Aminotransferase Activity Research Articles

Mitigating effect of pomegranate peel extract against the furan induced testicular injury by apoptosis, steroidogenic enzymes and oxidative stress

Furan is generated in a wide array of heat-treated foods through thermal degradation, leading to severe impairments in the male reproductive system. The main objective of this study was to investigate the potential of pomegranate peel extract (PGPE) in mitigating testicular dysfunctions induced by furan. Male rats were categorized into four groups: control/untreated, PGPE, furan, and PGPE + furan group. The study results revealed that furan-treated rats exhibited significantly elevated aminotransferase and phosphatase activity, and also generated increased oxidative stress, and reduced antioxidative stress protein activity. Additionally, protein content levels (ALT, AST, ALP, and ACP) and activities of steroidogenic Leydig cell hydroxysteroid dehydrogenase (3β-HSD and 17β-HSD) enzymes were significantly decreased. Significant variations in testicular parameters, apoptotic genes (Bcl-2, P53, and Caspase3), inflammatory and anti-inflammatory cytokines (IL1β, IL10), male sex hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sperm quality were also observed. Furthermore, testicular histological abnormalities were confirmed by biochemical and molecular modifications. Notably, PGPE pre-treated furan-intoxicated animals exhibited significant improvements in most of the assessed parameters compared to furan-treated groups. In conclusion, PGPE presents essential preventive measures and a novel pharmacological potential therapy against furan-induced testicular injury.

Вплив блокади клітинних протеїнкіназ на обмін речовин при експериментальному цукровому діабеті

Prospective use of receptor protein kinase inhibitors (PKI) for the prevention and/or treatment of diabetic complications necessitates the study of their effect on carbohydrate, lipid, and protein metabolism in experimental models of type 1 (DM1) and type 2 (DM2) diabetes. DM1 was modeled in male Wistar rats with streptozotocin administration (50 mg/ kg), DM2 – by long-term (180 days) maintenance on a highcalorie fat diet (HFD; 56,7% fat) with the introduction of a lower dose of streptozotocin (25 mg/kg). For the treatment, we used insulin (“Actrapid Novo Nordisk”, Denmark) and a PKI inhibitor Sorafenib (“Cipla”, India), added orally in sachet form (150 mg/kg). Regardless of the diet type, the streptozotocin administration led to hyperglycemia, weight loss, glucose- and ketonuria, polyuria, and polydipsia. The severity of these manifestations was heightened in HFD rats, with a mortality rate of 53.3% observed (when modeling DM1 – 12%), likely attributed to the onset of liver failure. In HFD rats, slight hyperglycemia was noted only on the 150th day. All the diabetes models used were accompanied by significant hypercholesterolemia and hyperlipidemia. The addition of glucose to HFD rats increased the cholesterol content. HFD caused hypoproteinemia, metabolism suppression and increased transaminases activity. The established violations were largely restored with the use of PKI: glycemia level, body weight loss, the content of triglycerides and very low-density lipoproteins decreased; an increase in high-density lipoproteins and the normalization of pigment metabolism were observed.

Multifunctionality of arginine residues in the active sites of non-canonical d-amino acid transaminases

Structure-function relationships are key to understanding enzyme mechanisms, controlling enzyme activities, and designing biocatalysts. Here, we investigate the functions of arginine residues in the active sites of pyridoxal-5′-phosphate (PLP)-dependent non-canonical d-amino acid transaminases, focusing on the analysis of a transaminase from Haliscomenobacter hydrossis. Our results show that the tandem of arginine residues R28* and R90, which form the conserved R-[RK] motif in non-canonical d-amino acid transaminases, not only facilitates effective substrate binding but also regulates the catalytic properties of PLP. Non-covalent interactions between residues R28*, R90, and Y147 strengthen the hydrogen bond between Y147 and PLP, thereby maintaining the reactivity of the cofactor. Next, the R90 residue contributes to the stability of the holoenzyme. Finally, the R90I substitution induces structural changes that lead to substrate promiscuity, as evidenced by the effective binding of substrates with and without the α-carboxylate group. This study sheds light on the structural determinants of the activity of non-canonical d-amino acid transaminases. Understanding the structural basis of the active site plasticity in the non-canonical transaminase from H. hydrossis, which is characterized by effective conversion of d-amino acids and α-keto acids, may help to tailor it for industrial applications.

