Search Results (1,555)

Among the numerous compounds released as a result of human activities, endocrine-disrupting chemicals (EDCs) have attracted particular attention due to their widespread detection in human biological samples and their accumulation across various ecosystems. While early research primarily focused on their effects on reproductive health, it is now evident that EDCs may impact neurodevelopment, altering the integrity of neural circuits essential for cognitive abilities, emotional regulation, and social behaviors. These compounds may elicit epigenetic modifications, such as DNA methylation and histone acetylation, that result in altered expression patterns, potentially affecting multiple generations and contribute to long-term behavioral phenotypes. The effects of EDCs may occur though both direct and indirect mechanisms, ultimately converging on neurodevelopmental vulnerability. In particular, the gut–brain axis has emerged as a critical interface targeted by EDCs. This bidirectional communication network integrates the nervous, immune, and endocrine systems. By altering the microbiota composition, modulating immune responses, and triggering epigenetic mechanisms, EDCs can act on multiple and interconnected pathways. In this context, elucidating the impact of EDCs on neurodevelopmental processes is crucial for advancing our understanding of their contribution to neurological and behavioral health risks. Full article

The enzyme γ-glutamyl transpeptidase (GGT), located on the surface of cellular membranes, hydrolyzes extracellular glutathione (GSH) to guarantee the recycling of cysteine and maintain intracellular redox homeostasis. High expression levels of GGT on tumor cells are associated with increased cell proliferation and resistance against chemotherapy. Therefore, GGT inhibitors have potential as adjuvants in treating GGT-positive tumors; however, most have been abandoned during clinical trials due to toxicity. Recent studies indicate marine-derived ovothiols as more potent non-competitive GGT inhibitors, inducing a mixed cell-death phenotype of apoptosis and autophagy in GGT-overexpressing cell lines, such as the chronic B leukemic cell HG-3, while displaying no toxicity towards non-proliferative cells. In this work, we characterize the activity of two synthetic ovothiol analogs, L-5-sulfanylhistidine and iso-ovothiol A, in GGT-positive cells, such as HG-3 and HL-60 cells derived from acute promyelocytic leukemia. The two compounds inhibit the activity of membrane-bound GGT, without altering cell vitality nor inducing cytotoxic autophagy in HG-3 cells. We provide evidence that a portion of L-5-sulfanylhistidine enters HG-3 cells and acts as a redox regulator, contributing to the increase in intracellular GSH. On the other hand, ovothiol A, which is mostly sequestered by external membrane-bound GGT, induces intracellular ROS increase and the consequent autophagic pathways. These findings provide the basis for developing ovothiol derivatives as adjuvants in treating GGT-positive tumors’ chemoresistance. Full article

Parrotia subaequalis is a rare and endangered deciduous tree native to China, valued for its vibrant autumn foliage and ornamental appeal. Its leaves exhibit striking coloration, ranging from red to yellow and purple, yet the physiological and molecular mechanisms behind this variation remain poorly understood. Here, we combined transcriptomic, metabolomic, and physiological analyses to investigate pigment changes within the yellow leaf phenotype of P. subaequalis. Our findings revealed significant differences in gene expression and metabolic profiles between yellow and green leaves, particularly in starch and sucrose metabolism, photosynthesis, and carbon metabolism. Yellow leaves exhibited reduced photosynthetic capacity and carotenoid levels, alongside increased D-glucose concentration. These findings suggest that visible color transitions are likely driven by coordinated changes in carbohydrate metabolism, photosynthetic function, and organic compound accumulation. This study provides novel insights into the molecular and physiological mechanisms governing leaf pigmentation in an endangered tree, with useful information relevant to their conservation and sustainable utilization. Full article

