Hepatic Protein Research Articles

Ameliorative potential role of Rosmarinus officinalis extract on toxicity induced by etoposide in male albino rats.

The present work was showed to assess the effect of administration of rosemary extract on etoposide-induced toxicity, injury and proliferation in male rats were investigated. Forty male albino rats were arranged into four equal groups. 1st group, control; 2nd group, etoposide; 3rd group, co-treated rosemary & etoposide; 4th group, rosemary alone. In comparison to the control group, etoposide administration resulted in a significant increase in serum ALT, AST, ALP, total bilirubin, total protein, and gamma GT. In contrast; a significant decrease in albumin level in etoposide group as compared to G1. G3 revealed a significant decrease in AST, ALT, ALP, total protein and total bilirubin levels and a significant rise in albumin level when compared with G2. Serum levels of urea, creatinine, potassium ions, and chloride ions significantly increased; while sodium ions were significantly decreased in G2 when compared with G1. Also, there was an increase of MDA level for etoposide treated group with corresponding control rats. However, there was a remarkable significant decrease in SOD, GPX and CAT levels in G2 as compared to G1. There was a significant increase in serum hydrogen peroxide (H2O2) and Nitric oxide (NO) levels in group treated with etoposide when compared to control group. It was noticeable that administrated by rosemary alone either with etoposide had not any effect on the levels of H2O2 and Nitric oxide. Serum level of T3 and T4 was significantly increased in etoposide-administered rats in comparison with G1. The administration of rosemary, either alone or with etoposide, increased the serum levels of T3 and T4 significantly when compared to control rats. The gene expression analysis showed significant downregulation of hepatic SOD and GPx in (G2) when compared with (G1). The treatment with rosemary extract produced significant upregulation of the antioxidant enzymes mRNA SOD and GPx. MDA gene was increased in (G2) when contrasted with (G1). Treatment of the etoposide- induced rats with rosemary extract delivered significant decrease in MDA gene expression when compared with etoposide group. Rats treated with etoposide showed significant decline in hepatic Nrf2 protein expression, when compared with G1. While, supplementation of Etoposide- administered rats with the rosemary produced a significant elevation in hepatic Nrf2 protein levels. Additionally, the liver histological structure displayed noticeable degeneration and cellular infiltration in liver cells. It is possible to infer that rosemary has a potential role and that it should be researched as a natural component for etoposide-induced toxicity protection.

Long Non-Coding RNAs as Emerging Role in Prognosis of Alcohol Related Liver Disease

Chronic alcohol exposure significantly influences the prognosis and diagnosis of alcohol related liver disease (ALD), affecting gene expression and liver function. Hepatic proteins and non-coding RNAs are essential for many biological functions and disease progression. Regulatory processes associated with microRNAs and long non-coding RNAs (lncRNAs) are known enhanced by recent advances in RNA sequencing methods. This new importance of lncRNAs in hepatic disease progression encompasses their involvement in cellular growth, and regulation, necrosis, and the control of transcriptional factors. Regulation of cellular integrity and ECM accumulation are two of the many functions played by lncRNAs in hepatic fibrosis, a wound healing process characterized by the gradual formation of ECM during disease progression. In the context of hepatic disease progression, a multitude of lncRNAs actively participate in regulating cellular homeostasis, positioning them as potential therapeutic targets and valuable biomarkers in clinical practice. Acquiring insightful knowledge about the underlying biological processes and molecular mechanisms governing hepatic injuries is crucial for identifying specific and sensitive molecules that can facilitate hepatic regeneration. The studies are increasingly interested in understanding the function of lncRNAs in liver regeneration after long-term alcohol use. To better understand alcoholic liver disease clinically, this review seeks to clarify the predictive significance of lncRNAs regulatory factors in stimulating hepatic development and revitalization.