A Perspective on Male Contraceptive Therapeutics of Hydro-ethanol Extract of Seeds of <i>Luffa acutangula (L.) Roxb.</i> in Human and Albino Rat: An <i>In-vitro</i> Meta-Analysis Study

Traditionally Luffa acutangula (L.) Roxb. has been utilized as an herbal contraceptive. This in-vitro study has been performed to search out the male contraceptive efficacy of hydro-ethanol (60:40) extract of Luffa acutangula (LAHEE) seeds in a dose-specific manner (1, 2, and 4 mg/ml of in-vitro media). The percentages of motile, viable, hypo-osmotic swelled (HOS), and acrosomal intact of human and rat sperms were declined significantly (p<0.05) at the above-mentioned doses of LAHEE-exposed groups against the placebo group. The inhibitory concentration 50% value (IC50) of LAHEE was 2.5 mg/ml in human and 1.2 mg/ml in rat spermatozoa immobilization. The ∆5,3β and 17β hydroxysteroid dehydrogenase (HSD) activities of rat’s testicular tissues were inhibited significantly at p<0.05 in LAHEE-treated groups than the placebo group. Activities of superoxide dismutase (SOD) and catalase were significantly inhibited (p<0.05) along with the significant increment (p<0.05) in the quantity of thiobarbituric acid reactive substances (TBARS) in rat’s testes and epididymis, sperm pellets of humans and rats in LAHEE-treated groups against the placebo group without any significant difference (p>0.05) in above said sensors in the liver and cardiac tissues of rats. The non-toxic nature of LAHEE was indicated by no significant alterations (p>0.05) in the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) after LAHEE exposure in said tissues of rats. The LC-MS study of LAHEE identified the presence of oleic acid, dihydroquercetin, luteolin-7-glucoside, formononetin, luteolin 8-C-pentoside-6-C-hexoside, pterosin B, boldine and berberine. These findings interpreted that the LAHEE possesses spermiological inhibitory and hypo-testicular activities, which indicate a promising possibility to develop a potent herbal male contraceptive agent from this plant extract.

Evaluation of capillary miR-122 as a prognostic biomarker of paracetamol-induced liver toxicity.

Paracetamol (acetaminophen) overdose is a leading cause of acute liver failure in many Western countries. Diagnostic tools for this poisoning may be suboptimal in some cases and new biomarkers have been investigated. We investigated the role of capillary microRNA-122 (miR-122) as a prognostic biomarker of liver injury in the clinical management of patients with paracetamol overdose. In a paracetamol overdose patient cohort, miR-122 was measured by quantitative polymerase chain reaction in a blood drop obtained by a finger prick at the end of an antidote cycle treatment with N-acetylcysteine treatment (12h). Liver injury was defined as serum alanine aminotransferase (ALT) activity > 100IU/L collected at 10 or 20h after the start of treatment. Pearson's correlation analyses were performed. In patients with paracetamol overdose, capillary miR-122 was positively correlated with ALT measured at 10h and at 20h (r = 0.83, P < 0.0001; r = 0.96, P < 0.0001, respectively). This work supports the potential use of capillary miR-122 as a prognostic biomarker of liver injury throughout clinical management of patients with paracetamol overdose. Capillary miR-122 can be measured in a blood drop collected by a finger prick, a minimally invasive diagnostic test for patient stratification.

Biomarkers in Detection of Hepatitis C Virus Infection.

The hepatitis C virus (HCV) infection affects 58 million people worldwide. In the United States, the incidence rate of acute hepatitis C has doubled since 2014; during 2021, this increased to 5% from 2020. Acute hepatitis C is defined by any symptom of acute viral hepatitis plus either jaundice or elevated serum alanine aminotransferase (ALT) activity with the detection of HCV RNA, the anti-HCV antibody, or hepatitis C virus antigen(s). However, most patients with acute infection are asymptomatic. In addition, ALT activity and HCV RNA levels can fluctuate, and a delayed detection of the anti-HCV antibody can occur among some immunocompromised persons with HCV infection. The detection of specific biomarkers can be of great value in the early detection of HCV infection at an asymptomatic stage. The high rate of HCV replication (which is approximately 1010 to 1012 virions per day) and the lack of proofreading by the viral RNA polymerase leads to enormous genetic diversity, creating a major challenge for the host immune response. This broad genetic diversity contributes to the likelihood of developing chronic infection, thus leading to the development of cirrhosis and liver cancer. Direct-acting antiviral (DAA) therapies for HCV infection are highly effective with a cure rate of up to 99%. At the same time, many patients with HCV infection are unaware of their infection status because of the mostly asymptomatic nature of hepatitis C, so they remain undiagnosed until the liver damage has advanced. Molecular mechanisms induced by HCV have been intensely investigated to find biomarkers for diagnosing the acute and chronic phases of the infection. However, there are no clinically verified biomarkers for patients with hepatitis C. In this review, we discuss the biomarkers that can differentiate acute from chronic hepatitis C, and we summarize the current state of the literature on the useful biomarkers that are detectable during acute and chronic HCV infection, liver fibrosis/cirrhosis, and hepatocellular carcinoma (HCC).

