Modern biochemistry is producing vast amounts of chemical knowledge. Ontologies, such as the Chemical Entities of Biological Interest (ChEBI) ontology, can help organising this knowledge. With manual classification alone however, ontologies cannot keep up with the growth of their domain. In this work, we propose a novel taxonomy of 67 classes related to peptides, a large branch in ChEBI with nearly 15,000 compounds. The existing natural language definitions in ChEBI have been expanded and specified more precisely. These natural language definitions are accompanied by a logical axiomatisation in monadic second-order logic (MSOL). To use the axiomatisation for automated classification, a methodology has been developed that translates monadic second-order definitions first into partial first-order definitions and finally into an algorithmic classification. This connects three aspects important to ontological definitions: They reflect the opinions of experts, they are unambiguous, and they can be checked automatically. In our evaluation, we compare the results of our classification to the current taxonomy of ChEBI . This reveals potential inconsistencies in ChEBI as well as areas that might benefit from automated extensions. We also evaluate our natural-language definitions in an expert survey.Scientific contribution: This work provides precise natural-language definitions of 14 current ChEBI classes as well as 53 new peptide-related classes. These definitions are formalised in MSOL and come with an efficient implementation that allows for large-scale molecule classification, including a full classification of ChEBI and PubChem.
Autosomal dominant acute porphyrias are rare inherited disorders of haem biosynthesis characterised by accumulation of potentially neurotoxic porphyrin precursors and attacks of severe abdominal pain with autonomic and neuropsychiatric features. Disease severity ranges from asymptomatic individuals to those with recurrent, life-threatening attacks. The International Porphyria Network invited 34 acute porphyria specialists from 17 countries to form an expert panel. The invited group included clinicians from diverse specialities (ie, internal medicine, haematology, endocrinology, gastroenterology, hepatology, neurology, and biochemistry), together with laboratory scientists and patient representatives. The panel met online (in 2023-25) to develop 15 evidence-based recommendations with the use of the Grading of Recommendations, Assessment, Development, and Evaluations framework addressing attack prevention, management of sporadic and recurrent attacks, long-term follow-up, surveillance for primary liver cancer, and family screening. The guidelines support safe, consistent clinical care and improved outcomes, recognising global variation in resources and access to high-cost drugs, and highlighting priorities for future research.
To identify, characterize and determine the frequency of MED-12 exon 2 mutations in the uterine leiomyomas (ULs) of Nigerian women. MED-12 mutations are the most common molecular subtype of uterine leiomyomas and have been linked with ULs in Western populations. The frequency of MED-12 mutations among Nigerian women has not been established. Cross-sectional study. Nigerian women with uterine leiomyomas undergoing myomectomy. Fibroid weight and other characteristics such as age, weight, BMI, parity and age at menarche. Identification and frequency of MED-12 mutations. DNA was extracted from the fibroid and adjacent myometrial tissues, and the MED-12 gene (exon 2) was amplified by PCR, followed by Sanger sequencing. The sequencing data showed that 54.9% (56/102) of the fibroid tissues had MED-12 mutations compared with the adjacent myometrium. Of this percentage, 49.01% was found in codon 44, and c.131 G>A was the most frequent (24.51%), followed by c.130 G>C (5.88%). Other mutations were found in codons 43 (c.128 A>C) and 36 (c.107 T>G). Three samples had a mutation at intron 1 (c.100-8T>A). In summary, we identified 11 variants at four positions. Further computational prediction analysis showed that of the 11 variants, only 27.3% were tolerated, and all variants were either disease-causing, passenger mutations or probably damaging. However, there was no significant difference between the characteristics of the women whose ULs were MED-12 positive and negative. Our study represents the first comprehensive analysis of MED-12 mutations in ULs of Nigerian women. This study indicates that analyzing MED-12 mutations in ULs of Nigerian women is essential for clinical practice and informing precision medicine for Nigerian women with ULs.
