A Significant Increase in the Incidence of Neonatal Hyperbilirubinemia and Phototherapy Treatment Due to a Routine Change in Laboratory Equipment.

CONTEXT.­: Total serum bilirubin (TSB) analysis is pivotal for diagnosing neonatal hyperbilirubinemia. Because of a routine change in laboratory equipment, our TSB assay changed from a diazo to a vanadate oxidase method. Upon implementation, TSB results were substantially higher in newborns than expected based on the validation. OBJECTIVE.­: To investigate the application of TSB and intermethod differences in neonates and their impact on phototherapy treatment. DESIGN.­: The diazo and vanadate methods were compared directly using neonatal and adult samples. Anonymized external quality control data were analyzed to explore interlaboratory differences among 8 commercial TSB assays. Clinical patient data were extracted from the medical records to investigate the number of newborns receiving phototherapy. RESULTS.­: The mean bias of the vanadate versus the diazo TSB method was +17.4% and +3.7% in neonatal and adult samples, respectively. External quality control data showed that the bias of commercial TSB methods compared with the reference method varied from -3.6% to +20.2%. Within-method variation ranged from 5.2% to 16.0%. After implementation of the vanadate TSB method, the number of neonates treated with phototherapy increased approximately threefold. CONCLUSIONS.­: Currently available TSB assays lack harmonization for the diagnosis of neonatal hyperbilirubinemia. Between-methods differences are substantially higher in neonatal compared with adult samples, highlighting the importance of including neonatal samples during assay validation. Close collaboration between laboratory specialists and clinicians is essential to prevent overtreatment or undertreatment upon the implementation of novel analyzers or assays. Also, harmonization of TSB assays, with an emphasis on neonatal application, is warranted.

Evaluation of immunotoxicity of sodium metavanadate following drinking water exposure in female B6C3F1/N mice in a 28-day study.

Sodium metavanadate (NaVO3 ) is a pentavalent vanadium compound used in the metal industry and dietary supplements; human exposure occurs through inhalation of fumes and dust and ingestion of NaVO3 -containing products. The objective of this study was to assess the potential immunotoxicity of NaVO3 . Female B6C3F1/N mice were exposed to 0-500 ppm NaVO3 in drinking water for 28 days and evaluated for effects on immune cell populations and innate, cellular-mediated, and humoral-mediated immunity. There was a decreasing trend in body weight (BW) and BW gain in NaVO3 exposed mice, with a decrease (p ≤ 0.05) in BW gain at ≥250 ppm, relative to control. Conversely, increasing trends in spleen weights and an increase (p ≤ 0.05) in the spleen:BW ratio at ≥250 ppm NaVO3 were observed. NaVO3 exposure altered antibody production against sheep red blood cells (SRBC). Antibody forming cells (AFC)/106 spleen cells exhibited a decreasing trend, with a decrease (p ≤ 0.05) at 500 ppm NaVO3 , concurrent with an increase in percent B cells. NaVO3 had no effect on the serum anti-SRBC IgM antibody titers or anti-keyhole limpet hemocyanin antibody production. Exposure to NaVO3 decreased the percentage of natural killer cells at all dose levels (p ≤ 0.05), with no effect on the lytic activity. NaVO3 altered T-cell populations at 500 ppm but had no effect on T-cell proliferative responses or the lytic activity of cytotoxic T cells. Collectively, these data indicate that NaVO3 exposure can adversely affect the immune system by inducing alterations in humoral-mediated immunity, specifically the AFC response, with no effect on cell-mediated or innate immunity.

Surface conditioning of PEEK post using Nd: YVO4 laser, photodynamic therapy, and sulfuric acid on the pushout bond strength to canal dentin.

