Decreased Alanine Aminotransferase Research Articles

Pharmacological Activation of AMPK Prevents Drp1-mediated Mitochondrial Fission and Alleviates Hepatic Steatosis In vitro.

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Adenosine monophosphate-activated protein kinase (AMPK) activation is beneficial for NAFLD treatment. Recent studies show the excessive fission of mitochondria during NAFLD progression, so targeting mitochondria dynamics may be a possible target for NAFLD. Still, little is known about whether AMPK regulates mitochondrial dynamics in hepar. This study investigated whether AMPK activation alleviates hepatic steatosis by regulating mitochondrial dynamics mediated by GTPase dynamin-related protein 1 (Drp1). Human hepatocyte line L-02 cells were cultured and subjected to palmitic acid (PA) treatment for 24 h to establish a hepatic steatosis model in vitro, which was pre-treated with different tool drugs. Hepatocyte function, hepatocyte lipid content, mitochondrial reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) were examined. The expression levels of genes and proteins associated with mitochondrial dynamics were assessed using reverse transcription-quantitative PCR and western blotting. The results indicated that 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an AMPK activator, improved hepatocyte function, as demonstrated by decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity (P<0.05 or P<0.01). In addition, AICAR decreased total cholesterol (TC) and triglyceride (TG) content and lipid deposition in hepatocytes (P<0.01); decreased ROS production; improved MMP (P<0.01); reduced fission-1 (Fis1) and mitochondrial fission factor (Mff) mRNA expression; and downregulated p-Drp1 (Ser 616) protein expression. In contrast, AICAR increased mitochondrial fusion factor mitofusin-1 (Mfn1) and mitofusin-2 (Mfn2) mRNA expression and upregulated p-Drp1 (Ser 637) protein expression. Mdivi-1, a Drp-1 inhibitor, was used to confirm whether mitochondrial dynamics regulated by Drp1-mediated the role of AICAR. Similar to AICAR, Mdivi-1 improved hepatocyte function and MMP significantly, decreased ROS production and lipid deposition, downregulated Fis1 and Mff mRNA expression, downregulated p-Drp1 (Ser 616) protein expression, and enhanced Mfn1 and Mfn2 mRNA and p-Drp1 (Ser 637) protein expression. However, Compound C, an AMPKspecific inhibitor, had less impact on the protective effect of Mdivi-1. The results demonstrated that AMPK activation has a protective effect on hepatic steatosis in vitro, largely dependent on the inhibition of Drp1-mediated mitochondrial fission.

Melhora dos parâmetros clínicos e laboratoriais em um cão com hepatite idiopática crônica após transplante de células mesenquimais alogênicas derivadas da medula óssea - relato de caso

ABSTRACT Chronic hepatitis (CH) is characterized by the replacement of hepatocytes for fibrotic tissue after injury, and treatment is not curative. Stem cell therapy has shown potential to reduce liver fibrosis. This report describes the management of a dog with CH with a mesenchymal cell-based approach. A 13-year old dog was presented with weight loss, vomiting, diarrhea, and lethargy. She was previously diagnosed with CH. Blood analysis showed hypoalbuminemia, increased serum activities of alanine aminotransferase (ALT) and alkaline phosphatase (ALP), and anemia. Three 2.5x106 bone marrow-derived mesenchymal cells transplantations were performed. After the first transplantation, the owner reported an improvement in clinical signs. Biochemistry evidenced a reduction in ALP activity. After the second administration, serum biochemistry showed a decrease in serum ALT and ALP activities, which kept falling after the third transplantation. There was an increase in albumin and total plasmatic proteins concentration. After six months, the dog came back for control and further improvement in clinical signs, new decrease in ALT activity and a mild increase in ALP concentration was observed. Increase in total and plasmatic protein were also observed. Stem cell-based therapy may be considered a promising alternative for liver diseases. It was safe and showed efficacy in this report.

Acute and Chronic Effects of Interval Aerobic Exercise on Hepcidin, Ferritin, and Liver Enzymes in Adolescents With Beta-Thalassemia Major.

