Serum Aspartate Aminotransferase Research Articles

Orbea variegata (L.) Haw in skin carcinogenesis: insights from an in vivo male Swiss mouse model study

ABSTRACT Skin cancer is the most widespread type of malignant tumor representing a major public health concern. Considering the numerous side effects associated with conventional treatments, phytotherapy may be regarded as a viable medicinal alternative. This study aimed to investigate the therapeutic potential of Orbea variegata (L.) Haw, an ornamental plant, in treating skin cancer using an animal model induced by a combination of ultraviolet (UV) irradiation and sulfuric acid treatment. The hydroethanolic extract of Orbea variegata underwent phytochemical characterization, identifying the presence of reducing sugars, coumarins, alkaloids, flavonoids, tannins, and saponins through qualitative screening. Quantitative analysis demonstrated significant amounts of phenolic compounds (29.435 ± 0.571 mg GAE/g of dry extract), flavonoids (6.711 ± 0.272 mg QE/g of dry extract), and tannins (274.037 ± 11.3 mg CE/g of dry extract). The administration the hydroethanolic extract in two concentrations (1 or 2 g/kg) to male Swiss mice exhibited no marked adverse effects, as evidenced by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activity levels. In addition, the extract significantly reduced skin hyperplasia and inflammation induced by UV/sulfuric acid treatment as noted in tissue analyses and decreased protein expression of nuclear proliferation marker (Ki-67). This improvement was associated with a marked decrease in oxidative stress, as indicated by diminished lipid peroxidation levels, and restoration of the activity of endogenous antioxidant enzyme catalase (CAT) to control levels. Our findings demonstrated the potential of Orbea variegata hydroethanolic extract to be considered as a treatment for skin cancer, exhibiting its apparent safety and efficacy in reducing inflammation and carcinogenesis in a UV/sulfuric acid-induced Swiss mouse model, attributed to its phytochemical content and associated antioxidant activities.

Effects of dietary β-sitosterol supplementation on growth performance, antioxidant ability, and disease resistance in largemouth bass Micropterus salmoides

β-sitosterol, as the most abundant phytosterol, has been shown to exert multiple biological roles in in vitro and in vivo animal studies. Largemouth bass (Micropterus salmoides) is an economical freshwater-farmed species widely cultivated in China due to its nutritious and delicious meat. This study investigated the effects of dietary β-sitosterol supplementation on largemouth bass farming. In the study, largemouth bass were fed with five levels of β-sitosterol (0, 20, 40, 80, and 160 mg/kg) supplementation in a commercial feed for four weeks. The growth performance, antioxidant ability, intestinal structure, immune-related gene expression, and resistance to pathogens such as Aeromonas hydrophila and largemouth bass virus (LMBRaV) were detected. The results revealed that β-sitosterol supplementation in feed increased the weight gain rate of largemouth bass, with 40 mg/kg supplementation displaying the best effect. The serum biochemical indices all showed an increase, including glucose and alkaline phosphatase. The intestinal villus length and muscularis propria thickness also increased, accompanied by elevated digestive enzyme activities, which promoted digestion and absorption of nutrients. Meanwhile, the levels of total cholesterol, aspartate aminotransferase, and alanine aminotransferase in serum decreased, indicating reduced liver damage. In addition, β-sitosterol supplementation effectively enhanced the antioxidant capacity of largemouth bass by decreasing malondialdehyde and elevating superoxide dismutase. Immune-related gene expression also changed. Pathogen infection tests revealed that β-sitosterol supplementation in feed had a certain protective effect against infection in largemouth bass, with the protection rate against A. hydrophila being higher than LMBRaV. The 40 mg/kg β-sitosterol supplementation group exhibited the best results. Collectively, the results revealed that the β-sitosterol can promote growth, improve enzyme activity, stimulate intestinal digestion, increase immune gene expression, and induce disease resistance in largemouth bass, with the optimal supplementation dosage being 40 mg/kg. β-sitosterol might be an excellent feed additive in aquaculture.

