Cre delivery to hepatocytes. Moreover, we demonstrated that multiple intravenous injections of Cre‐EVs facilitated functional Cre delivery to hepatocytes. To the best of our knowledge, this is the first study to simultaneously investigate the tissue distribution of FKBP12/FRB‐engineered EVs and their subsequent intracellular protein delivery in Ai9 Cre‐loxP reporter mice. These insights can inform preclinical research and contribute to developing next‐generation EV‐based platforms for delivering therapeutic proteins or genome editing technologies targeting the liver. [ABSTRACT FROM AUTHOR]

Simple Summary: Biogenic amines (BAs) originate from amino acid decarboxylation and are commonly used as markers of spoilage and putrefaction in food and feed, especially in improperly handled animal products. Detoxification of BAs occurs mainly in the intestinal tract by amine oxidases, but some factors may facilitate intestinal absorption. When consumed in high concentrations, BAs can impair colonic epithelium, intestinal functionality, and may cause other toxicological effects. This study aimed to evaluate the effects of diets based on hydrolyzed protein (hydrolyzed chicken liver powder—HCLP) or conventional intact protein (poultry by-product meal—PBPM) with increasing protein concentrations (24, 32, and 40%) on the consumption and metabolism of biogenic amines in adult dogs. The results showed that PBPM had higher concentrations of putrefactive BAs, as well as the diets with its inclusion. As a result, dogs consumed higher concentrations of putrefactive BAs with diets containing PBPM and higher protein concentrations. Despite the difference in BAs concentrations in the protein sources, there was only an increase in the fecal excretion of phenylethylamine in the HCLP32 and HCLP40 diets and the enzymatic activity of monoamine oxidase in the HCLP24 and PBPM32 diets. Our findings indicate that the inclusion of HCLP reduces the consumption of putrefactive BAs and that the BAs detoxification system is highly efficient in the intestinal tract of dogs. Biogenic amines are synthesized through the bacterial decarboxylation of amino acids, commonly found in high levels in animal by-product meals due to spoilage. Furthermore, biogenic amines and other metabolites can be produced by the fermentation of proteins in the hindgut according to the protein source and concentration of crude protein (CP) in the diet. Thus, this study aimed to evaluate two protein sources (poultry by-product meal (PBPM) and hydrolyzed chicken liver powder (HCLP)) and three CP concentrations (24, 32, and 40%) and their effects on the consumption and fecal excretion of biogenic amines, plasma monoamine oxidase (MAO) and diamine oxidase (DAO) activities, and total antioxidant capacity (TAC) of healthy adult dogs after 30 days of feeding the experimental diets. Twelve dogs were randomly distributed into six treatments (n = 6/treatment): PBPM24 (PBPM with 24% CP); PBPM32 (PBPM with 32% CP); PBPM40 (PBPM with 40% CP); HCLP24 (HCLP with 24% CP); HCLP32 (HCLP with 32% CP); HCLP40 (HCLP with 40% CP). The PBPM and PBPM-based diets had higher concentrations of putrescine, cadaverine, tyramine, histamine, agmatine, and total biogenic amines. In contrast, HCLP and HCLP-based diets contained higher concentrations of spermidine, phenylethylamine, and spermine. The PBPM and PBPM-diets had higher biogenic amine index (BAI) indicating lower quality due to the high content of putrescine, cadaverine and tyramine. Dogs fed diets with PBPM and higher protein concentrations consumed more putrescine, cadaverine, tyramine, agmatine, and total amines (p < 0.0001), while dogs fed with HCLP consumed more spermidine, phenylethylamine, and spermine (p < 0.0001). Fecal excretion of phenylethylamine was greater in dogs fed HCLP32 and HCLP40 diets (p = 0.045). Dogs fed with HCLP tended to excrete more spermidine and tryptamine via feces, while higher protein concentrations tended to increase fecal excretion of cadaverine (p < 0.10). Plasma MAO activity was higher in dogs fed HCLP24 and PBPM32 diets (p = 0.024). The plasma activities of DAO and TAC were not different between diets (p > 0.05). Although we did not evaluate the intestinal activities of MAO and DAO, our results suggest that healthy adult dogs have an efficient deamination process on the gut epithelium. [ABSTRACT FROM AUTHOR]

