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Glycyrrhizae Radix et Rhizoma (GRER) has been used as a medicinal plant and dietary supplements for its beneficial effect in immunomodulatory effects. Sulfur fumigation (SF) processing was widely used in the storage and maintenance of Chinese medicine because of its convenience and cheapness. However, the disadvantage of SF has been reported, but the systematic study of SF on GRER was deficient. In this paper, the active ingredients, sulfur-fumigated products, immunomodulatory effect, and liver injury of SF-GRER were studied. After SF, the liquiritin decreased from 4.49 ± 0.03 mg/g to 3.94 ± 0.08 mg/g (P < 0.01). Compared with the NSF-GRER group, the SF-GRER group showed a decreased immunoregulation in the thymus index, spleen index, and serum IL-6 and SOD levels (P < 0.05). After 2 weeks of continuous intragastric administration of SF-GRER in healthy mice, the level of serum aspartate aminotransferase (AST) significantly increased (P < 0.05) and the area of liver lesion significantly increased compared with the NSF-GRER (P < 0.05) group. The sulfonated products (m/z, 631.13) corresponding to liquiritin apioside (m/z, 551.17) and isoliquiritin apioside (m/z, 551.17) were screened out in SF-GRER by using UPLC-Orbitrap-MS. The sulfonated products provided in this paper were discovered for the first time and could be powerfully applied for the identification of SF-GRER. SF destroyed the chemical composition of GRER, inhibited immunoregulation, and induced liver injury. The feasibility of this processing method needs to be reconsidered. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease, a type of metabolic syndrome, continues to rise globally. Currently, there is no approved drug for its treatment. Improving lifestyle and exercise can alleviate symptoms, but patients' compliance is poor. More and more studies have shown the potential of Polygoni Multiflori Radix (PMR) in the treatment of NAFLD and metabolic syndrome. Therefore, this paper reviews the pharmacological effects of PMR and its main chemical components (tetrahydroxystilbene glucoside, emodin, and resveratrol) on NAFLD. PMR can inhibit the production of fatty acids and promote the decomposition of triglycerides, reduce inflammation, and inhibit the occurrence of liver fibrosis. At the same time, it maintains an oxidation equilibrium status in the body, to achieve the therapeutic purpose of NAFLD and metabolic syndrome. Although more standardized studies and clinical trials are needed to confirm its efficacy, PMR may be a potential drug for the treatment of NAFLD and its complications. However, the occurrence of adverse reactions of PMR has affected its extensive clinical application. Therefore, it is necessary to further study its toxicity mechanism, enhance efficacy and control toxicity, and even reduce toxicity, which will contribute to the safe clinical use of PMR. [ABSTRACT FROM AUTHOR]

For several years, research has been carried out on the effectiveness of solutions for perfusion and preservation of organs, including the liver. There is a search for an optimal pharmacological composition of these solutions, allowing to preserve or improve vital functions of the organ for as long as possible until it is transplanted into a recipient. Hormones due to their properties, often resulting from their pleiotropic effects, may be a valuable component for optimizing the composition of liver perfusion and preservation solutions. The paper presents the current state of knowledge on liver perfusion and preservation solutions modified with hormones. It also shows the characteristics of the hormones evaluated, taking into account their physiological functions in the body. [ABSTRACT FROM AUTHOR]

Titanium dioxide nanoparticles (TiO2) were used in various fields such as food industry, cosmetics, medicine, and agriculture. Despite the many advantages of nanotechnology, the adverse effects of nanoparticles are inevitable. The present study was conducted to evaluate the protective effect of bee bread on titanium dioxide (TiO2) nanoparticle toxicity. Male rats were randomly divided into four groups: Group 1 received daily by gavage (10 mL/kg bw) of distilled water, Group 2 received bee bread ethanolic extract (100 mg/kg bw), Group 3 received TiO2 (100 mg/kg bw) and distilled water (10 mL/kg bw), and Group 4 received TiO2 (100 mg/kg bw) and bee bread ethanolic extract (100 mg/kg bw). All treatments were given daily by gavage during 30 days. At the end of the experiment period, blood samples were collected to analyze fasting blood glucose, lipid profile (TC, TG, LDL-C, HDL-C, and VLDL-C), liver enzymes (AST, ALT, and LDH), total protein, urea, albumin, creatinine, sodium, potassium, and chloride ions. In addition, histological examinations of the kidneys, liver, and brain were investigated. The results showed that the subacute administration of TiO2 alone (100 mg/kg bw) had induced hyperglycemia (309 ± 5 mg/dL) and elevation of hepatic enzyme levels, accompanied by a change in both lipid profile and renal biomarkers as well as induced congestion and dilatation in the hepatic central vein and congestion in kidney and brain tissues. However, the cotreatment with bee bread extract restored these biochemical parameters and attenuated the deleterious effects of titanium nanoparticles on brain, liver, and kidney functions which could be due to its rich content on functional molecules. The findings of this paper could make an important contribution to the field of using bee bread as a detoxifying agent against titanium dioxide nanoparticles and other xenobiotics. [ABSTRACT FROM AUTHOR]

Anatomical analysis of liver region is critical in diagnosis and treatment of liver diseases. The reports of liver region annotation are helpful for doctors to precisely evaluate liver system. One of the challenging issues is to annotate the functional regions of liver through analyzing Computed Tomography (CT) images. In this paper, we propose a vessel-tree-based liver annotation method for CT images. The first step of the proposed annotation method is to extract the liver region including vessels and tumors from the CT scans. And then a 3-dimensional thinning algorithm is applied to obtain the spatial skeleton and geometric structure of liver vessels. With the vessel skeleton, the topology of portal veins is further formulated by a directed acyclic graph with geometrical attributes. Finally, based on the topological graph, a hierarchical vascular tree is constructed to divide the liver into eight segments according to Couinaud classification theory and thereby annotate the functional regions. Abundant experimental results demonstrate that the proposed method is effective for precise liver annotation and helpful to support liver disease diagnosis. [ABSTRACT FROM AUTHOR]

Identification of rhythmic gene expression from metabolic cycles to circadian rhythms is crucial for understanding the gene regulatory networks and functions of these biological processes. Recently, two algorithms, JTK_CYCLE and ARSER, have been developed to estimate periodicity of rhythmic gene expression. JTK_CYCLE performs well for long or less noisy time series, while ARSER performs well for detecting a single rhythmic category. However, observing gene expression at high temporal resolution is not always feasible, and many scientists are interested in exploring both ultradian and circadian rhythmic categories simultaneously. In this paper, a new algorithm, named autoregressive Bayesian spectral regression (ABSR), is proposed. It estimates the period of time-course experimental data and classifies gene expression profiles into multiple rhythmic categories simultaneously. Through the simulation studies, it is shown that ABSR substantially improves the accuracy of periodicity estimation and clustering of rhythmic categories as compared to JTK_CYCLE and ARSER for the data with low temporal resolution. Moreover, ABSR is insensitive to rhythmic patterns. This new scheme is applied to existing time-course mouse liver data to estimate period of rhythms and classify the genes into ultradian, circadian, and arrhythmic categories. It is observed that 49.2% of the circadian profiles detected by JTK_CYCLE with 1-hour resolution are also detected by ABSR with only 4-hour resolution. [ABSTRACT FROM AUTHOR]

Diffuse liver diseases are highly prevalent conditions around the world, including pathological liver changes that occur when hepatocytes are damaged and liver function declines, often leading to a chronic condition. In the last years, Magnetic Resonance Imaging (MRI) is reaching an important role in the study of diffuse liver diseases moving from qualitative to quantitative assessment of liver parenchyma. In fact, this can allow noninvasive accurate and standardized assessment of diffuse liver diseases and can represent a concrete alternative to biopsy which represents the current reference standard. MRI approach already tested for other pathologies include diffusion-weighted imaging (DWI) and radiomics, able to quantify different aspects of diffuse liver disease. New emerging MRI quantitative methods include MR elastography (MRE) for the quantification of the hepatic stiffness in cirrhotic patients, dedicated gradient multiecho sequences for the assessment of hepatic fat storage, and iron overload. Thus, the aim of this review is to give an overview of the technical principles and clinical application of new quantitative MRI techniques for the evaluation of diffuse liver disease. [ABSTRACT FROM AUTHOR]

Nonlinear contrast-enhanced ultrasound imaging schemes strive to suppress tissue signals in order to better visualize nonlinear signals from blood-pooling ultrasound contrast agents. Because tissue does not generate a subharmonic response (i.e., signal at half the transmit frequency), subharmonic imaging has been proposed as a method for isolating ultrasound microbubble signals while suppressing surrounding tissue signals. In this paper, we summarize recent advances in the use of subharmonic imaging in vivo. These advances include the implementation of subharmonic imaging on linear and curvilinear arrays, intravascular probes, and three-dimensional probes for breast, renal, liver, plaque, and tumor imaging. [ABSTRACT FROM AUTHOR]