A new model of portal vein thrombosis in rats with cirrhosis induced by partial portal vein ligation plus carbon tetrachloride and intervened with rivaroxaban

Background and aimsPortal vein thrombosis (PVT) is a common complication of liver cirrhosis that can aggravate portal hypertension. However, there are features of both PVT and cirrhosis that are not recapitulated in most current animal models. In this study, we aimed to establish a stable animal model of PVT and cirrhosis, intervene with anticoagulant, and explore the related mechanism.MethodsFirst, 49 male SD rats received partial portal vein ligation (PPVL), and 44 survival rats were divided into 6 groups: PPVL control group; 4-week, 6 -week, 8-week, and 10-week model group; and the rivaroxaban (RIVA)-treated group. The rats were intoxicated with or without carbon tetrachloride (CCl4) for 4–10 weeks. Seven normal rats were used as the normal controls. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and parameters for blood coagulation were all assayed with kits. Liver inflammation, collagen deposition and hydroxyproline (Hyp) levels were also measured. The extrahepatic macro-PVT was observed via portal vein HE staining, etc. The intrahepatic microthrombi was stained via fibrin immunohistochemistry. The portal blood flow velocity (PBFV) and diameter were detected via color Doppler ultrasound. Vascular endothelial injury was evaluated by von Willebrand Factor (vWF) immunofluorescence. Fibrinolytic activity was estimated by western blot analysis of fibrin and plasminogen activator inhibitor-1 (PAI-1).ResultsAfter PPVL surgery and 10 weeks of CCl4 intoxication, a rat model that exhibited characteristics of both cirrhosis and extra and intrahepatic thrombi was established. In cirrhotic rats with PVT, the PBFV decreased, both factors of pro- and anti-coagulation decreased, but with relative hypercoagulable state, vascular endothelial injured, and fibrinolytic activity decreased. RIVA-treated rats had improved coagulation function, increased PBFV and attenuated thrombi. This effect was related to the improvements in endothelial injury and fibrinolytic activity.ConclusionsA new rat model of PVT with cirrhosis was established through partial portal vein ligation plus CCl4 intoxication, with the characteristics of macrothrombi at portal veins and microthrombi in hepatic sinusoids, as well as liver cirrhosis. Rivaroxaban could attenuate PVT in cirrhosis in the model rats. The underlying mechanisms of PVT formation in the rat model and pharmacological action of rivaroxaban are related to the regulation of portal blood flow, coagulant factors, and vascular endothelial cell function.

A new strain of Saccharomyces cerevisiae in diets of lactating Holstein cows improved feed efficiency and lactation performance

Abstract This study compared the effects of feeding a new strain of Saccharomyces cerevisiae HSA2020 with a commercial strain on in vitro rumen fermentation and production performance of dairy cows. Permeate was used as a substrate for the laboratory production of the new strain of S. cerevisiae after the hydrolysis by β–galactosidase (5000 µ/mL at 37°C). Two experiments were conducted: in Experiment 1, the effects of three levels (1, 2 and 3 g/kg dry matter) of S. cerevisiae on in vitro ruminal fermentation kinetics were evaluated. In Experiment 2, for 60 days, sixty multiparous Holstein cows (639±24.8 kg BW, 3±1 parity, 7±1 days in milk, with a previous milk production of 23±2.0 kg/d) during the previous lactation, were randomly assigned to 3 treatments in a completely randomized design. Cows were fed without any additives (control treatment) or supplemented with 2 g/kg feed daily of laboratory produced (PY)or commercial (CY) S. cerevisiae. In Experiment 1, inclusion of PY and CY increased (P<0.05) gas production, propionate, and nutrient disappearance, while decreased (P<0.05) methane production and protozoal count. Moreover, in Experiment 2, PY followed by CY increased (P<0.01) nutrient digestibility, and serum concentrations of total protein, albumin, and glucose (P<0.05). Higher daily milk yield, and milk energy output were observed with PY and CY without affecting concentrations of milk components or milk fatty acid profile. Compared to control, increased feed efficiency was observed with PY and CY. Compared to PY, CY increased serum concentrations of urea-N and decreased triglycerides, while PY decreased serum aspartate transaminase and increased concentration of conjugated linoleic acids in milk. In early lactating cow diets, both strains of S. cerevisiae improved production performance at 2 g/kg improved production performance, and minimal differences between strains were found.

Effect of grape-derived products on the serum levels of enzymes mainly produced by the liver: A systematic review and meta-analysis of parallel randomized controlled trials.