AIM: To assess the push-out bond strength (PBS) of polyetheretherketone (PEEK) post-to-root dentin using post-surface conditioners i.e., Neodymium-doped yttrium orthovanadate (Nd: YVO4) and Riboflavin (RF) and Rose Bengal (RB) mediated photodynamic therapy (PDT) compared to sulfuric acid (SA). MATERIALS AND METHODS: Decoronation of forty human single-rooted premolar teeth was performed. Followed by chamber opening, working length (WL) was established at 15 mm. Root canal preparation was completed using ProTaper Ni-Ti rotary system till F3 finishing file along with root canal disinfection. The canals were dried with paper cones followed by obturation using gutta-percha (GP) and AH sealer. Post space was prepared by drilling out 11 mm of GP using a Gates Glidden drill #3. PEEK posts were fabricated using the CAD-CAM system and then randomly allocated into 4 groups based on the post-surface conditioning (n = 10). Group 1: SA, group 2: PDT RF, group 3: PDT RB, and group 4: Nd: YVO4 laser. The PEEK post was then cemented in their respective canal. PBS and failure mode assessment were performed using a universal testing machine and stereomicroscope at 40x magnification. The SBS data set was subjected to a one-way analysis of variance (ANOVA) and Tukey's Post Hoc test at a significance level of 0.05. RESULTS: The samples in group 4 (Nd: YVO4 laser) coronal third (7.99±0.24 MPa) demonstrated the highest PBS. The apical third of samples in group 1 PEEK post surface conditioned with SA (5.15± 0.52 MPa) exhibited the minimum values of PBS. Intergroup comparison analysis showed that samples in group 1 (SA), group 2 (RF activated by PDT), group 3 (RB activated by PDT), and group 4 (Nd: YVO4 laser) demonstrated comparable outcomes of bond scores (p>0.05) CONCLUSION: Neodymium-doped yttrium orthovanadate (Nd: YVO4) and riboflavin and Rose bengal activated by photodynamic therapy (PDT) have been investigated as potential alternatives for the surface conditioning of PEEK (polyetheretherketone) posts.

Toxicity studies of sodium metavanadate and vanadyl sulfate administered in drinking water to Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice.

Oral human exposure to vanadium may occur due to its presence in food and drinking water and its use in dietary supplements. The most prevalent oxidation states of vanadium in food and drinking water have been characterized as tetravalent and pentavalent. Vanadyl sulfate and sodium metavanadate were selected as representative tetravalent (V4+) and pentavalent (V5+) test articles for these studies, respectively. To assess the potential for oral toxicity of vanadium compounds with differing oxidation states under similar test conditions, the 3-month National Toxicology Program (NTP) toxicity studies of sodium metavanadate and vanadyl sulfate were conducted in male and female Sprague Dawley (Hsd:Sprague Dawley SD) rats (including perinatal exposure) and in B6C3F1/N mice. Drinking water concentrations for sodium metavanadate (0, 31.3, 62.5, 125, 250, and 500 mg/L) and vanadyl sulfate (0, 21.0, 41.9, 83.8, 168, and 335 mg/L) were selected on the basis of previously published 14-day drinking water studies conducted as part of the NTP vanadium research program. (Abstract Abridged).

Quantitative effects of bilirubin structural photoisomers on the measurement of direct bilirubin via the vanadate oxidation method.

BACKGROUND: Exposing blood serum samples to ambient white light-emitting diode (WLED) light may accelerate bilirubin photoisomer production. We previously demonstrated the quantitative effect of bilirubin configurational isomers (BCI) on direct bilirubin (DB) value using the vanadate oxidation method. However, the effects of bilirubin structural photoisomers (BSI) remain unclear. METHODS: In Study 1, the relationship between WLED irradiation time and BSI production was examined. Serum samples from five neonates were irradiated with WLED light for 0, 10, 30, 60 and 180 min. Bilirubin isomer concentration and BSI production rates were calculated. In Study 2, we performed quantitative investigation of BSI effect on DB values: Differences in DB, BCI and BSI values before and after irradiation were calculated as ⊿DB, ⊿BCI and ⊿BSI, respectively. Assuming the coefficient of BCI affecting DB values was 'a', relational expression was ⊿DB = a*⊿BSI + 0.19*⊿BCI. Serum samples from 15 neonates were irradiated with green LED light for 10 and 30 s. The respective bilirubin isomer levels were measured, and the coefficient was derived. RESULTS: In Study 1, the median BSI production rate was 0.022 mg/dL per min in specimens with an unconjugated bilirubin concentration of 10.88 mg/dL. In Study 2, assuming that ⊿DB-0.19*⊿BCI was Y and ⊿BSI was X, the relational expression was Y = 0.34X-0.03 (R2 = 0.87; p < .01) and a = 0.34. CONCLUSIONS: Under ambient WLED light, serum sample generated 1.3 mg/dL BSIs in 1 h. Approximately 34% (0.44 mg/dL) of BSI concentrations was measured as DB when using the vanadate oxidation method according to the above equation.