Fructus Ligustri Lucidi is a well-known invigorator in Chinese materia medica with hepatoprotective effect, anticancer activity, antioxidant activity, and so on. And oleanolic acids are the major pharmacologically active components in Fructus Ligustri Lucidi. So it has great value in medical health, and may be developed to a complementary and alternative medicine through further research. In this paper, the advances in research on pharmacological effects of Fructus Ligustri Lucidi were summarized by reviewing the recent related literature. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the potential drug-drug interactions of the Shuganjieyu capsule by establishing a Chronic Unpredictable Mild Stress (CUMS) depression model combined with the Cocktail probe substrate method. Methods. The whole study was divided into the single-dose and multiple-dose groups. Animals were randomly divided into further subgroups in each group. Following chronic unpredictable mild stress model development, Shuganjieyu capsules were administered to the drug administration group. The single-dose subgroup received the drug for one day, and the multiple-dose subgroup received the drug for three months. Liver microsomes of each group were extracted, and the effects of the Shuganjieyu capsule on the CYP450 enzyme were investigated by liquid chromatography-mass spectrometry (LC-MS) (LC-MS) based on the Cocktail probe substrate method. The immunohistochemical method and RT-qPCR were used to detect the activity of CYP450 immunoprotein in rat liver. Results. In the single-dose subgroup, there were no statistical differences between the administration and model groups. In the multiple-dose subgroup, the conversion and protein expression rates of CYP1A2 and CYP2C19 were significantly increased in the model group compared with the blank group. In the administration group, the conversion and protein expression rates of CYP1A2 and CYP2C19 were inhibited. Conclusion. Long-term administration of the Shuganjieyu capsule could relieve depression-related behaviors in CUMS rats and downregulate the CYP1A2 and CYP2C19 enzyme activities in CUMS rats by inhibiting the expression of CYP1A2 and CYP2C19 protein. Long-term administration of the Shuganjieyu capsule may affect the bioavailability of other drugs metabolized by CYP1A2 and CYP2C19 enzymes, but the clinical guidance's specific significance needs to be clarified further. [ABSTRACT FROM AUTHOR]

Objective. To observe the improvement effect of aerobic exercise on liver tissue of rats with NAFLD, explore whether it can reduce NAFLD symptoms without drug dependence, and provide certain data support for the relief of NAFLD by aerobic exercise. Methods. 40 healthful male SD rats have been divided into ordinary diet and high-fat diet. To observe whether the molding is forming after 6 weeks, then divide the rats into control (C), model (M), and exercise (E) group. E group received 8-week aerobic exercise intervention. Serum and liver samples were taken and analyzed after the last intervention. Results. The morphological of hepatocytes between C and M group becomes different, and the accumulation of fat and inflammatory cells was significant, suggesting that NAFLD symptoms appeared, that is, the model was successfully established. Compared with M group, the morphology of rats in E group was improved in varying degrees. The quantity of ALT, AST, and MDA of rats in M group is increased, and the SOD activity is significantly reduced (P < 0.01). However, aerobic exercise intervention changed those result (P < 0.01). Conclusions. Aerobic exercise can relieve oxidative stress damage, lipid peroxidation levels, and chronic inflammatory status in rats with NAFLD, which can reduce NAFLD symptoms without drug dependence, and is expected to become a means of NAFLD treatment. [ABSTRACT FROM AUTHOR]

Objective. The aims of this study were to investigate the impact of TAK-242 on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) signal transduction pathway in rats with hepatic fibrosis (HF) using the liver gut axis and to investigate the molecular mechanism of its intervention on HF. Methods. SPF grade SD male rats were randomly allocated to the control, model, and TAK-242 groups. For 8 weeks, the model and TAK-242 groups received 3 mL·kg-1 (the initial dose 5 mL·kg-1) intraperitoneal injections of 40% CCL4 olive oil solution. TAK-242 (5 mg·kg-1) was administered once a day for 5 days after modeling. The pathological alterations of liver and small intestine tissues in each group were observed using H&E and Masson staining. ELISA was used to measure serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBIL), total bilirubin (TBIL), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). RT-qPCR was utilized to identify the mRNA expression level of IL-1β, IL-6, TNF-α, TLR4, MyD88, and NF-κB in rat liver and small intestine tissues. The protein level of IL-1β, IL-6, TNF-α, TLR4, MyD88, and NF-κB protein in rat liver and small intestine tissues was determined utilizing Western blot and IHC. Results. TAK-242 significantly reduced AST, ALT, TBIL, and DBIL expression in HF rats' serum (P < 0.01) and alleviated liver tissue injury. Hematoxylin-eosin (H&E) and Masson staining revealed inflammatory cell infiltration and fibrous proliferation in the liver and small intestine tissue in the model group and partial cell swelling in the TAK-242 group, which indicated a considerable improvement compared to the model group. RT-qPCR, Western blot, and IHC data indicated that TAK-242 reduced the IL-1β, IL-6, TNF-α, TLR4, MyD88, and NF-κB expression in the liver and small intestine tissues of HF rats. Conclusion. TAK-242 might downregulate the TLR4/MyD88/NF-κB signal pathway through the liver-gut axis, suppress the inflammatory response, and eventually alleviate HF in rats. [ABSTRACT FROM AUTHOR]

Background. Inflammation is a frequent phenomenon in the pathogenesis of hepatic disorders leading to fibrosis and cirrhosis. Phytopharmaceuticals developed from traditional medicine can provide effective therapeutic alternatives to conventional medications. Datura stramonium (DS) has reported traditional uses in inflammatory diseases. In this study, we have tried to validate its potential as a source of anti-inflammatory agents. Methods. Powdered leaf part of DS was extracted using ethyl acetate (EA) to provide the extract (DSL-EA). Lymphocyte and macrophage viability and acute toxicity assays established the safety profile, while nitric oxide (NO) scavenging assay estimated the in vitro anti-inflammatory potential. Noninvasive anti-inflammatory, antidepressant, and antinociceptive activities were monitored using BALB/c mice using low and high doses (150 and 250 mg/kg). Major inflammatory studies were performed on Sprague-Dawley male rats using CCl4-induced liver injury model. Disease induction was initiated by intraperitoneal injections of CCl4 (1 mL/kg of 30% CCl4 in olive oil). The rats were divided into six groups. The anti-inflammatory potential of DSL-EA in low and high doses (150 and 300 mg/kg, respectively) was assessed through hematological, biochemical, liver antioxidant defense, oxidative stress markers, and histological studies as well as the expression of Nrf2 and iNOS. Results. DSL-EA exhibited prominent in vitro NO scavenging (IC50: 7.625 ± 0.51 μg/mL) and in vivo anti-inflammatory activity in paw and anal edema models. In CCl4 model, hematological investigations revealed vasotonic effects. Liver functionality was significantly (P < 0.001 − 0.05) improved in DSL-EA-treated rats. The activity level of endogenous antioxidant enzymes in liver tissues was improved in a manner identical to silymarin. The extract reduced the percent concentration of oxidative stress markers in liver tissues. Furthermore, DSL-EA displayed restorative effects on histological parameters (H and E and Masson's trichrome staining). Immunohistochemistry studies showed marked decline in Nrf2 expression, while overexpression of iNOS was also observed in disease control rats. The damage was distinctly reversed by the extract. [ABSTRACT FROM AUTHOR]

Lead pollution is a major environmental challenge worldwide. Therefore, dietary interventions that are aimed at preventing lead's deleterious effects on body organs are needed. The study's goal was to study and compare the protective effect of cold and hot beverages of Roselle (Hibiscus sabdariffa L.) red calyces (CRB and HRB, respectively) on liver and kidney insufficiency associated with lead exposure in male rats. Adult albino rats (32 males) were divided into four groups of equal number, including a normal control (group 1), while groups from 2 to 4 received lead acetate (20 mg/kg body weight/day) and were kept untreated (group 2). The 3rd and the 4th groups received CRB and HRB (0.5 ml/100 g body weight/day), respectively, for 6 weeks. The gain in the body and relative weights of the liver and kidneys were calculated. Liver and kidney functions were determined in serum, while lead, delta-aminolevulinic acid dehydratase, and oxidative stress markers were established in tissues. Specimens from the liver and kidney of sacrificed rats were histopathologically examined. The total activity of antioxidants and total content of anthocyanin of both beverages were determined. Lead exposure resulted in its accumulation in tissues, leading to overweight and liver and kidney insufficiency along with oxidative stress, which was further confirmed by histological staining. CRB was more efficient than HRB in preventing the deleterious effects of lead intoxication. Due to their antioxidant properties, the present study proved that Roselle red calyx beverages, particularly the cold ones, are protective agents against lead-associated disorders in a rat model. [ABSTRACT FROM AUTHOR]