This study aimed to determine the acute and chronic effects of interval aerobic exercise on hepcidin, ferritin, and liver enzymes in adolescents with beta-thalassemia major. Twenty-six beta-thalassemia major adolescents referred to the Thalassemia Clinic and Research Center were selected as study participants and randomly divided into control (n = 13) and training (n = 13) groups. Participants performed 3 sessions per week for 45minutes in each session for 8 weeks of aerobic interval exercise with an intensity of 50% to 65% of the heart rate reserve. Blood samples were taken before, immediately after the exercise session, and 48hours after the last training session, and liver enzymes aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase (ALP), ferritin, and hepcidin were evaluated. The results showed a decrease in aspartate aminotransferase, ALT, ALP, ferritin, and hepcidin levels due to 8 weeks of aerobic interval training (P = .14, P = .97, P = .03, P < .001, P < .001; respectively). Intergroup changes in all variables except ALT and hepcidin were significant (P < .05). Besides, acute aerobic exercise increased levels of aspartate aminotransferase, ALT, ferritin, and hepcidin (P = .04, P = .52, P < .001, P < .001; respectively), whereas ALP levels decreased (P < .001). In addition, changes in ALP and hepcidin levels were significant between the 2 groups (P = .05, P < .001; respectively). Based on the study's results, it can be concluded that 8 weeks of aerobic interval training can decrease ferritin and hepcidin levels, but acute aerobic exercise increases them.

Comparison of preoperative and postoperative serum thiol/disulfide levels in patients undergoing laparoscopic sleeve gastrectomy for morbid obesity.

Obesity, a prevalent chronic disease, results from an imbalance between energy intake and expenditure. The oxidative stress associated with obesity stems from an imbalance between reactive oxygen species and the cell's antioxidant defense system. Oxidative stress can cause many diseases. The assessment of thiol/disulfide balance, a biochemical test, can be used to detect oxidative stress. The aim of this study is to determine the changes in oxidative stress associated with obesity after obesity surgery by assessing the thiol/disulfide levels. The study was conducted with 40 volunteer patients with a body mass index (BMI) above 40 who underwent obesity surgery at Harran University Hospital General Surgery. Thiol and disulfide levels and other blood parameters were measured from the preoperative and postoperative 2nd and 6th-month blood samples of the patients. BMI was calculated by recording the weights and heights of the cases. Patients with diseases that could affect oxidative stress measurements and those using medication were excluded from the study, and the analyses were performed accordingly. The results showed a statistically significant decrease in native thiol, disulfide, reduced thiol, oxidized thiol, glucose, ALT (alanine aminotransferase), ALP (alkaline phosphatase), total cholesterol, HDL (high-density lipoprotein), triglyceride, and BMI values between the preoperative, 2-month postoperative, and 6-month postoperative measurements (p<0.05). Restrictive methods such as sleeve gastrectomy in individuals with morbid obesity led to weight control and a decrease in adipose tissue, reducing oxidative stress and increasing antioxidant response.

Clinical, Gender, Socioeconomic Characteristics and Outcomes of Individuals Receiving Hepatitis B Treatment in Ethiopia: 18-Month Follow-Up.

There is a lack of real-world data on hepatitis B (HBV) treatment in Africa. We conducted a single-center 18-month prospective cohort study in Ethiopia to understand clinical, laboratory, and demographic variables associated with HBV treatment. One hundred fifty HBV-positive patients were included: 51 on treatment, 99 with no treatment. Median age was similar between groups. Those on treatment were more likely to be male (86%), report higher coffee intake (90% versus 70%, P < 0.05), lower khat intake (0% versus 9%, P = 0.08), lower alcohol consumption (0% versus 5%, P = 0.1), and had attained higher levels of education (56% versus 42%, P = 0.19). Individuals on treatment had higher median aspartate aminotransferase (AST), alanine aminotransferase (ALT), HBV DNA, and median Aminotransferase-to-Platelet Ratio Index and Fibrosis-4 scores. At 6 and 12 months, those on treatment showed a decrease in median AST, ALT, and fibrosis scores and had less hepatocellular carcinoma development at 6 months (2% versus 4%). Our study highlights potential demographic disparities in HBV treatment as well as benefits in a real-life setting in Africa.

Copy Number Variation in the GSTM1 and GSTT1 Genes and the Risk of Liver Cirrhosis in Eastern Ethiopia.