Circadian misalignment caused by altered feeding behaviors disrupts metabolic homeostasis and endocrine rhythms. Asprosin, a fasting-induced adipokine derived from the cleavage of profibrillin-1 (FBN1), stimulates hepatic glucose release and activates hypothalamic pathways that regulate appetite. Although asprosin's metabolic functions are increasingly recognized, its temporal expression patterns and interactions with peripheral and central tissues remain insufficiently explored. This study aimed to investigate the circadian expression patterns of the orexigenic hormone asprosin and its receptor OLFR734 in metabolically relevant tissues and the olfactory bulb of male Balb/c mice. Male Balb/c mice (n = 28) were evaluated at defined circadian time points. Quantitative real-time PCR, immunohistochemistry, and ELISA were used to assess the gene and protein expressions of asprosin and OLFR734, together with circulating levels of asprosin, glucose, and melatonin. Asprosin and OLFR734 showed significant diurnal oscillations (p <0.05-p <0.0001). Peak serum asprosin levels coincided with nocturnal melatonin elevation and reduced glucose concentrations. Tissue-specific variations were observed in both central and peripheral expression patterns. These results demonstrate that the asprosin-OLFR734 axis manifests a pronounced circadian rhythmicity, underscoring its pivotal role in the temporally coordinated regulation of appetite and glucose homeostasis. Such rhythmicity offers critical insight into the intricate endocrine mechanisms that govern nocturnal metabolic adaptations and provides a conceptual framework for future research on the temporal orchestration of energy balance and metabolic function.
The binding of cyclic adenosine monophosphate (cAMP) to hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels regulates cardiac pacemaking but key aspects of the mechanism of ligand-dependent regulation remain unresolved. Here, we examine the role of the lipid environment by reconstituting purified human HCN channels into lipid nanodiscs and measuring successive cAMP binding to single HCN channels using nanophotonic waveguides. Regardless of nanodisc size or lipid composition, cAMP molecules bind cooperatively to HCN channels in lipid bilayers, unlike channels solubilized in detergents. The affinity of the first ligand remains unchanged across conditions, indicating that the bilayer selectively alters higher-order ligation states. Cryo-EM structures of apo- and holo-HCN channels reveal additional lipid densities that are weak or absent in detergent-solubilized preparations. Together, these findings show that the lipid bilayer is both necessary and sufficient to induce cooperative ligand binding in HCN channels, thereby enhancing their sensitivity to gating stimuli.
Ataxia disorders have complex symptomology and few treatment options. Limited information is available on symptoms and quality of life with ataxia from the perspective of patients and caregivers. We aimed to assess whether trends in symptoms and quality of life varied by ataxia type and disease stage. We conducted an anonymous, international survey of 680 National Ataxia Foundation Members, including 587 people with ataxia and 93 caregivers. Data was analyzed for the whole group, by ataxia type, and by Functional Disability Stage (FDS). Respondents self-reported the first symptoms experienced, symptoms currently experienced, and the one symptom that currently has the greatest impact on their life. Impaired balance (51%, n = 343) and coordination (24%, n = 161) were the most reported first symptoms noticed by respondents across ataxia types. Impaired balance (92%, n = 627), impaired coordination (80%, n = 546), and fatigue (70%, n = 479) were the most prevalent symptoms across ataxia types and FDS. Impaired balance (65%, n = 443) was the most reported symptom as having the greatest impact on respondents' day-to-day life. While there were commonalities between FDS and ataxia types, some subtype differences emerged amongst self-reported first symptom, symptom prevalence, and symptoms impacting daily living. This study highlights trends in symptomology across ataxia types and disease stages from the perspective of people with ataxia and caregivers. While similarities exist across ataxia types, variation in which symptoms most impact quality of life across disease stages underscores the importance of selecting patient-relevant clinical trial outcome measures and endpoints. These findings can further guide clinicians in prioritizing symptom management and treatment planning, while supporting more meaningful, patient-centered discussions about disease impact.