Analysis of Physical Parameters and Chemical Composition of Offal From Puławska Fattening Pigs Raised in Deep Litter and Slatted Floor Housing Systems

Abstract The objective of this study was to comparatively analyse the physical parameters, basic chemical composition and the macro- and microelement content of offal obtained from fattening pigs raised in deep litter and slatted floor housing systems. The experiment involved a group of 80 Puławska fatteners, including 40 pigs kept in deep-litter pens (group I) and 40 pigs in slatted pens without bedding (group II). Offal (tongues, kidneys, hearts, lungs and livers) was evaluated for weight, physical characteristics (pH45, pH24, WHC), chemical composition (water, protein, fat) and the content of minerals: macro- (K, Na, Mg, Ca) and microelements (Zn, Fe, Mn, Cu). Based on the results obtained, associations were found between housing system and basic chemical composition of some offal, i.e. percentage of water (slatted floor<deep litter) and protein (slatted floor>deep litter) in lungs, content of protein (slatted floor>deep litter) and fat (slatted floor<deep litter) in liver, and content of fat in heart (slatted floor<deep litter). The amount of macro- and microelements was significantly differentiated by the housing system with regard to the kidneys: potassium, magnesium, calcium and manganese (slatted floor<deep litter), sodium (slatted floor>deep litter); lungs: sodium (slatted floor>deep litter), potassium (slatted floor<deep litter); and liver: iron (slatted floor>deep litter) and copper (slatted floor<deep litter). In general, the housing system of fattening pigs modified the physical parameters and chemical composition of the analysed offal.

Depletion of ApoA5 aggravates spontaneous and diet-induced nonalcoholic fatty liver disease by reducing hepatic NR1D1 in hamsters.

Background: ApoA5 mainly synthesized and secreted by liver is a key modulator of lipoprotein lipase (LPL) activity and triglyceride-rich lipoproteins (TRLs). Although the role of ApoA5 in extrahepatic triglyceride (TG) metabolism in circulation has been well documented, the relationship between ApoA5 and nonalcoholic fatty liver disease (NAFLD) remains incompletely understood and the underlying molecular mechanism still needs to be elucidated. Methods: We used CRISPR/Cas9 gene editing to delete Apoa5 gene from Syrian golden hamster, a small rodent model replicating human metabolic features. Then, the ApoA5-deficient (ApoA5-/-) hamsters were used to investigate NAFLD with or without challenging a high fat diet (HFD). Results: ApoA5-/- hamsters exhibited hypertriglyceridemia (HTG) with markedly elevated TG levels at 2300 mg/dL and hepatic steatosis on a regular chow diet, accompanied with an increase in the expression levels of genes regulating lipolysis and small adipocytes in the adipose tissue. An HFD challenge predisposed ApoA5-/- hamsters to severe HTG (sHTG) and nonalcoholic steatohepatitis (NASH). Mechanistic studies in vitro and in vivo revealed that targeting ApoA5 disrupted NR1D1 mRNA stability in the HepG2 cells and the liver to reduce both mRNA and protein levels of NR1D1, respectively. Overexpression of human NR1D1 by adeno-associated virus 8 (AAV8) in the livers of ApoA5-/- hamsters significantly ameliorated fatty liver without affecting plasma lipid levels. Moreover, restoration of hepatic ApoA5 or activation of UCP1 in brown adipose tissue (BAT) by cold exposure or CL316243 administration could significantly correct sHTG and hepatic steatosis in ApoA5-/- hamsters. Conclusions: Our data demonstrate that HTG caused by ApoA5 deficiency in hamsters is sufficient to elicit hepatic steatosis and HFD aggravates NAFLD by reducing hepatic NR1D1 mRNA and protein levels, which provides a mechanistic link between ApoA5 and NAFLD and suggests the new insights into the potential therapeutic approaches for the treatment of HTG and the related disorders due to ApoA5 deficiency in the clinical trials in future.

