Investigate sodium orthovanadate molecular mechanisms in diabetes-aggravated ulcerative colitis, focusing on Nrf2/Keap1 antioxidant and NF-κB/IL-6 inflammatory pathways.

Ethylene plays an indispensable role in regulating plant growth and stress responses. However, the mechanisms underlying the regulation of Na+/H+ homoeostasis by ethylene and subsequent mediation of maize growth under salt stress remain unclear. ZmACO2, which encodes ethylene biosynthesis enzyme 1-aminocyclopropane-1-carboxylate oxidase2, is induced by salt stress. Thus, ZmACO2-overexpressing (ACO2-OE) and mutant (aco2-cr) plants were used to investigate how ethylene regulates Na+/H+ homoeostasis in maize under salt stress. The aco2-cr mutants exhibited significantly lower Na⁺ accumulation and Na⁺/K⁺ ratios than the wild-type and ACO2-OE plants. This phenotype was attributed to their higher expression of ZmSOS1 and ZmHKT1, which increased root net Na⁺ efflux by 20.65% and decreased Na⁺ transport from roots to shoots by 42.49% (p < 0.001), respectively. Compared to the other plants, aco2-cr mutants showed higher ZmMHA2 expression and plasma membrane H+-ATPase activities, which promoted net root H+ efflux to provide a greater H+ proton gradient for salt-overly-sensitive 1 (SOS1). Inhibition efficiencies of Na+ efflux and H+ influx by sodium orthovanadate were lower in aco2-cr mutants than in ACO2-OE and wild-type plants under salt stress; however, ACO2-OE plants showed a salt-sensitive phenotype. Overall, these findings showed that salt-induced ethylene inhibited plasma membrane H+-ATPase and SOS1 from disrupting Na+/H+ homoeostasis, thereby decreasing Na+ efflux in maize roots and also provided a strategy to improve salt tolerance by optimising ethylene levels in maize.

Prostate cancer is one of the most prevalent malignancies in developed countries. Although new anticancer agents are being evaluated in models of this cancer, there is a scarcity of studies on the effects of sodium metavanadate (NaVO3). Therefore, the aim of this study was to investigate the effects of sodium metavanadate on the growth, viability, and survival of prostate cancer cells and to compare these results with those for sodium orthovanadate (Na3VO4). The experiments were conducted on DU-145 cells incubated with either sodium metavanadate or sodium orthovanadate. The impact of these vanadium compounds on cell growth was assessed using the MTT assay and crystal violet staining. Subsequently, the effects of sodium metavanadate and sodium orthovanadate on cell survival and the cell cycle were examined using propidium iodide and Hoechst 33342 staining, followed by analysis with fluorescence microscopy and flow cytometry. Both sodium metavanadate and sodium orthovanadate inhibited the growth of DU-145 cells, with IC50 values of 12.74 ± 5.38µM and 8.94 ± 2.90µM, respectively. This inhibition was attributed to apoptosis and necrosis, as well as cell cycle arrest at the G1/S checkpoint. The findings suggest that sodium metavanadate and sodium orthovanadate are potential anticancer agents against prostate cancer, effective at low concentrations.

Hormone residues, especially in aquatic products, have become a serious threat to food safety. The development of sensitive, affordable, on-site, and quick detection methods for hormone residues still faces great challenges. Herein, taking methyltestosterone (MT) as a representative analyte, a competitive lateral flow immunoassay (LFIA) platform was constructed using ultrabright lanthanide-doped luminescent nanoparticles, i.e. YVO4:Eu, as the label probe. The YVO4:Eu NPs were obtained by a facile hydrothermal method using lanthanide ions and sodium orthovanadate as the precursors and polyacrylic acid as the surface modifier. Owing to the advantages of high fluorescence quantum yield, abundant surface functional groups, good dispersity and good water solubility, the harvested YVO4:Eu NPs are a competitive and promising label probe in LFIA. The YVO4:Eu LFIA test strips showed a detection limit, i.e. 0.1 ng mL-1, which was about 1 to 2 orders of magnitude lower than that of most reported methods. Furthermore, the proposed test strips were successfully applied for the quantitative, accurate, and quick screening of MT in fish samples. This work reports a competitive luminescent label probe for food safety and quality control.

