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Endometrial cancer (EC) is the most common gynecologic malignancy, yet effective therapies for advanced and recurrent disease remain limited. Sodium butyrate (NaB), a gut microbiota-derived short-chain fatty acid (SCFA) with known anticancer activity, remains poorly understood in EC. In this study, we investigated the anticancer effects of NaB in two EC cell lines, HEC1A and AN3CA. NaB dose-dependently inhibited cell viability, colony formation, and migration in both cell lines, with HEC1A cells exhibiting greater sensitivity. NaB differentially modulated epithelial-mesenchymal transition (EMT)-related markers between the two cell lines. NaB markedly induced apoptosis in HEC1A cells, whereas AN3CA cells showed resistance to apoptotic cell death, despite mitochondrial membrane depolarization occurring in both cell lines. Cell cycle analysis revealed subG1-accumulation in HEC1A cells and G1 phase arrest in AN3CA cells. Notably, NaB potently suppressed thymidylate synthase (TS) at both mRNA and protein levels in both cell lines, representing the first demonstration of TS suppression by NaB in EC. NaB also broadly reprogrammed pyrimidine metabolism by downregulating de novo synthesis enzymes while upregulating salvage pathway components. Taken together, these findings suggest that TS suppression and pyrimidine metabolic reprogramming are important components of the in vitro response of EC cells to NaB. These results provide mechanistic insight into the metabolic effects of NaB in EC and support further investigation of this pathway in pharmacologically relevant and locally applicable therapeutic contexts.

HMGB1 acts as an alarmin when released from stressed or dying cells. In vitro, HMGB1 has previously been demonstrated to readily form complexes with other molecules and through intermolecular disulfide bond formation form homodimers. Recently, dimerized HMGB1 was identified in serum of LPS-challenged mice. In cancer, HMGB1 has been described as having both tumour-promoting and tumour-suppressing features, possibly dependent on the form of HMGB1 released into the tumour microenvironment. Factors determining the form in which HMGB1 is released remain, however, largely unexplored. We therefore investigated the form of HMGB1 released during different cell death modes and in response to LPS stress using various tumour cell lines. Supernatants were collected from ten non- and LPS-treated tumour cell lines and necrotic, apoptotic and pyroptotic THP-1 monocytic cells, to assess active and passive secretion of HMGB1. Released proteins were concentrated by TCA-precipitation and analysed by Western blotting under reducing and non-reducing conditions to detect monomeric, dimeric, or HMGB1-protein complexes. Co-immunoprecipitation and LC-MS/MS were used to identify binding partners of extracellular HMGB1. Tumour cells were found to release monomeric HMGB1 and HMGB1 heterocomplexes in the 50-60 kDa range, as indicated by their persistent high molecular weight under reducing conditions. Furthermore, we identified that HMGB1 interacts with ribosomal proteins, histone H2B, and SRP9 following LPS treatment of microglial SIM-A9 cells. HMGB1 readily formed heterocomplexes, but not homodimers in vitro across multiple cell lines, with differences between LPS-treated and untreated conditions. The form of released HMGB1 was influenced by cell type, cell death mode, and LPS stress.

Hereditary angioedema (HAE) is a rare congenital disorder characterized by recurrent episodes of subcutaneous and submucosal swelling, which can progress to life-threatening laryngeal obstruction. The most common form of HAE results from mutations in the SERPING1 gene, which encodes C1-esterase inhibitor (C1-INH). HAE belongs to the broader category of serpinopathy, in which misfolded serine protease inhibitors polymerize and are retained within the endoplasmic reticulum, leading to both loss-of-function and toxic gain-of-function effects. This study aims to develop a stable patient-derived cell line that accurately represent the molecular and cellular processes underlying HAE and serves as a replicable platform for drug discovery and therapy. Two HAE patients were recruited; peripheral blood mononuclear cells were obtained to generate patient-specific induced pluripotent stem cell (iPSC) lines. The HAE-iPSC cell lines were verified for their pluripotency and differentiated into hepatocytes for further physio-pathological studies. The generated iPSC lines were genetically identical to the donors, expressed canonical pluripotency markers, and demonstrated trilineage differentiation potential through embryoid body formation and expression of germ layer markers. Importantly, immunohistochemical analysis revealed intracellular retention and aggregation of C1-INH protein. We also demonstrated that the dominant-negative effect of the mutant C1-INH could be ameliorated by androgen treatment, a well-established agent in long-term prophylactic therapy for HAE. This is the first development of patient-derived iPSC models of HAE. These models not only exhibit key molecular features of HAE but also provide a versatile platform for mechanistic studies and preclinical drug testing.

