Aspartate Aminotransferase Activities Research Articles

Embelin mitigates hepatotoxicity induced by isoniazid and rifampicin in rats

Isoniazid and rifampicin are reliable drugs against tuberculosis, but while effective, their use is associated with the risk of drug-induced liver damage. Embelin, a natural parabenzoquinone derived from the Embelia ribes plant, has gained attention for its potential therapeutic properties, antioxidant and organ-protective effects. The study aimed to assess the hepatoprotective properties of embelin against liver dama­ge induced by isoniazid and rifampicin in rats. Wistar rats were used, and liver damage was induced by administration of isoniazid (100 mg/kg) and rifampicin (100 mg/kg). Embelin was given at doses of 50, 75, and 100 mg/kg for 21 days. All the drugs were given orally. Serum levels of the oxidative stress markers, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) activity measured by enzymatic assay kits (Elabscience, China), and the levels of tumour necrosis factor-α (TNF-α), interleukins IL-1β and IL-6 measured by ELISA kits (Randox, UK) were estimated. Embelin administration at varying doses effectively restored AST, ALT, ALP, SOD and catalase activity and notably decreased MDA and nitric oxide concentration as well as expression of inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum of animals with drug-induced liver damage. These findings underscore embelin’s hepatoprotective effects, likely attributed to its radical scavenging properties and ability to suppress cytokine production. Keywords: antioxidant effect, cytokine suppression, embelin, hepatoprotection, isoniazid, rifampicin

Formic acid as an antibiotic alternative in broiler diets: effects on growth, carcass characteristics, blood chemistry, and intestinal microbial load

This study explored the ability of formic acid (FA) to replace antibiotics in broiler chicken diets. It examined how FA affected the chickens' growth, carcass characteristics, blood chemistry, and gut bacteria. The experiment randomly assigned 300 one-day-old (Ross 308) broiler chicks to 5 groups, each divided into 6 replicates with 10 unsexed chicks. The following were the treatments: 1st group, negative control (NC): only received a basal diet; 2nd group, positive control (PC): received a basal diet supplemented with 0.5 grams of Colistin antibiotic per kilogram of diet; 3rd, 4th, and 5th groups (FA2, FA4, and FA6) these groups received a basal diet along with formic acid added at increasing levels: 2, 4, and 6 Cm3 per kilogram of diet, respectively. Results found no significant differences in live body weight (LBW) or body weight gain (BWG) between treatment groups, except for LBW at one week and BWG at 0 to 1 and 4 to 5 wk of age. No significant variations were found in feed intake (FI) and feed conversion ratio (FCR) among the treatment groups, excluding FI and FCR at 1 to 2 wk of age. The treatments significantly impacted carcass traits, dressing percentage, breast meat, thigh meat, spleen, giblets, blood levels of urea, creatinine, total protein, globulin, and albumin, as well as the activity of enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in chicks fed different diets compared to control groups. The addition of FA to the diet significantly impacted antioxidant levels. Also, the FA2 group had the highest total bacterial count (TBC). However, the FA6 group was the opposite; it had the lowest levels of harmful bacteria, such as E. coli and Coliform. Supplementing broiler diets with formic acid improves blood parameters, antioxidant activity, and gut bacteria counts, with 4.0 cm³ formic acid/kg diet supplementation promoting optimal broiler health and product quality.

Environmentally responsive changes in mucus indicators and microbiota of Chinese sturgeon Acipensersinensis

The impact of environmental factors on the health of the endangered Chinese sturgeon (Acipenser sinensis) and the potential hazards associated with sample collection for health monitoring pose urgent need to its conservation. In this study, Chinese sturgeons were selected from indoor and outdoor environments to evaluate metabolic and tissue damage indicators, along with a non-specific immune enzyme in fish mucus. Additionally, the microbiota of both water bodies and fish mucus were determined using 16S rRNA high-throughput sequencing. The correlation between the indicators and the microbiota was investigated, along with the measurement of multiple environmental factors. The results revealed significantly higher levels of two metabolic indicators, total protein (TP) and cortisol (COR) in indoor fish mucus compared to outdoor fish mucus (p < 0.05). The activities of acid phosphatase (ACP), alkaline phosphatase (ALP), creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were significantly higher in indoor fish, serving as indicators of tissue damage (p < 0.05). The activity of lysozyme (LZM) was significantly lower in indoor fish (p < 0.01). Biomarker analysis at the phylum and genus levels in outdoor samples revealed that microorganisms were primarily related to the catabolism of organic nutrients. In indoor environments, microorganisms displayed a broader spectrum of functions, including ecological niche establishment, host colonization, potential pathogenicity, and antagonism of pathogens. KEGG functional enrichment corroborated these findings. Dissolved oxygen (DO), electrical conductivity (EC), ammonia nitrogen (NH3–N), turbidity (TU), and chemical oxygen demand (COD) exerted effects on outdoor microbiota. Temperature (TEMP), nitrate (NO3−), total phosphorus (TP), and total nitrogen (TN) influenced indoor microbiota. Changes in mucus indicators, microbial structure, and function in both environments were highly correlated with these factors. Our study provides novel insights into the health impacts of different environments on Chinese sturgeon using a non-invasive method.