Polymorphisms in glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) can cause an entire gene deletion. The current methodology can accurately identify GSTM1 and GSTT1 copy number variants (CNVs), which may shed light on the true contribution of each gene copy to the cellular detoxification process and disease risk. Because liver cirrhosis is becoming a critical worldwide health issue, this study determined the CNVs of GSTM1 and GSTT1 and their relationship to the risk of liver cirrhosis. In this study, we compared 106 patients with liver cirrhosis to 104 healthycontrols. Real-time PCR was used to identify the CNVs of GSTM1 and GSTT1. Logistic and linear regression models were used to estimate the relationship between liver cirrhosis and clinical chemistry variables with the CNVs, respectively. In 3.3% of the study participants, >2 copies of the GSTM1 or GSTT1 genes were detected. GSTT1 carriers had a significantly lower risk of liver cirrhosis (p<0.05) compared with individuals who had homozygous deletion (adjusted odds ratio (AOR) = 0.47; 95% CI: 0.25, 0.86). This risk reduction was significant (p<0.05) in patients with a single copy of the GSTT1 gene (AOR = 0.48; 95% CI: 0.25, 0.91). Those with ≥2 copies of combined GSTM1 and GSTT1 also had a significantly (p<0.05) lower risk of developing liver cirrhosis compared with double null genotypes (AOR = 0.38; 95% CI: 0.16, 0.91, p trend <0.001). Moreover, ≥2 copies of combined GSTM1 and GSTT1 genes were associated with a substantial decrease in alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels, respectively. A single copy number of GSTT1, and ≥2 copies of combined GSTM1 and GSTT1 genes were associated with a reduced risk of liver cirrhosis in Ethiopians. These findings underscore the importance of gene-environment interactions in the multifactorial development of liver cirrhosis.

Lipid peroxidation and changes in major antioxidant markers in copper quinolate fungicide-exposed rats.

The present study investigated the toxic effects of sub-chronic exposure to copper quinolate (CuQ) fungicide on liver and kidney function. Twenty-four adult male Wistar rats were equally divided into a control group, and three treated groups received, respectively, by oral gavage, three increasing doses of CuQ: 47; 67.1; and 94mg/kg b.w corresponding, respectively, LD50/100, LD50/70, and LD50/50 daily for 8weeks. CuQ resulted in a significant increase in the serum enzymatic activity of aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and the serum levels of urea, creatinine, uric acid, and malondialdehyde, along with a marked decrease in alanine aminotransferase (ALT) activity, and the contents of total protein and albumin compared to those of the control group. Furthermore, glutathione content and the enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx) decreased significantly in a dose-dependent manner with respect to CuQ. The adverse effects of CuO were supported by the histopathological evaluations of liver and kidney tissues. Conclusively, sub-chronic CuQ exposure was shown to induce kidney and liver oxidative damage and dysfunction.

Effect of exercise-based interventions in nonalcoholic fatty liver disease: A systematic review with meta-analysis.

The global burden of nonalcoholic fatty liver disease (NAFLD) is rapidly increasing. This study aimed to evaluate the effect of exercise on intrahepatic lipid (IHL), serum alanine aminotransferase (ALT), body mass index (BMI), and insulin resistance in NAFLD patients. We searched MEDLINE, Embase, Cochrane CENTRAL, KMbase, and the Korean Studies Information Service System through April 2022. The included studies were randomised control trials (RCTs) of exercise, in which IHL was measured using magnetic resonance imaging in adult NAFLD patients. Eleven RCTs with 577 participants were included in this meta-analysis. Exercise was significantly associated with a reduction in IHL (mean difference (MD), -2.03; 95% CI, -3.26 to -0.79; P=0.001) and a decrease in ALT (MD, -4.17; 95% CI, -6.60 to -1.73; P=0.0008). Regarding the duration of exercise, maintaining exercise for more than 3 months significantly improved IHL (MD, -3.62; 95% CI, -5.76 to -1.48; P=0.0009), while exercise for less than 3 months did not (MD, -1.23; 95% CI, -2.74 to 0.29; P=0.11). BMI and insulin resistance did not improve significantly with exercise. We found that exercise improved IHL and ALT levels in NAFLD patients. The effect of exercise is particularly increased when one engages in exercises that last longer than 3 months.

Effect of combined seeds of Sesemum indicum and Moringa oleifera compounded feed on liver function markers of alloxan-induced diabetic albino rats

This study investigated the effect of combined seeds of Sesemum indicum (SI) and Moringa oleifera (MO) on liver function markers in alloxan-induced diabetic albino rats. 54 albino rats were divided into 9 groups of 6 animals each. Group 1 served as the normal control and received standard feed diet, Group 2 (Diabetic control) received intraperitoneal injection of 140mg/kg of Alloxan, Group 3 (Positive control) received 5mg/kg of glibenclamide, Group 4; diabetic rats fed diet containing 15% of SI. Group 5; diabetic rat fed with 15% of MO diet, Group 6; diabetic rat fed with combination of 15% SI and 15% MO compounded diet. Group 7; diabetic rat fed with 30% of SI diet. Group 8; diabetic rat fed with 30% of MO diet. Group 9; diabetic rat fed with combination of 30% MO and 30% SI diet. The Feed was compounded and was given daily for 14 days. Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, albumin, and bilirubin were estimated to assess hepatic function using spectrophotometric method. Results showed a significant decrease in ALT, ALP, AST, and bilirubin levels when fed with compounded feeds at (p&lt;0.05). Also feeding of diet with combined seeds significantly (P&lt;0.05) increased the total protein and albumin in induced rats. Overall, compounded feed with combined seeds of SI and MO exhibited a promising anti-diabetic activity and normalized the liver enzyme activities which appeared comparable to the control glibenclamide in alloxan-induced diabetes hence, may be recommended for treatment/management of diabetes mellitus.