Antioxidant Effect of Ethanol Extract of C. sativus on Streptozotocin-Induced Diabetic Rat Liver

The present study investigated the antioxidant effect of ethanol extract of Cucumis sativus on streptozotocin (STZ)-induced diabetic rat liver. Adult male Wistar albino rats (n = 25, mean weight = 215 ± 15 g) were randomly assigned to five groups of 5 rats each: normal control, diabetic control, metformin, 200 mg/kg body weight (bwt) extract and 300 mg/kg bwt extract groups. Diabetes mellitus was induced in the rats via intraperitoneal injection of 50 mg/kg bwt STZ. The diabetic rats were then treated for 21 days with either metformin (50 mg/kg bwt) or the extract at doses of 200 and 300 mg/kg bwt, respectively. Activities of antioxidant enzymes such as catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) as well as antioxidant molecules like retinoic acid, ascorbic acid and α-tocopherol were evaluated in liver homogenate. The results showed that induction of diabetes mellitus with STZ significantly increased the fasting blood glucose (FBG) concentrations of the rats (p < 0.05). However, treatment of the diabetic rats with the extract markedly reduced the FBG concentration and body weights of rats (p < 0.05). Treatment of diabetic Wistar rats with ethanol extract of C. sativus significantly increased activities of the antioxidant enzymes and molecules as well as concentrations of nitric oxide (NO), but it markedly reduced the concentrations of hepatic total protein (TP) and malondialdehyde (MDA) (p < 0.05). These results suggest that ethanol extract of the medicinal plant can enhance antioxidant defense in the liver of STZ-induced diabetic rats.

Irg1/itaconate activates Nrf2/HO-1 pathway and mitigates septic liver injury in mice

Objectives: Immune-responsive gene 1 ( Irg1)-catalyzed production of itaconate is a bioactive metabolite with antibacterial, anti-inflammatory and antioxidant properties. Liver injury is closely related to poor outcomes in septic patients, while prevention of liver injury is essential for the pharmacological control of sepsis. This study investigated the pathological and pharmacological significance of Irg1/itaconate in septic liver injury. Methods: Septic liver injury was induced in mice by injecting lipopolysaccharide (LPS; 15 mg/kg) intraperitoneally. The hepatic mRNA and protein contents of Irg1 were detected. To investigate the pathological meaning of Irg1, septic liver injury was induced in Irg1 knockout mice and their wild-type (WT) littermates, and the degree of liver injury, hepatic inflammation, oxidative stress and the activation of nuclear erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) were subsequently determined. Finally, to explore the gene’s pharmacological potential, 4-octyl itaconate (4-OI; 50 mg/kg), a derivative of itaconate that could cross cell membranes, was administered intraperitoneally. The mobilization of Nrf2/HO-1 and liver injury were then evaluated. Results: The level of Irg1 expression was dramatically enhanced in mice with septic liver injury. Additionally, Irg1 deletion leaded to higher ALT and AST levels, elevated inflammatory and oxidative-stress indicators and compromised stimulation of the Nrf2/HO-1 pathway. However, administering 4-OI restored the Nrf2/HO-1 pathway which mitigated liver injury and inhibited hepatic inflammation and oxidative stress. Conclusions: The results figured that elevation of Irg1 might be a protective event that control the progress of septic liver injury, while 4-OI might have latent significance for the pharmaceutical intervention of septic liver injury.

Hepatoprotective efficacy of Lagenaria siceraria seeds oil against experimentally carbon tetrachloride-induced toxicity.