EVALUATION OF SOME LIVER ENZYMES AND ALPHA-FETOPROTEIN IN WORKERS OCCUPATIONALLY EXPOSED TO E-WASTE IN NNEWI, ANAMBRA STATE NIGERIA

BACKGROUND: The advent of electricity has spurred significant technological advancements, leading to the production of numerous electrical and electronic devices. This progress, however, has resulted in a surge of largely irreparable electronic waste (e-waste) being constantly shipped to Nnewi, a metropolitan city with large-scale commercial and industrialactivities. E-waste contains thousands of chemicals, many of which are toxic to humans upon exposure.AIM OF THE STUDY: To evaluate the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and serum levels of alpha-fetoprotein (AFP) in workers occupationally exposed to e-waste.METHODOLOGY: The study comprised 40 e-waste workers (exposed group) and 40 healthy individuals (control group). Approximately 5 ml of venous blood was collected from each participant. The liver enzymes – ALT, AST, and ALP were evaluated colorimetrically, while AFP was assayed by Enzyme-linked Immunosorbent Assay (ELISA) method. Data obtained was statistically analyzed using SPSS windows version 25 with significance set as p&lt;0.05 at 95% confidence interval; Independent T-test, descriptive statistics and Pearson correlation were employed where relevant. Results were presented as means ± standard deviation in contingency tables.RESULT: There was no significant difference (p&gt;0.05) in the activities of ALT, AST, ALP and serum level of AFP between the exposed subjects and the control. However, significantly negative correlation was found between age and ALT (r = -0.294; p= 0.024), while DOE also had negative correlation with ALP (r= -0.294; P= 0.024) - all among e-waste exposed group.CONCLUSION: This study has shown that exposure to e-waste may not have a harmful effect on the liver function, since there was no significant difference in the liver function enzymes, and serum levels of AFP. However, age and longer duration of exposure to e-waste could be detrimental to health.

The role of dietary Clostridium autoethanogenum protein in the growth, disease resistance, intestinal health and transcriptome response of Pacific white shrimp under different stocking densities

With the rapid development of intensive farming mode and the high price of fishmeal (FM), finding alternatives to FM and exploring the application under different stocking densities has become a focus of current research in aquaculture. In this research, the ability of Pacific white shrimp (Litopenaeus vannamei) to utilize Clostridium autoethanogenum protein (CAP) at different stocking densities was investigated from the aspects of growth, disease resistance, intestinal health and transcriptome response. A 3 × 2 factorial design stocking experiment was conducted, using L. vannamei fed diets of two protein sources (FM and CAP) at three stocking densities with 100 per m3 (low, LSD), 200 per m3 (medium, MSD) and 300 per m3 (high, HSD) for 8 weeks. At the end of the feeding trail, the growth performance and the resistance to Vibrio parahaemolyticus of shrimp decreased with the increase of stocking density, and dietary CAP could promote the effects at the same stocking density when compared with the FM group, with more notable enhancement effect at high stocking density was observed. There was a significant interaction between stocking density and protein source on the activities of alkaline phosphatase (AKP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), catalase (CAT), superoxide dismutase (SOD), lysozyme (LYS), amylase and lipase, most of which were significantly different between CAP and FM groups only at high stocking density. Analysis of 16S rDNA sequencing showed that dietary CAP increased the alpha diversity of intestinal microbiota, inhibited the colonization of pathogenic bacteria and enhanced the abundance of beneficial bacteria. Transcriptomics results showed that DEGs in the FM vs CAP group at the same stocking densities were mainly enriched in immune and metabolism-related pathways including Toll and Imd, PI3K-Akt, and JAK/STAT signaling pathway. Pearson correlation analysis revealed significant correlation between the top ten intestinal bacteria at the genus level and markedly enriched DEGs, also more were detected under high density situations. In conclusion, dietary CAP could not only promote the growth of shrimp, but also improves the immunity and metabolism, and maintains the intestinal health of shrimp when compared with dietary FM, along with more pronounced improvement effect at high-density stocking. The results implied that CAP had a great potential as a novel protein source in shrimp intensive aquaculture.