Toxicological effects of meloxicam on physiological and antioxidant status of common carp (Cyprinus carpio).

Fish in aquatic environments are end consumers of the food chain and are widely used for the evolution effects of environmental pollution and their interactions in aquatic ecosystem. In the present study, common carp (Cyprinus carpio) fingerlings were selected to assess the potential risk and aquatic toxicity of meloxicam as a non-steroidal anti-inflammatory and a commonly used pharmaceutical drug. In order to evaluate meloxicam toxicological effect on haematological, antioxidant status, enzymological and histological parameters, based on its LC50 24h acute toxicity (10.05mgL-1 ), fish fingerlings were exposed to four doses of meloxicam including; 0 (control), 0.1 (low), 1 (medium) and 2mgL-1 (high) under static bioassay method for 28 days. The results showed that sublethal doses of meloxicam significantly decreased alanine aminotransferase, alkaline phosphatase, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) levels in comparison with the control group after 28 days (p<0.05). However, red blood cell, haematocrit, haemoglobin and malondialdehyde values in fish exposed to meloxicam significantly increased alongside its concentration (p<0.05) more than the control group after 28 days. SOD, CAT and GPX mRNA expression levels in gill, liver, kidney and brain organ of fish under meloxicam treatment were significantly down-regulated compared to the control group (p<0.05). Histopathological assessment showed the increased vacuolation in hepatocytes in liver of fish exposure to medium and high doses of meloxicam. In conclusion, meloxicam induces oxidative stress in common carp which results a disruption of physiological and health status of this species based on our current findings.

BMSC-exosomes miR-25-3p Regulates the p53 Signaling Pathway Through PTEN to Inhibit Cell Apoptosis and Ameliorate Liver Ischemia‒reperfusion Injury.

Hepatic ischemia‒reperfusion injury (HIRI) is a pathological phenomenon during liver surgery, and bone marrow-mesenchymal stem cell (BMSC) exosomes (BMSC-Exos) regulate cell apoptosis and reduce ischemia‒reperfusion injury. We aimed to investigate the roles of BMSC-Exos and miR-25b-3p (enriched in BMSC-Exos) in HIRI and elucidate the underlying mechanisms. An HIRI mouse model was constructed and preinjected with BMSC-Exos, agomir-miR-25, agomir-miR-NC, or PBS via the tail vein. Compared with mice with HIRI, mice with HIRI preinjected with BMSC-Exos had significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated liver necrosis (P < 0.05). Quantitative hepatic transcriptomics showed that mice with HIRI preinjected with BMSC-Exos exhibited increased cell division, hematopoietic or lymphoid organ development and metabolic processes. miRNA sequencing of BMSC-Exos revealed that miR-25, which is related to I/R injury, was enriched in the exosomes. Compared with HIRI + NC mice, HIRI + miR-25b-3p mice had significantly increased miR-25b-3p expression, decreased ALT/AST levels and apoptosis-related protein expression (P < 0.05), and alleviated liver necrosis. The proliferation of AML-12 cells transfected with miR-25b-3p was significantly higher than that in the mimic NC group (P < 0.01) after hypoxia induction, and the apoptosis rate of cells was significantly lower than that in the NC group (P < 0.01). PTEN was identified as a miR-25b-3p target gene. PTEN expression was significantly diminished in miR-25b-3p-transfected AML12 cells (P < 0.05). HIRI + agomir-miR-25 mice displayed reduced PTEN expression and decreased p53 and cleaved caspase 3 levels compared to HIRI + NC mice. We revealed the roles and underlying mechanisms of BMSC-Exos and miR-25 in HIRI, contributing to the prevention and treatment of HIRI.

Melatonin downregulates the increased hepatic alpha-fetoprotein expression and restores pancreatic beta cells in a streptozotocin-induced diabetic rat model: a clinical, biochemical, immunohistochemical, and descriptive histopathological study.

Diabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes. This study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how β-cells of the pancreas in diabetic rats respond to MT administration. Forty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively. MT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the β-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic β-cells; its antioxidant effect also reduced hepatocyte injury. Collectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic β-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes.