This work reports the development of epoxy-based biocomposites via the valorization of coconut fiber, with tailored thermal and mechanical properties obtained by varying the reinforcement and curing system. An organosolv process was used to extract lignin from natural coconut fiber (NCF) using a 90% v/v aqueous acetic acid solution combined with 2% v/v HCl at 110 °C for 1 h, yielding organosolv coconut fiber lignin (OCFL) and modified coconut fiber (MCF). The polymeric matrix was composed of diglycidyl ether of bisphenol A containing 0 or 50 wt% OCFL, while NCF and MCF were used as reinforcements. The biocomposites were prepared with a matrix-to-reinforcement mass ratio of 80:20 and cured with either a protic or an aprotic ionic liquid, specifically 10 wt% [HMIM][HSO4] at 180 °C or 10 wt% [BMIM][PF6] at 220 °C for 1 h. The biocomposites were characterized by thermogravimetry, constant-pressure calorimetry, gel content, water absorption, chemical resistance, scanning electron microscopy and dynamic mechanical analysis. The results show that the thermal, thermos-oxidative, chemical, and mechanical properties of the biocomposites can be modulated by controlling the type of reinforcement, the lignin content in the matrix, and the curing ionic liquid. The valorization of coconut solid residues through a sustainable organosolv-based route thus enables the design of thermosetting materials with high glass transition temperatures, high gel content, and self-extinguishing behavior suitable for high-performance applications, with potential to partially replace petroleum-derived materials in selected sectors of the chemical industry.
Delirium is a common complication following coronary artery bypass graft (CABG) surgery, associated with longer hospital stays, increased morbidity, and higher healthcare costs. To evaluate the effectiveness of a multicomponent care bundle in preventing postoperative delirium among patients undergoing CABG surgery. This single-blind, non-randomised trial included 94 patients consecutively allocated by time period (47 per group). The primary outcome was delirium incidence at postoperative day 1 assessed by a blinded neurologist using DSM-5 criteria. Delirium subtypes were classified by RASS scores. The control group received standardised care; the study group received standardised care plus continuous family presence, patient-selected music, and earplug use. Cortisol, ACTH, glucose, sleep quality, pain, and anxiety were evaluated. Statistical significance was set at p < 0.05. At postoperative day 1, delirium incidence assessed by DSM-5 criteria was 14.9% in the study group vs. 38.3% in controls (p = 0.013; OR = 0.28, 95% CI: 0.10-0.76; ARR = 23.4%). Hyperactive delirium was markedly lower (2.1% vs. 14.9%). At postoperative days 1 and 2, cortisol, ACTH, glucose, pain, and anxiety levels were lower, and sleep quality was higher in the study group. Adherence to all bundle components exceeded 90%. The multicomponent care bundle was associated with significant reduction in postoperative delirium (NNT = 4.3), particularly hyperactive delirium, and improvements in stress biomarkers and psychological well-being. High adherence supports feasibility of this low-cost, nurse-led intervention. Randomised trials are needed to confirm causality.
Renal Fanconi syndrome (RFS) refers to a generalized dysfunction of the proximal tubule, including impaired 1-α hydroxylation of vitamin D. Consequently, rickets is a typical complication. Clinical observations in children with severe nutritional vitamin D deficiency sometimes include proximal tubular dysfunction, raising the possibility that lack of vitamin D could not only be a consequence of RFS but also a cause of it, although this has never been confirmed. Observations in Mendelian disorders with their genetically defined pathophysiology can provide clearer insights. We performed a retrospective review of 2 cases with vitamin D deficiency due to loss-of-function variants in CYP27B1. Additionally, we performed an in silico search for vitamin D-responsive elements (VDRE) in the promoter region of genes encoding proximal tubular transporters. Both cases presented with clinical rickets that had been resistant to supplementation with cholecalciferol. Biochemistries at presentation showed a non-anion gap metabolic acidosis, generalized aminoaciduria and urinary phosphate wasting consistent with proximal tubular dysfunction. Symptoms resolved upon treatment with active vitamin D. VDRE motifs were identified in the promoters of SLC34A1 and SLC34A3. Our observations support the notion of vitamin D deficiency as a cause of RFS and suggest that unresolved cases of RFS should be actively investigated for it.