Oral L-arginine supplements are popular mainly for their nitric oxide mediated vasodilation, but their physiological impact is not fully known. L-arginine is a substrate of several enzymes including arginase, nitric oxide synthase, arginine decarboxylase, and arginine: glycine amidinotransferase (AGAT). We have published a study on the physiological impact of oral L- and D-arginine at 500 mg/kg/day for 4 wks in male Sprague-Dawley rats. We investigated the effects of oral L-arginine and D-arginine at a higher dose of 1000 mg/kg/d for a longer treatment duration of 16 wks in 9-week-old male Sprague-Dawley rats. We measured the expression and activity of L-arginine metabolizing enzymes, and levels of their metabolites in the plasma and various organs. L-arginine did not affect the levels of L-arginine and L-lysine in the plasma and various organs. L-arginine decreased arginase protein expression in the upper small intestine, and arginase activity in the plasma. It also decreased AGAT protein expression in the liver, and creatinine levels in the urine. L-arginine altered arginine decarboxylase protein expression in the upper small intestine and liver, with increased total polyamines plasma levels. Endothelial nitric oxide synthase protein was increased with D-arginine, the presumed metabolically inert isomer, but not L-arginine. In conclusion, oral L-arginine and D-arginine at a higher dose and longer treatment duration significantly altered various enzymes and metabolites in the arginine metabolic pathways, which differed from alterations produced by a lower dose shorter duration treatment published earlier. Further studies with differing doses and duration would allow for a better understanding of oral L-arginine uses, and evidence based safe and effective dose range and duration. [ABSTRACT FROM AUTHOR]

Drug-metabolizing enzymes (DMEs) and transporters play a major role in drug efficacy and safety. They are regulated at multiple levels and by multiple factors. Estimating their expression and activity could contribute to predicting drug pharmacokinetics and their regulation by drugs or pathophysiological situations. Determining the expression of these proteins in the liver, intestine, and kidney requires the collection of biopsy specimens. Instead, the isolation of extracellular vesicles (EVs), which are nanovesicles released by most cells and present in biological fluids, could deliver this information in a less invasive way. In this article, we review the use of EVs as surrogates for the expression and activity of DMEs, uptake, and efflux transporters. Preliminary evidence has been provided for a correlation between the expression of some enzymes and transporters in EVs and the tissue of origin. In some cases, data obtained in EVs reflect the induction of phase I-DMEs in the tissues. Further studies are required to elucidate to what extent the regulation of other DMEs and transporters in the tissues reflects in the EV cargo. If an association between tissues and their EVs is firmly established, EVs may represent a significant advancement toward precision therapy based on the biotransformation and excretion capacity of each individual. [ABSTRACT FROM AUTHOR]

Objective: To investigate the therapeutic effect and possible mechanism of sinomenine(SIN) on type 2 diabetic(T2DM) mice with liver cancer(HCC). Methods: Eight-week-old male BALB/c mice(20-25 g) were divided into Control, T2DM+HCC,SIN-L, SIN-M and SIN-H group. Mice in the Control group were fed normally, and mice in other groups were injected intraperitoneally with streptozotocin(STZ) and inoculated with hepatocellular carcinoma cells(H22) in liver parenchyma to establish T2DM combined with HCC mice model. Mice in the SIN-L, SIN-M and SIN-H group were intraperitoneally injected with 10, 20 and 40 mg/kg/d of sinomenine, respectively. Mice in the Control group and T2DM+HCC group were intraperitoneally injected with 0.5 m L of normal saline respectively. All the mice were treated for 21 days. 24 hours after the last administration, the liver index was calculated and fasting blood glucose(FPG), fasting insulin(FINS), serum total cholesterol(TC), triglyceride(TG)], alanine aminotransferase(ALT), aspartate aminotransferase(AST) and lactate dehydrogenase(LDH), liver superoxide dismutase(SOD), catalase(CAT), Glutathione peroxidase(GSH-PX)and malondialdehyde(MDA) levels were detected. Liver morphology was observed by hematoxylin and eosin(HE) staining. The protein expression of BCL2, BAX, P53, signal transducer and activator of transcription 3(STAT3), cytokine signal inhibitor 3(SOCS3) and sterol regulatory element binding protein-1(SREBP-1) in liver tissue were detected by Western blot. Results: The median survival time of T2DM+HCC group, SIN-L group, SIN-M group and SIN-H group was 25, 32, 35 and 41 days respectively(P＜0.001), the median survival time of mice extended with the increase of sinomenine concentration. Compared with T2DM+HCC group, the levels of FPG, FINS, TC and TG in SIN-L, SIN-M and SIN-H group decreased, serum ALT, AST and LDH levels decreased, the basic rules of hepatic cell arrangement, edema, vacuolar degeneration, inflammatory cell infiltration and other lesions were significantly reduced, liver index decreased, liver SOD, CAT and GSH-PX levels increased, liver MDA level decreased, liver BCL2 protein expression decreased, liver BAX and P53 protein expression increased(P＜0.05). Compared with T2DM+HCC group, the expression of p-STAT3(Tyr705), SOCS3 and SREBP-1 protein in liver of SIN-L, SIN-M and SIN-H group decreased in a dose-dependent manner(P＜0.05). Conclusion: Sinomenine can effectively prolong the survival time of type 2 diabetic mice with liver cancer, improve the blood glucose and lipid levels as well as the live function, and inhibit the growth of cancer cells, which may be related to the inhibition of STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