Effect of repeated semen ejaculation on sperm quality and selected biochemical markers of canine semen

The aim of this study was to evaluate the quality parameters and selected biochemical markers of canine semen sampled at 24-h intervals over a period of 5 days, preceded by 6 months of sexual abstinence. Full ejaculates were obtained from 6 dogs. Ejaculate volume and total sperm counts in the ejaculate decreased gradually on successive sampling days. The percentage of total motile spermatozoa (TMOT), percentage of progressively motile spermatozoa (PMOT), sperm plasma membrane integrity (SPMI), and sperm mitochondrial membrane potential (MMP) increased on successive days of sampling. In addition, ATP content increased in spermatozoa. Total protein content (TPC) and the activity of aspartate aminotransferase (AAT), alkaline phosphatase (AP), and acid phosphatase (AcP) decreased in seminal plasma. Repeated ejaculation over a period of 5 days induced changes in the qualitative and quantitative parameters of canine semen. A decrease in the values of some biochemical markers of semen, secreted by the epididymis and the prostate gland, could point to disturbances in the secretory activity of these organs. Canine semen sampled after prolonged sexual abstinence is generally characterized by less desirable quality parameters, and this observation should be taken into consideration when semen is collected for artificial insemination or preservation. Semen quality can be significantly improved by repeating the sampling procedure after 24 hours. One the other hand, repeated sampling on successive days can significantly decrease total sperm counts in the ejaculate. As a result, a sufficient number of semen doses for artificial insemination may not be obtained from a single ejaculate.

Light perception and related alternation of physiological performance in spotted knifejaw Oplegnathus punctatus

Light is one of the main environmental factors that affects the behavior and physiology of fish. In the present study, the behavioral responses, retinal histology, hematological parameters (white blood cell [WBC], red blood cell [RBC], hemoglobin [Hb] hematocrit [Hct]), hepatic antioxidant enzyme (superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSH-Px]) activity, aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) activities, malondialdehyde (MDA) content, histological alterations, apoptosis, and stress-related gene expression (hsp70, hsp90a, hsp90b) of spotted knifejaw were investigated under different light colors. The results showed that the residence time of spotted knifejaw plants significantly decreased under red and blue light stimuli but significantly increased under green light. Moreover, a positive and negative phototaxis of the spotted knifejaw under green and red lights was observed. However, retinal structure (relative thickness, cell number, and size) remained unchanged after red and green light treatment for 12 h. WBC and RBC numbers, Hb and Hct contents, hepatic SOD, CAT, GSH-Px, ALT and AST activities, and MDA levels were significantly increased after red and green light treatment for 12 h. Moreover, red and green light treatment caused hepatocyte vacuolization and nuclear migration and significantly increased the percentage of apoptotic cells. Hepatic hsp70, hsp90a, and hsp90b mRNA levels were significantly upregulated under red and green stimuli. Furthermore, the values of the above parameters under red light treatment were significantly greater than those under green light treatment. The aforementioned parameters nearly recovered to normal levels after the fish returned to normal light for 12 h. In conclusion, in spotted knifejaw, green light promoted attraction and red light avoidance, while red light could induce a more sensitive physiological response than green light. These findings expand the current knowledge on light perception and aid in the management of spotted knifejaw in captivity.

A mixture of free and microencapsulated essential oils combined with turmeric and tannin in the diet of cattle in the growing and finishing phase: A new tool to enhance productivity

The study was conducted to evaluate whether adding a blend containing free and microencapsulated essential oils, combined with turmeric and tannin, can replace monensin as a performance improver, positively influencing animal health and meat quality. Fourteen male cattle with an average initial body weight of 253 kg and ten females with an average initial body weight of 239 kg were included in the experiment in a confinement system. The animals were divided into four independent groups: Males (M-PHYTO, inclusion of the phytogenic mixture; M-MONEN, inclusion of monensin); Females (F-PHYTO, inclusion of phytogenic; F-MONEN, inclusion of monensin). The diets were formulated for an average daily gain of 1.5 kg, with food provided twice daily. Data and biological samples were collected on days 33, 100, and 153. M-PHYTO and F-PHYTO showed greater average daily gain and body weight, with a tendency to consume more dry matter and feed efficiency. However, the apparent digestibility of nutrients was higher in animals in the MONEN group than those in the PHYTO group, regardless of sex. The total number of leukocytes in cattle in the M-PHYTO and F-PHYTO groups was higher due to the higher lymphocyte count in the blood of these animals. The activity of gamma-glutamyltransferase and aspartate aminotransferase in animals that consumed the phytogenic mixture was lower compared to animals that consumed monensin. TBARS levels were lower in the serum and meat of cattle in the M-PHYTO and F-PHYTO groups, as were the total thiol concentration and glutathione S-transferase activity in the blood and meat of these animals. Bacterial activity was greater in the rumen fluid of cattle that consumed the phytogenic, as demonstrated by the methylene blue reduction test. The total production of short-chain fatty acids and acetic acid showed an interaction between treatment and days for both sex classes and an effect of treatment for females, with a higher concentration in the rumen in the M-PHYTO and F-PHYTO groups. Propionic acid affected treatment and the treatment x day interaction for males and females, with the M-PHYTO and F-PHYTO groups showing higher concentrations. There was an interaction between treatment and day in the acetate/propionate ratio, being lower in M-PHYTO and F-PHYTO cattle. Treatment between ruminal microbiota groups had no effect. The rib eye area had more significant gains when consumed phytogenic by males and females. The subcutaneous and sirloin fat thickness was greater in F-PHYTO animals than in the control group; however, in males, the result was the opposite. The sum of polyunsaturated fatty acids in meat was higher in M-PHYTO compared to M-MONEN and lower in F-PHYTO meat compared to F-MONEN. These results indicate that the phytogenic mixture is a potential performance improver in the diet of growing and finishing cattle, regardless of sex, but meat characteristics differ between males and females.