The aim of this study was to investigate the effects of some metals and chemical agents in vitro [5 mM] on the activity of acid phosphatase (AF) from the roots of Pisum sativum L. plants. The AF activity was determined using p-nitrophenyl phosphate as a substrate. It was shown that CoSO4, CoCl2, CaCl2, MgSO4 and CdCl2 did not significantly modify the AF activity. Pb(NO3)2 showed a slight inhibition of ≈ 13%, while FeSO4, KCl and NaCl exerted a moderate inhibition of 28, 29 and 36%, respectively, on the AF activity. However, CuSO4, MnSO4, ZnSO4 and ZnCl2 demonstrated a more pronounced enzymatic inhibition of 41, 48, 56 and 63%, respectively. A more pronounced enzymatic inhibition (42-52%) was also observed for some phosphate ions. In vitro testing of specific inhibitors of AF showed that sodium orthovanadate, sodium and ammonium molybdate almost completely inhibit FA.

Mycoplasma iowae is an economically significant pathogen that causes reduced hatchability, late embryo mortality and leg deformities, chondrodystrophy and skeletal lesions in poults. While prevention is essential in the control of infection, the appropriate administration of antibiotics may reduce economic losses during outbreaks. As a first step in the exploration of antimicrobial resistance mechanisms in M. iowae, target modification and efflux pump activity were examined in the present study. Point mutations were analyzed in previously described antibiotic binding sites in the whole genome sequences of 99 M. iowae strains. Mismatch amplification mutation assays (MAMAs) were designed and validated for the differentiation of mutations corresponding to elevated minimum inhibitory concentration (MIC) values for fluoroquinolones. Broth microdilution assays were performed to evaluate the effect of efflux pump inhibitors. In the presence of orthovanadate (OV), MIC values were significantly lower than in the absence of OV for spiramycin, tilmicosin, tylosin and oxytetracycline, which may indicate the presence of an active efflux system in M. iowae. Putative promoter regions of efflux-related genes were predicted and characterized. Genetic mutations, previously described in other bacteria, were described to be associated with elevated fluoroquinolone, macrolide and lincomycin MICs in M. iowae, although certain resistant phenotypes remained unexplained, promoting future examinations for deeper insights. The developed MAMAs may support rapid identification of M. iowae strains with elevated MIC values for fluoroquinolones. The better understanding of the efflux pump mechanisms enables the development of alternative methods for the support of therapy against this pathogen.

Eight pairs of undescribed trichostatin analogue enantiomers, (±)-karstmycins A-H (1a/1b-8a/8b), and three new enantiomers (9a-11a) together with five known analogues (9b-11b, 12, and 13) were isolated from karst cave-derived Streptomyces sp. DX6D14. The structures and absolute configurations of the new compounds were determined by extensive spectroscopic analysis, as well as nuclear magnetic resonance chemical shifts, optical rotation, and electronic circular dichroism calculations. Compounds 1 and 2 were rare trichostatins featuring a nitrile group, and compounds 3-5 were characterized by a unique piperidin-2-one moiety at the end of the branched C7 side chain. Compounds 3a and 3b showed PTP1B inhibitory activity with IC50 values of 27 ± 2 and 12 ± 2 μM, respectively, compared to the positive control, sodium orthovanadate (IC50: 14 ± 1 μM). A kinetic study indicated that the most potent compound 3b was a mixed-type inhibitor for PTP1B. Molecular docking simulation revealed that 3b simultaneously interacted with the catalytic site and the peripheral site of PTP1B.