The Effect of Mesenchymal Stem Cell-Derived Exosomes and miR17-5p Inhibitor on Multicellular Liver Fibrosis Microtissues.

Although several studies have been conducted on modeling human liver disease, it is still challenging to mimic nonalcoholic fatty liver disease in vitro. Here, we aimed to develop a fibrotic liver microtissue composed of hepatocytes, hepatic stellate, and endothelial cells. In addition, the therapeutic effects of umbilical cord mesenchymal stem cell-derived exosomes (UC-MSC-EXO) and anti-miR17-5p as new antifibrotic drugs were investigated. To create an effective preclinical fibrosis model, multicellular liver microtissues (MLMs) consisting of HepG2, LX2, and HUVECs were cultured and supplemented with a mixture of palmitic acid and oleic acid for 96 hr. Then, MLMs were exposed to UC-MSC-EXO and anti-miR17-5p in different groups. The results of cell viability, reactive oxygen species (ROS) production, liver enzyme levels, inflammation, and histopathology were analyzed to assess the treatment efficacy. Furthermore, the expression of collagen I (COL I) and α-smooth muscle actin (α-SMA) as critical matrix components, transforming growth factor beta (TGF-β), and miR-17-5p were measured. Free fatty acid supplementation causes fibrosis in MLMs. Our results demonstrated that UC-MSC-EXO and anti-miR17-5p attenuated TGF-β1, interleukin-1β, and interleukin-6 in all experimental groups. According to the suppression of the TGF-β1 pathway, LX2 activation was inhibited, reducing extracellular matrix proteins, including COL I and α-SMA. Also, miR-17-5p expression was elevated in fibrosis conditions. Furthermore, we showed that our treatments decreased alanine aminotransferase and aspartate aminotransferase, and increased albumin levels in the culture supernatant. We also found that both MSC-EXO and MSC-EXO + anti-miR17-5p treatments could reduce ROS production. Our findings indicated that anti-miR17-5p and MSC-EXO might be promising therapeutic options for treating liver fibrosis. Furthermore, EXO + anti-miR had the best effects on boosting the fibrotic markers. Therefore, we propose this novel MLM model to understand fibrosis mechanisms better and develop new drugs.

Green Synthesis of Zinc Oxide-Nanoparticles from Ziziphus Spina-Christi Leaves Extract: Characterization and Their Protective Effects Against Liver Disturbances in Adenine-Exposed Male Rats

Zinc oxide nanoparticles (ZnO-NPs) have a significant feature due to their uses in various fields including medicine, biosensors, food additives, and electronic materials. This study aimed to the green synthesis of ZnO-NPs using aqueous extract of Ziziphus-spina christi leaves (Sider) and evaluates its protective roles against liver disorders after adenine-exposed male rats. Thirty-six male rats (3 months in age and weighing 200 ± 5 g) were randomly divided into 6 equal groups as following: Control adenine, Ziziphus-spina christi, ZnO-NPs, adenine + Ziziphus-spina christi and adenine + ZnO-NPs for 30 days. At the end of 30 days, the activity of (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), superoxide dismutase (SOD) and concentrations of reduced glutathione (GSH) and nitric oxide (NO) were determined, as well as the liver histopathological alterations were investigated. Moreover, the body weight of all rats was measured over a week. The synthesized ZnO-NPs was characterized using several techniques. UV-Visible analysis showed a specific absorption peak at 362 nm. In Fourier Transform Infrared spectroscopy (FT-IR) absorption bands of Zn-O stretching bonding showed between 400 and 500 cm−1. Their crystallinity, hexagonal shape, size, and the specific surface area for the dry ZnO-NPs were also determined using the techniques of X-ray diffraction (XRD) and scanning electron microscopy (SEM) respectively. Results showed significant decreases in ALT, AST and ALP in both groups adenine + Ziziphus-spina christi leaves extract and adenine + ZnO-NPs in comparison to the adenine group (p &lt; 0.05), as well as significant increases in body weight. Significant decrease was also demonstrated in NO level associated with an increase in SOD, and GSH. Based on these results, it can be said that ZnO-NPs and Ziziphus-spina christi leaves effectively protect against adenine-induced liver disorders, these were confirmed by improvements marked in histological changes of liver tissue of rats. GRAPHICAL ABSTRACT

Protective mechanism of Coprinus comatus polysaccharide on acute alcoholic liver injury in mice, the metabolomics and gut microbiota investigation

Coprinus comatus polysaccharide (CCP) has significant hepatoprotective effect. To explore hepatoprotective mechanism of CCP, the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis. Simultaneously, hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota. The results showed that CCP significantly decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride (TG) levels in serum of alcoholic liver disease (ALD) mice. Histopathological examination showed that CCP can significantly improve liver damage. Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group, ALD group and CCP group, including taurine, xanthosine, fumaric acid and arachidonic acid, among others. Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism, biosynthesis of unsaturated fatty acids, amino acids metabolism and lipid metabolism. Additionally, CCP inhibited an increase in the number of Clostridium perfringens, Enterobacteriaceae and Enterococcus, and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice. All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.