The p21+ perinecrotic hepatocytes produce the chemokine CXCL14 after a severe acetaminophen overdose promoting hepatocyte injury and delaying regeneration

Fifty percent of all acute liver failure (ALF) cases in the United States are due to acetaminophen (APAP) overdose. Assessment of canonical features of liver injury, such as plasma alanine aminotransferase activities are poor predictors of acute liver failure (ALF), suggesting the involvement of additional mechanisms independent of hepatocyte death. Previous work demonstrated a severe overdose of APAP results in impaired regeneration, the induction of senescence by p21, and increased mortality. We hypothesized that a discrete population of p21+ hepatocytes acquired a secretory phenotype that directly impedes liver recovery after a severe APAP overdose. Leveraging in-house human APAP explant liver and publicly available single-nuclei RNAseq data, we identified a subpopulation of p21+ hepatocytes enriched in a unique secretome of factors, such as CXCL14. Spatial transcriptomics in the mouse model of APAP overdose confirmed the presence of a p21+ hepatocyte population that directly surrounded the necrotic areas. In both male and female mice, we found a dose-dependent induction of p21 and persistent circulating levels of the p21-specific constituent, CXCL14, in the plasma after a severe APAP overdose. In parallel experiments, we targeted either the putative senescent hepatocytes with the senolytic drugs, dasatinib and quercetin, or CXCL14 with a neutralizing antibody. We found that targeting CXCL14 greatly enhanced liver recovery after APAP-induced liver injury, while targeting senescent hepatocytes had no effect. These data support the conclusion that the sustained induction of p21 in hepatocytes with persistent CXCL14 secretion are critical mechanistic events leading to ALF in mice and human patients.

The Research of Antagonistic Endophytic Bacterium Bacillus velezensis CSUFT-BV4 for Growth Promotion and Induction of Resistance to Anthracnose in Camellia oleifera.

Camellia oleifera (C. oleifera) is one of the four main, woody, edible oil tree species in the world, while C. oleifera anthracnose is mainly caused by the fungus Colletotrichum fructicola (C. fructicola), which severely affects the yield of C. oleifera and the quality of tea oil. Bacillus velezensis (B. velezensis) CSUFT-BV4 is an antagonistic endophytic bacterium isolated from healthy C. oleifera leaves. This study aimed to investigate the biocontrol potential of strain CSUFT-BV4 against C. oleifera anthracnose and its possible functional mechanism, and to determine its growth-promoting characteristics in host plants. In vitro, CSUFT-BV4 was shown to have efficient biofilm formation ability, as well as significant functions in the synthesis of metabolic substances and the secretion of probiotic substances. In addition, the CSUFT-BV4 fermentation broth also presented efficient antagonistic activities against five major C. oleifera anthracnose pathogens, including C. fructicola, C. gloeosporioides, C. siamense, C. camelliae, and C. kahawae, and the inhibition rate was up to 73.2%. In vivo, it demonstrated that the growth of C. oleifera treated with CSUFT-BV4 fermentation broth was increased in terms of stem width, plant height, and maximum leaf area, while the activities of various defense enzymes, e.g., superoxide dismutase (SOD), phenylalanine aminotransferase (PAL), and polyphenol oxidase (PPO), were effectively increased. The remarkable antagonistic activities against C. oleifera anthracnose, the growth-promoting characteristics, and the induction of host defense responses indicate that endophytic bacterium CSUFT-BV4 can be effectively used in the biological control of C. oleifera anthracnose in the future, which will have a positive impact on the development of the C. oleifera industry.

Maximum storage time of refrigerated blood and frozen plasma samples from tambaqui, Colossoma macropomum