The liver is crucial for maintaining normal metabolism in the body. Various substances, such as toxic chemicals, drugs, and alcohol, can damage hepatocyte cells, leading to metabolic imbalances. The experiment aimed to determine the efficacy of Lagenaria siceraria seed oil (LSS) as a hepatoprotective agent against acute hepatotoxicity triggered by carbon tetrachloride (CCl4). A total of 20 rats were randomly separated into four groups. The control group: rats received 2 ml of distilled water orally, followed by 1.25 ml of olive oil intraperitoneally (i.p.) after 30 minutes. CCL4 group: rats were given a single intraperitoneal dose of 1.25 ml/kg b.w. of CCl4 in a 1:1 mixture with olive oil. Silymarin group: received 100 mg of silymarin per kg of b.w. diluted in 2 ml of distilled water orally, followed by CCl4 treatment after 30 minutes. LSS oil group: received LSS oil at 3g/kg b.w. orally, followed by CCl4 treatment after 30 minutes. Blood samples were collected to assess liver enzymes (AST, ALT, and ALP), proteins and bilirubin fractions, and redox status (catalase, reduced glutathione (GSH), and malondialdehyde (MDA)) were assessed in hepatic tissues. Changes in liver histopathological examination were also evaluated. In CCl4-treated rats, there was a significant increase in serum liver marker enzyme activity (ALP, AST, and ALT) along with a significant elevation (p < 0.05) in total bilirubin, indirect bilirubin, and direct bilirubin compared to the control rats. However, all these parameters decreased in the CCl4+ Silymarin and CCl4+LSS groups compared to CCl4-treated rats. There was a significant decline in total protein level and serum albumin in all experimental groups compared to the control, while globulin levels significantly increased in all experimental groups. There was a significant (p < 0.05) reduction in the level of GSH and catalase, with an increase in MDA level in CCl4 rats compared to other rats. Histopathological investigation of the LSS-treated group showed a hepatoprotective effect against CCl4. The study revealed that LSS oil has antioxidant activity against CCl4-induced toxicity.

Evaluation of Alanine Aminotransferase (Alt), Aspatate Aminotransferase (Ast) and Albumin (Alb) Among Blood Donors Infected with Hepatitis B and C Virus and Malaria in Ife Central Local Government Area, Ile Ife, Osun State, Nigeria

Liver diseases are responsible for over one and half million deaths annually and are characterized by permanent inflammatory processes that predispose to liver cancer.Liver function biomarkers are important indices that help in assessment of disease severity. Several studies reveal changes in activity level of liver enzymes and protein in the serum due to Plasmodium infection and Hepatitis infection. Liver enzymes play an important role in the assessment of liver function because of liver injury resulting in cytolysis or necrosis that causes release of enzymes into circulation. Infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are major global health problems. Moreover, infection with these viruses might associate with increased mortality rate as the infection may predisposes to the development of serious liver diseases such as liver cirrhosis, liver failure and hepatocellular carcinoma (HCC). The objectives of the study are to determine the prevalence Hepatitis B and C infections among blood donors, analyze the relationship between socio- demographic variables and Alanine aminotransferase (ALT), Aspatate aminotransferase (AST) and Albumin (ALB), analyze the relationship between malarial and ALT and AST and evaluate the effect of hepatitis infections on the liver cells. The study was conducted in Ife Central Local Government .Area, Ile Ife, Osun State. Five (5) ml of venous blood was obtained from each of 400 blood donors into plain bottles and labeled accordingly. Sera were separated from aliquots of the blood and screened for hepatitis-B and C surface antigens (HBsAg and HCV), and enzymes such as aspatate aminotransferase (AST) and alanine aminotransferase (ALT). The total percentage of elevated AST was 14(3.5%), ALT 15 (3.8%) and ALB 32(8.0%), while that the least AST 24 (6.0%), ALT 23 (4.8%) and ALB 6 (1.5%). There was significant difference between Occupation and ALT (p= 0.040) and ALB (p= 0.030), Marital status and AST (p=0.014), ALT (p= 0.012), ALB (p=0.014), there was no significant difference between HCV and AST (p=0.532), ALT (p=0.532), but with ALB (p=0.000). There was no significant difference between HBV and AST ( p=0.285), ALT (p=0.593) and ALB (p=0.033), the general hepatitis viral infection had no significant difference with AST ( p=0.516), ALT (p=0.516), but with ALB (p= 0.000), There was no significant difference between malaria infection and AST (p= 0.906), ALT (p= 0.999) and ALB (p= 0.718). in conclusion, although the prevalence hepatitis B and C viral infections was low and there was no significant relationship between the Alanine aminotransferase (ALT), Aspatate aminotransferase,(AST) and Hepatitis infection in the local government, critical screening of blood donors is of prime importance because they serve as an asymptomatic reservoirs and a potential source of transmission of these infections. The strengthening of creating awareness on the general public regarding HBsAg and HCV transmission and prevention should be of paramount important.