Heteroleptic oxidovanadium(IV)-malate complex improves glucose uptake in HepG2 and enhances insulin action in streptozotocin-induced diabetic rats.

Diabetes mellitus, a complex and heterogeneous disease associated with hyperglycemia, is a leading cause of mortality and reduces life expectancy. Vanadium complexes have been studied for the treatment of diabetes. The effect of complex [VO(bpy)(mal)]·H2O (complex A) was evaluated in a human hepatocarcinoma (HepG2) cell line and in streptozotocin (STZ)-induced diabetic male Wistar rats conditioned in seven groups with different treatments (n = 10 animals per group). Electron paramagnetic resonance and 51V NMR analyses of complex A in high-glucose Dulbecco's Modified Eagle Medium (DMEM) revealed the oxidation and hydrolysis of the oxidovanadium(IV) complex over a period of 24 h at 37 °C to give low-nuclearity vanadates "V1" (H2VO4-), "V2" (H2V2O72-), and "V4" (V4O124-). In HepG2 cells, complex A exhibited low cytotoxic effects at concentrations 2.5 to 7.5 µmol L-1 (IC50 10.53 µmol L-1) and increased glucose uptake (2-NBDG) up to 93%, an effect similar to insulin. In STZ-induced diabetic rats, complex A at 10 and 30 mg kg-1 administered by oral gavage for 12 days did not affect the animals, suggesting low toxicity or metabolic impairment during the experimental period. Compared to insulin treatment alone, complex A (30 mg kg-1) in association with insulin was found to improve glycemia (30.6 ± 6.3 mmol L-1 vs. 21.1 ± 8.6 mmol L-1, respectively; p = 0.002), resulting in approximately 30% additional reduction in glycemia. The insulin-enhancing effect of complex A was associated with low toxicity and was achieved via oral administration, suggesting the potential of complex A as a promising candidate for the adjuvant treatment of diabetes.

Use of Nd:YVO4 laser, photodynamic therapy, sulfuric acid and sand blasting on improving bond integrity of PEEK to resin cement with adhesive.

AIM: The present study aimed to inspect and compare several PEEK surface treatments modifications using Photodynamic therapy (PDT), Neodymium-doped yttrium orthovanadate (Nd:YVO4) laser, Sulphuric acid (H2SO4), and sandblasting (SB) when bonded to composite resin via an adhesive system MATERIAL AND METHODS: One hundred disk-shaped PEEK specimens were prepared by CAD-CAM milling and randomly distributed into five groups based on surface treatment methods: group1: Control (no treatment), group 2: PDT, group 3: Nd:YVO4 laser, group 4: H2SO4 and group 5 sandblasting. Later bonding was pursued using resin cement with an adhesive system. Measurements of surface roughness employing a surface profilometer, water contact angle by the static drop method, SBS by universal Testing machine, and failure modes of de-bonded PEEK specimens by Stereomicroscope were attained. Execution of statistical analysis was performed by two-way analysis of variance ANOVA and Tukey's post hoc test (p>0.05). The Shapiro-Wilk normality test and Bartlett's test for homoscedasticity were also performed. RESULTS: The highest SBS was exhibited by Nd:YVO4 laser (16.33 ± 0.71 MPa) and the lowest SBS was observed in the control group (9.4 ± 1.02). However, PEEK specimen luted with resin cement treated with PDT (16.21 ± 0.14 MPa) and H2SO4 (15.23 ± 0.63 MPa) displayed a comparable SBS to Nd:YVO4 laser (p>0.05). The results of Ra exhibited that PEEK material when exposed to Nd:YVO4 laser (15.252 ± 1.581 µm) unveiled the highest Ra. Nd:YVO4 laser (131.25 ± 2.9 µm) and PDT (130.24 ± 3.7 µm) showed comparable WCA values (p>0.05).Adhesive failure was dominant. CONCLUSION: PEEK surface treated with photodynamic therapy and Neodymium-doped yttrium orthovanadate laser and bonded to composite resin via an adhesive system significantly improved shear bond strength, surface roughness, and water contact angle.