Blood analysis is an important tool for monitoring the health status of fish, but the time between collection and analysis can affect the outcome of the analysis. This study sought to determine the maximum time refrigerated blood and frozen plasma samples of the tambaqui, Colossoma macropomum, can be stored without affecting analysis. Samples from 12 fish were obtained, stored under refrigeration at 4 °C and evaluated after 0, 24, 48, 72, and 96 h, while samples from 14 fish were centrifuged, and the resulting plasma was frozen at −20 °C and then evaluated after 0, 8, 12, 16 and 20 weeks. The parameters analyzed were hematocrit (Ht), hemoglobin content (Hb), total erythrocytes (RBC), total (WBC) and differential leukocytes, total thrombocytes (TC), glucose content (Glc), total protein (TP), triglyceride content (TG), total cholesterol (CoT), and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). For refrigerated whole blood samples, mean corpuscular hemoglobin content (MCHC) showed a transient decline in 24 h, and there were decreases in WBC, TC, Glc and TG that persisted until the 72 h sample point (for Glc and TG) or persisted until the 96 h sample point (for WBC and TC). A decrease in RBC was noted from 48 h on, while ALT was significantly higher in the 96 h sample. Significant decreases in lymphocytes, monocytes, neutrophils and eosinophils were noted from 48 h of storage on, while a significant decline in basophil counts were noted over the last two sampled timepoints. The coefficient of variation was greatest at the 96 h timepoint, indicating increased variability in measured parameters after 4 d of refrigeration. Plasma samples frozen at −20 °C showed a significant variation in ALT after 8 weeks, and increases in TP and TG after 20 weeks. Therefore, it is recommended that refrigerated tambaqui whole blood samples be analyzed within 24 h and frozen tambaqui plasma samples analyzed within 8 weeks.

Growth performance, health status, gut microbiome, and expression of immune and growth-related genes of rainbow trout (Oncorhynchus mykiss) fed diets with pea protein replacement of fish meal

The need for fish meal constrains fish farming and significantly impacts sustainability of the aquaculture industry. Hence, it is important to investigate the use of plant-based protein sources in fish diets. The present study was conducted to determine the effects of different levels of fish meal (FM) replacement by pea protein (PP) in a 60-day feeding experiment in rainbow trout, Oncorhynchus mykiss. Effects on growth performance, body composition, hematology, serum biochemistry and immunology, and immune (TNF-α, IL1-ß and Il-8) and growth-related (GH and IGFI) gene expression were investigated. Five experimental diets (45% protein and 20% lipid) differed in replacement level of FM by PP at rates of 0% (control (PP0)), 25% (PP25), 50%(PP50), 75%(PP75) and 100%(PP100). Fish were fed with experimental diets in triplicate twice daily. The best growth performance was obtained in PP0 and PP25 groups. While fat ratios of fish fillets significantly differed (p < 0.05), there was no significant effects on protein ratios (p < 0.05). There was no significant change in the hematological values of fish, except those fed the PP100 diets, which displayed a reduction in eyrthocyte counts, hemoglobin content and hematocrit. As PP supplementation increased fish showed elevated serum glucose, total protein, cholesterol and myeloperoxidase activity and decreased glutamic pyruvic transaminase and alkaline phosphatase activity. Fish fed diets with between 25 and 75% replacement showed a decline in lactic acid bacteria in the gut. Significant increases in expression were observed in the liver of the PP25 fish relative to the 0% control for all immune and growth-related genes except for IL1-ß. These data suggest that up to 25% of FM can be replaced by PP without any adverse effects on rainbow trout.

Antagonizing Activin A/p15INK4b Signaling as Therapeutic Strategy for Liver Disease.

Activin A is involved in the pathogenesis of human liver diseases, but its therapeutic targeting is not fully explored. Here, we tested the effect of novel, highly specific small-molecule-based activin A antagonists (NUCC-474/555) in improving liver regeneration following partial hepatectomy and halting fibrosis progression in models of chronic liver diseases (CLDs). Cell toxicity of antagonists was determined in rat hepatocytes and Huh-7 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Hepatocytes and hepatic stellate cells (HSCs) were treated with activin A and NUCC-555 and analyzed by reverse transcription-polymerase chain reaction and immunohistochemistry. Partial hepatectomized Fisher (F)344 rats were treated with NUCC-555, and bromodeoxyuridine (BrdU) incorporation was determined at 18/24/36/120/240 h. NUCC-555 was administered into thioacetamide- or carbon tetrachloride-treated F344 rats or C57BL/6 mice, and the fibrosis progression was studied. NUCC-474 showed higher cytotoxicity in cultured hepatic cells; therefore, NUCC-555 was used in subsequent studies. Activin A-stimulated overexpression of cell cycle-/senescence-related genes (e.g., p15INK4b, DEC1, Glb1) was near-completely reversed by NUCC-555 in hepatocytes. Activin A-mediated HSC activation was blocked by NUCC-555. In partial hepatectomized rats, antagonizing activin A signaling resulted in a 1.9-fold and 2.3-fold increase in BrdU+ cells at 18 and 24 h, respectively. Administration of NUCC-555 in rats and mice with progressing fibrosis significantly reduced collagen accumulation (7.9-fold), HSC activation indicated by reduced alpha smooth muscle actin+ and vimentin+ cells, and serum aminotransferase activity. Our studies demonstrate that activin A antagonist NUCC-555 promotes liver regeneration and halts fibrosis progression in CLD models, suggesting that blocking activin A signaling may represent a new approach to treating people with CLD.