Previously, we showed that vasorelaxant effects of trans-4-methoxy-β-nitrostyrene (T4MN) in rat aorta were mediated through stimulation of the soluble guanylate cyclase (sGC) pathway. The present study tested the hypothesis that bonding of the methoxy electron-donor group at the meta-position instead of the para-position into the aromatic moiety might enhance the interaction of the nitroderivative with sGC. For this purpose, vascular effects of the trans-3-methoxy-β-nitrostyrene (T3MN) were studied in rat aorta. In endothelium-intact preparations, T3MN was 100 times more potent as a vasorelaxant than its stereoisomer, T4MN. T3MN-induced vasodilatory effects remained unaffected by indomethacin, MDL-12,330A or glybenclamide but were significantly reduced by endothelium removal, L-NAME, ODQ, LY294002, TEA, 4-AP, and apamin. Under Ca2+-free conditions, T3MN was unresponsive to transient contractions evoked by caffeine, whereas it inhibited contractions induced by (i) the protein kinase C activator phorbol 12-myristate 13-acetate, (ii) the tyrosine phosphatase inhibitor sodium orthovanadate, (iii) exogenous calcium influx via receptor- or voltage-operated Ca2+ channels and (iv), in an ODQ-preventable manner, those evoked by PHE or Ca2+ influx through stores-operated Ca2+ channels activated by thapsigargin-induced Ca2+ store depletion. In conclusion, T3MN induced a potent vasorelaxant effect that seems to be mediated partly by an endothelium-dependent mechanism involving activation of the Akt/eNOS/NO pathway and partly by an endothelium-independent mechanism through activation of the sGC/cGMP/PKG pathway in vascular smooth muscle, leading to inhibition of Ca2+ influx from the extracellular milieu and IP3-sensitive intracellular Ca2+ release as well as activation of potassium channels.

This study introduces novel approaches against multidrug-resistant bacteria using nanozymes and phosphatase inhibitors. Beet-derived SN-CNPs exhibited robust phosphatase-like activity and selectively disrupted bacterial membranes, while sodium orthovanadate (SOV) inhibited phosphatases essential for cell wall synthesis, exerting bactericidal effects. Combined application of SN-CNPs and SOV enhanced antimicrobial efficacy against E. coli and L. lactis, highlighting a synergistic mechanism. The findings underscore phosphatase-centered strategies as a paradigm shift from conventional ROS-dependent therapies and open new avenues for multi-targeted antimicrobial interventions.

Inflammatory processes can disrupt tissue homeostasis and promote metabolic disturbances, including insulin resistance. Pro-inflammatory cytokines, such as tumor necrosis factor (TNF), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6), mediate this process. Since skeletal muscle is one of the major insulin-sensitive tissues, it is crucial to search for molecular links that promote insulin resistance during inflammation. Protein tyrosine phosphatases (PTPs) negatively regulate insulin signaling in multiple organs and models. To gain insight into the potential interactions of cytokines and PTPs in skeletal muscle, we characterized the effects and kinetics of cytokine stimulation on insulin signaling in murine C2C12 muscle cells. The protein level and activities of PTP non-receptor type 1 (PTPN1/PTP1B) and type 2 (PTPN2/TCPTP) were evaluated after cytokine stimulation and addressed by pharmacological inhibition or siRNA-mediated knockdown (KD). TNF, IL-1β and IL-6 elicited different kinetics and expression patterns of the respective PTPs and insulin signaling molecules, while surprisingly, insulin action was preserved. Furthermore, PTPN1 and PTPN2 had only minor effects on insulin signaling in C2C12 cells with siRNA-mediated compensatory PTP regulation. However, pan-PTP inhibition by sodium orthovanadate confirms that PTPs are negative regulators of insulin signaling. In summary, our data provide insights into the balance of the physiological and pathophysiological effects of cytokines and targeting individual PTPs to regulate insulin signaling in C2C12 cells. Additionally, our findings highlight the complex dynamics and interplay of cytokines, PTPs and metabolic pathways. This should be acknowledged when new therapeutic tools are developed to address inflammation-induced diseases such as type 2 diabetes or related comorbidities.