Dietary saccharin sodium supplementation improves the production performance of dairy goats without residue in milk in summer

The purpose of this study was to investigate the effects of dietary saccharin sodium supplementation on production performance, serum biochemical indicators, and rumen fermentation of dairy goats in summer. Twelve Guanzhong dairy goats with similar body weight, days in milk, and milk yield were randomly divided into two dietary treatments: (1) CON: basal diet; (2) SS: basal diet + 150 mg/kg saccharin sodium on the basis of dry matter. The experiment lasted 35 d, including 7 d for adaptation and 28 d for dietary treatments, sampling and data collection. Each dairy goat was housed individually in a clean separate pen with ad libitum access to diet and water. The goats fed SS diet had increased dry matter intake (DMI; P = 0.037), 4% fat corrected milk yield (P = 0.049), energy corrected milk yield (P = 0.037), milk protein yield (P = 0.031), and total solids yield (P = 0.036). Serum activity of aspartate aminotransferase (P = 0.047) and concentrations of 70-kDa heat shock protein (P = 0.090), malondialdehyde (P = 0.092), and total protein (P = 0.057) were lower in goats fed SS diet than those fed CON diet. Supplementation of saccharin sodium tended to increase activity of glutathione peroxidase in serum (P = 0.079). The concentrations of rumen total volatile fatty acid (P = 0.042) and butyrate (P = 0.038) were increased by saccharin sodium supplementation. Dietary supplementation of saccharin sodium increased the relative abundance of Lachnobacterium (P = 0.022), Pseudoramibacter (P = 0.022), Shuttleworthia (P = 0.025), and Syntrophococcus (P = 0.037), but reduced the relative abundance of Prevotella_1 (P = 0.037) and Lachnospiraceae_UCG_008 (P = 0.037) in rumen. Saccharin sodium was observed in feces and urine of goats fed diet supplemented with saccharin sodium, but saccharin sodium was undetectable in the milk of goats receiving SS diet. In conclusion, administration of saccharin sodium was effective in increasing fat and energy corrected milk yield by increasing DMI and improving rumen fermentation and antioxidant capacity of dairy goats in summer. In addition, saccharin sodium residue was undetectable in the milk.

The ameliorative effect of methanol extract of Ricinodendron heudelotii (Baill.) leaves on paracetamol-induced hepatotoxicity in Wistar rats

Plants are a rich source of antioxidants that are produced naturally. Therefore, this study was aimed to evaluate the effect of the plant Ricinodendron heudelotii (Baill.) in the attenuation of paracetamol (PCM) hepatotoxicity in Wistar rats. Twenty-four male albino Wistar rats weighing between 200 and 250 g were divided into four groups, with six rats each. Group 1 served as the control group, receiving just distilled water. Groups 2 and 3 received orally 250 mg/kg bwt/day PCM and 300 mg/kg bwt/day methanol extract of Ricinodendron heudelotii (Baill.) leaves for two weeks, respectively. For group 4, the Ricinodendron heudelotii (Baill.) leaf extract was pre-administered for 1 week before receiving 300 mg/kg bwt/day Ricinodendron heudelotii (Baill.) leaves extract and 250 mg/kg bwt/day PCM for 2 weeks. As a marker of liver damage, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Liver tissue reduced glutathione (GSH) concentration, superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase activities were utilized to determine antioxidant state, while malondialdehyde (MDA) concentration was employed as a lipid peroxidation indicator. When compared to the control group, the activities of serum AST, ALT, SOD, and MDA levels were considerably (p < 0.05) higher in the PCM group, although GSH level and GST and catalase activities were significantly lower. In comparison to the PCM group, co-administration of PCM with Ricinodendron heudelotii (Baill.) extract decreased serum AST and ALT activities. This study shows that the leaf extracts of Ricinodendron heudelotii (Baill.) protects Wistar rats’ livers from PCM-induced oxidative stress by increasing antioxidant enzymes.

Effects of yellow mealworm (Tenebrio molitor) larvae meal on the growth performance, serum biochemical parameters and caecal metabolome in broiler chickens