The human lipidome comprises numerous complex lipids, dysregulation of which can contribute to the pathogenesis of a wide range of diseases. Despite the high heritability of parts of the lipidome, the genetic architecture of many circulating lipid species and their structure remains mostly unknown. Thus, we perform genome-wide association studies on 970 lipid species and 267 fatty acid composite measures using samples from the population-based Rhineland Study (n = 6096). We validate our findings using corresponding data from two other independent cohorts, including FinnGen (n = 7266) and EPIC-Potsdam (n = 1188). Out of 217 lead genomic loci, we find 136 to be novel, such as FDFT1. Using mendelian randomization and individual-level gene expression data, we identify 43 possible causal associations between candidate genes and corresponding lipid species, including FDFT1 - diacylglycerol (16:0/18:0). Our findings provide new insights into the intricate genetic underpinnings of lipid metabolism, which may facilitate risk stratification and discovery of new therapeutic targets.
The metabolic enzyme lactate dehydrogenase C4 (LDHC4) is aberrantly expressed in cancers and linked to poor prognosis. However, its role in lung adenocarcinoma (LUAD) and the molecular mechanisms beyond glycolysis remain unclear. This study investigates whether LDHC4 promotes LUAD by modulating protein lactylation, a lactate-derived post-translational modification, focusing on the tumor suppressor retinoblastoma protein (RB1). LDHC4 expression and its correlation with clinicopathological features and survival were analyzed using public databases (UALCAN, Kaplan-Meier Plotter, LOGpc) and validated in a cohort of 90 paired LUAD tissues via immunohistochemistry. The functional impact of LDHC4 on proliferation, migration, and invasion was assessed in A549 and PC-9 cells using gain- and loss-of-function models. The global lactylation profile was analyzed using DIA-based lactylation proteomics on the Astral platform. The interaction between RB1 and E2F1 (E2F transcription factor 1) was examined through molecular dynamics simulations, co-immunoprecipitation (Co-IP), and immunofluorescence. The functional consequences of site-specific RB1 lactylation at lysine 900 (RB1-K900lac) were determined using RB1-K900R mutant constructs and cell cycle analysis. LDHC4 was significantly overexpressed in LUAD tissues, correlating with poor patient survival, and was an independent prognostic risk factor. In vitro, LDHC4 promoted LUAD cell proliferation, migration, and invasion, and its tumor-promoting role was corroborated in an LUAD xenograft model, in which derived tumors exhibited increased volume and weight compared with mock-transfected controls. Mechanistically, LDHC4 overexpression elevated global protein lactylation levels and specifically increased lactylation of RB1. Bioinformatics and molecular dynamics simulations identified K900 as a key conserved residue for RB1-E2F1 binding; its lactylation destabilized the complex by increasing structural fluctuation and weakening intermolecular interactions. Cellular experiments confirmed that the lactylation-resistant RB1-K900R mutant bound E2F1 more strongly than wild-type RB1. Functionally, cells expressing RB1-K900R exhibited suppressed malignant phenotypes and G1/S cell cycle arrest, accompanied by downregulation of CDKs/cyclins and upregulation of P21. This study uncovers a novel LDHC4-driven oncogenic axis in LUAD. LDHC4 facilitates RB1 lactylation at the K900 residue, which disrupts the RB1-E2F1 tumor-suppressive complex, leading to cell cycle dysregulation and tumor progression. These findings may position the "LDHC4-RB1 lactylation" axis as a promising therapeutic target for LUAD.