The nutritional role of zinc (Zn) and boron (B) in the plant-animal-human food chain is highly topical worldwide research. Our data indicated that Zn-B complex (ZBC)-based dietary supplements can be used as stable non-toxic formulations, with high intestinal absorption rate, inducing alpha2-macroglobulin (A2M) expression for longevity and healthy life. ZBC is metabolized by hydrolysis, mainly at the absorption site (intestinal level), and most of it is excreted in the urine. Within seven hours from the administration in mice, almost the entire amount of orally absorbed ZBC is eliminated in a metabolized form. The highest amount of A2M protein in mouse liver was determined by immunoabsorbance assay in the chronic experiment (1000mg/kg of ZBC), followed by the subchronic experiment (at the same dose of ZBC), and by the acute experiment (5000mg/kg of ZBC). [ABSTRACT FROM AUTHOR]

Calorie restriction (CR) extends life span by modulating the mechanisms involved in aging. We quantified the hepatic proteome of male C57BL/6 mice exposed to graded levels of CR (0%–40% CR) for 3 months, and evaluated which signaling pathways were most affected. The metabolic pathways most significantly stimulated by the increase in CR, included the glycolysis/gluconeogenesis pathway, the pentose phosphate pathway, the fatty acid degradation pathway, the valine, leucine, and isoleucine degradation pathway, and the lysine degradation pathway. The metabolism of xenobiotics by cytochrome P450 pathway was activated and feminized by increased CR, while production in major urinary proteins (Mups) was strongly reduced, consistent with a reduced investment in reproduction as predicted by the disposable soma hypothesis. However, we found no evidence of increased somatic protection, and none of the 4 main pathways implied to be linked to the impact of CR on life span (insulin/insulin-like growth factor [IGF-1], nuclear factor-κB [NF-κB], mammalian Target of Rapamycin [mTOR], and sirtuins) as well as pathways in cancer, were significantly changed at the protein level in relation to the increase in CR level. This was despite previous work at the transcriptome level in the same individuals indicating such changes. On the other hand, we found Aldh2 , Aldh3a2 , and Aldh9a1 in carnitine biosynthesis and Acsl5 in carnitine shuttle system were up-regulated by increased CR, which are consistent with our previous work on metabolome of the same individuals. Overall, the patterns of protein expression were more consistent with a "clean cupboards" than a "disposable soma" interpretation. [ABSTRACT FROM AUTHOR]

This research intended to assess the energy metabolism indices (BHBA, NEFA and glucose) and evaluate the diagnostic relevance of oxidative stress indicators oxidant (MDA) and antioxidant (TAC and PON-1 enzyme), lipid profile and liver enzymes in pregnancy toxaemia in ewes. The study comprised a total number of 72 late pregnant ewes (14-20 weeks of gestation). Ewes were divided based on the result of clinical and biochemical findings (glucose and BHBA) into three groups; a clinical pregnant toxemic group (CPTG) (n=36), a subclinical PTG (n=20) and a control group (CG) (n=16). Blood samples were collected for each group and a panel of biochemical parameters was measured. Most of the biochemical markers showed notable variations in comparison with the control group (P < 0.05). BHBA, NEFA, MDA, Liver enzymes (ALT, AST and γGT), Triglycerides and VLDL in clinical and subclinical pregnant toxaemic groups showed a significant increase above normal values of control group (P < 0.05). Glucose, TAC, PON-1 enzyme, Cholesterol, HDL, LDL and serum proteins in clinical and subclinical pregnant toxaemic groups showed a significant decrease below normal values of control group (P < 0.05). Based on these findings, we suggest that monitoring changes in the presented energy metabolism indices, oxidant-antioxidant status, lipid profile, liver enzymes and protein assays in late pregnant ewes could be useful in early diagnosis of pregnancy toxaemia. The present study also showed that paraoxonase-1 enzyme (PON1) appears to hold potential as a biomarker for diagnosis of pregnancy toxaemia in ewes. [ABSTRACT FROM AUTHOR]