Protective role of Quercetin against the possible harmful effects of Tartrazine, which is widely used. These doses have been studied for the first time in the literature. Rats were divided: Control, Tartrazine, Quercetin, and Tartrazine + Quercetin. The substances were administered for 30 days. Afterward, liver tissues and blood samples were collected and biochemically and histopathologically analyzed. An increase was noted in oxidant (MDA, SOD) and oxidative stress index parameters (TOS, OSI) while decreases were seen in antioxidant parameters (GSH, CAT, TAS), inflammation markers (TNF-α, IL-6), apoptosis (Caspase 3) and histopathological deterioration (heterochromatic with pyknotic nuclei, pericentral hepatocyte necrosis, and inflammatory cell infiltration) in liver tissue. There was also an increase in oxidative stress index, inflammation markers, and liver function tests (ALT, AST, ALP, Direct and Total Bilirubin) in serum samples of the tartrazine group. In the quercetin group, antioxidant parameters in liver tissue increased, whereas oxidant parameters, inflammation markers, and liver function tests in serum samples decreased. Improvements in both biochemical, blood, and histopathological parameters were observed with the concomitant administration of quercetin compared to the tartrazine group. Tartrazine caused hepatotoxicity by increasing oxidative stress, inflammation, and apoptosis in the liver tissues. Additionally, it led to widespread damage by elevating inflammation and worsening liver function test results in blood samples. Quercetin, however, showed strong antioxidant, anti-inflammatory, and apoptotic effects. We recommend daily use of quercetin to protect the liver from the harmful effects of tartrazine.

The NTRK1, NTRK2, and NTRK3 genes encode the TRKA, TRKB, and TRKC receptors, critical for nervous system development. Gene fusions involving neurotrophic tyrosine receptor kinase (NTRK) are found in various cancers. In the pediatric population, NTRK gene fusions have been identified in up to 5.3% of high-grade gliomas (HGGs) and 2.5% of low-grade gliomas (LGGs). The prevalence is notably higher in young children, particularly in infantile hemispheric gliomas, where the fusion frequency is about 20%. Targeted therapies with TRK inhibitors (TRKi), including larotrectinib and entrectinib, have shown promising efficacy with rapid and durable responses for patients with LGGs and HGGs. TRKi are usually well tolerated, but on-target and off-target adverse events have been reported, such as increased AST/ALT, fatigue, decreased neutrophil, weight gain, and fractures with entrectinib. Resistance to TRKi arises from on-target mutations or new pathway activations, with second-generation inhibitors addressing some resistant cases. Despite efficacy, challenges remain in diagnosis, treatment access, and long-term safety, particularly regarding cognitive development and bone health. Overall, TRKi represent a significant advance for treating NTRK fusion-positive CNS tumors, especially in pediatric populations, offering new hope for patients with limited treatment options. Further studies are required to optimize their use and address unresolved challenges.

The present study investigated the effects of graded dietary inclusion of black soldier fly larvae powder (BSFLP) as a partial replacement of soybean meal on semen quality and oxidative status in Luxi game breeding cock. Five levels of BSFLP inclusion diets (isocaloric and isonitrogenous) at 0, 5, 10, 15, or 20% were fed to Luxi game breeding cocks (n = 40) to assess semen quality parameters, antioxidant enzyme activities, and biochemical indicators. The results showed that, compared with the control group, dietary supplementation with 10-20% BSFLP improved sperm motility, viability, and acrosome integrity in Luxi game breeding cocks (p < 0.05). Moreover, sperm linearity, swing, curvilinear motion speed, linear motion speed, and lateral swing amplitude were improved (p < 0.05). However, no statistically significant effects were found for progressive motility, average path velocity (VAP), mean angular displacement of the sperm head trajectory (MAD), or beat cross frequency (BCF) (p > 0.05). Compared with the control group, the activities of CAT, GSH, GR, and SOD in semen were significantly increased (p < 0.05), and the content of MDA in semen was significantly decreased (p < 0.05) when 5-20% BSFLP was added to the diet. Additionally, there were no significant differences in serum ALT, AST, TP, ALB, and ALP among Luxi game breeding cocks supplemented with 10-20% BSFLP (p > 0.05). Polynomial contrast analysis revealed significant linear responses for several reproductive and antioxidant parameters, whereas quadratic effects were not detected. Biochemical indicators were unaffected by the inclusion of BSFLP, suggesting that dietary BSFLP up to 20% did not adversely affect liver-related or metabolic parameters under the conditions of this study. Hence, the present study concludes that the dietary inclusion of 5-20% BSFLP can serve as an effective alternative protein source to enhance semen quality and antioxidant enzyme activity in the Luxi game breeding cock.