In this paper, we present a combined experimental andcomputationalstudy of a cobalt­(II) complex with the organic ligand benzyltriethylammoniumbromide. The complex was characterized by IR spectroscopy and single-crystalX-ray crystallography. The molecular geometries, electronic transitions,and vibrational frequencies were calculated using density functionaltheory (DFT) at the B3LYP/LanL2DZ level. Based on the unit cell parametersobtained from experimental data, DFT calculations were performed tocorrelate with the vibrational spectrum analysis. The theoreticalparameters derived from DFT showed strong agreement with the experimentalresults. A qualitative description of the charge-transfer characterwas carried out using natural bond orbital (NBO) analysis. The energiesof the highest occupied molecular orbital (HOMO) and lowest unoccupiedmolecular orbital (LUMO) were calculated, and the band gap was determined.Furthermore, the complex demonstrated significant degradation of methyleneblue (MB) under sunlight irradiation. In vitro, the cobalt­(II) complexexhibited strong inhibitory activity against key inflammatory enzymes,particularly myeloperoxidase (MPO), with a half-maximal inhibitoryconcentration (IC50) of 80.45 μM, compared to 4-aminobenzoicacid hydrazide (ABAH, IC50 = 9.46 μM). It also showedpotent inhibitory effects on obesity-related enzymes such as lipase(IC50 = 41.93 μM) compared to orlistat (IC50 = 32.75 μM). Regarding diabetes-related targets, the complexeffectively inhibited α-amylase (IC50 = 21.75 μM)in comparison to acarbose (ACR, IC50 = 18.08 μM),and promoted insulin signaling by inhibiting dipeptidyl peptidase-4(DPP-4, IC50 = 22.01 μM) compared to sitagliptin(STG, IC50 = 4.07 μM). Additionally, it exhibitedmoderate inhibitory activity against protein tyrosine phosphatase1B (PTP1B, IC50 = 10.88 μM), approximately 2.1 timesless potent than sodium orthovanadate (SV, IC50 = 5.24μM). A molecular docking approach was employed to investigatethe binding affinities and molecular interactions of the two ligandsforming the Co­(II) complex with several protein targets (PDB IDs:3BAJ, 4A5S, 1LPB, 5MFA, and 1T49). The docking results revealed thatthe complex, through interactions such as hydrogen bonding, π–πstacking, carbon–hydrogen interactions, π–anion,π–cation, and π–alkyl interactions, exhibitspromising inhibitory potential against the selected enzymes: α-amylase,dipeptidyl peptidase-4 (DPP-4), lipase, promyeloperoxidase (proMPO),and protein tyrosine phosphatase 1B (PTP1B).

Non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are major hepatic disorders characterized by lipid accumulation, oxidative stress, and inflammation, yet they differ fundamentally in aetiology. While NAFLD is primarily driven by insulin resistance and metabolic syndrome, AFLD arises from chronic alcohol consumption and the hepatotoxic effects of its metabolites. Current therapeutic approaches for both conditions are limited, often relying on lifestyle modifications or nonspecific pharmacological agents, with suboptimal outcomes. Sodium orthovanadate (SOV), an inorganic vanadium compound, has emerged as a novel candidate due to its multifaceted pharmacological profile. Acting as an insulin mimetic, SOV enhances insulin signalling and glucose uptake, while also exerting potent antioxidant and anti-inflammatory effects. These properties make it uniquely suited to address both metabolic and alcohol-related liver dysfunction. Preclinical studies have demonstrated SOV’s ability to reduce hepatic steatosis, normalize lipid profiles, improve mitochondrial function, and suppress inflammatory cytokines. Notably, its mechanism of action in NAFLD primarily involves modulation of glucose and lipid metabolism via PI3K/Akt pathways, whereas in AFLD, it acts by attenuating oxidative damage and downregulating NF-κB-mediated inflammation. Despite these promising outcomes, clinical translation is constrained by concerns regarding long-term toxicity. Nevertheless, SOV holds significant potential as a dual-purpose therapeutic agent targeting the complex pathophysiology of fatty liver diseases.

Ectophosphatase activities and phosphate transport mechanisms in Tritrichomonas foetus and their impact on parasite proliferation.