To study the effects of extracellular vesicles (EVs) derived from primary myometrial and leiomyoma cells, as well as suitable cell lines, and to evaluate the release of EVs following omega-3 fatty acid treatment and their impact on fibronectin protein expression in recipient myometrial cells. Case-control laboratory study. University institute and university hospital. Patients with uterine fibroids. Primary cells were obtained from uterine tissue samples (leiomyoma and healthy myometrium) of premenopausal women (41-49 years) undergoing surgery. Immortalized myometrial (A00-9) and leiomyoma (A00-10) cell lines were also used. Cross-sectional in vitro study comparing untreated and omega-3-treated primary and immortalized myometrial and leiomyoma cells. EVs were isolated after 48 hours of treatment, characterized by Nanoparticle Tracking Analysis (NTA) and Transmission Electron Microscopy (TEM), and then used to treat myometrial cell lines. Fibronectin expression was measured in recipient cells. EVs were isolated and fractionated into small (s) and large (l) EVs. sEVs release was significantly induced by EPA treatment (p<0.05). EVs derived from leiomyoma cells showed a trend toward increased fibronectin expression in recipient myometrial cells, whereas EVs from omega-3-treated leiomyoma cells showed attenuated effects. EVs from myometrial cells, treated or untreated, did not alter fibronectin expression. Results were consistent across biological replicates (n=3). (s): These data suggest that leiomyoma-derived EVs contribute to fibrotic changes in surrounding myometrium and that omega-3 fatty acids can modulate EV release and EVs-mediated pro-fibrotic signaling. This may represent a potential proof-of-concept strategy for managing fibroid-associated fibrosis, though further in vivo validation is required.

Five previously undescribed isoquinoline alkaloids, including one thalifaberine-type aporphine-benzylisoquinoline (ABI) (1), two aporphine-type (2-3), and two oxoaporphine-type alkaloids (4-5), together with fifteen known alkaloids (6-20) were isolated from the roots of Thalictrum baicalense Turcz.ex Regel. Their structures were established on the basis of spectroscopic data and ECD calculations. Cytotoxicity assays revealed that several isolated alkaloids exhibited inhibitory effects against HL-60, HepG2, U937 and HCT116 human cancer cell lines, with IC50 values ranging from 2.41 to over 50 &#x3bc;M. Notably, the undescribed compound 5 exhibited inhibitory activity with an IC50 value of 14.78 &#xb1; 1.53 &#x3bc;M against the HL-60 cancer cell lines.

The sodium leak channel non-selective (NALCN) is a key regulator of resting membrane potential and cellular excitability in neurons and endocrine cells. Gain-of-function de novo pathogenic variants in NALCN cause severe neurodevelopmental disorders with a broad and heterogeneous clinical spectrum. Partial inhibition of NALCN has been proposed as a therapeutic strategy; however, progress has been limited by the absence of selective pharmacological modulators. This gap largely reflects the lack of a robust heterologous expression system suitable for high-throughput screening, as functional NALCN requires multiple ancillary subunits and its constitutive expression is toxic in commonly used cell lines such as HEK293. To address these challenges, we developed a multitransposon-based approach to generate inducible HEK293 cell lines that stably express the complete NALCN channelosome, including wild-type and disease-associated variants. We further demonstrate that NALCN current expression is cell cycle-dependent, enabling the definition of optimized conditions for consistent and reproducible electrophysiological recordings. Using these cell lines, we conducted a systematic pharmacological characterization of the NALCN channelosome by patch-clamp electrophysiology and identified several candidate modulators that are currently under evaluation. Notably, we revisited NALCN modulation by N-benzhydryl quinuclidine compounds and found that these compounds can restore locomotor phenotypes in an animal model of NALCN gain-of-function. Together, this work establishes a foundational platform for the discovery of NALCN-targeting compounds and opens new therapeutic avenues not only for NALCN-associated neurodevelopmental diseases, but also potentially for psychiatric disorders, chronic pain, and cancer.