In recent years, an increase in the incidence of liver diseases has been reported all over the world. This study aims to comprehensively summarize and quantitatively analyze the existing evidence concerning the effectiveness of grape-derived products on liver enzymes through a systematic review and meta-analytic approach. PubMed, Scopus, Cochrane Library, and ISI Web of Science were comprehensively searched until January 2024. Articles that reported the effect of grape-derived products on serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels were included. Weighted mean differences (WMDs) were pooled using a random-effects model. Nine studies were included in the meta-analysis. The results revealed that grape-derived products did not significantly change the concentrations of ALT (WMD: -2.70 IU/L, 95% CI: -6.14 to 0.75, p = 0.12), and AST (WMD: -1.42 IU/L, 95% CI: -3.54 to 0.70, p = 0.18). However, a significant reduction was observed in serum ALP levels (WMD: -5.49 IU/L, 95% CI: -9.57 to -1.4, p = 0.008). The present findings suggest that grape-derived products positively influence serum ALP levels among adults. However, a more comprehensive decision necessitates additional studies.

Foot-and-mouth disease-associated myocarditis is age dependent in suckling calves

Myocarditis is considered a fatal form of foot-and-mouth disease (FMD) in suckling calves. In the present study, a total of 17 calves under 4 months of age and suspected clinically for FMD were examined for clinical lesions, respiratory rate, heart rate, and heart rhythm. Lesion samples, saliva, nasal swabs, and whole blood were collected from suspected calves and subjected to Sandwich ELISA and reverse transcription multiplex polymerase chain reaction (RT-mPCR) for detection and serotyping of FMD virus (FMDV). The samples were found to be positive for FMDV serotype “O”. Myocarditis was suspected in 6 calves based on tachypnoea, tachycardia, and gallop rhythm. Serum aspartate aminotransferase (AST), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH), and cardiac troponins (cTnI) were measured. Mean serum AST, cTn-I and LDH were significantly higher (P < 0.001) in < 2 months old FMD-infected calves showing clinical signs suggestive of myocarditis (264.833 ± 4.16; 11.650 ± 0.34 and 1213.33 ± 29.06) than those without myocarditis (< 2 months old: 110.00 ± 0.00, 0.06 ± 0.00, 1050.00 ± 0.00; > 2 months < 4 months: 83.00 ± 3.00, 0.05 ± 0.02, 1159.00 ± 27.63) and healthy control groups (< 2 months old: 67.50 ± 3.10, 0.047 ± 0.01, 1120.00 ± 31.62; > 2 months < 4 months: 72.83 ± 2.09, 0.47 ± 0.00, 1160.00 ± 18.44). However, mean serum CK-MB did not differ significantly amongst the groups. Four calves under 2 months old died and a necropsy revealed the presence of a pathognomic gross lesion of the myocardial form of FMD known as “tigroid heart”. Histopathology confirmed myocarditis. This study also reports the relevance of clinical and histopathological findings and biochemical markers in diagnosing FMD-related myocarditis in suckling calves.

Toxicological Effects of Commonly Used Mosquito Coil Smoke on Liver and Lung Function in Rats

The utilization of mosquito coils as a household-level strategy for mosquito control is widely practiced in malaria-endemic regions spanning Africa, Asia, and South America. However, the continuous application of mosquito coils has prompted significant apprehensions concerning environmental and health implications. This research aims to evaluate the potential hepatic and pulmonary toxicities associated with the inhalation of mosquito coil smoke in rat subjects over both sub-chronic and chronic durations. A questionnaire was used to make inquiries regarding the prevalent types and brands of mosquito coils employed, the manner in which they are used, the durations for which they are utilized. A total of twenty-four albino rats were categorized into three distinct groups: the control group and two exposed groups. These groups were subjected to distinct brands of mosquito coil smoke across two distinct exposure regimens – a sub-chronic exposure lasting 4 weeks and a chronic exposure spanning 12 weeks. Following the exposure periods, blood samples were collected for the analysis of serum-based and biochemical markers, including serum aspartate aminotransferase (AST), alanine aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), bilirubin, serum bicarbonate, and Lactate dehydrogenase (LDH), oxygen saturation, C-reactive protein, total protein, and microscopic analysis of lung tissue and liver tissue. The histopathological analysis of lung tissue was appropriately included. However, the analysis of liver tissue was omitted. The results demonstrated a significant elevation in the levels of these biochemical markers among the exposed rats in comparison to the control group. Concurrently, a decrease in blood oxygen saturation was noted in the exposed rats when contrasted with the control group. Conversely, the serum concentrations of high-sensitivity C-reactive protein, total protein, and alanine aminotransferase (ALT) did not exhibit notable differences in relation to the control group. Additionally, microscopic analysis of lung tissue indicated the presence of histopathological lesions in the exposed rats, suggesting a detrimental impact of mosquito coil smoke exposure in a time-dependent progression.