Sodium orthovanadate (vanadate), a potent inhibitor of p53, has been shown in earlier work to alleviate total-body irradiation (TBI)-induced hematopoietic syndrome. However, as p53 plays a crucial role in normal spermatogenesis, its suppression may raise concerns about potential adverse effects on male reproductive function. In this study, we investigated whether vanadate exacerbates impairment of male fertility when administered for hematopoietic protection under TBI conditions. Trp53 wild-type male ICR mice received a single intraperitoneal injection of vanadate or vehicle, followed by exposure to 6Gy-TBI, corresponding to a testicular dose of 4.8Gy. This radiation dose is sufficient to induce hematopoietic syndrome and temporary infertility. Spermatogenic function was assessed by analyzing testicular haploid cell populations and sperm morphology. Fertility recovery was evaluated through mating tests with virgin females, and transgenerational outcomes were assessed by analyzing litter size, fetal body weight, and implantation numbers. Our findings demonstrate that vanadate effectively rescued survival of irradiated animals under conditions known to induce the hematopoietic syndrome, without adversely affecting spermatogenesis. On the contrary, vanadate appeared to promote recovery from temporary infertility, likely through partial suppression of p53 accumulation and Bbc3 expression. This effect was more pronounced in Trp53 heterozygous mice, particularly in those irradiated at a young age. Importantly, the offspring derived from vanadate treated males with recovered fertility exhibited normal development, at least in terms of morphology. Taken together, vanadate confers hematopoietic protection under TBI without compromising, and possibly even supporting, male reproductive recovery. These findings suggest its potential for clinical use with low risk to male fertility.

Alcoholic fatty liver disease (AFLD) is a leading cause of chronic liver disease worldwide, contributing to significant morbidity and mortality. Despite its growing prevalence, no FDA-approved pharmacological treatments exist, leaving lifestyle modifications as the primary intervention. AFLD pathogenesis involves a complex interplay of lipid accumulation, oxidative stress, insulin resistance, and inflammation, highlighting the need for innovative therapeutic approaches. However, sodium orthovanadate (SOV), an inorganic vanadium-based compound, is a potent inhibitor of protein tyrosine phosphatases (PTPs), including PTP1B-a key regulator of insulin signalling and metabolic homeostasis. SOV has demonstrated insulin-mimetic properties and has shown promise in preclinical models of metabolic disorders. Given the emerging role of PTP1B in hepatic insulin resistance and lipid dysregulation, we hypothesize that SOV may offer therapeutic benefits in AFLD by modulating biochemical parameters and oxidative stress in liver. In this study, we investigate the effects of SOV in two rodent models of AFLD: (1) alcohol-induced liver disease and (2) high-fat diet plus alcohol-induced liver disease. We assess Biochemical Parameters like alkaline Phosphatase (ALP), aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH), total bilirubin, cholesterol, uric acid, triglyceride. Tissue analysis like TBARS/MDA activity, Glutathione (reduced GSH) assay, Glutathione peroxidase (GPx) activity, Superoxide Dismutase, Catalase activity, and Histopathology to determine whether SOV can mitigate AFLD progression. Our research shows that SOV has promise as a treatment for fatty liver disease brought on by alcohol. Improvements in oxidative stress control,biochemical markers most likely mediate its hepatoprotective benefits. By uncovering the therapeutic potential of SOV, this study may pave the way for novel pharmacological strategies to combat fatty liver diseases.

Cadmium (Cd) is a toxic heavy metal introduced into the environment through natural and human activities. Populus alba is a promising species for phytoremediation due to its ability to synthesize thiol-peptides like glutathione (GSH) and phytochelatins (PCn), which play a crucial role in heavy metal detoxification. In this study, we developed an HPLC-ESI-MS/MS method to quantify intracellular and extracellular thiol-peptides in P. alba ‘Villafranca’ clone exposed to different Cd concentrations over short- and long-term periods. We also evaluated functional responses, including biometric traits and photosynthetic efficiency. Despite prolonged Cd exposure, plants showed high resistance, with no effects on growth or PSII performance. Cd treatment significantly increased PCn levels, particularly in roots, with PC2, PC3, and PC4 contributing to detoxification. Notably, GSH and PCn were detected extracellularly, suggesting a plasma membrane efflux mechanism. Sodium orthovanadate, an inhibitor of plasma membrane transporters, strongly reduced extracellular GSH and only partially affected PCn efflux. These results suggest that GSH and PCn may not share the same transport pathways. This study underscores the dual role of thiol-peptides in Cd detoxification, through intracellular sequestration and extracellular extrusion, and highlights P. alba as a model for studying Cd toxicity mitigation in plants.