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer mostly associated with asbestos exposure. Effective treatments are limited, and the prognosis is extremely poor. Therefore, the development of novel therapeutic approaches is highly desirable. Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that specifically kills target cells. It utilizes an antibody-IRDye700DX conjugate that binds target tumor cells. After near-infrared light irradiation of the tumor, rapid and highly selective cell damage results in immunogenic cell death. Anti-epidermal growth factor receptor (EGFR) antibody-IRDye700DX conjugate has already been approved in Japan for the treatment of head and neck cancer with near-infrared laser light activation. EGFR overexpression in MPM makes it a promising candidate for EGFR-targeted NIR-PIT, but its efficacy has not been reported previously. In this study, we investigated the therapeutic effects of NIR-PIT targeting EGFR using an MPM xenograft mouse model. In vitro, three MPM cell lines (NCI-H28, NCI-H226, and MSTO-211H) showed EGFR overexpression on the cell surface. EGFR-targeted NIR-PIT induced cell death in a dose-dependent manner in all MPM cell lines. In vivo, EGFR expression was verified, and anti-EGFR antibody binding was observed in both NCI-H226 and MSTO-211H tumors. After EGFR-targeted NIR-PIT, histological analysis demonstrated cancer cell death which significantly suppressed tumor growth in both tumor models and significantly extended survival in NCI-H226 tumor-bearing mice. Thus, these results suggest that EGFR-targeted NIR-PIT could be a promising treatment approach for MPM.

In grape, EXO70 subunits are essential components of the exocyst tethering complex, which is involved in complex assembly, plant growth and stress-related processes. However, the exact function it performs in facilitating tolerance to drought and cold conditions has yet to be clarified. In this study, we functionally characterized a grape EXO70 isoform, VvEXO70A1, which is predominantly localized at the plasma membrane. Evolutionary analysis of the EXO70 gene family across 11 species indicated that grape EXO70 genes share a conserved phylogenetic history with their orthologs from dicotyledons. The expression of VvEXO70A1 was elevated in overexpression (OE) lines Arabidopsis and grape calli exposed to water deficit and low-temperature treatments. Compared with wild type (WT), VvEXO70A1 overexpressing Arabidopsis and grape calli exhibited enhanced tolerance under these abiotic stresses, which was characterized by both lower levels of oxidative stress markers and a more active antioxidant machinery with substantially higher activities of major ROS-scavenging enzymes, including CAT, SOD, and POD. Notably, the transgenic plants were more sensitive to abscisic acid (ABA), displaying stronger ABA-induced stomatal closure. This phenomenon was further enhanced under drought stress, with the expression of the ABA signaling gene ABF4 being significantly upregulated. Cold stress-related genes (CBF1/2/3, ICE1/2, and ICE1a/b/c) were also strongly induced when the OE lines underwent low-temperature treatment. Overall, overexpression of VvEXO70A1 functions as a positive regulator, boosting tolerance to drought and cold conditions which was accompanied by reduced ROS damage and elevated expression levels of key stress-responsive genes associated with drought and cold in both transgenic Arabidopsis and grape calli.