Hepatic transcript profiling in beef cattle: Effects of feeding endophyte-infected tall fescue seeds.

The objective of our study was to evaluate the effect of endophyte-infected tall fescue (E+) seeds intake on liver tissue transcriptome in growing Angus × Simmental steers and heifers through RNA-seq analysis. Normal weaned calves (~8 months old) received either endophyte-free tall fescue (E-; n = 3) or infected tall fescue (E+; n = 6) seeds for a 30-d period. The diet offered was ad libitum bermudagrass (Cynodon dactylon) hay combined with a nutritional supplement of 1.61 kg (DM basis) of E+ or E- tall fescue seeds, and 1.61 kg (DM basis) of energy/protein supplement pellets for a 30-d period. Dietary E+ tall fescue seeds were included in a rate of 20 μg of ergovaline/kg BW/day. Liver tissue was individually obtained through biopsy at d 30. After preparation and processing of the liver samples for RNA sequencing, we detected that several metabolic pathways were activated (i.e., upregulated) by the consumption of E+ tall fescue. Among them, oxidative phosphorylation, ribosome biogenesis, protein processing in endoplasmic reticulum and apoptosis, suggesting an active mechanism to cope against impairment in normal liver function. Interestingly, hepatic protein synthesis might increase due to E+ consumption. In addition, there was upregulation of "thermogenesis" KEGG pathway, showing a possible increase in energy expenditure in liver tissue due to consumption of E+ diet. Therefore, results from our study expand the current knowledge related to liver metabolism of growing beef cattle under tall fescue toxicosis.

The ameliorative mechanism of Lactiplantibacillus plantarum NJAU-01 against D-galactose induced oxidative stress: a hepatic proteomics and gut microbiota analysis.

Probiotic intervention is an effective strategy to alleviate oxidative stress-related diseases. Our previous studies found that Lactiplantibacillus plantarum NJAU-01 (NJAU-01) exhibited antioxidant effects in a D-galactose (D-gal)-induced aging mouse model. However, the underlying mechanism remains to be unveiled. This study was aimed to investigate the ameliorative effect and mechanism of NJAU-01 against oxidative stress induced by D-gal. The results showed that NJAU-01 could reverse the tendency of a slow body weight gain induced by D-gal. NJAU-01 relieved hepatic oxidative stress via increasing the hepatic total antioxidant capacity and antioxidant enzyme activities including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). Moreover, the malondialdehyde (MDA) level was reversed after NJAU-01 supplementation. The proteomic results showed that there were 201 differentially expressed proteins (DEPs) between NJAU-01 and D-gal groups. NJAU-01 regulated the expressions of glutathione S-transferase Mu 5 (Gstm5), glutathione S-transferase P2 (Gstp2) and NADH dehydrogenase 1α subcomplex subunit 7 (Ndufa7) related to oxidative stress, and autophagy protein 5 (Atg5) and plasma alpha-L-fucosidase (Fuca2) involved in autophagy, etc. 16S rDNA sequencing results showed that NJAU-01 supplementation could regulate the gut microbiota dysbiosis induced by D-gal via increasing the relative abundances of the phylum Firmicutes and the genus Lactobacillus and reducing the relative abundances of the phylum Bacteroidetes and the genera Lachnospiraceae_NK4A136_group as well as Prevotellaceae_UCG-001, etc.. Spearman correlation analysis results showed that the altered gut microbiota composition had a significant correlation with antioxidant enzyme activities and the DEPs related to oxidative stress. Overall, NJAU-01 alleviated hepatic oxidative stress induced by D-gal via manipulating the gut microbiota composition and hepatic protein expression profile.