The goal of this study was to evaluate the effects of Tenebrio molitor (TM) larvae meal on the growth performance, serum biochemical parameters and caecal metabolome of broiler chickens. A total of 600 1-d-old male Liangfenghua broilers were randomly assigned to five equal groups with 5 replicates and 24 birds in each replicate. The dietary treatments were as follows: the control group (TM0 group) was fed a basal diet, and the experimental groups were fed experimental diets in which 3% (TM3 group), 5% (TM5 group), 7% (TM7 group) and 9% (TM9 group) TM larvae meal included in the basal diet, respectively. The feeding period was 70 d. The results showed that body weight (BW) and average daily gain (ADG) significantly increased (p < 0.05) in response to dietary 3% TM larvae meal supplementation at the age of 70 d. Serum concentrations of triglyceride (TG) and serum activity of aspartate aminotransferase (AST) decreased (p < 0.05) in 3% TM larvae meal-fed broilers. UHPLC-MS/MS-based metabolomics analysis revealed that a total of 55 significantly different metabolites were obtained in the caecal contents of dietary TM larvae meal supplemented broilers. The relative contents of 28 metabolites such as trans-4-hydroxy-L-proline, thymine and retinoic acid were significantly up-regulated (FC > 1.5) and the relative contents of 27 metabolites like prostaglandin F2α, glucocorticoids and prostaglandin E2 were significantly down-regulated (FC < 0.667) in the TM3 group. The main altered pathways were clustered into arachidonic acid metabolism, primary bile acid metabolism and propionic acid metabolism. In conclusion, the results indicated that supplementation of 3% TM larvae meal can improve growth performance, reduce the activity of serum AST and the content of TG, and regulation of the pathways of lipid, amino acid, and sugar metabolism in the caecum of broilers by improving nutrient digestion and absorption.

Influence of the glutamate-glutamine cycle on valproic acid-associated hepatotoxicity in pediatric patients with epilepsy

Introduction Although valproic acid is generally well tolerated, hepatotoxicity is a common side effect in patients receiving long-term treatment. However, the mechanisms underlying valproic acid-associated hepatotoxicity remain elusive. Methods To investigate the mechanisms and explore the potential risk factors for valproic acid-associated hepatotoxicity, 165 age-matched pediatric patients were recruited for laboratory tests and glutamate-glutamine cycle analysis. Results The concentration of glutamate in patients with hepatotoxicity was significantly greater than that in control patients, while the concentration of glutamine in patients with hepatotoxicity was significantly lower than that in control patients (P <0.05). In addition, the frequencies of the heterozygous with one mutant allele and homozygous with two mutant alleles genotypes in glutamate-ammonia ligase rs10911021 were significantly higher in the hepatotoxicity group than those in the control group (47.1 percent versus 32.5 percent, P = 0.010; 17.6 percent versus 5.2 percent, P = 0.001, respectively). Moreover, heterozygous carriers with one mutant allele and homozygous carriers with two mutant alleles genotypes of glutamate-ammonia ligase rs10911021 exhibited significant differences in the concentrations of glutamine and glutamate concentrations (P ˂ 0.001 and P = 0.001, respectively) and liver function indicators (activities of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase, P <0.001, respectively). Furthermore, logistic regression analysis indicated that glutamate-ammonia ligase rs10911021 (P = 0.002, odds ratio: 3.027, 95 percent confidence interval, 1.521 − 6.023) and glutamate (P = 0.001, odds ratio: 2.235, 95 percent confidence interval, 1.369 − 3.146) were associated with a greater risk for hepatotoxicity, while glutamine concentrations were negatively associated with hepatotoxicity (P = 0.001, odds ratio: 0.711, 95 percent confidence interval, 0.629 − 0.804). Discussion Understanding pharmacogenomic risks for valproic acid induced hepatotoxicity might help direct patient specific care. Limitations of our study include the exclusive use of children from one location and concomitant medication use in many patients. Conclusion Perturbation of the glutamate-glutamine cycle is associated with valproic acid-associated hepatotoxicity. Moreover, glutamate-ammonia ligase rs10911021, glutamate and glutamine concentrations are potential risk factors for valproic acid-associated hepatotoxicity.

The impact of chrysanthemi indici flos-enriched flavonoid part on the model of hyperuricemia based on inhibiting synthesis and promoting excretion of uric acid

Ethnopharmacological relevanceIn recent years, in addition to hypertension, hyperglycemia, and hyperlipidemia, the prevalence of hyperuricemia (HUA) has increased considerably. Being the fourth major health risk factor, HUA can affect the kidneys and cardiovascular system. Chrysanthemi Indici Flos is a flavonoid-containing traditional Chinese patent medicine that exhibits a uric acid (UA)-lowering effect. However, the mechanisms underlying Chrysanthemi Indici Flos-enriched flavonoid part (CYM.E) mediated alleviation of HUA remain unelucidated. Aim of the studyThis study aimed to elucidate the efficacy of CYM.E in preventing and treating HUA and its specific effects on UA-related transport proteins, to explore possible mechanism. MethodsThe buddleoside content in CYM.E was determined through high-performance liquid chromatography. HUA was induced in mice models using adenine and potassium oxonate. Subsequently, mice were administered 10 mg/kg allopurinol, and 30, 60, and 90 mg/kg CYM.E to evaluate the effects of CYM.E on the of HUA mice model. Herein, plasma uric acid (UA), creatinine (CR), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) contents, along with serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured. Additionally, xanthine oxidase (XOD) and adenosine deaminase (ADA) activities in the liver were determined. The histomorphologies of the liver and kidney tissues were examined through hematoxylin and eosin staining. The messenger RNA (mRNA) expression of facilitated glucose transporter 9 (GLUT9), organic anion transporter (OAT)1, OAT3, and adenosine triphosphate binding cassette subfamily G2 (ABCG2) in the kidney was assessed by real-time quantitative polymerase chain reaction. Furthermore, the expression of urate transporter 1 (URAT1), GLUT9, OAT1, and OAT3 in the kidney, OAT4, and ABCG2 proteins was determined by immunohistochemistry and western blotting. ResultsThe buddleoside content in CYM.E was approximately 32.77%. CYM.E improved body weight and autonomous activity in HUA mice. Additionally, it reduced plasma UA, BUN, and CR levels and serum ALT and AST activities, thus improving hepatic and renal functions, which further reduced the plasma UA content. CYM.E reduced histopathological damage to the kidneys. Furthermore, it lowered plasma TC, TG, and LDL-c levels, thereby improving lipid metabolism disorder. CYM.E administration inhibited hepatic XOD and ADA activities and reduced the mRNA expression of renal GLUT9. CYM.E inhibited the protein expression of renal URAT1, GLUT9, and OAT4, and increased the mRNA and protein expression of renal OAT1, OAT3, and ABCG2. Altogether, these results show that CYM.E could inhibit the production and promote reabsorption of UA and its excretion.