Genetic characterization and pathogenic effects of Hepatozoon canis infection in police dogs in Egypt

BackgroundHepatozoon canis is a protozoan parasite transmitted to dogs through ingesting the arthropod vector (hard ticks), which contains mature protozoal oocysts harboring infectious sporozoites.AimsThis study aims to evaluate the blood parameters, biochemical assays and histopathological appraisal of infected police dogs with Hepatozoon canis, from kennels in the police academy of Egypt during 2020–2021.MethodsRed blood cells count, hemoglobin, hematocrit, blood platelets and white blood cells count from collected blood samples were analyzed, and serum albumin, creatinine, urea, aspartate aminotransferase and alanine aminotransferase were analyzed from serum samples. Polymerase chain reaction amplified the 18S ribosomal RNAgene of the Hepatozoon species for genetic analysis, and the deoxyribonucleic acid products were sequenced and added to GenBank.ResultsThe present study resulted in 5% of the police dog population being infested with Rhipicephalus sanguineus. This study registered the sequences of the Hepatozoon canis 18S ribosomal RNAgene in Egypt for the first time in Genbank (MW362244.1–MW362245.1). The biochemical assay revealed that the parasite severely affected the protein, significantly increasing serum albumin in positive polymerase chain reaction testing dogs.ConclusionA thorough inspection discovered that 100 police dogs had clinical symptoms like fever, emaciation and anemia, while the other 200 were healthy and had no evident clinical indicators.

Potential utility of l-carnitine for preventing liver tumors derived from metabolic dysfunction-associated steatohepatitis.

Recent reports have unveiled the potential utility of l-carnitine to alleviate metabolic dysfunction-associated steatohepatitis (MASH) by enhancing mitochondrial metabolic function. However, its efficacy at preventing the development of HCC has not been assessed fully. l-carnitine (2g/d) was administered to 11 patients with MASH for 10 weeks, and blood liver function tests were performed. Five patients received a serial liver biopsy, and liver histology and hepatic gene expression were evaluated using this tissue. An atherogenic plus high-fat diet MASH mouse model received long-term l-carnitine administration, and liver histology and liver tumor development were evaluated. Ten-week l-carnitine administration significantly improved serum alanine transaminase and aspartate transaminase levels along with a histological improvement in the NAFLD activity score, while steatosis and fibrosis were not improved. Gene expression profiling revealed a significant improvement in the inflammation and profibrotic gene signature as well as the recovery of lipid metabolism. Long-term l-carnitine administration to atherogenic plus high-fat diet MASH mice substantially improved liver histology (inflammation, steatosis, and fibrosis) and significantly reduced the incidence of liver tumors. l-carnitine directly reduced the expression of the MASH-associated and stress-induced transcriptional factor early growth response 1. Early growth response 1 activated the promoter activity of neural precursor cell expressed, developmentally downregulated protein 9 (NEDD9), an oncogenic protein. Thus, l-carnitine reduced the activation of the NEDD9, focal adhesion kinase 1, and AKT oncogenic signaling pathway. Short-term l-carnitine administration ameliorated MASH through its anti-inflammatory effects. Long-term l-carnitine administration potentially improved the steatosis and fibrosis of MASH and may eventually reduce the risk of HCC.

Phase Ib/II Study of Lacnotuzumab in Combination with Spartalizumab in Patients with Advanced Malignancies.

Blocking the colony-stimulating factor 1 (CSF-1) signal on tumor-associated macrophages can lead to an upregulation of checkpoint molecules, such as programmed cell death ligand 1 (PD-L1), thus causing resistance to this blockade. Combining spartalizumab (PDR001), a high-affinity, ligand-blocking, humanized anti-PD-1 immunoglobulin G4 antibody, with lacnotuzumab (MCS110), a high-affinity, humanized monoclonal antibody directed against human CSF-1 can potentially overcome this resistance. This was a multicenter, phase Ib/II trial using a combination of spartalizumab with lacnotuzumab in patients with advanced cancers, including anti-PD-1/PD-L1 treatment-resistant melanoma, and anti-PD-1/PD-L1 treatment-naïve triple-negative breast cancer, pancreatic cancer, and endometrial cancer (ClinicalTrials.gov identifier: NCT02807844). The primary objective of dose escalation phase Ib was to assess safety, tolerability, and recommended phase II dose. The primary objective of the phase II expansion study was to assess the combination's antitumor activity, including objective response rate and clinical benefit rate. A total of eight patients (five in phase Ib and three in phase II) were evaluable for adverse events (AEs) at our study site. All eight patients experienced at least grade 1 AE. The most common treatment-related AEs were increased serum aspartate aminotransferase (38%), fatigue (38%), anemia (25%), increased alkaline phosphatase (25%), hyperbilirubinemia (25%), hypocalcemia (25%), and hypoalbuminemia (25%). Most of these AEs were grade 1 or 2. None of the patients experienced grade 4 AEs and no drug-related fatal AEs were reported among the eight patients treated in the study. One (13%) patient had stable disease (SD) (captured as unknown by the study sponsor because the evaluation criteria set per protocol was not met) and three (38%) patients had progressive disease. Four (50%) patients developed clinical disease progression based on investigator evaluation. One patient with pancreatic cancer achieved immune-related SD for 26 months while on the study treatments. The study completed phase Ib dose escalation and phase II. However, gating criteria for efficacy were not met for expansion beyond 80 patients in phase II and the sponsor did not continue development of the combination of spartalizumab and lacnotuzumab for oncology indications. The potential signal of activity in pancreatic cancer should be further explored.