Background/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in other geographical regions. The aim of our retrospective study was to present the genetic variants identified in a group of 48 CF patients from the Moldova region (Romania), as well as to establish genotype–phenotype correlations. Methods: Genetic testing was initially performed for 38 CFTR mutations, and in heterozygous patients or those in whom no mutation was detected, CFTR gene sequencing (NGS) was performed. Results: The compound heterozygous genotype was identified in 26 (54.16%) of the patients (with one of the alleles being F508del), while 22 (45.83%) patients had the homozygous F508del genotype. The F508del variant was the most frequent (69.79%), followed by G542X (6.25%, 6/96). Several new variants were also identified that had not been reported in other studies from Romania (R1158X, K598*, R347H, c.2589_2599del, R496H, and CFTRdele2). Phenotypic manifestations in patients with CFTR class I, II, III and VII variants (homozygous and compound heterozygous) were more severe compared to those in patients with CFTR class IV, V and VI mutations, with the data obtained being consistent with those in the literature. Respiratory tract involvement was present in 77.08% of the patients, being more frequent in patients with the compound heterozygous genotype compared to the homozygous F508del genotype. Most patients had exocrine pancreatic insufficiency (EPI) (85.41%). Gastrointestinal manifestations included hepatocytolysis (66.66%) and biliary cirrhosis (0.41%). Meconium ileus was detected in 18.75% of patients, all with a compound heterozygous genotype. Conclusions: We compared the results obtained with data from the literature and correlated the detected CFTR variant (genotype) with the phenotypic manifestations, highlighting certain particularities present in some patients. Genetic testing allows for early diagnosis and adapted management, including personalized treatment for each patient. Identification of novel unclassified CFTR variants still remains a challenge for clinicians. NGS-based screening of heterozygous healthy carriers is important for both genetic counseling and prenatal diagnosis. Full article

Quinoa (Chenopodium quinoa Willd.) has emerged as a climate-resilient, nutrient-dense crop with increasing global popularity because of its adaptability under current environmental variations. To address the limited understanding of quinoa’s genotypic performance under local agro-environmental conditions, this study hypothesized that elite genotypes would exhibit significant variation in agronomic, physiological, and biochemical traits. This study aimed to elucidate genotypic variability among 23 elite quinoa lines under field conditions in Faisalabad, Pakistan, using a multidimensional framework that integrated phenological, physiological, biochemical, root developmental, and yield-related attributes. The results revealed that significant variation was observed across all measured parameters, highlighting the diverse adaptive strategies and functional capacities among the tested genotypes. More specifically, genotypes Q4, Q11, Q15, and Q126 demonstrated superior agronomic potential and canopy-level physiological efficiencies, including high biomass accumulation, low infrared canopy temperatures and sustained NDVI values. Moreover, Q9 and Q52 showed enhanced accumulation of antioxidant compounds such as phenolics and anthocyanins, suggesting potential for functional food applications and breeding program for improving these traits in high-yielding varieties. Furthermore, root trait analysis revealed Q15, Q24, and Q82 with well-developed root systems, suggesting efficient resource acquisition and sufficient support for above-ground plant parts. Moreover, principal component analysis further clarified genotype clustering based on trait synergistic effects. These findings support the use of multidimensional phenotyping to identify ideotypes with high yield potential, physiological efficiency and nutritional value. The study provides a foundational basis for quinoa improvement programs targeting climate adaptability and quality enhancement. Full article

Human induced pluripotent stem cell-derived cardiomyocytes (iCMs) provide a powerful platform for investigating cardiac biology. However, structural, metabolic, and electrophysiological immaturity of iCMs limits their capacity to model adult cardiomyocytes. Currently, no universally accepted criteria or protocols for effective iCMs maturation exist. This study aimed to identify practical culture conditions that promote iCMs maturation, thereby generating more physiologically relevant in vitro cardiac models. We evaluated the effects of short- and long-term culture in media supplemented with various stimulatory compounds under 2D conditions, focusing on intracellular content and localization of slow skeletal troponin I (ssTnI) and cardiac troponin I (cTnI) isoforms. Our findings demonstrate that the multicomponent metabolic maturation medium (MM-1) effectively enhances the transition toward a more mature iCM phenotype, as evidenced by increased cTnI expression and formation of cross-striated myofibrils. iCMs cultured in MM-1 more closely resemble adult cardiomyocytes and are compatible with high-resolution single-cell techniques such as electron microscopy and patch-clamp electrophysiology. This work provides a practical and scalable approach for advancing the maturation of iPSC-derived cardiac models, with applications in disease modeling and drug screening. Full article