The Role of Interferon-Induced Proteins with Tetratricopeptide Repeats 1 and 2 in Sepsis-Induced Acute Liver Injury.

Sepsis refers to a life-threatening organ dysfunction which can be resulted from the infection-induced dysregulated host response. A large number of inflammatory cytokines are released to act on the liver, making the liver one of the common target organs for the development of multiple organ dysfunction syndrome (MODS) in patients with sepsis. Sepsis-induced acute liver injury (SALI) can aggravate systemic disease. As a result, it is of great clinical significance to comprehend the molecular biological mechanism of SALI and to identify the markers for evaluating SALI. Interferon-induced proteins with tetratricopeptide repeats 1 and 2 (IFIT1, IFIT2) have been recognized as the anti-inflammatory factors that are widely expressed in various organs. The present study was aimed at clarifying the roles of IFIT1 and IFIT2 in the development of SALI. A two-sample Mendelian randomization (MR) analysis was employed. Summary statistics datas were obtained from GWAS for inflammatory factors [tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], IFIT2, and sepsis as well as liver injury. Independent SNPs were selected as instrumental variables (IVs). Inverse variance weighted (IVW) in the MR analysis was adopted as the primary method for estimating the causal associations of inflammatory factors and IFIT2 with two diseases, and the associations of inflammatory factors with IFIT2. Additionally, weighted median method, MR-Egger and sensitivity analyses were applied in assessing the robustness of the results and ensure the result reliability. Subsequently, 119 healthy volunteers, 116 patients with sepsis and 116 SALI patients were recruited. The ELISA method was employed to quantify the expression levels of TNF-α, IL-1β, and IL-6. Additionally, qRT-PCR was conducted to measure the expression of IFIT1 and IFIT2. Furthermore, the correlations of IFIT1 and IFIT2 with inflammatory factors, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were explored. As shown by the MR analysis, the genetically predisposed sepsis was significantly associated with the risk of IL-1β, with an odds ratio (OR) of 1.069 (95% confidence interval (CI), 1.015-1.127, p = 0.0119), and negatively associated with the risk of IL-6, with an OR of 0.880 (95% CI: 0.792-0.979, p= 0.0184). Meanwhile, there were positive causal effects of IL-6 (OR = 1.269, 95% CI: 1.032-1.561, p= 0.0238), IL-1β (OR = 1.106, 95% CI: 1.010-1.211, p = 0.0299) and IFIT2 (OR = 1.191, 95% CI: 1.045-1.359, p = 0.0090) on liver injury. Additionally, there was a positive causal effect of IFIT2 (OR = 1.164, 95% CI: 1.035-1.309, p= 0.0110) on IL-1β. Upon sensitivity analyses, there was weak evidence of such effects, indicating that the findings of this study were robust and reliable. Our results revealed the elevated levels of TNF-α, IL-1β, and IL-6 in the blood samples of sepsis and SALI patients (p < 0.0001). Conversely, IFIT1 and IFIT2 demonstrated the significantly decreased levels in peripheral blood mononuclear cells (PBMCs) of SALI patients (p < 0.0001). Furthermore, the expression levels of IFIT1 and IFIT2 were both negatively correlated with ALT activity (r = -0.3426, p = 0.0002; r = -0.3069, p = 0.0008) and AST activity (r = -0.2483, p = 0.0072; r = -0.3261, p = 0.0004), respectively. Moreover, the expression of IFIT1 and IFIT2 was both negatively related to the levels of TNF-α (r = -0.5027, p < 0.0001; r = -0.4218, p < 0.0001), IL-1β (r = -0.3349, p = 0.0002; r = -0.4070, p < 0.0001) and IL-6 (r = -0.2734, p = 0.0030; r = -0.3536, p < 0.0001), respectively. IFIT1 and IFIT2 can serve as the diagnostic markers for sepsis-related liver injury, and IFIT1 and IFIT2 may participate in the pathological process of sepsis-related liver injury by regulating inflammation and liver function.