4,4-Diallyl curcumin bis(2,2-hydroxymethyl)propanoate ameliorates nonalcoholic steatohepatitis in methionine-choline-deficient diet and Western diet mouse models.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that causes severe liver damage, fibrosis, and scarring. Despite its potential to progress to cirrhosis or hepatic failure, approved drugs or treatments are currently unavailable. We developed 4,4-diallyl curcumin bis(2,2-hydroxymethyl)propanoate, also known as 35e, which induces upregulation of mitochondrial proteins including carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II, heat shock protein 60, and translocase of the outer mitochondrial membrane 20. Among these proteins, the upregulated expression of CPT-I was most prominent. CPT-I plays a crucial role in transporting carnitine across the mitochondrial inner membrane, thereby initiating mitochondrial β-oxidation of fatty acids. Given recent research showing that CPT-I activation could be a viable pathway for NASH treatment, we hypothesized that 35e could serve as a potential agent for treating NASH. The efficacy of 35e in treating NASH was evaluated in methionine- and choline-deficient (MCD) diet- and Western diet (WD)-induced models that mimic human NASH. In the MCD diet-induced model, both short-term (2 weeks) and long-term (7 weeks) treatment with 35e effectively regulated elevated serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) concentrations and histological inflammation. However, the antisteatotic effect of 35e was obtained only in the short-term treatment group. As a comparative compound in the MCD diet-induced model, curcumin treatment did not produce significant regulatory effects on the liver triglyceride/total cholesterol, serum ALT/AST, or hepatic steatosis. In the WD-induced model, 35e ameliorated hepatic steatosis and hepatic inflammation, while increasing serum AST and hepatic lipid content. A decrease in epididymal adipose tissue weight and serum free fatty acid concentration suggested that 35e may promote lipid metabolism or impede lipid accumulation. Overall, 35e displayed significant antilipid accumulation and antifibrotic effects in the two complementary mice models. The development of new curcumin derivatives with the ability to induce CPT-I upregulation could further underscore their efficacy as anti-NASH agents.

Presence of eimerias in weaned alpacas and control alternative without causing liver damage

Considering eimeriosisin alpacasitis a fatal disease, raising the aim of providing an alternative to prophylactic control in alpacas. 30 weaned alpacas from CICAS “La Raya” of Cusco in August 2022were evaluated. These have been distributed in 3 groups of 10 alpacas. Toltrazuril was administered: group1(G1) 15 mg/kpv, group2 (G2) 22.5 mg/kpv and group3 (G3) control. Qualitative coproparasitological analysis of concentration by flotation. And quantitative analysis has been carried out using the modified McMaster method pre and post treatment. Possible liver damage was evidenced by serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). As results, 93.33% of weaned alpacas have presented eimeriosis. It has been shown a higher prevalence of E. macusaniensis(63.33%). In addition, 22.5 mg/kpv Toltrazuril partially controled E. macusaniensis. While 15 and 22.5 mg/kpv effectively control E. lamae. Furthermore, serum AST and ALT levels were 5.7 IU/L and 195.8 IU/L,respectively, post treatment with 22.5 mg/kpv Toltrazuril. In conclusion, Toltrazuril manages to control pathogenic eimeriae in alpacas, partially E. macusaniensis; buteffectively small eimeriae such as E. lamae. These doses do not alter liver function in weaned alpacas.