Assessment of Hepatoprotective and Antioxidant Effect of Acioa barteri Extract (ABE) in Alloxan-Induced Diabetic Rats

This study aimed to investigate the effects of Acioa barteri extract (ABE) on hepatocellular enzyme activity, hepatic function, and antioxidant stress indices in diabetic rats induced with alloxan. The antidiabetic effect of ABE was evaluated in six experimental groups: normal controls, diabetics untreated, diabetics treated with 200mg/kg, 400mg/kg, or 800 mg/kg ABE, and diabetics treated with 3 mg/kg Glibenclamide. ABE was orally administered to induce diabetes, and alloxan-monohydrate was intraperitoneally administered. Diabetic untreated rats exhibited significantly elevated levels of alkaline phosphatase, aspartate, and alanine transaminase activities, as well as higher concentrations of total bilirubin, conjugated bilirubin, and malondialdehyde. They also showed decreased levels of total protein, albumin, globulin, and protein-bound iodine, along with reduced antioxidant enzyme activity. In contrast, diabetic rats administered ABE demonstrated reduced hepatocellular enzyme activity and improved hepatic function. These rats exhibited increased levels of total protein, globulin, and albumin, as well as higher levels of glutathione, superoxide dismutase, glutathione peroxidase, and catalase activities, compared to diabetic untreated rats. The findings suggest that ABE may help prevent oxidative stress and improve hepatic functions in diabetic rats. ABE treatment led to decreased hepatocellular enzyme activity and improved hepatic function, along with increased antioxidant enzyme activities. These results highlight the potential of ABE as a therapeutic option for diabetes-induced liver dysfunction. Further research is warranted to explore its mechanisms of action and potential clinical applications.

Effects of supplementing coated methionine in a high plant-protein diet on growth, antioxidant capacity, digestive enzymes activity and expression of TOR signaling pathway associated genes in gibel carp, Carassius auratus gibelio.

This study explored the impacts of supplementation of different levels of coated methionine (Met) in a high-plant protein diet on growth, blood biochemistry, antioxidant capacity, digestive enzymes activity and expression of genes related to TOR signaling pathway in gibel carp (Carassius auratus gibeilo). A high-plant protein diet was formulated and used as a basal diet and supplemented with five different levels of coated Met at 0.15, 0.30, 0.45, 0.60 and 0.75%, corresponding to final analyzed Met levels of 0.34, 0.49, 0.64, 0.76, 0.92 and 1.06%. Three replicate groups of fish (initial mean weight, 11.37 ± 0.02g) (20 fish per replicate) were fed the test diets over a 10-week feeding period. The results indicated that with the increase of coated Met level, the final weight, weight gain (WG) and specific growth rate initially boosted and then suppressed, peaking at 0.76% Met level (P< 0.05). Increasing dietary Met level led to significantly increased muscle crude protein content (P< 0.05) and reduced serum alanine aminotransferase activity (P< 0.05). Using appropriate dietary Met level led to reduced malondialdehyde concentration in hepatopancreas (P< 0.05), improved superoxide dismutase activity (P< 0.05), and enhanced intestinal amylase and protease activities (P< 0.05). The expression levels of genes associated with muscle protein synthesis such as insulin-like growth factor-1, protein kinase B, target of rapamycin and eukaryotic initiation factor 4E binding protein-1 mRNA were significantly regulated, peaking at Met level of 0.76% (P< 0.05). In conclusion, supplementing optimal level of coated Met improved on fish growth, antioxidant capacity, and the expression of TOR pathway related genes in muscle. The optimal dietary Met level was determined to be 0.71% of the diet based on quadratic regression analysis of WG.

Unveiling the antimalarial properties of Terminalia ivorensis (A. Chev) stem bark aqueous extract: In vivo efficacy testing and in silico predictions