Photocatalytic Degradation of Palm Oil Mill Effluent (POME) Waste Using BiVO4 Based Catalysts.

Disposal of palm oil mill effluent (POME), which is highly polluting from the palm oil industry, needs to be handled properly to minimize the harmful impact on the surrounding environment. Photocatalytic technology is one of the advanced technologies that can be developed due to its low operating costs, as well as being sustainable, renewable, and environmentally friendly. This paper reports on the photocatalytic degradation of palm oil mill effluent (POME) using a BiVO4 photocatalyst under UV-visible light irradiation. BiVO4 photocatalysts were synthesized via sol-gel method and their physical and chemical properties were characterized using several characterization tools including X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), surface area analysis using the BET method, Raman spectroscopy, electron paramagnetic resonance (EPR), and UV-Vis diffuse reflectance spectroscopy (UV-Vis DRS). The effect of calcination temperature on the properties and photocatalytic performance for POME degradation using BiVO4 photocatalyst was also studied. XRD characterization data show a phase transformation of BiVO4 from tetragonal to monoclinic phase at a temperature of 450 °C (BV-450). The defect site comprising of vanadium vacancy (Vv) was generated through calcination under air and maxima at the BV-450 sample and proposed as the origin of the highest reaction rate constant (k) of photocatalytic POME removal among various calcination temperature treatments with a k value of 1.04 × 10-3 min-1. These findings provide design guidelines to develop efficient BiVO4-based photocatalyst through defect engineering for potential scalable photocatalytic organic pollutant degradation.

Relationship between Antioxidant Activity and Ligand Basicity in the Dipicolinate Series of Oxovanadium(IV) and Dioxovanadium(V) Complexes.

Oxidative stress plays an important role in the pathogenesis of many serious diseases, including cancer, atherosclerosis, coronary artery disease, Parkinson's disease, Alzheimer's disease, stroke and myocardial infarction. In the body's natural biochemical processes, harmful free radicals are formed, which can be removed with the help of appropriate enzymes, a balanced diet or the supply of synthetic antioxidant substances such as flavonoids, vitamins or anthocyanins to the body. Due to the growing demand for antioxidant substances, new complex compounds of transition metal ions with potential antioxidant activity are constantly being sought. In this study, four oxovanadium(IV) and dioxovanadium(V) dipicolinate (dipic) complexes with 1,10-phenanthroline (phen), 2,2'-bipyridyl (bipy) and the protonated form of 2-phenylpyridine (2-phephyH): (1) [VO(dipic)(H2O)2]·2 H2O, (2) [VO(dipic)(phen)]·3 H2O, (3) [VO(dipic)(bipy)]·H2O and (4) [VOO(dipic)](2-phepyH)·H2O were synthesized including one new complex, so far unknown and not described in the literature, i.e., [VOO(dipic)](2-phepyH)·H2O. The oxovanadium(IV) dipicolinate complexes with 1,10-phenanthroline and 2,2'-bipyridyl have been characterized by several physicochemical methods: NMR, MALDI-TOF-MS, IR, but new complex [VOO(dipic)](2-phepyH)·H2O has been examined by XRD to confirm its structure. The antioxidant activities of four complexes have been examined by the nitrotetrazolium blue (NBT) method towards superoxide anion. All complexes exhibit high reactivity with superoxide anion and [VOO(dipic)](2-phepyH)·H2O has higher antioxidant activity than L-ascorbic acid. Our studies confirmed that high basicity of the auxiliary ligand increases the reactivity of the complex with the superoxide radical.

Vanadyl nanocomplexes enhance photothermia-induced cancer immunotherapy to inhibit tumor metastasis and recurrence.