Fenofibrate, an active pharmaceutical ingredient (API) of the fibrate class approved by the U.S. Food and Drug Administration (FDA) for the treatment of hypercholesterolemia and hyperlipidemia, has emerged as a promising candidate for repurposing in cancer. Indeed, beyond its lipid-lowering effects, fenofibrate has demonstrated antitumor properties, including antiproliferative and cytotoxic effects in normoxia (21% O2) in preclinical models of GBM. In addition, fenofibrate may inhibit hypoxia-inducible factor-1 alpha (HIF-1&#x3b1;) and reduce the expression of hypoxia-inducible genes, potentially overcoming hypoxia-induced chemoresistance. These findings, combined with its established clinical safety profile, support further investigation of fenofibrate as a potential therapeutic strategy in GBM. On this basis, physico-chemical characterization of fenofibrate was assessed to determine its ability to cross the blood-brain barrier. We determined in vitro on GBM cell lines U251-MG, U87-MG and GL261, the efficacy of fenofibrate in decreasing GBM cell viability and proliferation under normoxia (21% O2) and hypoxia (1% and 0.2% O2). We investigated the kinetics of its internalization by HPLC. In addition, the safety of fenofibrate was evaluated on non-tumoral brain cells. Dunn's post-hoc test was used after a significant Kruskal-Wallis. Being practically insoluble in water, fenofibrate was dissolved in dimethyl sulfoxide (DMSO) for studies. Primary astrocytes showed no signs of toxicity following treatment with fenofibrate. The effect of fenofibrate on GBM cell lines was studied at various time points and exhibited a cell type-, time- and concentration-dependent cytotoxicity with an LC50 of 25, 43.7 and 49.6&#xa0;&#xb5;M for U251-MG, U87-MG and GL261 cells, respectively. Interestingly, fenofibrate uptake was confirmed, 12.9&#x2009;&#xb1;&#x2009;5.7% and 14.2&#x2009;&#xb1;&#x2009;6.6% of fenofibrate was found in U251-MG and U87-MG cells, respectively. Intracellular concentrations of fenofibrate increased over time and no precipitation was observed. In hypoxia (1% and 0.2% of O2), the cytotoxic effect of fenofibrate was still present, albeit decreased. Furthermore, fenofibrate induced a cytostatic effect on U251-MG and U87-MG under both normoxia (21% O2) and hypoxia (1% and 0.2% O2), reducing their proliferation. Under the experimental conditions tested, namely in vitro studies, fenofibrate appeared more efficient compared with temozolomide, the standard treatment for GBM. This study demonstrated the cytotoxic and cytostatic effect of fenofibrate on GBM cells. These results indicate that fenofibrate may be a therapeutic alternative for GBM treatment.

Drought threatens apple (Malus domestica) growth and productivity, often leading to irreversible economic losses. C1-papain family cysteine proteases are key enzymes in plant responses to abiotic stress, yet their specific roles under drought conditions remain largely uncharacterized in apple. Sequence analysis identified MdCP37 as a member of the C1-papain family. Here, we demonstrate that overexpression of MdCP37 (OE) in transgenic apple increases drought sensitivity, while RNAi-mediated silencing of MdCP37 enhances drought tolerance. Under drought stress, MdCP37-OE lines displayed reduced antioxidant enzyme activity and suppressed expression of drought-responsive genes, whereas RNAi lines exhibited opposite trends. Moreover, MdCP37 accelerated chlorophyll and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) degradation and promoted leaf senescence under drought conditions. Collectively, our findings establish MdCP37 as a negative regulator of drought tolerance in apple and offer theoretical support for improving drought resilience in apple breeding programs, particularly in arid regions.

NFS1 cysteine desulfurase (NFS1) a critical enzyme in iron&#x2011;sulfur (Fe-S) cluster biogenesis and mitochondrial iron homeostasis, plays a pivotal role in the dysregulation of iron metabolism, a recognized hallmark of cancer. However, the specific role and regulatory mechanisms of NFS1 in colorectal cancer (CRC) remain poorly understood. This study aimed to elucidate the function of NFS1 in CRC and to uncover the upstream molecular pathways governing its expression. The expression of NFS1 in CRC was comprehensively analyzed using public databases (TIMER2.0, TCGA, and TNMplot) and validated in clinical tissue samples and CRC cell lines by quantitative real-time PCR and Western blotting. Loss- and gain-of-function experiments were conducted in SW620 and LoVo cells to assess the effects of NFS1 on cell proliferation, migration, stemness, apoptosis, and ferroptosis, which were evaluated using Cell Counting Kit-8 (CCK-8), EdU, Transwell migration, sphere formation, flow cytometry, and specific metabolic assays. The regulatory mechanisms were investigated through cycloheximide (CHX) chase, ubiquitination, dual-luciferase reporter, and chromatin immunoprecipitation (ChIP) assays. Finally, a xenograft mouse model was established to validate the findings in vivo. NFS1 was significantly upregulated in CRC tissues and cell lines, with its expression associated with tumor-node-metastasis grade, lymph node metastasis, and tumor size. In vitro, NFS1 silencing suppressed CRC cell proliferation, migration, and stemness, while promoting apoptosis and ferroptosis. Mechanistically, tripartite motif containing 67 (TRIM67) directly interacted with NFS1 and promoted its ubiquitination and protein degradation. Conversely, the transcription factor CCAAT/enhancer-binding protein alpha (CEBPA) was found to bind to the NFS1 promoter and positively regulate its transcription. Functional rescue experiments demonstrated that the anti-tumor effects of TRIM67 overexpression or CEBPA silencing were effectively reversed by concurrent NFS1 overexpression. Further, the in vivo xenograft model confirmed that CEBPA knockdown inhibited tumor growth and tumor lung metastasis by downregulating NFS1. In CRC, the oncogenic transcription factor CEBPA positively regulated NFS1 transcription, while the E3 ligase TRIM67 promoted its ubiquitination and degradation. Both TRIM67 overexpression and CEBPA silencing suppressed the malignant progression of CRC by downregulating NFS1, highlighting the TRIM67/CEBPA/NFS1 axis as a potential therapeutic target.