Due to the spreading resistance to antimalarial drugs, new therapeutics are urgently needed, preferably with novel modes of action. Extracts from Terminalia ivorensis have previously been shown to possess activity in vitro against multidrug-resistant and drug-sensitive strains of Plasmodium falciparum. However, to the best of our knowledge, no scientific study has been published describing the antimalarial potential of these extracts through in vivo efficacy testing. This study aimed to determine the safety and antimalarial efficacy of the T. ivorensis stem bark aqueous extract (TiH2O) in a mouse model using the OECD 423 protocol and the suppressive and curative murine malaria models, and to predict in silico the pharmacokinetic properties and drug-likeness of two major phytochemical constituents. The in vivo antimalarial efficacy was assessed using the P. berghei NK65-infected mice. The TiH2O treatment impact on biochemical parameters was measured using established standard procedures. The pharmacokinetics prediction was achieved through the pkCSM predictor and Swiss ADME. The TiH2O extract was nontoxic in BALB/c mice at a lethal dose of 50 (LD50) &gt; 2000 mg/kg. The TiH2O extract displayed strong antimalarial efficacy with 100% parasitemia suppression at 200 mg/kg b.w. after 4 days of treatment while its oral administration at 400 mg/kg b.w. in the curative model significantly decreased P. berghei parasitemia by 94.07% with a median efficacy dose (ED50) of 96.80 mg/kg. The administration of TiH2O extract restored the histological parameters disrupted by P. berghei, and the transaminase (ALT and AST) activity, creatinine, and bilirubin levels significantly decreased compared to the negative control mice. In silico explorations showed that the main constituents leucodelphidin (leucodelphinidin) and ellagic acid of the TiH2O extract have drug-like properties, thus indicating that T. ivorensis might constitute a promising source of antimalarial chemical entities with good pharmacokinetics and drug-like properties. The results obtained further corroborated the preliminary in vitro antiplasmodial studies of T. ivorensis stem bark aqueous extract. The metabolome of TiH2O extract should be further profiled in the prospects of characterizing novel natural product scaffolds to support antimalarial drug discovery.

Venomous snakebites in children: a 10 year experience in South China

Introduction Many studies have focused on snakebites in adults, but very few have described snakebites in children. Methods We reviewed the clinical characteristics and outcomes of children with venomous snakebites aged less than 15 years who presented to a regional medical centre in South China from January 2013 to December 2022. Results A total of 69 envenomed patients were analyzed in our study; 42 (60.9 per cent) patients were male, and 59 (85.5 per cent) reported lower limb bites. Most bites (89.8 per cent) occurred between April and October. Twenty-seven patients received first aid management, and 47 required admission to the general ward. Antivenom was administered to 58 patients, glucocorticoids to 43 patients, antibiotics to 48 patients, and tetanus antitoxin to 40 patients. No fatalities were reported. The most common snake identified was Trimeresurus albolabris. Four were classified as dry bites, 15 as mild, 43 as moderate, and seven as severe. The most common local signs were pain and swelling, while the most common systemic effects were haematological complications. Patients with high severity scores had significantly higher lactate dehydrogenase activities, creatine kinase isoenzyme activities, aspartate aminotransferase activities, D-dimer concentrations, prothrombin times and lower fibrinogen concentrations. In a receiver operating characteristic curve analysis of the values with the highest Youden index, the following cut-offs proved significant: lactate dehydrogenase activity > 248.1 U/L, creatine kinase isoenzyme activities > 17.5 U/L, fibrinogen concentration < 1,455 mg/L, D-dimer concentration > 437.0 µg/L, aspartate aminotransferase activity > 26.1 U/L, and prothrombin time > 15.2 seconds. Discussion This study provides insight into the epidemiology, clinical profile, and management of snakebites in children. Data from the present study were compared with those from our previous adult study. Limitations include that 50.7 per cent of our snakebites were attributed to Trimeresurus albolabris. Therefore, the results of our study may not be generalizable to all snakebites. Conclusion The clinical symptoms were more severe in children than in adults in our previous study. Even though there were no fatalities, close monitoring should be performed to detect haematological and other potentially fatal complications promptly.

Androgenic Properties and Subchronic Toxicity of the Aqueous Extract of Pycnanthus angolensis (Welw.) Warb. Wood (Myristicaceae)