Conventional photothermal therapy (PTT) is insufficient to induce a strong and potent anti-tumor immune response. Herein, we present a vanadyl nanocomplex, which simultaneously serves as a photothermal agent (PTA) and an immunogenic cell death (ICD) inducer to enhance the anti-tumor immunity of PTT. The vanadyl nanocomplex (STVN) is constructed via facile one-step coordination assembly under ambient conditions. STVN not only has a strong and stable photothermal effect under near-infrared (NIR) irradiation, but also can cause severe endoplasmic reticulum (ER) stress by itself, leading to ICD and activating the systemic immune responses. In the absence of any adjuvants, NIR-irradiated STVN almost completely ablates primary tumors and simultaneously inhibits distant tumors in mice bearing bilateral melanoma. Meanwhile, the intratumorally injected STVN combined with NIR effectively suppressed melanoma lung metastasis as well as tumor recurrence, displaying that local STVN-mediated PTT could trigger a systemic anti-tumor immunity. Therefore, STVN, as a novel immunogenicity-enhanced PTA, affords a "one stone two birds" strategy for improved photothermia-induced cancer immunotherapy.

The role of available phosphorous in vanadate decontamination by soil indigenous microbial consortia.

Indigenous microbial consortia are closely associated with soil inherent components including nutrients and minerals. Although indigenous microbial consortia present great prospects for bioremediation of vanadate [V(V)] contaminated soil, influences of some key components, such as available phosphorus (AP), on V(V) biodetoxification are poorly understood. In this study, surface soils sampled from five representative vanadium smelter sites were employed as inocula without pretreatment. V(V) removal efficiency ranged from 81.7 ± 1.4% to 99.5 ± 0.2% in batch experiment, and the maximum V(V) removal rates were positively correlated with AP contents. Long-term V(V) removal was achieved under fluctuant hydrodynamic and hydrochemical conditions in column experiment. Geobacter and Bacillus, which were found in both original soils and bioreactors, catalytically reduced V(V) to insoluble tetravalent vanadium. Phosphate-solubilizing bacterium affiliated to Gemmatimonadaceae were also identified abundantly. Microbial functional characterization indicated the enrichment of phosphate ABC transporter, which could accelerate V(V) transfer into intercellular space for efficient reduction due to the structural similarity of V(V) and phosphate. This study reveals the critical role of AP in microbial V(V) decontamination and provides promising strategy for in situ bioremediation of V(V) polluted soil.

Cytotoxic effect of xyloglucan and oxovanadium (IV/V) xyloglucan complex in HepG2 cells.

It is well known that the chemical structure of polysaccharides is important to their final biological effect. In this study we investigated the cytotoxic effect of xyloglucan from Copaifera langsdorffii seeds (XGC) and its complex with oxovanadium (XGC:VO) on hepatocellular carcinoma cells (HepG2). After 72 h of incubation, XGC and XGC:VO (200 µg/mL) reduced cell viability in ~20% and ~40%, respectively. At same conditions, only XGC:VO increased in ~20% the LDH enzyme release. In permeabilized cells, incubated with XGC and XGC:VO (200 µg/mL) for 72 h, NADH oxidase activity was reduced by ~45% with XGC and XGC:VO. The succinate oxidase activity was reduced by ~35% with XGC and ~65% with XGC:VO, evidencing that polysaccharide complexation with vanadium could intensify its effects on the respiratory chain. According to this result, the mitochondrial membrane potential was also reduced by ~9% for XGC and ~30% for XGC:VO, when compared to the control group. Interestingly, ATP levels were more elevated for XGC:VO in respect to XGC, probably due the enhance in glycolytic flux evidenced by increased levels of lactate. These results show that the xyloglucan complexation with oxovanadium (IV/V) potentiates the cytotoxic effect of the native polysaccharide, possibly by impairment of oxidative phosphorylation.

BiVO4/Fe3O4@polydopamine superparticles for tumor multimodal imaging and synergistic therapy.