Design, synthesis, and biological evaluation of (E)-3-(3-methoxy-4-substituted phenyl)-acrylic acid derivatives: Role of compound S17 in regulating lipid accumulation via AMPK activation

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a global public health concern characterized by excessive lipid accumulation in the liver. Ferulic acid (FA), a common foodborne phenolic acid, has been shown to reduce lipid accumulation by activating adenosine monophosphate-activated protein kinase (AMPK) and suppressing the expression of sterol regulatory element-binding protein-1 (SREBP-1). In this study, we synthesized a new class of (E)-3-(3-methoxy-4-substituted phenyl)-acrylic acid derivatives as AMPK activators. Among these derivatives, compound S17 demonstrated a more potent inhibitory effect on lipid accumulation compared to its counterparts. Specifically, S17 notably diminished intracellular triglyceride (TG) levels and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which are indicators of liver function. In addition, S17 curtailed intracellular lipid accumulation by activating the AMPK signaling pathway and down-regulating the protein expression of SREBP-1 in free fatty acid (FFA)-induced HepG2 cells. Therefore, findings from this study strongly suggest that compound S17 may serve as a promising therapeutic candidate for the treatment of NAFLD.

Potential effects of Sargassum kjellmanianum as a dietary supplement on the growth performance, immunity response, antioxidant status, and ammonia resistance of yellow catfish (Pelteobagrus fulvidraco)

This study aimed to investigate the potential effects of seaweed Sargassum kjellmanianum (SK) as a dietary supplement on the growth performance, blood biochemistry, immunology, antioxidants, and ammonia stress resistance of yellow catfish, Pelteobagrus fulvidraco. Four diets containing 0 % SK (control), 2.5 % SK, 5 % SK, and 10 % SK were fed to fish for 8 weeks. After the feeding trial, the fish were exposed to ammonia for 72 h and their mortality was recorded. Compared with the control group, the growth performance was significantly increased in the 2.5 % and 5 % SK groups (P < 0.05). Serum albumin levels were significantly increased (P < 0.05), meanwhile serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels were significantly decreased in fish fed with 2.5 % and 5 % SK (P < 0.05). Interestingly, the serum AST and ALT activities were significantly increased in the 10 % SK group (P < 0.05). Additionally, serum lysozyme, acid phosphatase, and complement 4 levels were all significantly increased in all SK groups than those of the control group (P < 0.05). In addition, serum malondialdehyde levels were significantly decreased (P < 0.05). Meanwhile, the total antioxidant capacity, superoxide dismutase, and catalase levels were significantly increased in the 2.5 % and 5 % SK groups with relative to the control group (P < 0.05). Notably, the cumulative mortality rate was significantly higher (46.67 %) in the control fish than those fed the SK diets (35–38.33 %) (P < 0.05). Taken together, the results indicated that adding SK to the diet of yellow catfish can enhance growth performance, stimulate immune responses, improve antioxidant status, and increase resistance to ammonia stress. It is recommended to use concentrations between 2.5 % and 5.0 % in present study.

Variations of blood metabolites in single‐ and multiple‐bearing Ossimi ewes during the transition period

AbstractEvaluation of the metabolic profile indices allows early detection and treatment of various metabolic disorders during the transition period in ewes. This study aimed to determine the variations in the blood metabolites around lambing in Ossimi ewes. The blood metabolites were investigated in ewes with single (n = 27) and multiple (n = 9) lambs at 3‐ and 1‐week pre‐lambing and 3‐week post‐lambing. The plasma concentrations of glucose were higher in single‐bearing ewes than those in multiple‐bearing ewes (p &lt; .05), moreover, its lowest value was measured at 1‐week prepartum in both groups. Throughout the study period, the serum concentrations of non‐esterified fatty acids (NEFA) were significantly increased in ewes with multiple lambs compared to ewes with single lambs (p &lt; .05), and the highest value was found at 1‐week before parturition in both groups. In addition, the serum level of beta‐hydroxybutyric acid (BHBA) was higher at 3‐week postpartum, and it was significantly increased in multiple‐bearing ewes than that in single‐bearing ones (p &lt; .05) at 3‐week pre‐lambing. In both groups, the lowest values of total proteins were determined 1‐week before lambing, and its concentrations, at 3‐ and 1‐week prepartum, were higher in ewes with single lambs than those with multiple lambs (p &lt; .05). In contrast, the serum concentrations of albumin were significantly lowered 1‐week postpartum (p &lt; .05), and without significant differences between both groups (p &gt; .05). The serum activities of aspartate aminotransferase (AST) and gamma‐glutamyltransferase (GGT) were significantly increased at 1‐week after parturition in both groups (p &lt; .05). Furthermore, the serum activities of AST were higher in multiple‐bearing ewes than those in single‐bearing ones at 3‐week pre‐lambing and 3‐week post‐lambing (p &lt; .05). Variable positive and negative correlations were determined among the blood metabolites. In conclusion, physiological adaptations are associated with the fluctuation of the blood metabolites around lambing. The higher the number of foetuses the higher the metabolic variations in Ossimi ewes. Therefore, regular metabolic profiling for health monitoring may be necessary to avoid disease development during the transition period.