Ghrelin protects against ischemia/reperfusion-induced hepatic injury via inhibiting Caspase-11-mediated noncanonical pyroptosis

BackgroundIschemia/reperfusion (I/R) injury is a complication of liver transplantation. I/R-induced inflammatory cell death, namely, pyroptosis, that is triggered by overactive inflammasomes results in the production of proinflammatory cytokines. Hepatic I/R injury correlates with the activation of the Caspase-11-mediated pyroptosis pathway. We investigated whether ghrelin, which is a pleiotropic gut hormone, may have anti-hepatic I/R injury effects, but the mechanism by which Ghrelin ameliorates hepatic I/R -induced injury remains a mystery. MethodsHepatic I/R injury was induced in a mouse model by clamping the left and right lobes of the liver for 90 min followed by reperfusion for 6 h, 12 h, or 24 h. As treatment, a saline with or without ghrelin was infused via the tail vain. Hepatocytes were isolated using a two-step collagenase liver perfusion method. ResultsIn our study, treatment with ghrelin protected against hepatic I/R injury as shown by decreased alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels (p < 0.001) and reduced the histological injury in liver tissues compared with untreated controls. The LDH level of primary hepatocytes was increased by hypoxia/reoxygenation (H/R), and it was then restored to normal levels by ghrelin-treatment (p < 0.05). Western blotting analysis showed that ghrelin significantly inhibited the expression of pyroptosis-related proteins, including Caspase-11, GSDMD-N, NLRP3 and HMGB1, both in vivo and in vitro (all p < 0.05) compared with the untreated controls. Immunofluorescence showed that the expression of Gasdamin D (GSDMD) in hepatocytes was increased after I/R or H/R, whereas GSDMD expression was reduced by ghrelin treatment (p < 0.05). ConclusionsOur findings suggest that ghrelin ameliorated I/R-induced hepatic injury by inhibiting Caspase-11-mediated pyroptosis. Ghrelin may be a potential therapeutic option to prevent hepatic I/R injury after liver transplantation.

Evaluation of the effectiveness of telemedical technologies in patients with digestive diseases

BACKGROUND: The use of telemedical technologies (TMT) is widespread in providing care to patients of various profiles. However, TMTs are hardly ever used in gastroenterology, despite the extensive digitalization of healthcare. Potential sites for the use of TMTs among gastroenterological patients were assessed.&#x0D; AIM: The study aimed to assess the effectiveness and benefits of TMTs in patients with digestive diseases.&#x0D; &#x0D; Patients with colorectal cancer (CRC): Screening and postoperative management. The TMT intervention increased the number of patients screened for CRC compared to standard face-to-face counseling. In addition, the quality of preparation for colonoscopy was higher in patients who interacted with the physician via TMTs compared to the control group. Most studies reported positive effects of TMTs on quality of life and physical activity in patients with CRC. However, the study by K. Beaver et al. showed that the incidence of CRC recurrence did not differ in the TMT and face-to-face groups.&#x0D; Patients with nonalcoholic fatty liver disease (NAFLD): Correction of lifestyle. When assessing the use of TMTs among NAFLD patients, a significant decrease in alanine aminotransferase and aspartate aminotransferase activity was found compared to that in face-to-face management. The results of the body mass index reduction are contradictory. The most pronounced tendency towards weight loss was observed with the telemedical follow-up of patients over a 6-month period.&#x0D; Patients with irritable bowel syndrome (IBS): Treatment and monitoring of symptoms. Two directions are distinguished in the treatment of IBS by ТМТs. The first is cognitive behavioral therapy (CBT). H. Everitt et al. showed clinically significant improvement in 72.8% of cases after 12 months of web-based CBT. The advantages of using telemedicine in the delivery of CBT include the geographical independence of the physician and the patient, personalization of treatment, and the possibility of ongoing support for the patient and his or her family. The second direction is the use of special diets, such as low-fermentable nutrient diets (FODMAP). Patients following the FODMAP diet supervised by the mobile app reduced symptom severity (odds ratio 55; 95% confidence interval 1198, p=0.01). Special mobile apps (IBS Constant Care) were used to monitor the condition of patients with IBS, which analyze input data and assess severity, providing information to both the patient and the physician.&#x0D; Patients with inflammatory bowel disease (IBD): Patient training and telemonitoring. The study by L. Pang et al. proved that the patients quality of life in the telemedicine intervention group was significantly higher (p=0.03). Another advantage of using TMTs is the provision of access to educational materials about IBD and the possibility of remote contact with the treating physician. The patients ability to obtain necessary information reduces the need for unplanned visits to medical facilities, thus reducing the cost of organizing medical care for patients with IBD. The degree of IBD activity and risk of recurrence and adherence to therapy did not differ significantly between the telemedicine intervention group and the standard face-to-face follow-up group.&#x0D; &#x0D; METHODS: A literature search relevant to the review was conducted in the PubMed database. The studies taken for assessment were those on the use of TMTs among patients with IBD, IBS, NAFLD, and CRC. TMTs were used to access educational information and dietary recommendations, provide information on lifestyle adjustments and physical activity, remind patients to take medicines, consult with physicians, and assess disease activity by completing online questionnaires. The various studies used text messaging, e-mail, mobile apps, websites, and videoconferencing apps as a means of communication.&#x0D; RESULTS: The use of telemedicine in the management of patients with digestive diseases showed high efficiency. TMTs contribute to:&#x0D; &#x0D; Improved quality of life in patients with digestive diseases.&#x0D; Increasing physical activity of patients with CRC and NAFLD.&#x0D; Improved quality of CRC screening.&#x0D; Maintaining remission of IBD and CRC as effectively as face-to-face monitoring.&#x0D; &#x0D; Moreover, the use of TMTs allows personalized treatment, ensures the ongoing support of the patient and his or her family by the medical staff, and provides patients with access to quality educational materials about the disease.&#x0D; CONCLUSIONS: Thus, the use of TMTs is promising in the treatment of digestive diseases and requires wider introduction into practice.