Virgin coconut oil mitigates the hepatotoxic effect of atrazine and diabetes on liver enzymes in male Wistar rats

To assess the hepatoprotective action of Virgin Coconut Oil(VCO) in atrazine administered rats. Adult male Wistar rats weighing 180-200 g body weight were separated into two major experimental groups. 35 rats in the test group were divided into five sub-groups of 7rats: Subgroup (SG)1,2 and 3 received 10 ml/kg body weight of distilled water, 10 ml/kg VCO and 123 mg/kg Atrazine (ATZ) respectively, SG 4 was diabetic control group and SG 5 was diabetic group treated with 10 ml/kg of VCO for 2weeks, after which the animals were sacrificed and blood collected for analysis. 35 rats for the recovery group were also divided into 5 subgroups of 7 rats; SG1 and 2 received 10 ml/kg body weight of distilled water and 10 ml/kg of VCO, SG 3, 4 and 5 received 123 mg/kg of ATZ for 2 weeks. After the first 2 weeks, SG 1,2,3 continued the initial treatment while the rats in SG4 and SG5 were fed with 10 ml/kg of VCO and10 ml/kg of distilled water respectively. After 2 weeks, all the animals were sacrificed and blood collected for analysis. We observed a significant increase in the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of the diabetes control and diabetes treated with VCO groups compared to the normal control. In the groups administered with atrazine, the result showed elevations in serum AST and ALT. With VCO,a significant decrease in ALT levels when compared to the ATZ continued group was observed, further potentiating the hepatoprotective ability of VCO.

The Effected of Curcuma to Dysmenorrhea: A Systematic Review

Background: Dysmenorrhea or menstrual pain is a common health problem among reproduction women. The prevalence of dysmenorrhea was high in many countries including in Indonesia. Some previous studies showed that curcumin was effective reduced menstrual pain. Purpose: The aim of this study was to determine the effected of curcumin to dysmenorrhea. Method: This study used systematic review method with Randomize Control Trial (RCT) design. The data was collected by using electronic databases such as Google Scholar, Science Direct, Pubmed, Scopus, Web of Science, SpringerLink and EBSCOhost in last 10 years, or in 2013-2023. The keywords used curcumin, turmeric, curcuma longa, dysmenorrhea, menstrual pain. Results: There were 7 selected articles in this literature study. Curcumin reduced intensity and duration of dysmenorrhea; the increasing of vitamin D; the reducing of serum IgE, serum aspartate transaminase (AST) and direct bilirubin levels among women with dysmenorrhea. Conclusion: Curcumin was affected to reducing the severity and symptoms of dysmenorrhea.

Ameliorative effect of bofutsushosan (Fangfengtongshengsan) extract on the progression of aging-induced obesity.

This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid-albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome.

Effects of electroacupuncture of different intensities and durations on PERK/ATF4/CHOP signaling pathway in liver of non-alcoholic fatty liver disease rats.

To analyze the effects of electroacupuncture (EA) at "Fenglong" (ST40) and "Zusanli" (ST36) of different intensities and durations on rats with non-alcoholic fatty liver disease (NAFLD) based on the protein kinase R-like endoplasmic reticulum kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP) signaling pathway, so as to explore its mechanism underlying improvement of NAFLD. SD rats were randomly divided into normal diet group, high-fat model group, sham EA group, strong stimulation EA (SEA) group, and weak stimulation EA (WEA) group, with 15 rats in each group. Each group was further divided into 2, 3, and 4-week subgroups. NAFLD rat model was established by feeding a high-fat diet. After successful modeling, rats in the SEA and WEA groups received EA at bilateral ST40 and ST36 with dense and sparse waves (4 Hz/20 Hz) at current intensities of 4 mA (SEA group) and 2 mA (WEA group), lasting for 20 minutes, once a day, 5 days a week with 2 days of rest. The sham EA group only had the EA apparatus connected without electricity. Different duration subgroups were intervened for 2, 3, and 4 weeks. After the intervention, the contents of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rats were detected by an automatic biochemical analyzer；liver morphological changes were observed by Oil Red O staining；real-time fluorescence quantitative PCR and Western blot were used to detect the expression of PERK, ATF4, and CHOP mRNAs and proteins in the rat liver tissue. In the high-fat model group, there was a significant accumulation of red lipid droplets in the liver cells, which was reduced significantly in the SEA group at the 4th week. Compared with the normal diet group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins in the liver tissue were elevated (P<0.01) in the high-fat model group . Compared with the high-fat model group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, CHOP mRNAs and proteins in the liver tissue were decreased (P<0.01, P<0.05) in the SEA and WEA groups. Compared with the sham EA group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs were decreased (P<0.01, P<0.05) in the SEA and WEA groups, the expression of PERK, ATF4, and CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA group at the 2nd, 3rd, and 4th week, the expression of PERK and CHOP proteins at the 2nd, 3rd, 4th week and ATF4 protein at 2nd week in the liver tissue were decreased (P<0.01, P<0.05) in the WEA group. Compared with the SEA group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins in the liver tissue were elevated (P<0.05, P<0.01) in the WEA group. Compared with the 2-week time point within the groups, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and PERK proteins in the liver tissue were decreased (P<0.01, P<0.05) in the SEA and WEA groups at 3rd and 4th week, the expression of ATF4 proteins in the liver tissue was decreased (P<0.01) in the SEA group at 3rd and 4th week, and the expression of CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA group at 4th week and in the WEA group at 3rd and 4th week. Compared with the 3-week time point within the groups, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs were significantly decreased (P<0.05, P<0.01) in the SEA and WEA groups at 4th week, the expression of PERK and CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA and WEA groups at 4th week, and the expression of ATF4 protein in the liver tissue was decreased (P<0.05) in the SEA group at 4th week. EA at ST40 and ST36 can significantly improve liver function in NAFLD rats, and its mechanism of action may involve inhibiting PERK expression thereby targeting the downstream ATF4/CHOP signaling pathway to suppress endoplasmic reticulum stress, exerting a liver protective effect；the optimal effect was observed with EA intensity of 4 mA for 4 weeks.