Pericentriolar material 1 aggregation maintains cell survival upon prolonged replication stress.

Sodium orthovanadate is a non-selective protein tyrosine phosphatase inhibitor that can cause several types of kidney injury, including glomerulosclerosis, inflammation, and tubular damage. Cannabis is widely known for its medicinal use, and several studies have demonstrated its anti-diabetic and anti-inflammatory properties. The current study investigated the therapeutic effect of Lebanese cannabis oil extract (COE) against sodium orthovanadate-induced nephrotoxicity both in vitro and in vivo. Sprague Dawley male rats were intraperitoneally injected with 10 mg/kg sodium orthovanadate for 10 days followed by 5 mg/kg; 10 mg/kg; or 20 mg/kg intraperitoneal injection of cannabis oil extract, starting on day 4 until day 10. The body weight of the rats was monitored during the study, and clinical parameters, including serum urea, creatinine, and electrolytes, as well as kidney and heart pathology, were measured. Conditionally immortalized cultured rat podocytes were exposed to either sodium orthovanadate or selective phosphatase inhibitors, including DUSPi (DUSP1/6 inhibitor) and SF1670 (PTEN inhibitor), in the presence or absence of cannabis oil extract. MTS and an in vitro scratch assay were used to assess podocyte cell viability and migration, respectively. Western blot analysis was used to evaluate the phosphorylation levels of AKT and p38 MAPK. Rats injected with sodium orthovanadate displayed a marked reduction in body weight and an increase in serum creatinine and urea in comparison to the control non-treated group. All doses of COE caused a significant decrease in serum urea, with a significant decrease in serum creatinine observed at a dose of 20 mg/kg. Moreover, the COE treatment of rats injected with orthovanadate (20 mg/kg) showed a marked reduction in renal vascular dilatation, scattered foci of acute tubular necrosis, and numerous mitoses in tubular cells compared to the sodium orthovanadate-treated group. The cell viability assay revealed that COE reversed cytotoxicity induced by sodium orthovanadate and specific phosphatase inhibitors (DUSPi and SF1670) in rat podocytes. The in vitro scratch assay showed that COE partially restored the migratory capacity of podocytes incubated with DUSPi and SF1670. Time-course and dose-dependent experiments showed that COE (1 μg/mL) induced a significant increase in phospho-(S473)-AKT, along with a decrease in phospho (T180 + Y182) P38 levels. The current results demonstrated that Lebanese cannabis oil possesses important kidney protective effects against sodium orthovanadate-induced renal injury.

Autophagy-related genes (ATGs) play a crucial role in tumorigenesis and cancer progression. ATG10, a member of the ATG family, has been implicated in various malignancies, including endometrial cancer, hepatocellular carcinoma, acute leukemia, nasopharyngeal carcinoma, gastric cancer and colorectal cancer. Its overexpression is frequently associated with poor prognosis and increased disease progression. ATG10 promotes cancer growth and metastasis by modulating epithelial-mesenchymal transition and cell cycle regulators such as cyclin B1, CDK1 and CDK2. However, its activity can be inhibited by several factors, including DDX10, PTBP1, sodium orthovanadate, podofilox, SIRT6, FAT1, SOX2 and multiple microRNAs (e.g., miR-369-3p, miR-100-3p, miR-27b-3p, miR-197-3p, let-7i-5p and miR-552). This review explores the functional and clinical significance of ATG10 across various cancers, highlighting its potential as a biomarker and therapeutic target.

Regulation of anaplerotic enzymes by melatonin enhances resilience to cadmium toxicity in Vigna radiata (L.) R. Wilczek.