BACKGROUND: Despite tremendous progress has been achieved in tumor theranostic over the past decade, accurate identification and complete eradication of tumor cells remain a great challenge owing to the limitation of single imaging modality and therapeutic strategy. RESULTS: Herein, we successfully design and construct BiVO4/Fe3O4@polydopamine (PDA) superparticles (SPs) for computed tomography (CT)/photoacoustic (PA)/magnetic resonance (MR) multimodal imaging and radiotherapy (RT)/photothermal therapy (PTT) synergistic therapy toward oral epithelial carcinoma. On the one hand, BiVO4 NPs endow BiVO4/Fe3O4@PDA SPs with impressive X-ray absorption capability due to the high X-ray attenuation coefficient of Bi, which is beneficial for their utilization as radiosensitizers for CT imaging and RT. On the other hand, Fe3O4 NPs impart BiVO4/Fe3O4@PDA SPs with the superparamagnetic property as a T2-weighted contrast agent for MR imaging. Importantly, the aggregation of Fe3O4 NPs in SPs and the presence of PDA shell greatly improve the photothermal conversion capability of SPs, making BiVO4/Fe3O4@PDA SPs as an ideal photothermal transducer for PA imaging and PTT. By integrating advantages of various imaging modalities (CT/PA/MR) and therapeutic strategies (RT/PTT), our BiVO4/Fe3O4@PDA SPs exhibit the sensitive multimodal imaging feature and superior synergistic therapeutic efficacy on tumors. CONCLUSIONS: Since there are many kinds of building blocks with unique properties appropriating for self-assembly, our work may largely enrich the library of nanomateirals for tumor diagnosis and treatment.

Internal dose of vanadium in rats following repeated exposure to vanadyl sulfate and sodium orthovanadate via drinking water.

Vanadium is a ubiquitous environmental contaminant that exists in multiple oxidation states. Humans are exposed to vanadyl (V4+) and vanadate (V5+) from dietary supplements, food, and drinking water and hence there is a concern for adverse human health. The current investigation is aimed at identifying vanadium oxidation states in vitro and in vivo and internal concentrations following exposure of rats to vanadyl sulfate (V4+) or sodium metavanadate (V5+) via drinking water for 14 d. Investigations in simulated gastric and intestinal fluids showed that V4+ was stable in gastric fluid while V5+ was stable in intestinal fluid. Analysis of rodent plasma showed that the only vanadium present was V4+, regardless of the exposed compound suggesting conversion of V5+ to V4+ in vivo and/or instability of V5+ species in biological matrices. Plasma, blood, and liver concentrations of total vanadium, after normalizing for vanadium dose consumed, were higher in male and female rats following exposure to V5+ than to V4+. Following exposure to either V4+ or V5+, the total vanadium concentration in plasma was 2- to 3-fold higher than in blood suggesting plasma as a better matrix than blood for measuring vanadium in future work. Liver to blood ratios were 4-7 demonstrating significant tissue retention following exposure to both compounds. In conclusion, these data point to potential differences in absorption and disposition properties of V4+ and V5+ salts and may explain the higher sensitivity in rats following drinking water exposure to V5+ than V4+ and highlights the importance of internal dose determination in toxicology studies.

Ultrasensitive photoelectrochemical aptasensor for diclofenac sodium based on surface-modified TiO2-FeVO4 composite.

Herein, a photoelectrochemical (PEC) aptasensing platform was designed by integrating surface oxygen vacancy (OV) defects, Ti3+ self-doping, the heterojunction, and resonance energy transfer (RET) effect into one platform for the detection of diclofenac sodium (DCF). Briefly, OV defects were introduced on TiO2 nanospheres with simultaneous Ti3+ self-doping, followed by a well-separated deposition of FeVO4 nanoparticles on TiO2 to obtain a Ti3+-O-TiO2/FeVO4 heterojunction. The surface modification of OVs, Ti3+ doping, and deposition of FeVO4 were confirmed by SEM, XPS, EPR, DRS, and PEC measurements. The surface OVs and doping of Ti3+ species created a new donor (defect) energy level under the conduction band of TiO2, which minimized the bandgap and thereby improved the visible light absorption of TiO2. Moreover, the capture of photo-excited electrons by surface OVs could hinder the electron-hole recombination. Due to the intimate surface contact and perfect energy matching between TiO2 and FeVO4, the formation of heterojunction decreased the bandgap and facilitated the electron-hole separation of TiO2. All these above events contributed to the enhancement of the PEC signals, which were then quenched by the RET effect between Ti3+-O-TiO2/FeVO4 and Au nanoparticle (AuNP)-labeled cDNA that had been attached to its complementary DCF aptamer on Ti3+-O-TiO2/FeVO4|ITO. The addition of target-DCF detached AuNP-labeled cDNA from the electrode to recover the photocurrent, resulting in a "signal-on" PEC aptasensor that exhibited a 0.1-500-nM linear range and a detection limit of 0.069 nM for DCF, attributed to the excellent amplification of the proposed aptasensing platform.