MiR-199-5p mediates the regulation of autophagy by targeting mTOR signaling and involvement in ammonia detoxification under ammonia stress in yellow catfish (Pelteobagrus fulvidraco)

Ammonia is a widely distributed hazardous aquatic pollutant that poses a threat to the development of aquatic organisms. A two-stage study was carried out to the response of yellow catfish to ammonia stress.At stage 1, yellow catfish were subjected to 0 mg/L total ammonia nitrogen (T-AN, CON group) and 125 mg/L T-AN (AM group) for 96 h, respectively. At stage 2, yellow catfish in AM group were transferred to water containing 0 mg/L T-AN for a 48-h recovery experiment (AMR group). Ammonia exposure significantly increases serum ammonia (SA), total cholesterol (T-CHO), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels, while decreases glucose (Glu) level. Only SA, GLU, TCHO, and AST returned to normal levels in AMR group, while extensive hepatocyte necrosis and vacuolization persisted. The results showed that the liver possesses a certain degree of ammonia-lowering capacity, yet ammonia-induced liver damage is irreversible. Ammonia stress-induced 486 down-regulated and 18 up-regulated microRNAs (miRNAs). Functional enrichment analysis of the top 10 miRNAs highlighted significant effects of ammonia on the “mTOR signaling pathway” and “autophagy-animals”. Furthermore, the significant negative correlation between the expression levels of miR-199-5p and mTOR suggests that mTOR as a potential target gene of miR-199-5p. The levels of LC3B, autophagosomes (AP), and autolysosomes (AL) in the AM group decreased significantly after 24 h of ammonia stress but returned to baseline after 96 h. Additionally, increased numbers of AP and AL were observed in the AMR group, suggesting that hepatic autophagy is initially suppressed under ammonia stress, followed by spontaneous recovery. This study also found that the expression levels of urea and glutamine synthesis-related genes (cps 1; arg; otc; ass; asl, and gs) significantly increased in the AM and AMR groups. Additionally, the contents of urea and glutamine in the liver was significantly elevated in the AM group. This indicates a simultaneous occurrence of urea and glutamine synthesis with the activation of autophagy during ammonia detoxification. The miR-199-5p/mTOR axis may regulate liver autophagy, potentially contributing to ammonia detoxification. The study has provided novel targets for enhancing ammonia tolerance in fish through nutritional regulation.

The Effect of Barley Bran Polyphenol-Rich Extracts on the Development of Nonalcoholic Steatohepatitis in Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet

Oxidative stress and inflammation play a central role in the progression of nonalcoholic steatohepatitis (NASH), which can lead to liver cirrhosis. Barley bran has potential bioactivities due to its high content of functional substances, such as anthocyanins, with anti-inflammatory and anti-oxidative properties. Here, we investigated whether barley bran polyphenol-rich extracts (BP) can prevent NASH in Sprague–Dawley rats fed a high-fat and high-cholesterol diet including 1.25% or 2.5% cholesterol for 9 weeks. In the rat model of NASH with advanced hepatic fibrosis, BP prevented NASH development by ameliorating the histopathological findings of lobular inflammation. The BP also tended to attenuate serum aspartate aminotransferase level in this model. In the rat model of NASH with mild-to-moderate hepatic fibrosis, BP tended to attenuate the serum levels of transaminases. BP-dose-dependent effects were revealed for several parameters, including monocyte chemoattractant protein-1, transforming growth factor-β, and manganese superoxide dismutase gene expressions in the liver. These results suggest that BP may prevent NASH development or progression, presumably due to its anti-inflammatory and anti-oxidative properties.