Traditional pathogenic diagnosis presents defects such as a low positivity rate, inability to identify uncultured microorganisms, and time-consuming nature. Clinical metagenomics next-generation sequencing can be used to detect any pathogen, compensating for the shortcomings of traditional pathogenic diagnosis. We report third-generation long-read sequencing results and second-generation short-read sequencing results for ascitic fluid from a patient with liver ascites and compared the two types of sequencing results with the results of traditional clinical microbial culture. The distribution of pathogenic microbial species revealed by the two types of sequencing results was quite different, and the third-generation sequencing results were consistent with the results of traditional microbial culture, which can effectively guide subsequent treatment. Short reads, the lack of amplification, and enrichment to amplify signals from trace pathogens, and host background noise may be the reasons for the high error in the second-generation short-read sequencing results. Therefore, we propose that long-read-based rRNA analysis technology is superior to the short-read shotgun-based metagenomics method in the identification of pathogenic bacteria. [ABSTRACT FROM AUTHOR]

This study is aimed at comparing the antidiabetic and antioxidant potential of fenugreek and buckthorn which are commonly used in modulating diabetes in the Middle East. In this study, the antioxidant and antidiabetic activity of the aqueous extracts of the leaf and seed of fenugreek and buckthorn was tested in streptozotocin-induced diabetic male rats fed with a fat-rich diet for 8 weeks. Thirty-six male albino rats were divided into 6 groups (n = 6); the 1st group was the negative control. Diabetes was induced in the other 30 rats using streptozotocin, which were then divided into 5 groups; the 2nd was the untreated positive diabetic group, the 3rd was treated with fenugreek leaf aqueous extract, the 4th was treated with the fenugreek seed aqueous extract, the 5th was treated with buckthorn leaf aqueous extract, and the 6th was treated with buckthorn seed aqueous extract. The positive control group showed an increase in blood sugar, glycated hemoglobin, liver function enzymes, lactate dehydrogenase, kidney indices, total cholesterol, triglycerides, low- and very-low-density lipoprotein, immunoglobulins, and lipid peroxidation and a decrease in high-density lipoprotein, albumin, and antioxidant activity. The histology of the liver and testes showed severe histopathological alterations. Rats of groups 4-6 that were treated with the aqueous extract of the leaf and seed extract of fenugreek and buckthorn showed improvement of all biochemical and histopathological parameters. The seed extract of fenugreek and buckthorn showed more antioxidant activity than their leaves. [ABSTRACT FROM AUTHOR]

Purpose. Sepsis originates from the host inflammatory response, especially to bacterial infections, and is considered one of the main causes of death in intensive care units. Various agents have been developed to inhibit mediators of the inflammatory response; one prospective agent is β-sitosterol (βS), a phytosterol with a structure similar to cholesterol. This study is aimed at evaluating the effects of βS on the biomarkers of inflammation and liver function in cecal ligation and puncture- (CLP-) induced septic rats. Methods. Thirty male Wistar rats were divided equally into six groups as follows: sham, CLP, CLP+dexamethasone (DX, 0.2 mg/kg), CLP+βS (1 mg/kg), CLP+imipenem (IMI, 20 mg/kg), and CLP+IMI (20 mg/kg)+βS (1 mg/kg). Serum levels of IL-1β, IL-6, IL-10, AST, ALT, and liver glutathione (GSH) were assessed by ELISA. Liver expression levels of TNF-α and NF-κBi mRNAs were evaluated by RT-qPCR. Results. Serum concentrations of IL-1β, IL-6, IL-10, ALT, and AST and mRNA levels of TNF-α and NF-κBi were all significantly higher in septic rats than in normal rats (p < 0.05). Liver GSH content was markedly lower in the CLP group than that in the sham group. βS-treated rats had remarkably lower levels of IL-1β, IL-6, IL-10, TNF-α, NF-κBi, AST, and ALT (51.79%, 62.63%, 41.46%, 54.35%, 94.37%, 95.30%, 34.87%, and 46.53% lower, respectively) and greater liver GSH content (35.71% greater) compared to the CLP group (p < 0.05). Conclusion. βS may play a protective role in the septic process by mitigating inflammation. This effect is at least partly mediated by inhibition of the NF-κB signaling pathway. Thus, βS can be considered as a supplementary treatment in septic patients. [ABSTRACT FROM AUTHOR]

Background. The aim of this work was to study the toxic effects and target organs of Mosla chinensis Maxim (MCM) in rats and provide theoretical basis for clinical medication. Methods. The subchronic toxicity study was conducted on 60 male and female SD rats using the fixed-dose method for the treatment groups and 20 male and female SD rats for the control. At the subchronic toxicity study, the water extract of MCM with fixed doses of 0.2 g/kg/day, 2 g/kg/day, and 20 g/kg/day was administered for 90 days intragastric, and the control group was given the same amount of distilled water. After 90 days, the general conditions of the rats were observed. Assessment on safety of the extract was conducted by a subchronic toxicity test which mainly examined alteration occurrence in gut flora and urine metabolism. Results. There was no significant difference in physical signs, reactivity, and stool characteristics in the four groups. Compared with the control group, the number of red blood cells in the male 2 g/kg/day group and the female 0.2 g/kg/day group was significantly different (P < 0.05). The detection of serum biochemical indicators showed that MCM has an effect on liver and kidney function but has no physiological significance. The level of low-density lipoprotein in male rats was lower than that in the control group (P < 0.05). Compared with the control group, the blood glucose levels of female rats in the 0.2 g/kg/day, 2 g/kg/day, and 20 g/kg/day groups were significantly increased (P < 0.05). As far as the diversity of intestinal flora is concerned, feeding MCM for 90 days has an influence on the distribution of intestinal flora. The content of lactic acid bacteria increased, and the ratio of hard bacteria to Bacteroides (f/b) was also affected, but there was no significant difference. Conclusions. These findings showed that the long-term intragastric administration of the MCM is safe to use within its dose recommendation. But it could have a slight effect on the metabolism of uric acid by changing the composition of intestinal flora and affecting the metabolism of tryptophan. [ABSTRACT FROM AUTHOR]

Single-nucleotide polymorphisms (SNPs) of apolipoprotein C3 (APOC3) play important role in lipid metabolism, and dyslipidemia underlies nonalcoholic fatty liver disease (NAFLD). But the correlation of serum lipidomics, APOC3 SNPs, and NAFLD remains limited understood. Enrolling thirty-four biopsy-proven NAFLD patients from Tianjin, Shanghai, Fujian, we investigated their APOC3 genotype and serum lipid profile by DNA sequencing and ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), respectively. Scoring of hepatocyte steatosis, ballooning, lobular inflammation, and liver fibrosis was then performed to reveal the role of lipidomics-affecting APOC3 SNPs in NAFLD-specific pathological alterations. Here, we reported that APOC3 SNPs (rs4225, rs4520, rs5128, rs2070666, and rs2070667) intimately correlated to serum lipidomics in NAFLD patients. A allele instead of G allele at rs2070667, which dominated the SNPs underlying lipidomic alteration, exhibited downregulatory effect on triacylglycerols (TGs: TG 54 : 7, TG 54 : 8, and TG 56 : 9) containing polyunsaturated fatty acid (PUFA). Moreover, subjects with low-level PUFA-containing TGs were predisposed to high-grade lobular inflammation (TG 54 : 7, rho = − 0.454 and P = 0.007 ; TG 54 : 8, rho = − 0.411 and P =0.016; TG 56 : 9, rho = − 0.481 and P = 0.004). The significant correlation of APOC3 rs2070667 and inflammation grading [G/G vs. G/A+A/A: 0.00 (0.00 and 1.00) vs. 1.50 (0.75 and 2.00), P = 0.022 ] further confirmed its pathological action on the basis of lipidomics-impacting activity. These findings suggest an inhibitory effect of A allele at APOC3 rs2070667 on serum levels of PUFA-containing TGs, which are associated with high-grade lobular inflammation in NAFLD patients. [ABSTRACT FROM AUTHOR]

Rhein, the active ingredient of rhubarb, a medicinal and edible plant, is widely used in clinical practice. However, the effects of repeated intake of rhein on liver function and bile acid metabolism are rarely reported. In this work, we investigated the alterations of 14 bile acids and hepatic transporters after rats were administered with rhein for 5 weeks. There was no obvious injury to the liver and kidney, and there were no significant changes in biochemical indicators. However, 1,000 mg/kg rhein increased the liver total bile acid (TBA) levels, especially taurine-conjugated bile acids (t-CBAs), inhibited the expression of farnesoid X receptor (FXR), small heterodimer partner (SHP), and bile salt export pump (BSEP) mRNA, and upregulated the expression of (cholesterol 7α-hydroxylase) CYP7A1 mRNA. Rhein close to the clinical dose (10 mg/kg and 30 mg/kg) reduced the amounts of TBAs, especially unconjugated bile acids (UCBAs), and elevated the expression of FXR and multidrug resistance-associated protein 3 (Mrp3) mRNA. These results denote that rhein is relatively safe to use at a reasonable dose and timing. 30 mg/kg rhein may promote bile acid transport and reduce bile acid accumulation by upregulating the expression of FXR mRNA and Mrp3 mRNA, potentially resulting in the decrease in serum UBCAs. [ABSTRACT FROM AUTHOR]