The AMPK–mTOR Pathway Is Inhibited by Chaihu Shugan Powder, Which Relieves Nonalcoholic Steatohepatitis by Suppressing Autophagic Ferroptosis

Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), which is distinguished by the accumulation of fat in the liver, damage to liver cells, and inflammation. Chaihu Shugan powder (CSP), a renowned traditional Chinese medicine (TCM) blend extensively utilized in China to address liver disease, has demonstrated its efficacy in reducing lipid buildup and effectively combating inflammation. Hence, the primary objective of this research is to examine the impacts and possible mechanisms of CSP on NASH through assessments of liver histopathology, lipidomic analysis, and gene expression. To induce a mouse model of NASH, we employed a diet which deficient in methionine and choline, known as methionine–choline deficient (MCD) diet. Initially, we examined the impact of administering CSP to NASH mice by assessing the levels of serum and liver indicators. We found that CSP was able to reduce lipid buildup and inflammation in mice. In addition, a total of 1009 genes exhibited enrichment in both the autophagy and ferroptosis pathways. The liver protein levels of Adenosine monophosphate‐activated protein kinase–mammalian target of rapamycin (AMPK–mTOR)‐mediated autophagy and ferroptosis markers, such as p‐AMPKα/AMPKα, p‐mTOR/mTOR, Beclin‐1, microtubule associated protein 1 light chain 3 gamma (LC3), p62 (sequestosome 1 [SQSTM1/p62]), Kelch‐like ECH‐associated protein 1 (KEAP1), nuclear factor erythroid 2‐related factor 2 (Nrf‐2), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPX4), were restored by CSP. Furthermore, our findings indicated that the suppression of autophagy had a repressive impact on the occurrence of ferroptosis in the mouse model, indicating that autophagy activation likely plays a role in mediating ferroptosis in NASH.

An efficient strategy with a synergistic effect of hydrophilic and electrostatic interactions for simultaneous enrichment of N- and O-glycopeptides.

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.

Release of SMP30 in Extracellular Vesicles under Conditions of Ascorbic Acid Deficiency Is Involved with Acute Phase Response in ODS Rat.

Senescence marker protein-30 (SMP30) is a senescence marker molecule that exhibits lactonase activity in the ascorbic acid (AsA) biosynthesis pathway, except in primate mammals, including humans. Although numerous studies have shown that hepatic AsA deficiency causes acute-phase responses, details of the relationship between SMP30 expression and acute-phase responses in AsA-deficient conditions remain to be elucidated. Here, we investigated the effects of AsA deficiency on the relationship between SMP30 and acute liver injury in osteogenic disorder Shionogi (ODS) rats, which have a hereditary defect in AsA biosynthesis. Male-ODS rats (4 wk old) were pair-fed an AsA-free diet with distilled or 0.1% AsA-dissolved water for 14 d. Under AsA-deficient conditions, hepatic SMP30 protein level was decreased and liver injury markers, the serum aspartate aminotransferase/alanine transaminase ratio and cytokine-induced neutrophil chemoattractant-1 (CINC-1) concentration, were elevated. In contrast, SMP30 protein level in extracellular vesicles (EVs) was significantly increased in addition to the positive acute proteins haptoglobin and asialoglycoprotein receptor 1 (ASGPR1), hepatic-derived specific markers expression under AsA-deficient conditions. AsA deficiency also activated signal transducer and activator of transcription 3 (STAT3) which is linked to EVs release in the liver. These results suggest that the release of SMP30 in EVs by AsA deficiency is involved with acute-phase responses.