Phospholipase D inhibitors screening: Probing and evaluation of ancient and novel molecules.

Phospholipase D (PLD) is a ubiquitous enzyme that cleaves the distal phosphoester bond of phospholipids generating phosphatidic acid (PA). In plants, PA is involved in numerous cell responses triggered by stress. Similarly, in mammals, PA is also a second messenger involved in tumorigenesis. PLD is nowadays considered as a therapeutic target and blocking its activity with specific inhibitors constitutes a promising strategy to treat cancers. Starting from already described PLD inhibitors, this study aims to investigate the effect of their structural modifications on the enzyme's activity, as well as identifying new potent inhibitors of eukaryotic PLDs. Being able to purify the plant PLD from Vigna unguiculata (VuPLD), we obtained a SAXS model of its structure. We then used a fluorescence-based test suitable for high-throughput screening to review the effect of eukaryotic PLD inhibitors described in the literature. In this regard, we found that only few molecules were in fact able to inhibit VuPLD and we confirmed that vanadate is the most potent of all with an IC50 around 58 µM. Moreover, the small-scale screening of a chemical library of 3120 compounds allowed us to optimize the different screening's steps and paved the way towards the discovery of new potent inhibitors.

Evaluating the effects of vanadyl sulfate on biomarkers of oxidative stress and inflammation in renal tissue of rats with diabetes type 2

Vanadyl sulfate (VS) is an ingredient in some food supplements and experimental drugs. This study was designed to assay the effects of VS on biomarkers of oxidative stress and inflammation in renal tissue of rats with diabetes type 2. 30 male Wistar rats were divided into three equal groups as follow: non-diabetics, non-treated diabetics and VS-treated diabetics. Diabetes type 2 has been induced through high fat diet and fructose in the animals. Diabetic rats were treated with 25 mg/kgBW of VS in water for 12 weeks. At the end of study, glucose and insulin were measured using commercially available kits in serum and biomarkers of oxidative stress and inflammation in renal homogenates of animals were measured by related methods. Compared to controls, glucose and insulin were increased significantly in non-treated diabetic rats (p-value <0.05) that showed the induction of diabetes type 2 in rats. The results showed that in VS-treated diabetic rats compared to the non-treated diabetic group, vanadyl sulfate significantly reduced the glucose and insulin secretion and changed renal inflammatory and oxidative markers, except protein carbonyl so that we couldn't find any significant changes. Our study showed that vanadyl supplementation had positive effects on oxidative stress and inflammation biomarkers in kidney of diabetic rats

Enhanced photoconversion performance of NdVO4/Au nanocrystals for photothermal/photoacoustic imaging guided and near infrared light-triggered anticancer phototherapy.

Although neodymium vanadate (NdVO4) has been investigated and applied in some fields owing to its intensive ultraviolet (UV) light absorption, weak absorption in visible (Vis) and near infrared (NIR) regions constrains its environmental remediation and biomedical applications. Herein, plasmonic precious metal Au as light trapping agent is deposited onto NdVO4 to form metal/semiconductor hybrid nanostructure for improving the Vis/NIR light absorption. NdVO4/Au heterojunction nanocrystals (NCs) were synthesized by NdVO4 nanorods (NRs) and plasmonic Au nanoparticles (NPs), followed by introducing polyvinylpyrrolidone (PVP) to enhance stability and biocompatibility, which exhibit elevated photocatalytic performance for organic dye degradation, photothermal conversion effect as high as 32.15% and cytotoxic reactive oxygen species (ROS) production ability. NdVO4/Au can be internalized efficiently via endocytosis and cause apparent phototoxicity on HeLa cells. In vivo experiments further show that NdVO4/Au can act as a high-efficiency NIR light-triggered anticancer agent with excellent tumor inhibition effect. In addition, based on outstanding light-to-heat conversion performance and thermal expansion effect under NIR irradiation, NdVO4/Au provides photothermal (PT) and photoacoustic (PA) dual-modal imaging platform for precise cancer diagnosis and treatment. STATEMENTS OF SIGNIFICANCE: It's the first report on integrating precious metal Au and rare earth orthovanadates semiconductor into NdVO4/Au heterojunction NCs. The as-prepared NdVO4/Au heterojunction NCs exhibits improved absorption in Vis/NIR region and increased generation efficiency of photo-induced electron/hole pairs due to the LSPR effect, which results in enhanced photothermal conversion efficiency and the production ability of cytotoxic O2- and OH in comparison with pristine NdVO4. For further clinical application, NdVO4/Au heterojunction NCs could be served as anticancer therapeutic agent for PA/PT dual-modal imaging guided and NIR-triggered photothermal/photodynamic synergistic anticancer treatment.