Monitoring biochemical parameters is an essential component of pharmacological safety and routine clinical practice. Abnormalities in hepatic and renal function observed during hospitalization may reflect pharmacological exposure, underlying disease processes, or their interaction. However, real-world data describing the frequency and distribution of such laboratory abnormalities in hospital settings remain limited. This study aimed to evaluate the prevalence of biochemical abnormalities of hepatic and renal function among patients receiving pharmacological therapy and to assess the frequency of laboratory alterations associated with commonly prescribed drug groups. A retrospective observational study was conducted using laboratory data from the Department of Clinical Biochemistry. The analysis included 3,500 adult patients who underwent biochemical testing while receiving pharmacological therapy between January 2023 and December 2025. The evaluated parameters included alanine aminotransferase, aspartate aminotransferase, serum creatinine, urea, sodium, and potassium. Patients were categorized according to the main pharmacological therapy received, including antibiotics, non-steroidal anti-inflammatory drugs, and antihypertensive medications. Abnormal values were defined according to institutional laboratory reference ranges. Among the 3,500 patients included in the analysis, 52.3% were male and 47.7% were female, with a mean age of 56.8±15.4 years. Antibiotics were prescribed to 41.6% of patients, non-steroidal anti-inflammatory drugs to 33.2%, and antihypertensive medications to 25.2%. Elevated alanine aminotransferase levels were observed in 18.9% of patients, while increased aspartate aminotransferase levels were detected in 15.4%. Hepatic enzyme abnormalities were more frequently observed among patients receiving antibiotics and non-steroidal anti-inflammatory drugs, with statistically significant differences between therapy groups (p<0.05). Renal function abnormalities were identified in 14.7% of patients for creatinine and 12.9% for urea, particularly among patients treated with non-steroidal anti-inflammatory drugs. Electrolyte disturbances were less frequent, with hyponatremia observed in 6.1% and hyperkalemia in 4.3% of cases. Overall, 27.6% of patients exhibited at least one clinically relevant biochemical abnormality during hospitalization while receiving pharmacological therapy. A considerable proportion of hospitalized patients receiving pharmacological therapy present with clinically significant biochemical abnormalities affecting hepatic, renal, or electrolyte parameters. Although causality cannot be established in this retrospective design, these findings underscore the importance of systematic laboratory monitoring as part of hospital-based pharmacovigilance and patient safety strategies.
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Protein-based mosaic-8 nanoparticles displaying eight SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) elicited broadly cross-reactive antibodies that could protect from zoonotic spillovers. Here, we extend the mosaic-8 concept to mRNA by encoding membrane-bound RBD quartets (four linked RBDs) as dual quartet RBD-mRNA and dual quartet RBD-EABR-mRNA, the latter leveraging ESCRT- and ALIX-binding region (EABR) technology for display on cell surfaces and secreted virus-like particles. Compared with protein-based mosaic-8, mRNA-encoded mosaic-8 induced equivalent or enhanced antibody breadth, neutralization potencies, and conserved epitope targeting, while eliciting enhanced T cell responses and more balanced IgG subclass profiles consistent with potentially superior Fc effector functions. Finally, systems serology-polyclonal epitope mapping (SySPEM) revealed distinct IgG-subclass-specific epitope signatures across mRNA, EABR-mRNA, and protein vaccines, demonstrating that the mode of antigen display can shape epitope recognition. Successful conversion of a multivalent protein vaccine to mRNA platforms informs the design of broadly protective vaccines and advances mosaic-8 toward clinical development.
RNA modifications regulate post transcriptional gene expression, yet most computational methods model each modification independently and overlook competition among modification types at a single site. We present EvoRMD, a biologically contextualized and interpretable framework for RNA modification prediction. EvoRMD combines RNA language model embeddings with structured metadata, including species, organ, cell type, and subcellular localization, and uses attention to identify informative sequence positions. A shared multiclass classifier produces context conditioned predictions across 11 modification types. EvoRMD achieves strong performance and provides interpretable insights through attention patterns and motif analyses, supporting biologically grounded prioritization of candidate RNA modifications.