Protection of Liver Functions and Improvement of Kidney Functions by Twelve Weeks Consumption of Cuban Policosanol (Raydel®) with a Decrease of Glycated Hemoglobin and Blood Pressure from a Randomized, Placebo-Controlled, and Double-Blinded Study with Healthy and Middle-Aged Japanese Participants.

Policosanol consumption has been associated with treating blood pressure and dyslipidemia by increasing the level of high-density lipoproteins-cholesterol (HDL-C) and HDL functionality. Although policosanol supplementation also ameliorated liver function in animal models, it has not been reported in a human clinical study, particularly with a 20 mg doage of policosanol. In the current study, twelve-week consumption of Cuban policosanol (Raydel®) significantly enhanced the hepatic functions, showing remarkable decreases in hepatic enzymes, blood urea nitrogen, and glycated hemoglobin. From the human trial with Japanese participants, the policosanol group (n = 26, male 13/female 13) showed a remarkable decrease in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from baseline up to 21% (p = 0.041) and 8.7% (p = 0.017), respectively. In contrast, the placebo group (n = 26, male 13/female 13) showed almost no change or slight elevation. The policosanol group showed a 16% decrease in γ-glutamyl transferase (γ-GTP) at week 12 from the baseline (p = 0.015), while the placebo group showed a 1.2% increase. The policosanol group exhibited significantly lower serum alkaline phosphatase (ALP) levels at week 8 (p = 0.012), week 12 (p = 0.012), and after 4-weeks (p = 0.006) compared to those of the placebo group. After 12 weeks of policosanol consumption, the ferric ion reduction ability and paraoxonase of serum were elevated by 37% (p < 0.001) and 29% (p = 0.004) higher than week 0, while placebo consumption showed no notable changes. Interestingly, glycated hemoglobin (HbA1c) in serum was lowered significantly in the policosanol group 4 weeks after consumption, which was approximately 2.1% (p = 0.004) lower than the placebo group. In addition, blood urea nitrogen (BUN) and uric acid levels were significantly lower in the policosanol group after 4 weeks: 14% lower (p = 0.002) and 4% lower (p = 0.048) than those of the placebo group, respectively. Repeated measures of ANOVA showed that the policosanol group had remarkable decreases in AST (p = 0.041), ALT (p = 0.008), γ-GTP (p = 0.016), ALP (p = 0.003), HbA1c (p = 0.010), BUN (p = 0.030), and SBP (p = 0.011) from the changes in the placebo group in point of time and group interaction. In conclusion, 12 weeks of 20 mg consumption of policosanol significantly enhanced hepatic protection by lowering the serum AST, ALT, ALP, and γ-GTP via a decrease in glycated hemoglobin, uric acid, and BUN with an elevation of serum antioxidant abilities. These results suggest that improvements in blood pressure by consumption of 20 mg of policosanol (Raydel®) were accompanied by protection of liver function and enhanced kidney function.