Aims: Pycnanthus angolensis (Welw.) Warb. also known as “Etengué” in the Baka language, is a medicinal plant used by the Baka Pygmies of Cameroon to treat erectile dysfunction. This study aimed to evaluate the androgenic activity and subchronic toxicity of the aqueous extract of Pycnanthus angolensis wood.&#x0D; Study Design: Experimental design.&#x0D; Place and Duration of Study: Laboratory of Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, between November 2022 and October 2023.&#x0D; Methodology: Twenty-five male Wistar strain rats were divided into 5 groups of 5 rats each including a positive control group that received testosterone enanthate (5 mg/kg) intramuscularly once a week; a normal control group that received distilled water (10 ml/kg) and three test groups which received 134 and 267 and 533 mg/kg of the aqueous extract of Pycnanthus angolensis daily per os. On the 29th day, the animals were killed, and several biochemical parameters were assessed for androgenic properties.&#x0D; Results: At a dose of 134 mg/kg, the extract significantly increased (p&lt;0.05) the levels of testicular cholesterol, testosterone and serum prostatic acid phosphatase activity compared to those of the normal control. A toxicity study showed that at doses of 134 and 267 mg/kg, the extract did not induce any significant variation (p&gt;0.05) in the creatinine level, but a significant reduction (p&lt;0.05) in of aspartate and alanine aminotransferase activities was recorded. Histopathology revealed destruction of testicular spermatozoa at a dose of 533 mg/kg compared to that of the controls.&#x0D; Conclusion: These results showed that at a dose of 134 mg/kg, the aqueous extract of Pycnanthus angolensis (Welw.) Warb. wood is capable of stimulating the production of androgens and is tolerated by the rat's body. Our results justified the traditional use of this plant for the treatment of male infertility and erectile dysfunction.

Hepatoprotective effect of jojoba oil against lead-induced toxicity in rats

Background Previous investigations showed that jojoba oil exhibited a protective effect against hepatotoxicity caused by different toxicants, however, to the best of our knowledge, no prior research has been done to determine the effectiveness of jojoba oil in protecting against lead toxicity. Objective This study assessed the hepatoprotective properties of jojoba oil against lead toxicity in rats. Materials and methods The study included four groups, each consisting of six Sprague Dawley male rats, and orally administered jojoba oil (JO group), lead acetate (LA group), and lead acetate plus jojoba oil (protective group) Results and conclusion The results showed that lead acetate-induced hepatotoxic effects were revealed by increased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities with hepatic histomorphological changes. There was a significant increase in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol, while levels of high-density lipoprotein-cholesterol significantly declined compared to normal rats. Additionally, lead acetate triggered oxidative damage of hepatocytes, evidenced by a significant increase of malondialdehyde levels and a decrease of reduced glutathione levels and activities of superoxide dismutase and glutathione S-transferase. Administration of lead was associated with a change in the distribution of cells over different cell cycle phases, characterized by a marked increase in the sub G1 cell population and a significant decrease in the G0/G1 cell population. Supplementation of jojoba oil with lead acetate relieved the toxic impacts of lead acetate with an enhancement of the liver enzyme activities, antioxidant status, lipid profile parameters, and histopathological alterations. In conclusion, jojoba oil might be an effective natural product that offers a promising preventive action towards lead-induced liver damage in rats.

The multidirectional assessment of moderate caloric restriction and metformin treatment in obese patients.

Obesity treatment is often burdensome for patients. We used the combination of moderate caloric restriction (CR) with hypoglycemic metformin to assess their multidirectional effect in obese patients. One group was treated only with moderate CR (n=21) the second was treated with moderate CR and 800 mg metformin twice daily (n=23). Serum was drawn before and after treatment. The following parameters were monitored: anthropometric, cardiovascular, inflammatory, metabolic, and markers characteristic for thyroid, liver, pancreas, and kidney functions. Both tested groups did not significantly differ in most tested parameters after the treatment. Two groups reduced anthropometric parameters (body mass, body mass index (BMI), waist circumference) and fat mass but also muscle and fat-free mass, improving systolic blood pressure, insulin and leptin concentration, insulin sensitivity, leptin to adiponectin ratio, and inflammatory markers. Unfortunately, there was little impact on improving dyslipidemia and the thyroid and liver parameters. Free triiodothyronine (fT3) and gamma glutamyl transferase (GGT) activity were decreased in both groups, but triglycerides were reduced only in patients treated with moderate CR. Metformin with CR treatment decreases uric acid and aspartate aminotransferase (AspAT) activity. Metformin treatment with moderate CR in obese patients mainly improved insulin sensitivity, resulting in a reduction of patients with glucose intolerance, improved anthropometric, cardiovascular, and inflammatory mediators, and only slightly enhanced liver and thyroid function. No changes in kidney and pancreas function were observed during the treatment. In conclusion, eight weeks of CR alone and CR with metformin in obese adults improved anthropometric and metabolic markers, reduced muscle mass, fT3, GGT, proinflammatory, and CV parameters, and displayed no changes in kidney and pancreas function. The group treated with metformin after the treatment was still more obese and had higher C-reactive protein (CRP) and homeostasis model assessment-an index of insulin resistance (HOMA-IR), but despite this, considerably reduced the number of patients with glucose intolerance.