Rhein, the active ingredient of rhubarb, a medicinal and edible plant, is widely used in clinical practice. However, the effects of repeated intake of rhein on liver function and bile acid metabolism are rarely reported. In this work, we investigated the alterations of 14 bile acids and hepatic transporters after rats were administered with rhein for 5 weeks. There was no obvious injury to the liver and kidney, and there were no significant changes in biochemical indicators. However, 1,000 mg/kg rhein increased the liver total bile acid (TBA) levels, especially taurine-conjugated bile acids (t-CBAs), inhibited the expression of farnesoid X receptor (FXR), small heterodimer partner (SHP), and bile salt export pump (BSEP) mRNA, and upregulated the expression of (cholesterol 7α-hydroxylase) CYP7A1 mRNA. Rhein close to the clinical dose (10 mg/kg and 30 mg/kg) reduced the amounts of TBAs, especially unconjugated bile acids (UCBAs), and elevated the expression of FXR and multidrug resistance-associated protein 3 (Mrp3) mRNA. These results denote that rhein is relatively safe to use at a reasonable dose and timing. 30 mg/kg rhein may promote bile acid transport and reduce bile acid accumulation by upregulating the expression of FXR mRNA and Mrp3 mRNA, potentially resulting in the decrease in serum UBCAs. [ABSTRACT FROM AUTHOR]

Gene differential expression studies can serve to explore and understand the laws and characteristics of animal life activities, and the difference in gene expression between different animal tissues has been well demonstrated and studied. However, for the world-famous rare and protected species giant panda (Ailuropoda melanoleuca), only the transcriptome of the blood and spleen has been reported separately. Here, in order to explore the transcriptome differences between the different tissues of the giant panda, transcriptome profiles of the heart, liver, spleen, lung, and kidney from five captive giant pandas were constructed with Illumina HiSeq 2500 platform. The comparative analysis of the intertissue gene expression patterns was carried out based on the generated RNA sequencing datasets. Analyses of Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network were performed according to the identified differentially expressed genes (DEGs). We generated 194.52 GB clean base data from twenty-five sequencing libraries and identified 18,701 genes, including 3492 novel genes. With corrected p value <0.05 and |log2FoldChange| >2, we finally obtained 921, 553, 574, 457, and 638 tissue-specific DEGs in the heart, liver, spleen, lung, and kidney, respectively. In addition, we identified TTN, CAV3, LDB3, TRDN, and ACTN2 in the heart; FGA, AHSG, and SERPINC1 in the liver; CD19, CD79B, and IL21R in the spleen; NKX2-4 and SFTPB in the lung; GC and HRG in the kidney as hub genes in the PPI network. The results of the analyses showed a similar gene expression pattern between the spleen and lung. This study provided for the first time the heart, liver, lung, and kidney's transcriptome resources of the giant panda, and it provided a valuable resource for further genetic research or other potential research. [ABSTRACT FROM AUTHOR]

Long-term muscle fatigue is a major cause of injury. Drugs/nutrients from herbal medicines that prevent fatigue remain a major research focus. In China, a prescription composed of Polygonati Rhizoma and Notoginseng Radix et Rhizoma has been commonly used as a herb and food nutrient, providing protection against fatigue in the clinic. To date, the mechanisms through which this prescription prevented fatigue are unknown. Here, we identified the effects of this prescription on muscle fatigue based on energy and oxidation regulation. Fatigue mouse models were produced through weight-bearing exhaustive swimming. Mice were intragastrically administered prescription extracts (1 and 2 g/kg) for four weeks. Changes in exhaustive swimming times, antifatigue biochemical indicators, oxidative status, and energy metabolism were investigated. The prescription prolonged the exhaustive swimming time of the mice. The content of lactic acid and blood urea nitrogen in the serum was also markedly reduced by the prescription. The content of liver glycogen and lactate dehydrogenase in the serum increased. The prescription also significantly reduced malondialdehyde levels and increased the levels of superoxide dismutase and glutathione peroxidase. The levels of ATPase, complexes I and II in the mitochondria of hind-leg skeletal muscle, and serum creatine kinase also increased in response to the prescription. Our results indicated that the prescription could effectively alleviate muscle fatigue status by promoting energy metabolism and antioxidation ability. The prescription therefore represents a useful drug/nutrient strategy to alleviate muscle fatigue. [ABSTRACT FROM AUTHOR]

Hepatic protective effects of Ligularia fischeri (LF) and Aronia melanocarpa (AM) against alcohol were investigated in vitro and in vivo test. LF, AM, and those composed mixing material (LF+AM) were treated in HepG2 cell. Alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities were significantly increased in each singleness extract and mixed composite. The protective effect on alcoholic liver damage was investigated by animal models. Serum alcohol level and acetaldehyde level were significantly decreased by LF+AM treatment in acute experimental model. In the chronic mouse model study, we had found that the increased plasma liver damage index (alkaline phosphatase) by alcohol treatment was declined by oral administration of LF+AM extraction composite. As well as, it was identified that the protection effect was induced by increasing catalase activity and suppressing COX-2, TNF-α, MCP-1, and IL-6 mRNA expressions. CYP2E1 mRNA expression was also increased. These results suggest that oral ingestion of LF and AM mixed composite is able to protect liver against alcohol-induced injury by increasing alcohol metabolism activity and antioxidant system along with decreasing inflammatory responses. [ABSTRACT FROM AUTHOR]

Parenteral nutrition (PN) is a life-saving therapy for patients with intestinal failure, but parenteral nutrition-associated liver disease (PNALD) limits its long-term use. The present study is aimed at determining which pathways are altered most notably in a rat model of PNALD. We randomly assigned male Sprague-Dawley (SD) rats into two different groups, whereby they received either enteral nutrition (EN) or PN. Liver tissues were harvested from all rats 7 days later for metabolomic profiling. The composition of primary conjugated bile acids was altered, the synthesis of polyunsaturated fatty acids was reduced, the conversion of pyruvate to acetyl-CoA was blocked, and the synthesis of phosphatidylcholine was inhibited in rats with PNALD. Riboflavin, which is involved in the electron transfer process in the mitochondrial electron transport chain, was remarkably decreased in PNALD rats. A deficiency of polyunsaturated fatty acids, riboflavin, choline, and taurine might be involved in the progression of PNALD. The implications of these findings for the field of medicine are that supplementation with polyunsaturated fatty acids, riboflavin, choline, and taurine might have potential as therapeutic strategies for PNALD and also shed light on the mechanisms of PNALD. [ABSTRACT FROM AUTHOR]

This study is aimed at elucidating how aspirin could systemically and simultaneously normalize nonalcoholic fatty liver disease (NAFLD) and atherosclerosis through both in vitro and in vivo studies in hyperlipidemic conditions. We evaluated the effects and mechanism of aspirin on the levels of various biomarkers related to NAFLD, atherosclerosis, and oxidative phosphorylation in cells and animals of hyperlipidemic conditions. The protein levels of biomarkers (PPARδ, AMPK, and PGC-1α) involved in oxidative phosphorylation in both the vascular endothelial and liver cells were elevated by the aspirin in hyperlipidemic condition. Also in the stimulation pathway of oxidative phosphorylation by aspirin, PPARδ was a superior regulator than AMPK and PGC-1α in HepG2 cells. In the vascular endothelial cells, the phosphorylated endothelial nitric oxide synthase level was increased by the treatment. The protein levels of biomarkers related to lipid synthesis were decreased by the treatment in the liver cells. In rabbits administered with cholesterol diet, the levels of triglyceride, HDL-cholesterol, and alanine amino transferase in serums were ameliorated by the aspirin treatment, the levels of ATP and TNFα were increased or decreased, respectively, by the aspirin in liver and aorta tissues, and mannose receptor and C-C chemokine receptor type 2 levels were increased or decreased by the aspirin in spleen, respectively. The elevated levels of macrophage antigen, angiotensin II type1 receptor, and lipid accumulation were decreased in both the liver and aorta tissues in the aspirin-treated group. In conclusion, aspirin can systemically and simultaneously ameliorate NAFLD and atherosclerosis by inhibiting lipid biosynthesis and inflammation and by elevating catabolic metabolism through the activation of the PPARδ-AMPK-PGC-1α pathway. Furthermore, aspirin may normalize atherosclerosis and NAFLD by modulating the mannose receptor and CCR2 in macrophages. [ABSTRACT FROM AUTHOR]