Schizandrin C regulates lipid metabolism and inflammation in liver fibrosis by NF-κB and p38/ERK MAPK signaling pathways.

Liver fibrosis is considered a sustained wound healing response and metabolic syndrome, and its therapy is of great significance for chronic liver disease. Schizandrin C, as one lignan from hepatic protectant Schisandra chinensis, can depress the oxidative effect and lipid peroxidation, and protect against liver injury. In this study, C57BL/6J mice were used to estimate a liver fibrosis model by CCl4, and Schizandrin C exerted an anti-hepatic fibrosis effect, as evidenced by decreased alanine aminotransferase, aspartate aminotransferase and total bilirubin activities in serum, lower hydroxyproline content, recuperative structure and less collagen accumulation in the liver. In addition, Schizandrin C reduced the expressions of alpha-smooth muscle actin and type Ι collagen in the liver. In vitro experiments also revealed that Schizandrin C attenuated hepatic stellate cell activation in both LX-2 and HSC-T6 cells. Furthermore, lipidomics and quantitative real-time PCR analysis revealed that Schizandrin C regulated the lipid profile and related metabolic enzymes in the liver. In addition, the mRNA levels of inflammation factors were downregulated by Schizandrin C treatment, accompanied by lower protein levels of IκB-Kinase-β, nuclear factor kappa-B p65, and phospho-nuclear factor kappa-B p65. Finally, Schizandrin C inhibited the phosphorylation of p38 MAP kinase and extracellular signal-regulated protein kinase, which were activated in the CCl4 fibrotic liver. Taken together, Schizandrin C can regulate lipid metabolism and inflammation to ameliorate liver fibrosis by nuclear factor kappa-B and p38/ERK MAPK signaling pathways. These findings supported Schizandrin C as a potential drug for liver fibrosis.

A Potential Resuscitation Route on Battlefield: Immediate Intraperitoneal Fluid Administration Post-burn Shows Satisfactory Fluid Absorption and Anti-shock Effects.

Timely fluid resuscitation remains the key to the early treatment of severe burns. Intraperitoneal (IP) fluid administration is a simple, rapid resuscitation strategy via a puncture in the abdominal wall. This study aimed to evaluate the fluid absorption and anti-shock effects of IP delivery in the early stage after severe burns. A 30% total body surface area full-thickness burn model was established using male C57BL/6 mice. A total of 126 mice were randomly assigned into six groups (n = 21): the sham injury group (SHAM), the burn group without fluid resuscitation (NR), and the four IP resuscitation groups (IP-A/B/C/D, each being intraperitoneally administered with 60, 80, 100, and 120 mL/kg of sodium lactate Ringer's solution post-injury). Three-hour post-burn, six mice in each group were randomly selected and sacrificed for blood and tissue sampling to detect the IP fluid absorption rate and evaluate organ damage because of low perfusion. The remaining 15 mice in each group were observed for the vital signs within 48-h post-injury, and their survival rate was calculated. The 48-h survival rate increased in the IP-A (40.0%), IP-B (66.7%), IP-C (60.0%), and IP-D (13.3%) groups, compared with the NR group (0%). The mean arterial pressure, body temperature, and heart rate of mice were significantly stabilized in the IP groups. For the first 3-h post-injury, the absorption rates of groups IP-A (74.3% ± 9.5%) and IP-B (73.3% ± 6.9%) were significantly higher than those of groups IP-C (59.7% ± 7.1%) and IP-D (48.7% ± 5.7%). The levels of arterial blood pH, partial pressure of oxygen, partial pressure of carbon dioxide, lactate, and hematocrit were better maintained in the IP groups. Intraperitoneal resuscitation remarkably reduced the injury scores in burn-induced histopathology of the liver, kidneys, lungs, and intestines, accompanied by decreased alanine transaminase, creatinine, interleukin-1, and tumor necrosis factor-α in plasma, and augmented superoxide dismutase 2 and inhibited malondialdehyde in tissues. Group IP-B has the best performance for these indices. Intraperitoneal administration of isotonic saline post-burn can be adequately and rapidly absorbed, thereby boosting circulation and perfusion, precluding shock, alleviating organ damage caused by ischemia and hypoxia, and significantly increasing the survival rate. This technique, with a potential to be a supplement to existing resuscitation methods on the battlefield, is worth further investigation.