Curcumin alleviates zearalenone-induced liver injury in mice by scavenging reactive oxygen species and inhibiting mitochondrial apoptosis pathway

Curcumin (CUR) is a compound extracted from turmeric that has a variety of functions including antioxidant and anti-inflammatory. As an estrogen-like mycotoxin, zearalenone (ZEN) not only attacks the reproductive system, but also has toxic effects on the liver. However, whether CUR can alleviate ZEN-induced liver injury remains unclear. This paper aims to investigate the protective effect of CUR against ZEN-induced liver injury in mice and explore the molecular mechanism involved. BALB/c mice were randomly divided into control (CON) group, CUR group (200 mg/kg b. w. CUR), ZEN group (40 mg/kg b. w. ZEN) and CUR+ZEN group (200 mg/kg b. w. CUR+40 mg/kg b. w. ZEN). 28 d after ZEN exposure and CUR treatment, blood and liver samples were collected for subsequent testing. The results showed that CUR reversed ZEN-induced hepatocyte swelling and necrosis in mice. It significantly reduced the serum alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice (p < 0.05). In addition, CUR significantly reduced hepatic ROS, malondialdehyde, hydrogen peroxide and apoptosis levels in mice (p < 0.05). Quantitative RT-PCR and Western blot results showed that CUR significantly reduced the expression of Bax and Caspase3, and reversed the increase of Nrf2, HO-1 and NQO1 expression in the liver of mice induced by ZEN (p < 0.05). In conclusion, CUR alleviated ZEN-induced liver injury in mice by scavenging ROS and inhibiting the mitochondrial apoptotic pathway.

Spontaneous clearance of serum HCV-RNA after splenectomy in a patient with HCV-related liver cirrhosis and portal hypertension: a case report

BackgroundSpontaneous clearance of chronic hepatitis C virus (HCV) is rare in adults. A T-lymphocyte response is thought to be involved in HCV-RNA clearance. Splenectomy reportedly has a beneficial effect on T cell immune function in patients with cirrhosis. To the best of our knowledge, the present report is the first to describe spontaneous clearance of serum HCV-RNA within 1 year after splenectomy in a patient with cirrhosis.Case presentationA 55-year-old man with HCV cirrhosis was transferred to our institution with advanced pancytopenia, splenomegaly, and gastric varices. He had a 1-year history of ascites, edema, and general fatigue. The patient had a Child–Pugh score of 8 and serological type 1 HCV; the HCV-RNA level was 4.7 log IU/mL. Contrast-enhanced computed tomography showed gastric varices and marked splenomegaly (estimated spleen volume of 2175 mL). Esophagogastroduodenoscopy revealed enlarged gastric varices with no red color sign, and the varices were larger than those 1 year prior. He was diagnosed with decompensated HCV-related liver cirrhosis and portal hypertension. We considered direct-acting antiviral (DAA) therapy; however, DAA therapy was not approved in Japan for patients with decompensated cirrhosis at that time. Hand-assisted laparoscopic splenectomy was performed to improve the worsening portal hypertension. Further, we planned the initiation of DAA therapy after surgery, when such therapy would become available. DAA therapy was approved 1 year after splenectomy. At that time, we measured the HCV-RNA level before the initiation of DAA therapy; unexpectedly, however, serum HCV-RNA was not detectable, and the virus continued to disappear during the following 4 years. His liver function (total bilirubin, albumin, and prothrombin time) and pancytopenia improved during the 5 years postoperatively. The serum aspartate and alanine aminotransferase levels normalized between 1 and 5 years postoperatively. Esophagogastroduodenoscopy showed no change in the gastric varices during the 5 years after surgery. The patient remained asymptomatic and continued to do well.ConclusionsWe have presented a case of spontaneous clearance of HCV-RNA after splenectomy in a patient with cirrhosis and portal hypertension. Splenectomy may be associated with disappearance of HCV-RNA based on previous reports. More cases should be accumulated and evaluated.