Therapeutic resistance is a major cause of treatment failure in glioblastoma (GBM), highlighting the need for physiologically relevant models to identify actionable resistance mechanisms. While two-dimensional (2D) cultures are widely used for target discovery, they poorly represent the tumor microenvironment. In contrast, three-dimensional (3D) spheroid cultures better recapitulate spatial heterogeneity, hypoxic gradients, and stress-adaptive signaling observed in tumors. We applied an integrated 2D-3D quantitative proteomic approach to identify microenvironment-dependent regulators of chemoresistance in GBM. Proteomic profiling was performed in U87MG and U251MG cells grown as 2D monolayers or 3D spheroids. Differentially expressed proteins were validated by quantitative RT-PCR, and functional studies were conducted using genetic depletion followed by assessment of temozolomide (TMZ) sensitivity. Comparative analysis identified 13 proteins consistently differentially expressed between 2D and 3D cultures: NDUFB5, RNGTT, MLK4, SYN1, DDX5, EIF2AK2, ITGA1, ZNF33B, ZNF343, WDR19, JPH3, CCT8L2, and FNDC3A. Among these, Mixed Lineage Kinase 4 (MLK4) showed strong and reproducible upregulation in 3D spheroids in both GBM cell lines. Genetic depletion of MLK4 significantly increased TMZ sensitivity without affecting basal cell viability, suggesting a specific role in therapy response. Notably, MLK4 expression was induced only under 3D conditions. MLK4 functions as a microenvironment-responsive regulator of chemoresistance in GBM. These findings demonstrate that 3D culture systems reveal clinically relevant resistance pathways not detectable in conventional 2D models and highlight 3D proteomic profiling as a powerful strategy for identifying therapeutically actionable targets.

Uveal melanoma (UVM) is a highly aggressive intraocular malignancy with limited treatment options and a poor prognosis, particularly following metastasis. Oxidative stress plays a complex, dual role in tumor progression, but the regulatory roles of long non-coding RNAs (lncRNAs) in the oxidative stress response within UVM remain largely unexplored. The objective of this study was to investigate the regulatory mechanism of the lncRNA MIAT/miR-4306/CXCR4 axis in modulating oxidative stress and apoptosis in uveal melanoma (UVM), and to develop an oxidative stress-related prognostic gene signature. This study integrated transcriptomic data from UVM patient tissues and public databases to construct an oxidative stress-related competing endogenous RNA (ceRNA) network. Bioinformatic analyses, including differential expression, weighted gene co-expression network analysis, and prognostic modeling, were employed. The functional roles of the identified lncRNA MIAT, miR-4306, and CXCR4 in apoptosis and oxidative stress were investigated in UVM cell lines. Techniques included quantitative real time polymerase chain reaction (qRT-PCR), Western blot, flow cytometry for apoptosis, and assays for oxidative stress markers. We identified a novel ceRNA axis wherein the lncRNA MIAT is upregulated in UVM and acts as a molecular sponge for miR-4306, leading to the derepression of its target gene, CXCR4. Functionally, lncRNA MIAT overexpression alleviated hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis, while miR-4306 exerted opposing, tumor-suppressive effects. CXCR4 was confirmed as a direct target of miR-4306 and mediated the protective effects of the MIAT/miR-4306 axis on cell survival. Furthermore, a prognostic risk model based on oxidative stress-related genes from the network effectively stratified patients into high- and low-risk groups with distinct survival outcomes and immune infiltration patterns. Our findings elucidated a critical lncRNA MIAT/miR-4306/CXCR4 regulatory axis that modulated oxidative stress resistance and apoptosis in UVM. This axis represented a promising therapeutic target, and the developed oxidative stress-related gene signature may serve as a valuable prognostic tool for UVM patients.