Self-assembled CeVO4/Ag nanohybrid as photoconversion agents with enhanced solar-driven photocatalysis and NIR-responsive photothermal/photodynamic synergistic therapy performance.

The plasmonic cerium vanadate (CeVO4) semiconductor and plasmonic silver (Ag) metal exhibit a localized surface plasmon resonance (LSPR) effect in the visible (Vis)-light region; however, weak absorption in the near-infrared (NIR) region restricts their environmental remediation and biomedical application. Herein, CeVO4/Ag nanohybrids with self-assembled heterostructure and improved Vis/NIR light absorption were synthesized from CeVO4 nanosheets and AgNO3 solution, which could serve as potential solar-driven catalytic agents and near-infrared (NIR) light responsive anticancer agents. Oleic acid-stabilized CeVO4 nanosheets were modified with the HS-PEG1000-OH by the thiol-ene click reaction and presented self-assembly morphology in aqueous solution due to hydrophobic-hydrophobic interactions. Sulfhydryl (-SH) groups provided stable sites for Ag+ ions on the surface of CeVO4, and Ag+ ions could be directly reduced by Ce3+ ions to form CeVO4/Ag heterojunction nanocrystals (NCs). Due to the higher absorption in the Vis/NIR light region than CeVO4 nanosheets, CeVO4/Ag NCs led to the improved solar light responsive photocatalytic degradation of organic dyes. Upon the exposure of these NCs to an 808 nm laser, CeVO4/Ag NCs show high photothermal conversion efficiency, ROS generation ability and photoacoustic (PA) signal for implementing PA imaging-guided photothermal/photodynamic synergistic cancer therapy with better tumor inhibition effect.

Hypoxia protects against the cell death triggered by oxovanadium-galactomannan complexes in HepG2 cells.

BACKGROUND: Polysaccharides from various sources have been used in traditional medicine for centuries. The beneficial pharmacological effects of plant-derived polysaccharides include anti-tumor activity. METHODS: Here, we evaluated the anti-cancer effect of the MSAGM:VO complex under hypoxic conditions (1% oxygen). MSAGM:VO is a complex of the hydrolysate of galactomannan (MSAGM) from Schizolobium amazonicum with oxovanadium (IV/V). The hepatocellular carcinoma (HCC) cell line HepG2 was selected as HCC are one of the most hypoxic solid tumors. RESULTS: Our results showed that the strong apoptotic activity of MSAGM:VO observed in HepG2 cells under normoxic conditions was completely lost under hypoxic conditions. We found a dynamic balance between the pro- and anti-apoptotic members of the Bcl-2 protein family. The expressions of anti-apoptotic Mcl-1 and Bcl-XL increased in hypoxia, whereas the expression of pro-apoptotic Bax decreased. MSAGM:VO strongly induced autophagy, which was previously characterized as a pro-survival mechanism in hypoxia. These results demonstrate total elimination of the anti-cancer activity of MSAGM:VO with activation of autophagy under conditions of hypoxia. CONCLUSION: Although this study is a proof-of-concept of the impact of hypoxia on the potential of polysaccharides, further study is encouraged. The anti-tumor activity of polysaccharides could be achieved in normoxia or through raising the activity of the immune system. In addition, combination strategies for therapy with anti-autophagic drugs could be proposed.