Aggression is a complex social behaviour observed in many animal species, including dogs, and remains a major global concern due to its serious implications for public safety and animal welfare. This study focuses on Pit Bull dogs, a breed frequently associated with severe aggression episodes in many countries, making them an appropriate model for investigating the neuroanatomical factors underlying canine aggression. To better understand its underlying mechanisms, this study investigated neuroanatomical and biochemical factors associated with aggression in Pit bulls. 14 dogs were selected for MRI analysis based on their aggression scores obtained through a aggression assesment survey derived from Canine Behavioral Assessment and Research Questionnaire. The dogs underwent MRI scans and blood and urine sampling and were divided into control and aggressive groups. MRI analyses focused on the prefrontal cortex, amygdala, and hippocampus. Biochemical analyses included serum or plasma levels of serotonin, dopamine, vasopressin, adrenaline, noradrenaline, testosterone, cortisol, and adrenocorticotropic hormone, along with urinary concentrations of their metabolites; metanephrine, vanillylmandelic acid, homovanillic acid, and 5-hydroxyindoleacetic acid. Results showed significantly decreased prefrontal cortex volumes and increased amygdala volumes in aggressive dogs compared to controls. Testosterone and dopamine levels were also significantly higher in the aggressive group. These findings suggest that structural alterations in key brain regions, combined with hormonal and neurotransmitter imbalances, may contribute to a maladaptive neurocognitive profile. Reduced top-down control by the prefrontal cortex may fail to inhibit exaggerated threat perception and emotional reactivity mediated by the amygdala, leading to aggressive behaviour in Pit bulls.
Maternal iron deficiency anemia (iron deficiency anemia) is a persistent global health challenge with increased risk of adverse perinatal outcomes. A recent multicenter clinical trial found reduced rates of low birthweight infants in mothers treated initially (early second trimester) with IV ferric carboxymaltose compared to oral iron. Secondary findings included improved hematologic indices 4 weeks post-treatment, as well as reduced rate of stillbirth with single dose IV iron infusion. We aimed to determine if the initial response to iron therapy was associated with risk of stillbirth and other adverse perinatal outcomes in pregnant singletons with moderate iron deficiency anemia STUDY DESIGN: This is a secondary analysis of a multi-center randomized controlled trial in India that compared single dose intravenous iron to oral iron for the initial management of moderate iron deficiency anemia (Hb 7.0-9.9g/dL) at 14-17 weeks gestation. The primary outcome for this secondary analysis is stillbirth. Secondary outcomes were early preterm birth <34 weeks, small for gestational age infants (<10%ile). The predictors of interest were maternal hemoglobin, ferritin, and transferrin saturation (TSAT), measured at 20-24 weeks gestation. Longitudinal hematologic and iron indices through pregnancy and association with outcomes were also assessed. Relative risk of each outcome based on post-treatment hemoglobin, ferritin, and TSAT was assessed with Poisson regression, adjusting for maternal age, BMI, parity, treatment modality, baseline Hb, and study site. Two-sided alpha=0.05 used for all analyses. Given that most nutrients exhibit U-shaped or threshold risk curves, we also fit models allowing for a quadratic function for the relationship between hematologic parameters at all times and risk of each event RESULTS: 4252 participants were included in this analysis, 1421, 1424, 1407 received intravenous ferric derisolmaltose, ferric carboxymaltose, and oral iron respectively. In evaluating the linear relationship, each unit of increasing Hb response at 20-24 weeks was significantly associated with reduced risk of stillbirth (RR 0.74 (0.56, 0.98). In evaluating the quadratic relationship, we found that there was a significantly progressively increased risk of stillbirth (p<0.0001) and early preterm birth< 34 weeks (p=0.01). Although there was a significant quadratic relationship identified with small for gestational age infant and Hb (p=0.008), the relative risk of SGA and lower Hb was not statistically significant. Inadequate improvement in hemoglobin at 20-24 weeks following iron therapy in pregnancies complicated by moderate iron deficiency anemia is associated with increased risk of stillbirth and early preterm birth. Our findings highlight the potential importance of early screening and treatment of maternal anemia,. Given the association between persistent anemia at 20-24 weeks and adverse outcome, prospective trials should focus on whether early pregnancy, or even preconception, improvement in hemoglobin is an effective intervention to prevent adverse perinatal outcomes such as stillbirth and early preterm birth.