Yishen Bugu Ye (YSBGY), a traditional Chinese medicine comprising 12 types of medicinal herbs, is often prescribed in China to increase bone strength. In this study, the antiosteoporotic effects of YSBGY were investigated in C57BL/6 mice afflicted with dexamethasone- (Dex-) induced osteoporosis (OP). The results showed that YSBGY reduced the interstitial edema in the liver and kidney of mice with Dex-induced OP. It also increased the number of trabecular bone elements and chondrocytes in the femur, promoted cortical bone thickness and trabecular bone density, and modulated the OP-related indexes in the femur and tibia of OP mice. It also increased the serum concentrations of type I collagen, osteocalcin, osteopontin, bone morphogenetic protein-2, bone morphogenetic protein receptor type 2, C-terminal telopeptide of type I collagen, and runt-related transcription factor-2 and reduced those of tartrate-resistant acid phosphatase 5 and nuclear factor of activated T cells in these mice, suggesting that it improved osteoblast differentiation and suppressed osteoclast differentiation. The anti-inflammatory effect of YSBGY was confirmed by the increase in the serum concentrations of interleukin- (IL-) 33 and the decrease in concentrations of IL-1, IL-7, and tumor necrosis factor-α in OP mice. Furthermore, YSBGY enhanced the serum concentrations of superoxide dismutase and catalase in these mice, indicating that it also exerted antioxidative effects. This is the first study to confirm the antiosteoporotic effects of YSBGY in mice with Dex-induced OP, and it showed that these effects may be related to the YSBGY-induced modulation of the osteoblast/osteoclast balance and serum concentrations of inflammatory factors. These results provide experimental evidence supporting the use of YSBGY for supporting bone formation in the clinical setting. [ABSTRACT FROM AUTHOR]

Objective. It is sometimes difficult to obtain complete/partial response of large hepatocellular carcinoma (HCC) nodules by trans-arterial chemoembolization/embolization (TACE/TAE). The aim is retrospective investigation of tumor response of large HCC nodules (>7 cm) treated by the new TACE technique, repeated alternate infusion of cisplatin solution, and sparse gelatin slurry under balloon occlusion (RAIB-TACE). Materials and Methods. A microballoon catheter was placed at a proximal portion of the hepatic artery (subsegmental to the lobar level hepatic artery), and alternate infusion of cisplatin solution and sparse gelatin slurry were repeated under balloon occlusion until stasis of gelatin slurry beyond the catheter was seen. RAIB-TACE of multiple proximal hepatic and extrahepatic collateral arteries were performed to treat hemi-lobe or more of the liver while avoiding infusion into gastric and cystic arteries for 19 large nodules (>7 cm) in 19 patients without portal venous invasion. All patients underwent dynamic CT/MRI 1–3 months after RAIB-TACE, and tumor response of each large nodule was evaluated based on modified RECIST criteria. Results. CR, PR, SD, and PD were achieved in 11, 8, 0, and 0 nodules, respectively. CR and PR were considered as success, and the ratio of success was 100%. Major complications were abscess formation in the necrotic nodule (n = 1) which was treated by drainage tube placement, and subsegmental level liver infarction (n = 1) which recovered uneventfully. Conclusion. New TACE technique, RAIB-TACE, was useful to achieve successful response of large HCC nodules. [ABSTRACT FROM AUTHOR]

Background. Hepatic fibrosis and granuloma formation as a consequence of tissue entrapped eggs produced by female schistosomes characterize the pathology of Schistosoma mansoni infection. We have previously shown that single-sex infection with female schistosomes mitigates hepatic fibrosis after secondary infection. This was associated with an increased expression of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), known as a negative regulator of T cell activation. Based on these findings, we hypothesized that administration of agonistic CTLA-4-Ig (Belatacept) is capable to prevent and/or treat hepatic fibrosis during schistosomiasis. Methods. Mice were infected with 50 S. mansoni cercariae and CTLA-4-Ig, or appropriated control-Ig was administered for 4 weeks. Preventive treatment started 4 weeks after infection, before onset of egg production, and therapeutic treatment started 8 weeks after infection when hepatic fibrosis was already established. Results. When given early after infection, livers of CTLA-4-Ig-treated mice showed significantly reduced collagen deposition and decreased expression of profibrotic genes in comparison to controls. In addition, administration of CTLA-4-Ig suppressed the inflammatory T cell response in infected mice. If therapy was started at a later time point when fibrogenesis was initiated, CTLA-4-Ig had no impact on hepatic fibrosis. Conclusion. We could demonstrate that an early preventive administration of CTLA-4-Ig suppresses effector T cell function and therefore ameliorates liver fibrosis. CTLA-4-Ig administration after onset of egg production fails to treat hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Background. Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ALCF) is a complicated syndrome with extremely high short-term mortality. -e artificial liver support system (ALSS) may improve the liver function for patients with HBV-ACLF, but the data on its short-term outcomes are insufficient in China. Methods. We recruited HBV-ACLF patients in this nationwide, multicenter, retrospective study. Patients with HBV-ACLF were diagnosed by the COSSH-ACLF criteria. Propensity score matching (PSM) analysis was used to generate compared pairs. -e short-term (28/90 days) survival rates between the standard medical therapy (SMT) group and ALSS group were calculated using a Kaplan-Meier graph. Result. In total, 790 patients with HBV-ACLF were included in this retrospective study; 412 patients received SMT only (SMT group), and 378 patients received SMTand ALSS treatment (ALSS group). PSM generated 310 pairs and eliminated the baseline differences between the two groups (p > 0.05 for all baseline variables). -e probabilities of survival on day 28 were 65.2% (205/310) in the ALSS group and 59.0% (185/310) in the SMTgroup; on day 90, they were 51.0% (163/310) and 42.3% (136/310). -e short-term (28/90 days) survival rates of the ALSS group were significantly higher than those of the SMTgroup (p = 0.0452 and p = 0.0187, respectively). Compared to receiving SMTalone, treatment with ALSS was associated with a significant reduction in serum bilirubin levels and the model for end-stage liver disease (MELD) scores at day 7 and day 28. Multivariate logistic regression analysis revealed that older age, high total bilirubin (T-Bil), low albumin, high ALT, high MELD scores, and high COSSH-ACLF grade were independent baseline factors associated with poor prognosis. Conclusions. -is retrospective study found that compared to SMT, the ALSS improved the short-term (28/90 days) survival rates and laboratory parameters in HBV-ACLF patients. -e ALSS had a better therapeutic effect than SMT for patients with HBV-ACLF in China. [ABSTRACT FROM AUTHOR]

Background. Serine hydroxymethyltransferase 2 (SHMT2) activity ensures that cells have a survival advantage in ischemic conditions and regulates redox homeostasis. In this study, we aimed to investigate the role of SHMT2 after hepatic ischemia-reperfusion (IR), which involves hypoxia, ischemic conditions, and cell apoptosis. Methods. A 70% IR model was established in C57BL/6J mice with or without SHMT2 knockdown. H&E staining, liver weight/body weight, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels and cell apoptosis were tested to analyze liver damage and function. Then, the related cellular signals were probed. Results. The level of SHMT2 protein was significantly increased at 24 h and 48 h after IR (p<0.001). Mice in the shSHMT2 group showed more necrotic areas and histological damage at 24 h (p<0.01) after IR and higher levels of serum ALT and AST (p<0.05) compared with those of mice in the scramble group. After IR for 24 h, the expression of TUNEL in the shSHMT2 group was significantly higher than that in the scramble group, as shown by histological analysis (p<0.01). Mechanistically, the JNK/P53 signaling pathway was activated by IR, and knockdown of SHMT2 exacerbated hepatocyte apoptosis. Conclusions. Knockdown of SHMT2 worsens IR injury through the ROS/JNK/P53 signaling pathway. Our discovery expands the understanding of both molecular and metabolic mechanisms involved in IR. SHMT2 is a possible therapeutic target to improve the prognosis of liver transplantation (LT) and subtotal hepatectomy. [ABSTRACT FROM AUTHOR]