Portulaca oleracea L. extract relieve mice liver fibrosis by inhibiting TLR-4/NF-κB, Bcl-2/Bax and TGF-β1/Smad2 signalling transduction

Portulaca oleracea L. are annual herb, which has various pharmacological effects including hepatoprotective property. However, the effect of Portulaca oleracea L. (POL-1) in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and its mechanism of action have not been clarified. POL-1 ameliorated the CCl4-induced liver fibrosis in mice, as shown by decreased collagen deposition and the decreased expression of liver fibrosis marker collagen I and α-smooth muscle actin (α-SMA) mRNA. In addition, treatment with POL-1 suppressed the proliferation of activated human hepatic stellate cell line (LX-2). POL-1 inhibited the oxidative stress and inflammation in fibrotic livers of mice. Mechanistically, POL-1 inhibited the CCl4-induced expression of toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa-B (NF-κBp65) p65, Bcl2-associated X (Bax), transforming growth factor-β1 (TGF-β1) and drosophila mothers against decapentaplegic 2 (Smad2) proteins, upregulated B-cell lymphoma −2 (Bcl-2) proteins in livers of mice. These findings suggested that POL-1 attenuated liver fibrosis.

Systematic Multiomic Analysis of PKHD1L1 Gene Expression and Its Role as a Predicting Biomarker for Immune Cell Infiltration in Skin Cutaneous Melanoma and Lung Adenocarcinoma.

The identification of genetic factors that regulate the cancer immune microenvironment is important for understanding the mechanism of tumor progression and establishing an effective treatment strategy. Polycystic kidney and hepatic disease 1-like protein 1 (PKHD1L1) is a large transmembrane protein that is highly expressed in immune cells; however, its association with tumor progression remains unclear. Here, we systematically analyzed the clinical relevance of PKHD1L1 in the tumor microenvironment in multiple cancer types using various bioinformatic tools. We found that the PKHD1L1 mRNA expression levels were significantly lower in skin cutaneous melanoma (SKCM) and lung adenocarcinoma (LUAD) than in normal tissues. The decreased expression of PKHD1L1 was significantly associated with unfavorable overall survival (OS) in SKCM and LUAD. Additionally, PKHD1L1 expression was positively correlated with the levels of infiltrating B cells, cluster of differentiation (CD)-8+ T cells, and natural killer (NK) cells, suggesting that the infiltration of immune cells could be associated with a good prognosis due to increased PKHD1L1 expression. Gene ontology (GO) analysis also revealed the relationship between PKHD1L1-co-altered genes and the activation of lymphocytes, including B and T cells. Collectively, this study shows that PKHD1L1 expression is positively correlated with a good prognosis via the induction of immune infiltration, suggesting that PKHD1L1 has potential prognostic value in SKCM and LUAD.

The Effect of Malaria Disease on Liver Function in Children Below 5 Years of Age

Malaria continues to be a major global health concern in tropical regions, especially affecting children between the ages of 1 and 5. The aim of this study is to assess the influence of malaria on hepatocellular function in this vulnerable age group. The enrollment of 582 randomly selected children was approved ethically, and parental consent was obtained. Of these, 396 were in the test group (who tested positive for malaria), and 186 were in the control group (apparently healthy). Giemsa-stained thin and thick films were used to confirm the diagnosis of malaria, and serum markers such as SGOT, SGPT, ALP, and gamma glutamyl transferase were used to assess hepatocellular function while the malaria diagnosis was made. As further markers of liver health, albumin and protein levels were evaluated. The findings showed that, in comparison to the control group, children with malaria parasitemia had statistical significantly higher levels of ALP, SGOT, SGPT, and Gamma Glutamyl Transferase as well as lower levels of total protein and albumin (p &lt; 0.05). This suggests a significant effect on liver function in children with malaria, ages 1 to 5. Finally, our research highlights the connection between liver impairment in young children and malaria parasitemia. To improve early detection and management of liver-related complications in affected children, we recommend adding hepatic function assessments to routine evaluations, especially in malaria-endemic areas.

Antioxidant properties of bovine liver protein hydrolysates and their practical application in biphasic systems.

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. 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. 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. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Different response of females and males Neotropical catfish (Rhamdia quelen) upon short-term temperature increase.