Kratom and kratom products are increasingly used in Western countries for pain management, mood disorders, and opioid withdrawal. Despite perceptions of safety, kratom can cause hepatotoxicity and clinically relevant herb-drug interactions, particularly with medications metabolized by cytochrome P450 (CYP) enzymes. We report a 45-year-old male with stable psychiatric conditions on nortriptyline and lisdexamfetamine, who developed mild, reversible liver enzyme elevations and supratherapeutic nortriptyline levels during chronic kratom use (raw, dry leaf, two tablespoons daily for five to six years). Initial labs showed aspartate aminotransferase (AST) 33 U/L, alanine aminotransferase (ALT) 70 U/L, alkaline phosphatase (ALP) 136 U/L, gamma-glutamyl transferase (GGT) 141 U/L, and nortriptyline 350 mcg/L. Dose reduction of nortriptyline partially corrected serum levels, but liver enzyme elevations persisted. Kratom discontinuation led to normalization of both liver function tests and nortriptyline levels within three weeks. This case illustrates two clinically important considerations: kratom-induced liver injury (KILI) and a CYP-mediated herb-drug interaction. The patient's use of raw leaf contrasts with commercial products, which may include concentrated extracts, 7-hydroxymitragynine (7OHMG)-enriched formulations, or ethanol-based preparations, potentially increasing hepatotoxicity and interaction risk. Even mild liver enzyme elevations in patients using kratom warrant evaluation, particularly with concurrent CYP-metabolized medications. Clinicians should educate patients about product variability, monitor liver function and drug levels, and consider temporary kratom discontinuation to assess causality. This case reinforces the growing evidence of kratom's hepatotoxic potential and the importance of integrating pharmacokinetic considerations into patient care.

N6-methyladenosine (m6A), a prevalent mRNA modification, plays a key role in cancer. m6A-associated single nucleotide polymorphisms (m6A-SNPs) have been implicated in various diseases, but their role in Hepatocellular Carcinoma (HCC) is unclear. This study aimed to identify HCC-related m6A-SNPs and validate their clinical relevance. We integrated HCC genome-wide association study (GWAS) data with the RMVar database to screen for candidate m6A-SNPs, which were further prioritized by expression quantitative trait locus (eQTL) and differential gene expression analyses. Final validation was performed in a case-control cohort comprising 800 HCC patients and 800 matched controls from a northern Chinese population. In silico analysis identified 331 HCC-related m6A-SNPs, 176 of which exhibited eQTL signals. Among them, 19 SNPs corresponded to 19 genes that showed differential expression in at least one public dataset. Further case-control study showed that 12 of these 19 SNPs were significantly associated with HCC risk or clinical progression. Notably, after false discovery rate (FDR) correction, rs7947978 was associated with an increased risk of overall and HBV-related HCC, rs61560753 was associated with tumor number, and rs9875668 and rs3847607 were linked to clinical liver function parameters (rs9875668 with AST, ALT and AST/ALT ratio; rs3847608 with AST). This comprehensive analysis indicates that specific m6A-SNPs are implicated in HCC susceptibility and progression, highlighting their potential as biomarkers for risk prediction and therapeutic targeting.

This study evaluated the effects of increasing concentrations of HepatoMax, a standardized multi-component phytogenic supplement, on growth performance, carcass traits, lipid profile, hepatic enzymes, antioxidant status, serum metabolites, and multivariate physiological responses in broiler chickens. Birds received drinking water supplemented with 0.0, 0.25, 0.50, or 1.00 mL/L HepatoMax. Supplementation significantly improved performance parameters, with the 0.50 mL/L group showing the highest weight gain (2871 g; P < 0.0001) and improved feed conversion ratio (1.78 vs. 1.92 in control; P < 0.0001). Breast and thigh meat yield increased, while abdominal fat markedly decreased at the moderate dose (P < 0.0001). Blood lipid profiles were significantly improved, characterized by reductions in triglycerides, LDL, VLDL, and total cholesterol and increased HDL (P < 0.0001). Hepatic enzyme activities (AST, ALT, ALP) were substantially reduced, indicating enhanced liver function. Antioxidant status was markedly enhanced, as evidenced by higher GPX and SOD activities and lower MDA concentration, demonstrating reduced oxidative stress (P < 0.0001). Serum total protein, globulin, and albumin increased, whereas glucose and bilirubin fractions decreased, supporting improved metabolic regulation. Principal component analysis showed that the first two components explained 81.8% of total variance and clearly separated treatment groups. The primary axis reflected a contrast between metabolic stress indicators and growth-antioxidant efficiency, while the second axis was associated with lipid deposition and treatment response. Overall, HepatoMax supplementation, particularly at 0.50 mL/L, promoted coordinated improvements in growth performance, liver function, antioxidant capacity, and lipid metabolism.