Oxysterols such as 7-ketocholesterol (7KCh) contribute to the pathogenesis of autoimmune and chronic inflammatory diseases by inducing oxidative stress and promoting pro-inflammatory immune cell activation. Dendritic cells (DCs) play a central role in maintaining immune tolerance, and their dysregulation is a key driver of autoimmunity. Targeting DCs by using natural compounds offers a promising strategy to restore redox balance and suppress aberrant immune responses. This study investigated the immunomodulatory and antioxidant properties of Lupeol, a natural triterpenoid, in human monocyte-derived DCs exposed to 7KCh. Flow cytometry and cytokine profiling demonstrated that Lupeol preserved the immature, tolerogenic phenotype of DCs by promoting a dose-dependent increase in the anti-inflammatory cytokine IL-10. Lupeol also inhibited the 7KCh-induced upregulation of maturation markers (CD83, CD86) and suppressed the release of pro-inflammatory cytokines IL-1β and IL-12p70. Functionally, Lupeol-treated DCs directed T cell polarization toward an anti-inflammatory and regulatory profile while dampening the inflammatory responses triggered by 7KCh. This immunoregulatory effect was further supported by the decreased secretion of the pro-inflammatory cytokines IL-1β and IL-12p70 in DC culture supernatants. Mechanistic analyses using immunofluorescence showed that Lupeol alone significantly increased nuclear NRF2 levels and upregulated HO-1 expression. Western blot analysis further confirmed Lupeol’s ability to activate the KEAP1-NRF2 signaling pathway, as evidenced by increased expression of NRF2 and its downstream target, NQO1. The use of ML385, a selective NRF2 inhibitor, in ROS and cytokine assays supported the involvement of NRF2 in mediating the Lupeol antioxidant and anti-inflammatory effects in DCs. Notably, the oxidative burden induced by 7KCh limited the full activation of NRF2 signaling triggered by Lupeol. Furthermore, docking and MM/PBSA analyses revealed the specific interactions of Lupeol with the kelch domain of KEAP1. These findings suggest that Lupeol may serve as a promising orally available immunomodulatory agent capable of promoting tolerogenic DCs, offering potential applications in autoimmune and other chronic inflammatory diseases. Full article

Acyl-CoA dehydrogenase 9 deficiency is considered as a rare neuromuscular syndrome with an autosomal recessive transmission. The ACAD9 protein presents two essential functions, i.e., the limiting step enzyme of the fatty acid β-oxidation pathway and one of the complex’s compounds involved in the respiratory chain complex I assembly. Thus, loss-of-function mutations are known to convey mitochondrial cytopathologies. A patient with a mild and late-onset phenotype, suffering from exercise intolerance and hypertrophic cardiomyopathy, was diagnosed as a compound heterozygote of the ACAD9 gene. The first c.1240C> T p.Arg414Cys variant has been previously reported and is known to be responsible for ACAD9 deficiency. However, the second c.1636G> A p.Val546Met variant has never been described. The goal was to investigate the eventual pathogenicity of this new genetic variant. For this purpose, molecular cloning was generated to express the ACAD9 gene with the V546M variant in a cell line (ACAD9mut) and compared to cells expressing the wild-type ACAD9. Then, the mitochondrial respiration, ATP production, the mitochondrial network, and the oxidative phosphorylation’s composition were investigated to reveal the effects of the V546M variant. While avoiding to affect the amount of the respiratory chain’s complexes, the new ACAD9 variant was entirely responsible for reducing over 50% of the mitochondrial complex I activity. Full article