We previously demonstrated that angiotensin-(1-7) (Ang-(1-7)), an essential endocrine factor, inhibits the NLRP3 inflammasome by regulating reactive oxygen species (ROS) in fibrotic livers. We also demonstrated that the NLRP3 inflammasome contributes to the liver damage induced by pyroptosis after heatstroke. However, the role of Ang-(1-7) in the hepatocytes under heat stress remains uncertain. We aimed to examine the change in angiotensin peptides in the livers affected by heatstroke and the effect on the ROS-NLRP3 inflammatory signalling pathway. In vivo, increased angiotensin II (Ang II) and decreased Ang-(1-7) in the serum of heatstroke patients suffering from hepatic dysfunction were observed. The change in angiotensin peptides was considered a potential biomarker that could be used to predict hepatic dysfunction. Enhanced Ang II and attenuated Ang-(1-7) levels were also observed in the liver tissue of heatstroke rats, which were consistent with their receptors and converting enzymes. Hepatic damage associated with increased ROS and protein expression levels of NOX4, NLRP3, caspase-1, and IL-1β was attenuated by AVE 0991, an analogue of Ang-(1-7). In vitro, pyroptosis, characterized by activated caspase-1 and IL-1β, was observed in hepatocytes under heat stress, which was enhanced by Ang II and attenuated by antioxidants, NOX4 siRNA, and AVE 0991. In summary, AVE 0991 attenuates pyroptosis and liver damage induced by heat stress by inhibiting the ROS-NLRP3 inflammatory signalling pathway. [ABSTRACT FROM AUTHOR]

There has been a remarkable interest in finding lipid inhibitors from natural products to replace synthetic compounds, and a variety of oriental medicinal herbs are reported to have biological activity with regard to lipid inhibition. Buginawa (Bugi) is a novel combined formula that contains twelve medicinal herbs with potential for weight loss induction. We hypothesized that Bugi may have antiobesity effects in 3T3-L1 preadipocytes and in a high-fat diet- (HFD-) induced mouse model. In this study, 3T3-L1 cells were treated with varied concentrations of Bugi (62.5, 125, or 250 μg/mL). Bugi treatment inhibited adipocyte differentiation by suppressing adipogenic transcription genes, including peroxisome proliferator-activated receptor γ protein (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1 (SREBP1), and CCAAT/enhancer-binding protein β (C/EBPβ). Mice were fed a normal diet or an HFD for 11 weeks, and Bugi was simultaneously administered at 50 or 100 mg/kg. Bugi administration significantly reduced body weight gain and white adipose tissue (WAT) weight and effectively inhibited lipid droplet accumulation in epididymal white adipose tissue (eWAT) and liver tissue. Further, Bugi treatment suppressed mRNA levels of PPARγ, C/EBPα, and SREBP1 in eWAT and liver tissue. Our findings demonstrate that Bugi could be an effective candidate for preventing obesity and related metabolic disorders. [ABSTRACT FROM AUTHOR]

In parallel with the prevalence metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in most countries. It features a constellation of simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even hepatocellular carcinoma. There are no approved drugs for effective management of NAFLD and NASH. Jianpi Huoxue formula (JPHX) mainly consists of Atractylodes macrocephal (Baizhu), Salvia miltiorrhiza (Danshen), Rasux Paeonia Alba (Baishao), Rhizoma Alismatis (Zexie), and Fructus Schisandrae Chinensis (Wuweizi), which may have beneficial effects on NAFLD. The aim of the study was to identify the effect of JPHX on NAFLD. A NAFLD model was induced by methionine-choline-deficient food (MCD) in Wistar rats and orally administered with simultaneous JPHX, once a day for 8 weeks. Hepatocellular injury, lipid profile, inflammation, fibrosis, and apoptosis were evaluated. The results showed that JPHX significantly decreased the abnormal serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the MCD model (P<0.05). Furthermore, JPHX protected MCD diet-fed rats from accumulation of hepatic triglycerides (TG) and total cholesterol (TC). Histological examination demonstrated that JPHX noticeably normalized the NAFLD activity score (NAS). Moreover, JPHX ameliorated liver inflammation by decreasing TNF-α levels and reduced collagen and matrix metalloproteinases in MCD diet-fed rats. In addition, JPHX prevented rats from MCD-induced cellular apoptosis, as suggested by TUNEL staining, and suppressed the activation of caspase 3 and 7 proteins. JPHX also inhibited the phosphorylation of JNK. In conclusion, JPHX exhibited a hepatoprotective effect against NAFLD in an MCD experimental model. [ABSTRACT FROM AUTHOR]

Muscle growth and fat deposition are the two important biological processes in the development of pigs which are closely related to the pig production performance. Long intergenic noncoding RNAs (lincRNAs), with lack of coding potential and the length of at least 200nt, have been extensively studied to play important roles in many biological processes. However, the importance and molecular regulation mechanism of lincRNAs in the process of muscle growth and fat deposition in pigs are still to be further studied comprehensively. In our study, we used the data, including liver, abdominal fat, and longissimus dorsi muscle of 240 days' age of two F2 full-sib female individuals from the white Duroc and Erhualian crossbreed, to identify 581 putative lincRNAs associated with pig muscle growth and fat deposition. The 581 putative lincRNAs shared many common features with other mammalian lincRNAs, such as fewer exons, lower expression levels, and shorter transcript lengths. Cross-tissue comparisons showed that many transcripts were tissue-specific and were involved in the important biological processes in their corresponding tissues. Gene ontology and pathway analysis revealed that many potential target genes (PTGs) of putative lincRNAs were involved in pig muscle growth and fat deposition-related processes, including muscle cell proliferation, lipid metabolism, and fatty acid degradation. In Quantitative Trait Locus (QTLs) analysis, some PTGs were screened from putative lincRNAs, MRPL12 is associated with muscle growth, GCGR and SLC25A10 were associated with fat deposition, and PPP3CA, DPYD, and FGGY were related not only to muscle growth but also to fat deposition. Therefore, it implied that these lincRNAs might participate in the biological processes related to muscle growth or fat deposition through homeostatic regulation of PTGs, but the detailed molecular regulatory mechanisms still needed to be further explored. This study lays the molecular foundation for the in-depth study of the role of lincRNAs in the pig muscle growth and fat deposition and further provides the new molecular markers for understanding the complex biological mechanisms of pig muscle growth and fat deposition. [ABSTRACT FROM AUTHOR]

Lycopene rich food and dark chocolate are among the best-documented products with a broad health benefit. This study explored the systemic effect of lycopene and dark chocolate (DC) on gut microbiota, blood, liver metabolism, skeletal muscle tissue oxygenation and skin. 30 volunteers were recruited for this trial, 15 women and 15 men with a mean age of 55 ± 5.7 years and with moderate obesity, 30 < BMI < 35 kg/m2. They were randomized and divided into five equal interventional groups: three received different formulations of lycopene, one of them with a 7 mg daily dose and two with 30 mg; another group was given 10 g of DC with 7 mg lycopene embedded into its matrix, and the last group received 10 g DC. The trial was double-blinded for the three lycopene groups and separately for the 2 DC groups; the trial lasted for 1 month. By the end of the trial there were dose-dependent changes in the gut microbiota profile in all three lycopene groups with an increase of relative abundance of, e.g., Bifidobacterium adolescentis and Bifidobacterium longum. This was also accompanied by dose-dependent changes in the blood, liver metabolism, skeletal muscle and skin parameters. Consumption of DC resulted in increased relative abundance of, e.g., Lactobacillus and a reduction of corneocyte exfoliation. This is the first study which reports the prebiotic potential of lycopene and DC. [ABSTRACT FROM AUTHOR]

The metabolic syndrome is defined by impaired carbohydrate metabolism and lipid disorders and often accompanied by hypertension, all of which will lead to obesity and insulin resistance. Glucocorticoids play a regulatory role in the metabolism of proteins, lipids, and carbohydrates. There is growing evidence for a role of glucocorticoids in the development of the metabolic syndrome. The most important factor that regulates the access of endogenous glucocorticoids to receptors after release of glucocorticoids and their diffusion into the cytoplasm of target cells is the steroid metabolism involving a microsomal enzyme, 11β-hydroxysteroid dehydrogenase (11β-HSD). The changes in intracellular glucocorticoid metabolism in the pathogenesis of obesity indicate the participation of modulation by 11β-HSD1, which may represent a new therapeutic target for the treatment of diseases such as type 2 diabetes, visceral obesity, or atherosclerosis. The aim of our study was to determine the fast and effective method to assess inhibition activity of compounds in relation with 11β-hydroxysteroid dehydrogenase. The material for this study was human liver and kidney microsomes. In this study we used ELISA technique using 96-well microplates coated with antibodies which were specific for analyzed enzymes. The method can quickly and efficiently measure the inhibition of both 11β-HSD1 and 11β-HSD2. This method can be used to search for and determine inhibitors of this enzyme. Cortisone and cortisol were used as the substrates for corresponding enzyme assays. Furthermore, 3-N-allyl-2-thiouracil derivatives were used by us for comparison purposes in developing the method, although, due to their structure, those derivatives have not previously been considered as potential inhibitors of 11β-HSD1. 3-N-Allyl-2-thiouracil derivatives are a group worth considering, because by modifying their structure (e.g., by introducing other substituents into the pyrimidine ring) it will be possible to obtain an increase in the activity of compounds in this regard. In conclusion, this study shows an efficient and fast method of determining inhibition activity of compounds in relation with 11β-hydroxysteroid dehydrogenase. [ABSTRACT FROM AUTHOR]