Itaconate is an immunomodulatory metabolite that links metabolism and inflammation. Li et al. uncover a mechanism by which itaconate and 4-octyl itaconate suppress cytokine signaling through the alkylation of tyrosine kinase 2 and Janus kinase 1. This study reveals a direct metabolic control of inflammation and highlights its therapeutic potential in sepsis.
Colorectal cancer (CRC) remains one of the leading causes of cancer mortality, with a poor survival rate of less than 15%. Imatinib (IM) and Zebularine (ZEB) alone have shown potential effects in CRC treatment, but their combination has not been thoroughly studied. This study investigates the potential effects of IM and ZEB in colon cancer cells to provide a novel therapeutic agent for managing CRC. Cell growth inhibition, oxidative stress markers, and cell cycle progression were assessed in HCT-116 cells treated with IM, ZEB, and their combinations. ZEB uptake levels were analyzed by LC-MS/MS, apoptosis was quantified by flow cytometry, and gene expression changes were analyzed by qPCR. The expression of metastatic markers, apoptotic regulators, and EGFR was assessed. Both IM and ZEB inhibited cell growth in a concentration-dependent manner, and their combination showed synergistic effects. The combination significantly enhanced oxidative stress. The combination therapy increased apoptosis and necrosis. Furthermore, the combination induced significant S-phase arrest in the cell cycle. The combination treatment reduced metastatic markers (MMP9, MMP2), and the apoptotic marker Caspase-9 was upregulated. Additionally, the Bcl-2 protein, a key regulator of apoptosis, was significantly downexpressed. Remarkably, the combination treatment showed significant inhibition in EGFR levels. Both IM and ZEB combination showed promise in the management of CRC by inducing oxidative stress, promoting apoptosis, and modulating critical genes involved in metastasis and apoptosis. Further investigation will be needed to verify their application in preclinical and clinical settings.
Reptiles often inhabit environments that are in close proximity to humans and livestock, creating opportunities for parasite transmission. They are common in areas where they find shelter, food and warmth. The Bengal monitor lizard (Varanus bengalensis), a member of the family Varanidae, represents one of the largest groups of extant poikilothermic predators. Monitor lizards are known to harbor several tick species that serve as vectors for a variety of pathogens. No prior information is available in the literature regarding ticks infesting V. bengalensis in Pakistan as well as regarding the occurrence of Toxoplasma gondii in these ticks. Therefore, we aimed to determine the molecular prevalence of T. gondii in Amblyomma gervaisi ticks (n = 93) collected from 24 V. bengalensis in Buner District, Khyber Pakhtunkhwa Province, Pakistan, between May and September 2023. Polymerase chain reaction (PCR) amplified a 300 bp fragment specific for the ITS-1 region of T. gondii in 10 of the 93 (11%) A. gervaisi ticks. DNA sequencing and BLAST analysis confirmed the presence of T. gondii. Phylogenetic analysis showed that these sequences clustered with the ITS-1 sequences of T. gondii detected in reptiles and mammals from Pakistan, Brazil, China, Tunisia and Portugal. The prevalence of T. gondii in A. gervaisi was not limited to a specific tick sex, feeding stage or month of sampling. However, among the tick developmental stages, nymphs had the highest rate of T. gondii infection. In conclusion, for the very first time from Pakistan, we are reporting the presence of T. gondii in A. gervaisi that were infesting monitor lizards. We recommend that similar and large scale studies should be conducted in all those areas of Pakistan that are unexplored for the presence of T. gondii in A. gervaisi ticks. Prevalence of this parasite should also be screened in all the animals harboring these as well as other tick species. This will help in better understanding of T. gondii transmission to new hosts that will lead toward its effective control.