Non-small cell lung cancer (NSCLC) is a predominant form of lung cancer that is often diagnosed at an advanced metastatic stage. The processes of cancer cell migration and invasion involve epithelial-to-mesenchymal transition (EMT), which is crucial for metastasis. Targeting cancer aggressiveness with effective plant compounds has gained attention as a potential adjuvant therapy. Eurycomanone (ECN), a bioactive quassinoid found in the root of Eurycoma longifolia Jack, has demonstrated anti-cancer activity against various carcinoma cell lines, including human NSCLC cells. This study aimed to investigate the in vitro effects of ECN on the migration and invasion of human NSCLC cells and to elucidate the mechanisms by which ECN modulates the EMT in these cells. Non-toxic doses (≤IC20) of ECN were determined using the MTT assay on two human NSCLC cell lines: A549 and Calu-1. The results from wound healing and transwell migration assays indicated that ECN significantly suppressed the migration of both TGF-β1-induced A549 and Calu-1 cells. ECN exhibited a strong anti-invasive effect, as its non-toxic doses significantly suppressed the TGF-β1-induced invasion of NSCLC cells through Matrigel and decreased the secretion of MMP-2 from these cancer cells. Furthermore, ECN could affect the TGF-β1-induced EMT process in various ways in NSCLC cells. In TGF-β1-induced A549 cells, ECN significantly restored the expression of E-cadherin by inhibiting the Akt signaling pathway. Conversely, in Calu-1, ECN reduced the aggressive phenotype by decreasing the expression of the mesenchymal protein N-cadherin and inhibiting the TGF-β1/Smad pathway. In conclusion, this study demonstrated the anti-invasive activity of eurycomanone from E. longifolia Jack in human NSCLC cells and provided insights into its mechanism of action by suppressing the effects of TGF-β1 signaling on the EMT program. These findings offer scientific evidence to support the potential of ECN as an alternative therapy for metastatic NSCLC. Full article

Nymphs of the ambar mutant of Orius laevigatus (Fieber) are orange-colored instead of the yellowish color of the wild-type individuals. Since there were no previous studies of the pigments of this species, we searched for differences in pigments of the pteridine family between both strains. Fluorescent compounds from nymph extracts were separated by cellulose thin-layer chromatography (TLC) and by size exclusion chromatography, followed by LC/MS/MS. The present study has allowed the identification for the first time in O. laevigatus of erythropterin, leucopterin, 7-methylxanthopterin, xanthopterin, isoxanthopterin, pterin, and biopterin. The quantification was performed by fluorometry after elution of the pteridines previously separated by TLC. The results showed that the orange color in the ambar nymphs was due to the accumulation of the orange pigment erythropterin. Additionally, mutant nymphs exhibited significantly elevated levels of pterin and reduced levels of leucopterin. The possibility that these differences were due to differences in xanthine dehydrogenase (XDH) activity was tested; the results indicated that XDH deficiency is unlikely to be responsible for the mutant phenotype. Considering that the ambar mutation is recessive, the mutant phenotype should, most likely, be due to a disruption in downstream metabolic steps involved in erythropterin processing. Full article

Hair, as a non-invasive biospecimen, retains metabolic deposits from sebaceous glands and capillaries, reflecting substances from the peripheral circulation, and provides valuable biochemical information linked to phenotypes, yet its application in animal disease research remains limited. This work applied ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) to compare the hair metabolomic characteristics of healthy forest musk deer (FMD, Moschus berezovskii) and those diagnosed with hemorrhagic pneumonia (HP), phytobezoar disease (PD), and abscess disease (AD). A total of 2119 metabolites were identified in the FMD hair samples, comprising 1084 metabolites in positive ion mode and 1035 metabolites in negative ion mode. Differential compounds analysis was conducted utilizing the orthogonal partial least squares–discriminant analysis (OPLS-DA) model. In comparison to the healthy control group, the HP group displayed 85 upregulated and 92 downregulated metabolites, the PD group presented 124 upregulated and 106 downregulated metabolites, and the AD group exhibited 63 upregulated and 62 downregulated metabolites. Functional annotation using the Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that the differential metabolites exhibited significant enrichment in pathways associated with cancer, parasitism, energy metabolism, and stress. Receiver operating characteristic (ROC) analysis revealed that both the individual and combined panels of differential metabolites exhibited area under the curve (AUC) values exceeding 0.7, demonstrating good sample discrimination capability. This research indicates that hair metabolomics can yield diverse biochemical insights and facilitate the development of non-invasive early diagnostic techniques for diseases in captive FMD. Full article