This study evaluated the polyphenol content of leaf extracts from Artemisia monosperma (AM) and investigated their antioxidant properties, cytotoxic effects, and potential to induce DNA damage in human cancer cell lines. High-performance liquid chromatography (HPLC) quantified polyphenols in methanolic (AMM), ethanolic (AME), and aqueous (AMA) extracts, identifying 13 compounds in AME and 12 in AMA. AMM exhibited the strongest antioxidant activity (IC50&#x2009;=&#x2009;24&#xa0;&#xb5;g/ml). Both AME and AMM demonstrated potent anticancer activity against HCT-116 (IC&#x2085;&#x2080; = 0.38&#xa0;&#xb5;g/mL for AMM) and HUH-7 (IC&#x2085;&#x2080; = 21.95&#xa0;&#xb5;g/mL for AMM) cells, while exhibiting minimal cytotoxicity toward normal skin fibroblast cells (BJ-1; IC&#x2085;&#x2080; = 13.05&#xa0;&#xb5;g/mL for AMM), with AMM demonstrating particular selectivity for HCT-116 cells. AMM induced DNA fragmentation and modulated apoptosis-related gene expression (Bax, Bcl-2, p53) in HUH-7 cells and caused cell cycle arrest at G0/G1 phase in HCT-116 cells. Molecular docking further supported AMM's apoptosis activity. These results position A. monosperma as a rich source of bioactive polyphenols and antioxidants, with AMM showing promise as a therapeutic agent, especially for colorectal cancer.

Resistance to third-generation EGFR-TKIs such as naquotinib and osimertinib remains a major obstacle in the treatment of non-small cell lung cancer (NSCLC). Epithelial-mesenchymal transition (EMT) is a key mechanism driving drug resistance and metastatic progression. Cilengitide, a cyclic RGD peptide targeting integrins, has shown potential in suppressing EMT-associated signaling. This study examined the effects of cilengitide and its derivatives on TGF-&#x3b2;1-induced EMT, migration, and invasion in EGFR-TKI-resistant NSCLC cells. Naquotinib- and osimertinib-resistant HCC827 cell lines were established and analyzed using 2D and 3D culture models. EMT marker expression, cell viability, migration, and invasion were assessed following treatment with cilengitide derivatives (R-1, R-7, R-8). Combination treatment with dovitinib, an FGFR inhibitor, was also evaluated. Experimental approaches included qRT-PCR, western blotting, wound-healing assays, invasion assays, and whole-mount organoid staining. Resistant cells exhibited reduced epithelial markers and increased mesenchymal markers, along with enhanced migration and invasion upon TGF-&#x3b2;1 stimulation. Cilengitide and its derivatives significantly inhibited TGF-&#x3b2;1-induced EMT, migration, and invasion, with stronger effects observed in 3D organoid models. Among the derivatives, cilengitide (R-8) most effectively suppressed vimentin expression and ERK1/2 phosphorylation. Combination treatment with dovitinib further enhanced the inhibition of migration and invasion, suggesting synergistic potential.

MYB36 was recently identified as a transcription factor (TF) that may be involved in isoflavonoid metabolism and stress responses in the model legume Lotus japonicus. To further explore its role, we performed a comparative transcriptomic and (iso)flavonoid profiling analysis of wild-type (WT) plants and two independents homozygous Ljmyb36 mutant lines under two abiotic stress conditions: UV-B irradiation and salinity. The results obtained showed a markedly distinct and almost reciprocal global transcriptomic response of WT plants under both types of stress conditions. Under UV-B irradiation, genes related to isoflavonoid biosynthesis were induced, accompanied by increased isoflavonoid accumulation. In contrast, under salt stress, most of the genes modulated in the mutants corresponded to genes specifically involved in isoflavonoid, but not flavonol biosynthesis, highlighting candidate genes potentially regulated by MYB36. Metabolite profiling also indicated opposite changes in flavonoid and isoflavonoid metabolite in response to salt and UV-B treatments, reflecting the reciprocal patterns of gene expression found in salt and UV-B treatment conditions. These results suggest a role, for the first time, of MYB36 as a specific transcription factor in the regulation of (iso)flavonoid biosynthesis. In addition, the results obtained support the role of MYB36 as a crucial TF in the response to salt stress in legume plants.