Objective. It is difficult to control small hepatocellular carcinoma (HCC) nodules adjacent to the Glisson sheath (GS) by trans-arterial chemoembolization (TACE) probably due to multiple small tumor feeders directly branching from the trunk artery. The purpose of this study was to conduct a retrospective evaluation of a new TACE technique called the repeated alternate infusion of cisplatin solution and gelatin slurry distal to balloon occlusion (RAIB-TACE), for the treatment of small HCC nodules adjacent to GS. Materials and Methods. Small nodules less than 4 cm attached to proximal portion of the subsegmental to lobar level portal branch were retrospectively selected. Between January 2011 and April 2014, 29 nodules in 29 patients were treated by super-selective lipiodol TACE/balloon-occluded TACE (B-TACE) (Lip-TACE group). Since April 2014, treatment protocols for small nodules adjacent to GS were changed, and 14 nodules in 12 patients were treated by RAIB-TACE (RAIB-TACE group). In RAIB-TACE group, alternate infusion of cisplatin solution and sparse gelatin slurry (mixture of 80 mg of gelatin fragments and 20 mL of contrast medium) were repeated until arterial flow was ceased. In Lip-TACE group, lipiodol was used as drug carrier and dense gelatin slurry (mixture of 80 mg of gelatin fragments and 2 mL of contrast medium) as embolization material. Dynamic CT/MRI was obtained 1-3 months after TACE, and response of each nodule was evaluated basing on modified RECIST criteria. Results. In RAIB-TACE group, all 14 nodules (100%) were diagnosed as CR or PR. In Lip-TACE group, 18 of 29 (62.1%) were diagnosed as CR or PR. There was a statistically significant difference in objective response ratio between the groups (p=0.008, Fisher's test). Biloma (n=1) and benign stricture of the right hepatic duct (n=1) were seen in RAIB-TACE group. The biloma shrunk without treatment and the patient had no symptom, but the patient with biliary stricture repeated cholangitis and was treated by administration of antibiotics. Conclusion. The study results show that RAIB-TACE is more effective than lipiodol TACE/B-TACE for small hepatocellular carcinoma adjacent to GS. We speculate that one of the reasons to explain why Lip-TACE is inferior to RAIB-TACE is that viscous lipiodol or dense gelatin slurry could not flow into small tumor feeders effectively. [ABSTRACT FROM AUTHOR]

Background. Motion is a major source of blurring and ghosting in recovered MR images. It is more challenging in Dynamic Contrast Enhancement (DCE) MRI because motion effects and rapid intensity changes in contrast agent are difficult to distinguish from each other. Material and Methods. In this study, we have introduced a new technique to reduce the motion artifacts, based on data binning and low rank plus sparse (L+S) reconstruction method for DCE MRI. For Data binning, radial k-space data is acquired continuously using the golden-angle radial sampling pattern and grouped into various motion states or bins. The respiratory signal for binning is extracted directly from radially acquired k-space data. A compressed sensing- (CS-) based L+S matrix decomposition model is then used to reconstruct motion sorted DCE MR images. Undersampled free breathing 3D liver and abdominal DCE MR data sets are used to validate the proposed technique. Results. The performance of the technique is compared with conventional L+S decomposition qualitatively along with the image sharpness and structural similarity index. Recovered images are visually sharper and have better similarity with reference images. Conclusion. L+S decomposition provides improved MR images with data binning as preprocessing step in free breathing scenario. Data binning resolves the respiratory motion by dividing different respiratory positions in multiple bins. It also differentiates the respiratory motion and contrast agent (CA) variations. MR images recovered for each bin are better as compared to the method without data binning. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) is a major concern in clinical studies as well as in postmarketing surveillance. It is necessary to establish an animal model of DILI for thorough investigation of mechanisms of DILI and searching for protective medications. This article reviews the current status and future perspective on establishment of DILI models based on different hepatotoxic drugs, as well as the underlying mechanisms of liver function damage induced by specific medicine. Therefore, information from this article can help researchers make a suitable selection of animal models for further study. [ABSTRACT FROM AUTHOR]

To explore the antitumor effect of hypoxia-inducible factor-1α short hairpin RNA (HIF-1α shRNA) delivered by ultrasound targeted microbubble destruction (UTMD) and transcatheter arterial embolization (TAE) on rats with hepatic cancer. After the models of transplantation hepatoma were established, Wistar rats were randomly divided into 4 groups: Control group, UTMD group, TAE group, and UTMD+TAE group. Contrast-enhanced ultrasound (CEUS) was used to monitor tumor size on day 14 after four different treatments. Western blotting and immunohistochemistry were applied to measure the protein level of HIF-1α and VEGF in the hepatic cancer tissue. In comparison with UTMD+TAE group (21.25±10.68 days), the mean survival time was noticeably shorter in the Control group and TAE group (13.02±4.30 days and 15.03±7.32 days) (p<0.05, respectively). There was no statistical difference between UTMD+TAE group and UTMD group of the mean survival time (p>0.05). In addition, our results proved that the tumor sizes in UTMD+TAE group were obviously smaller than those in other groups (p<0.05, respectively). By CEUS, we clearly found that the tumor size was the smallest on day 14 in the UTMD+TAE group. The western blotting and immunohistochemistry results proved that the protein levels of HIF-1α and VEGF in UTMD+TAE group were obviously lower than those in TAE group and Control group on days 7 and 14 (p<0.05, respectively). However, there was no statistical difference between UTMD+TAE group and UTMD group (p>0.05). In this study we tried to explore the antitumor effect through a combination of UTMD-mediated HIF-1α shRNA transfection and TAE on rats with hepatic cancer. Our results showed that UTMD-mediated HIF-1α shRNA transfection and TAE can obviously silence HIF-1α and VEGF expression, thereby successfully inhibiting the growth of the tumor. [ABSTRACT FROM AUTHOR]

Qushi Huayu Decoction (QHD), an important clinically proved herbal formula, has been reported to be effective in treating fatty liver induced by high-fat diet in rats. However, the mechanism of action has not been clarified at the metabolic level. In this study, a urinary metabolomic method based on gas chromatography-mass spectrometry (GC-MS) coupled with pattern recognition analysis was performed in three groups (control, model, and QHD group), to explore the effect of QHD on fatty liver and its mechanism of action. There was obvious separation between the model group and control group, and the QHD group showed a tendency of recovering to the control group in metabolic profiles. Twelve candidate biomarkers were identified and used to explore the possible mechanism. Then, a pathway analysis was performed using MetaboAnalyst 3.0 to illustrate the pathways of therapeutic action of QHD. QHD reversed the urinary metabolite abnormalities (tryptophan, uridine, and phenylalanine, etc.). Fatty liver might be prevented by QHD through regulating the dysfunctions of phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and tryptophan metabolism. This work demonstrated that metabolomics might be helpful for understanding the mechanism of action of traditional Chinese medicine for future clinical evaluation. [ABSTRACT FROM AUTHOR]

Hepatic stellate cells (HSCs) play an important role in hepatic fibrogenesis and inflammatory modulation. Endotoxin is dramatically increased in portal venous blood after serious injury and can contribute to liver damage. However, the mechanism underlying endotoxin's effects on HSCs remains largely unknown. Oridonin is a bioactive diterpenoid isolated from Rabdosia rubescens that exhibits anti-inflammatory properties in different tissues. In the present study, we determined the effects of oridonin on endotoxin-induced inflammatory response and signaling pathways in vitro. The production of proinflammatory cytokines in activated human HSCs line LX-2 was measured by ELISA and Western blots. Immunofluorescence and nuclear fractionation assay were used to determine NF-κB activity. Oridonin treatment significantly inhibited LPS-induced proinflammatory cytokines IL-1β, IL-6, and MCP-1 production as well as cell adhesion molecules ICAM-1 and VCAM-1. Additionally, oridonin blocked LPS-induced NF-κB p65 nuclear translocation and DNA binding activity. Oridonin prevented LPS-stimulated NF-κB regulator IKKα/β and IκBα phosphorylation and IκBα degradation. Combined treatment of oridonin and an Hsp70 substrate binding inhibitor synergistically suppressed LPS-stimulated proinflammatory cytokines and NF-κB pathway activation. Therefore, oridonin inhibits LPS-stimulated proinflammatory mediators through IKK/IκBα/NF-κB pathway. Oridonin could be a promising agent for a hepatic anti-inflammatory. [ABSTRACT FROM AUTHOR]