Mechanistic insight into the hepatoprotective effect of Moringa oleifera Lam leaf extract and telmisartan against carbon tetrachloride-induced liver fibrosis: plausible roles of TGF-β1/SMAD3/SMAD7 and HDAC2/NF-κB/PPARγ pathways

The increasing prevalence and limited therapeutic options for liver fibrosis necessitates more medical attention. Our study aims to investigate the potential molecular targets by which Moringa oleifera Lam leaf extract (Mor) and/or telmisartan (Telm) alleviate carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Liver fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 50% CCl4 (1 ml/kg) every 72 hours, for 8 weeks. Intoxicated rats with CCl4 were simultaneously orally administrated Mor (400 mg/kg/day for 8 weeks) and/or Telm (10 mg/kg/day for 8 weeks). Treatment of CCl4-intoxicated rats with Mor/Telm significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to CCl4 intoxicated group (P < 0.001). Additionally, Mor/Telm treatment significantly reduced the level of hepatic inflammatory, profibrotic, and apoptotic markers including; nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), transforming growth factor-βeta1 (TGF-β1), and caspase-3. Interestingly, co-treatment of CCl4-intoxicated rats with Mor/Telm downregulated m-RNA expression of histone deacetylase 2 (HDAC2) (71.8%), and reduced protein expression of mothers against decapentaplegic homolog 3 (p-SMAD3) (70.6%) compared to untreated animals. Mor/Telm regimen also elevated p-SMAD7 protein expression as well as m-RNA expression of peroxisome proliferator-activated receptor γ (PPARγ) (3.6 and 3.1 fold, respectively p < 0.05) compared to CCl4 intoxicated group. Histopathological picture of the liver tissue intoxicated with CCl4 revealed marked improvement by Mor/Telm co-treatment. Conclusively, this study substantiated the hepatoprotective effect of Mor/Telm regimen against CCl4-induced liver fibrosis through suppression of TGF-β1/SMAD3, and HDAC2/NF-κB signaling pathways and up-regulation of SMAD7 and PPARγ expression.

Expression of hepatic genes involved in bile acid metabolism in dairy cows with fatty liver

Bile acids are cholesterol-derived molecules that are primarily produced in the liver. In nonruminants with fatty liver, overproduction of bile acids is associated with liver injury. During the transition period, fatty liver is a metabolic disorder that can affect up to 50% of high-producing dairy cows. The purpose of this study was to provide a comprehensive evaluation on hepatic bile acid metabolism in dairy cows with fatty liver by assessing expression changes of genes involved in bile acid synthesis, export and uptake. The serum activities of aspartate aminotransferase, alanine aminotransferase and glutamate dehydrogenase and concentration of total bile acids were all greater, whereas serum concentration of total cholesterol was lower in cows with fatty liver than in healthy cows. Content of total bile acids was higher but total cholesterol was slightly lower in liver tissues from fatty liver cows than from healthy cows. The hepatic mRNA abundance of cholesterol 7a-hydroxylase (CYP7A1), hydroxy-delta-5-steroid dehydrogenase, 3 β- and steroid delta-isomerase 7 (HSD3B7) and sterol 12α-hydroxylase (CYP8B1), enzymes involved in the classic pathway of bile acid synthesis, was higher in fatty liver cows than in healthy cows. Compared with healthy cows, the hepatic mRNA abundance of alternative bile acid synthesis pathway-related genes sterol 27-hydroxylase (CYP27A1) and oxysterol 7α-hydroxylase (CYP7B1) did not differ in cows with fatty liver. The protein and mRNA abundance of bile acid transporter bile salt efflux pump (BSEP) were lower in the liver of dairy cow with fatty liver. Compared with healthy cows, the hepatic mRNA abundance of bile acid transporters solute carrier family 51 subunit α (SLC51A), ATP binding cassette subfamily C member 1 (ABCC1) and 3 (ABCC3) was greater in cows with fatty liver, whereas the solute carrier family 51 subunit β (SLC51B) did not differ. The expression of genes involved in bile acid uptake, including solute carrier family 10 member 1 (NTCP), solute carrier organic anion transporter family member 1A2 (SLCO1A2) and 2B1 (SLCO2B1) was upregulated in dairy cows with fatty liver. Furthermore, the hepatic protein and mRNA abundance of bile acid metabolism regulators farnesoid X receptor (FXR) and small heterodimer partner (SHP) were lower in cows with fatty liver than in healthy cows. Overall, these data suggest that inhibition of FXR signaling pathway may lead to the increased bile acid synthesis and uptake and decreased secretion of bile acids from hepatocytes to the bile, which elevates hepatic bile acids content in dairy cows with fatty liver. As the hepatotoxicity of bile acids has been demonstrated on nonruminant hepatocytes, it is likely that the liver injury is induced by increased hepatic bile acids content in dairy cows with fatty liver.

Machine learning-based model for predicting tumor recurrence after interventional therapy in HBV-related hepatocellular carcinoma patients with low preoperative platelet-albumin-bilirubin score.

This study aimed to develop a prognostic nomogram for predicting the recurrence-free survival (RFS) of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with low preoperative platelet-albumin-bilirubin (PALBI) scores after transarterial chemoembolization (TACE) combined with local ablation treatment. We gathered clinical data from 632 HBV-related HCC patients who received the combination treatment at Beijing You'an Hospital, affiliated with Capital Medical University, from January 2014 to January 2020. The patients were divided into two groups based on their PALBI scores: low PALBI group (n=247) and high PALBI group (n=385). The low PALBI group was then divided into two cohorts: training cohort (n=172) and validation cohort (n=75). We utilized eXtreme Gradient Boosting (XGBoost), random survival forest (RSF), and multivariate Cox analysis to pinpoint the risk factors for RFS. Then, we developed a nomogram based on the screened factors and assessed its risk stratification capabilities and predictive performance. The study finally identified age, aspartate aminotransferase (AST), and prothrombin time activity (PTA) as key predictors. The three variables were included to develop the nomogram for predicting the 1-, 3-, and 5-year RFS of HCC patients. We confirmed the nomogram's ability to effectively discern high and low risk patients, as evidenced by Kaplan-Meier curves. We further corroborated the excellent discrimination, consistency, and clinical utility of the nomogram through assessments using the C-index, area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Our study successfully constructed a robust nomogram, effectively predicting 1-, 3-, and 5-year RFS for HBV-related HCC patients with low preoperative PALBI scores after TACE combined with local ablation therapy.