Climate change has been one of the most discussed topics in the world. Global warming is characterized by an increase in global temperature, also in aquatic environments. The increased temperature can affect aquatic organisms with lethal and sublethal effects. Thus, it is necessary to understand how different species respond to temperature. This study aimed to evaluate how the Neotropical catfish species Rhamdia quelen responds to temperature increases. The fish were exposed to temperatures of 25°C (control) and 30°C after gradual temperature increase for 7days. After 96h in each temperature, the fish were anesthetized, blood was collected, and after euthanasia, brain, liver, posterior kidney, gills, muscle, and gonads were collected. The gonads were used for sexing, while other tissues were used for the hematological, biochemical, genotoxic, and histopathological biomarkers analysis. Hepatic proteomic analysis with a focus on energy production was also carried out. Blood parameter changes in both sexes, including an increase in glucose in males, leukopenia in females, and genotoxicity in both sexes. Hepatic proteins related to energy production were altered in both sexes, but mainly in males. Others biomarker alterations, such as histopathological, were not observed in other tissues; however, the antioxidant system was affected differently between sexes. These showed that R. quelen juveniles, at temperatures higher than its optimum temperature such as 30°C, has several sublethal changes, such as hematological alterations, antioxidant system activation, and energetic metabolism alteration, especially in males. Thus, short-term temperature rise can affect females and males of R. quelen differently.

Dehulled Adlay (Coix lachryma-jobi L.) ameliorates hepatic gluconeogenesis and steatosis in streptozotocin/high-fat diet-induced diabetic rats.

Adlay (Coix lachryma-jobi L.) is a traditional Chinese herbal medicine with various biological activities. We investigated the anti-diabetic effects of different parts of adlay seeds, including polished adlay (PA), adlay bran (AB) and dehulled adlay (DA) in a streptozotocin (STZ)/high fat diet (HFD) diabetic rat model (DM). DM rats supplemented with or without PA (43%), AB (3%), or DA (46%) diet for 8 weeks. The plasma glucose and insulin levels and the insulin resistance index (HOMA-IR) were increased in DM group; among the three adlay diets, DA has the best effects attenuating all of these alterations in DM rats. Both AB and DA alleviated diabetes-impaired glucose tolerance. The increased hepatic phosphoenolpyruvate carboxykinase protein expression in DM group was improved by all of the three adlay diets. The increased ratio of glucose-6-phosphatase to glucokinase in DM group was suppressed by DA supplementation, further suggesting DA diet is most effective among the three diets. Both AB and DA diets had beneficial effects against hepatic steatosis, with better effects observed in DA group. These results suggest that the DA diet, composed of both polished adlay and adlay bran, possesses the best potential to improve glucose homeostasis, at least in part, by alleviating hepatic glucose metabolism and steatosis.

Maternal exposure to E 551 during pregnancy leads to genome-wide DNA methylation changes and metabolic disorders in the livers of pregnant mice and their fetuses

The widespread use of nanoparticles in the food industry has raised concerns regarding their potential adverse effects on human health, particularly in vulnerable populations, including pregnant mothers and fetuses. However, studies evaluating the reproductive and developmental toxicity of food-grade nanomaterials are limited. This study investigated the potential risks of prenatal dietary exposure to food-grade silica nanoparticles (E 551) on maternal health and fetal growth using conventional toxicological and epigenetic methods. The results showed that prenatal exposure to a high-dose of E 551 induces fetal resorption. Moreover, E 551 significantly accumulates in maternal and fetal livers, triggering a hepatic inflammatory response. At the epigenetic level, global DNA methylation is markedly altered in the maternal and fetal livers. Genome-wide DNA methylation sequencing revealed affected mCG, mCHG, and mCHH methylation landscapes. Subsequent bioinformatic analysis of the differentially methylated genes suggests that E 551 poses a risk of inducing metabolic disorders in maternal and fetal livers. This is further evidenced by impaired glucose tolerance in pregnant mice and altered expression of key metabolism-related genes and proteins in maternal and fetal livers. Collectively, the results of this study highlighted the importance of epigenetics in characterizing the potential toxicity of maternal exposure to food-grade nanomaterials during pregnancy.