One of the leading causes of death worldwide, cirrhosis, is a liver condition characterized by chronic necrosis, inflammation, and fibrosis. Hepatoprotective compounds, such as antioxidants, can prevent fibrosis. Macroalgae (seaweed) contain high amounts of antioxidant compounds and are plentiful; indeed, species such as Sargassum fluitans Borgesen (Phaeophyceae) carpet many beaches in the Caribbean Basin. An in vivo assay was done evaluating the possible hepatoprotective effect of a Sargassum fluitans ethanol extract. Two murine liver damage models were employed: acetaminophen (APAP) in Balb/c mice to induce acute damage; carbon tetrachloride (CCl4) in Wistar rats to induce chronic damage. Serum liver enzyme levels and relative liver weight were measured, and histopathological and immunohistochemical analyses of liver tissue sections were done. Both APAP and CCl4 significantly raised serum enzyme marker enzymes. Administration of 50 mg/kg S. Fluitans ethanol extract reduced this APAP- and CCl4-induced elevation to normal levels. This effect was corroborated by the extract's inhibition of inflammation and fibrosis in liver tissue observed in the histopathological analysis. The analyzed S. fluitans ethanol extract exhibited an in vivo hepatoprotective effect in acute and chronic liver injury models. [ABSTRACT FROM AUTHOR]

Rationale and Objectives. To investigate the utility of intravoxel incoherent motion MRI (IVIM-MRI) and R2⁎ mapping in diagnosing early stage liver fibrosis in a radiation-induced rat model. Materials and Methods. Thirty rats were randomly divided into three groups with 10 rats in each group. Liver fibrosis was induced by exposure of right lobe of liver in each animal to 20 Gy of radiation. MRI examination was conducted at baseline, one month, two months, and three months after radiation using T1WI, T2WI, IVIM-DWI, and R2⁎ sequences. The pathological examination included hematoxylin eosin, masson trichrome, and prussian blue staining. D, D⁎, f, and R2⁎ values were measured in both left and right lobes for quantitative analysis. Results. Regarding the surviving 23 rats, eight rats were diagnosed with stage F0, ten with stage F1, and five with stage F2 liver fibrosis using METAVIR Scores. The D values of right lobes decreased (P<0.05), and R2⁎ values increased (P<0.01) significantly as fibrosis levels increased. But there was no statistical difference in D⁎ (P=0.970) and f values (P=0.079). R2⁎ value showed a strong positive correlation (r=0.819, P<0.001), while D value showed a negative correlation with fibrosis stages (r=-0.424, P<0.001). D⁎ (r=0.029, P=0.744) and f values (r=-0.055, P=0.536) were poorly correlated with fibrosis levels. Conclusion. IVIM-MRI and R2⁎ mapping are useful techniques for evaluating the severity of liver fibrosis in a radiation-induced rat model, and R2⁎ value is the most sensitive parameter in detecting early stage fibrosis. [ABSTRACT FROM AUTHOR]

Dimethylnitrosamine (DMN) is a potent hepatotoxin, carcinogen, and mutagen. In our previous study, a candidate gallic acid (GA) that widely exists in food and fruit was selected for its capability to alleviate DMN toxicity in vivo. We aimed to investigate the therapeutic potential of GA against DMN-induced liver fibrosis. During the first four weeks, DMN was administered to rats via intraperitoneal injection every other day, except the control group. GA or silymarin was given to rats by gavage once daily from the second to the sixth week. GA significantly reduced liver damage in serum parameters and improved the antioxidant capacity in liver and kidney tissues. Cytokines involved in liver fibrosis were measured at transcriptional and translational levels. These results indicate that GA exhibits robust antioxidant and antifibrosis effects and may be an effective candidate natural medicine for liver fibrosis treatment. [ABSTRACT FROM AUTHOR]

Medicinal plants are efficient modulators of oxidative stress associated with diabetes mellitus. This study evaluated the cardio-, reno-, and hepato-antioxidant status of hydroethanolic extract of Costus afer on streptozotocin-intoxicated diabetic rats. Experimental animals were daily administered with hydroethanolic extract of C. afer by oral intubation for eight weeks (60 days), after which the levels of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and lipid peroxidation marker (MDA) were evaluated in the heart, liver, and kidney homogenates. Plasma biochemical parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total protein, creatinine, and urea were determined. Meanwhile, parts of the heart, kidneys, and liver were histopathologically examined. Streptozotocin administration induced toxicity in the cardiac, hepatic, and renal tissues by stimulating significant increases (p<0.05) in the levels of CAT and SOD, GSH, and MDA. Similarly, significant increases (P<0.05) in the levels of ALT, AST, urea, and total protein were observed in streptozotocin treated rats, whereas decreases were observed in the levels of ALP, LDH, and creatinine. Following the treatments with C. afer hydroethanolic extract prevented the effect of streptozotocin by maintaining the tissue antioxidant status (CAT, SOD, GSH, and MDA) and the plasma biochemical parameters (AST, ALT, ALP, LDH, creatinine, and urea) towards the normal ranges. The histopathological examination revealed hepatovascular congestion and leucocyte infiltration as well as renovascular congestion, glomerulosclerosis, and tubular clarification in the untreated diabetic control and their absence in the group of animals treated with a high dose of C. afer extract. The findings of the present investigation suggest that C. afer possesses antioxidant activities capable of regulating drug induced tissue damage. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) causes a broad spectrum of toxicological effects to animals. Aquatic animals were more likely to accumulate Cd than terrestrial animals because of the living environment. Clearance of Cd in aquatic animals has become an important part of aquatic food safety. The present study was focused on the oxidative damage induced by Cd in the liver of grass carp Ctenopharyngodon idellus and the protective effect of vitamin E (VE) and metallothionein (MT). Grass carp were divided into four groups: the control group, Cd+phosphate-buffered saline (PBS) group, Cd+VE group, and Cd+MT group. All fish were injected with CdCl2 on the first day and then VE, MT, and PBS were given 4 days after injection, respectively. The liver function and antioxidant capacity of grass carp were evaluated. Cd administration resulted in damage of liver function and morphology in liver, which was expressed as the increased content of AST and ALT, rupture of organelles, and decrease of CAT, SOD, and GSH-Px activity. However, VE and MT treatments protected against Cd-induced damage of liver in grass carp by decreasing AST and ALT content, repairing organelles, and maintained the antioxidant system by elevating CAT, SOD, and GSH-Px activity and regulating related mRNA transcript expression. The results revealed that VE and MT might play an important role in the treatment of heavy metal poisoning through their antioxidative effects. [ABSTRACT FROM AUTHOR]

Background. Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Machine learning techniques were introduced to evaluate the optimal predictive clinical model of NAFLD. Methods. A cross-sectional study was performed with subjects who attended a health examination at the First Affiliated Hospital, Zhejiang University. Questionnaires, laboratory tests, physical examinations, and liver ultrasonography were employed. Machine learning techniques were then implemented using the open source software Weka. The tasks included feature selection and classification. Feature selection techniques built a screening model by removing the redundant features. Classification was used to build a prediction model, which was evaluated by the F-measure. 11 state-of-the-art machine learning techniques were investigated. Results. Among the 10,508 enrolled subjects, 2,522 (24%) met the diagnostic criteria of NAFLD. By leveraging a set of statistical testing techniques, BMI, triglycerides, gamma-glutamyl transpeptidase (γGT), the serum alanine aminotransferase (ALT), and uric acid were the top 5 features contributing to NAFLD. A 10-fold cross-validation was used in the classification. According to the results, the Bayesian network model demonstrated the best performance from among the 11 different techniques. It achieved accuracy, specificity, sensitivity, and F-measure scores of up to 83%, 0.878, 0.675, and 0.655, respectively. Compared with logistic regression, the Bayesian network model improves the F-measure score by 9.17%. Conclusion. Novel machine learning techniques may have screening and predictive value for NAFLD. [ABSTRACT FROM AUTHOR]

Probiotic Lactobacillus casei Shirota (LcS) is a potential decontaminating agent of aflatoxin B1 (AFB1). However, few studies have investigated the influence of diet, especially a high protein (HP) diet, on the binding of AFB1 by probiotics. This research was conducted to determine the effect of HP diet on the ability of LcS to bind AFB1 and reduce aflatoxin M1 (AFM1) in AFB1-induced rats. Sprague Dawley rats were randomly divided into three groups: A (HP only), B (HP + 108 CFU LcS + 25 μg AFB1/kg BW), and C (HP + 25 μg AFB1/kg BW). Levels of AST and ALP were higher in all groups but other liver function’s biomarkers were in the normal range, and the liver’s histology showed no structural changes. The urea level of rats in group B (10.02 ± 0.73 mmol/l) was significantly lower (p<0.05) than that of rats in group A (10.82 ± 0.26 mmol/l). The presence of carcinoma in the small intestine and colon was more obvious in group C than in group B. Moreover, rats in group B had significantly (p<0.05) lower AFM1 concentration (0.39 ± 0.01 ng/ml) than rats in group C (5.22 ± 0.28 ng/ml). Through these findings, LcS supplementation with HP diet alleviated the adverse effects of AFB1 by preventing AFB1 absorption in the small intestine and reducing urinary AFM1. [ABSTRACT FROM AUTHOR]