Villosiclava virens (anamorph: Ustilaginoidea virens), the causal fungal pathogen of rice false smut, has been found to produce various secondary metabolites. The albino strain LN02 is a natural albino phenotype mutant of V. virens due to its inability to produce ustilaginoidins. The fermentation of V. virens LN02 was performed in solid rice medium to obtain fungal cultures, which were chemically investigated. After removing the known metabolites, two new dimeric sorbicillinoids, namely ustisorbicillinols G (1) and H (2), were isolated from the ethyl acetate extract. Their structures were elucidated using spectroscopic data analyses and quantum chemical calculations. Compounds 1 and 2 displayed antibacterial activity towards Ralstonia solanacearum, Agrobacterium tumefaciens and Bacillus subtilis, with median inhibitory concentration (IC₅₀) values of 19.76–25.43 μg/mL for 1 and 25.35–45.48 μg/mL for 2. The discovery of new sorbicillinoids will increase the diversity of the secondary metabolites of V. virens and provide candidates for the creation of new antimicrobials as well. Full article

Breast cancer is one of the most common malignant tumors among women, which seriously threatens women’s health. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, characterized by poor prognosis, is an aggressive phenotype accounting for 15–20% of all kinds of breast cancers. Therefore, it has attracted great interest among researchers in discovering targeted therapy drugs countering HER2, and they have been considered as the pivotal therapeutic regimen for HER2-positive breast cancer patients. Nowadays, large progress has been achieved in HER2-targeted drugs, and this review categorizes them into four types according to the drug action mode, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs), antibody-drug conjugates (ADCs), and bispecific antibodies (bsAbs). The progress of HER2-targeted drugs reflects the discovery of drug targets, the screening of drug compounds, and the modification of antibodies, which offer diverse medical options and better therapeutic benefits for individual patients. In detail, we focus on the indication, administration, efficacy, strengths, and challenges of HER2-targeted drugs, concerning approved drugs and clinical trials. This review aims to provide significant references for the targeted therapeutic regimen and a more precise treatment strategy for HER2-positive breast cancer. Full article

Improving the quality of compounds in medicinal and aromatic plants is crucial due to their uses in the pharmaceutical, cosmetics, and food sectors. One way of influencing plant composition is through exposure to different light conditions. Therefore, a two-year field study (2023–2024) was conducted to investigate the impact of coloured shading nets on the physiology, essential oil (EO) content, and composition of three Mentha genotypes: Mentha × piperita ‘Multimentha’, Mentha × piperita ‘Fränkische Blaue’, and Mentha rotundifolia ‘Apfelminze’. In addition to an unshaded control, the Mentha plants were grown under red and blue shading nets. Plant height and vegetation indices were collected weekly. Biomass accumulation, EO content, and composition were determined for each harvest. Both red and blue shading were found to influence the physiological responses and EO compositions of the plants, with red shading promoting slightly higher p-menthone levels in ‘Fränkische Blaue’ and ‘Multimentha’, while blue shading slightly increased carvone levels in ‘Apfelminze’. While EO content varied across harvest seasons (spring, summer, and autumn), ‘Fränkische Blaue’ responded to red shading, demonstrating an increased EO content. The findings suggest that targeted use of coloured shading nets can modulate EO quality. However, genotype-specific responses highlight the necessity of further research to define shading applications for different species and genotypes. Full article

Endophytic bacteria inhabit plant tissues without damaging them and have specialized adaptation capabilities that allow them to establish themselves in this ecological niche. Endophytes produce numerous secondary metabolites with antimicrobial, anticancer, and pesticide properties, among others. In this study, endophytic bacteria were isolated and characterized from cocoa plants in a Brazilian municipality, with the view to evaluate their potential antagonistic activity on clinical bacterial strains. The isolates were identified through phenotypic analysis and molecular characterization. After bacterial isolation, it was possible to verify the presence of 11 different endophytic strains, with a bacterial load of up to 6.3 × 10³ CFU/g in each plant. The morphological and biochemical profile of the isolates varied. At the taxonomic level, these bacteria showed 99% similarity with the genera Microbacterium, Curtobacterium, Pseudomonas, Bacillus, Ralstonia, and Methylobacterium. The strains of the phylum Actinobacteria, which are known for producing natural bioactive compounds with high biotechnological potential, were effective in inhibiting Staphylococcus aureus ATCC and multidrug-resistant clinical strains. This work aims to expand knowledge about endophytes, with the aim of applying them in other sectors, such as the production of compounds against resistant human pathogens. Full article