Therapeutic effect of the solvent fraction of hexane leaf extract of Tapinanthus bangwensis (Engl. &amp; K. Krause) (Loranthaceae) in alloxan-induced pathology in diabetic rats

Plant-based products are gradually replacing pharmaceuticals in treating ailments, including diabetes, due to their safety, cost-effectiveness, potency, and availability. Therefore, the current study looked into the therapeutic effect of the solvent fraction of hexane leaf extract of Tapinanthus bangwensis (HEXETACF) (Loranthaceae) in alloxan-induced pathology in diabetic rats. The biochemical parameters were estimated using analytical grade kits via spectrophotometric method. The laboratory rats were distributed into group W (five rats on feed and water), group X (seven rats + 150 mg/kg alloxan solution only), group Y (seven rats + 150 mg/kg alloxan solution + 200 mg/kg BW silymarin for 21 days), and group Z (seven rats + 150 mg/kg alloxan solution + 250 mg/kg BW HEXETACF for 21 days). The results showed that HEXETACF and silymarin (SILY) reduced blood glucose concentration by 33.77% and 34.80%, respectively, after the 21st day of treatment (p &lt; 0.05). Additionally, alkaline phosphatase (ALP) and alanine aminotransferase (ALT) activity in SILY and HEXETACF were significantly decreased compared to the diabetic group (p &lt; 0.05), but no significant decrease in aspartate aminotransferase (AST) activity was observed between the test samples and the diabetic group. Furthermore, the test samples lowered malondialdehyde (MDA) levels, by improving glutathione, superoxide dismutase (SOD), and catalase (CAT) activity. The HEXETACF and SILY significantly decreased triglyceride levels (TG) compared to the diabetic group at p &lt; 0.05. They also reduced low-density lipoprotein (LDL) and cholesterol levels and increased the high-density lipoprotein levels compared to the diabetic group. Additionally, no significant decrease in serum electrolytes (Na+, K+, and Cl-), urea, and creatinine (including albumin and total protein) values was observed in HEXETACF and SILY, while hematological indices increased compared to the diabetic group. Histology results revealed that the test samples had normalized glomeruli, β-islet cells, and hepatocytes. However, a trace of mild congestion was noticed in the STDG. But edemic blood congestion was observed in the diabetic group. In conclusion, the current result demonstrated that HEXETACF may be a promising antidiabetic agent that could replace mSILY.

Comparative efficacy of sweated and non-sweated Salvia miltiorrhiza Bge. extracts on acute myocardial ischemia via regulating the PPARα/RXRα/NF-κB signaling pathway

Salvia miltiorrhiza Bge. (S. miltiorrhiza) is a well-known traditional Chinese medicine for the treatment of cardiovascular diseases. The processing of S. miltiorrhiza requires the raw herbs to sweat first and then dry. The aim of this study was to investigate the anti-acute myocardial ischemia (AMI) of S. miltiorrhiza extracts (including tanshinones and phenolic acids) before and after sweating, and to further explore whether the “sweating” primary processing affected the efficacy of S. miltiorrhiza. The AMI animal model was established by subcutaneous injection of isoprenaline hydrochloride (ISO). After treatment, the cardiac function of rats was evaluated by electrocardiogram (ECG), biochemical, and histochemical analysis. Moreover, the regulation of S. miltiorrhiza extracts on the peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor α (RXRα)/nuclear transcription factor-kappa B (NF-κB) signaling pathway of rats was assessed by the Western blotting. The results showed that sweated and non-sweated S. miltiorrhiza extracts including tanshinones and phenolic acids significantly reduced ST-segment elevation in ECG and the myocardial infarction area in varying degrees. Meanwhile, sweated and non-sweated S. miltiorrhiza reversed the activities of aspartate transaminase (AST), lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB), and superoxide dismutase (SOD), as well as the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in AMI rats. Concurrently, the results of Western blotting revealed that S. miltiorrhiza extracts regulated the PPARα/RXRα/NF-κB signaling pathway to exert an anti-inflammatory effect. Most importantly, sweated S. miltiorrhiza tanshinones extracts are more effective than the non-sweated S. miltiorrhiza, and the anti-inflammatory efficacy of tanshinones extract was also better than that of phenolic acid extract. Although phenolic acid extracts before and after sweating were effective in anti-AMI, there was no significant difference between them. In conclusion, both tanshinones and phenolic acids extracts of sweated and non-sweated S. miltiorrhiza promote anti-oxidative stress and anti-inflammatory against AMI via regulating the PPARα/RXRα/NF-κB signaling pathway. Further, the comparations between sweated and non-sweated S. miltiorrhiza extracts indicate that sweated S. miltiorrhiza tanshinones extracts have better therapeutic effects on AMI.