Search Results (13)

Examination of venom constituent bioactivities from diverse venomous animals shows certain highly conserved classes, including enzymes (e.g., phospholipases and metalloproteinases) and pore-forming proteins. While antivenoms targeting other unique and lethal venom components have proven to be life-saving, venom-enzyme-driven tissue damage and morbidity persists. Broad-acting enzyme inhibitors demonstrate the potential to augment antivenom approaches. In this study, we investigate the potential utility of certain broad-acting inhibitors in cubozoa for the first time. Fluorogenic assays were used to determine the phospholipase A₂ (PLA₂) and matrix metalloproteinase (MMP) activity of the Hawaiian box jellyfish, Alatina alata, and this was compared to representative elapid, viper, and bee venoms. In vitro, evaluation of selected small-molecule inhibitors demonstrated the ability and feasibility of the broad-acting therapeutic doxycycline, which inhibited the PLA₂ and MMP activity of A. alata (approximately 50% reduction at 0.1 mM (95% CI 0.06–0.15) and 2.1 mM (95% CI 1.4–3.0), respectively), in addition to both snake venoms. Additionally, copper gluconate broadly inhibited the PLA₂ activity of bee, snake, and jellyfish venoms. While all venoms are complex mixtures of bioactive molecules, these studies demonstrate that targeting common class components with broad-acting inhibitors shows promise in clinical and preclinical management. Full article

We focused on the effects of radical induction on cell differentiation and sebum production when antioxidants and oxidants were applied to normal hamster sebaceous gland cells. We also examined the relationship between sebum production and the reactive oxygen species (ROS) scavenging rate in these cells. Eight antioxidants (fullerene, epigallocatechin gallate, α-glucosylrutin, copper (II) gluconate, tannic acid, sodium copper-chlorophyllin, phytic acid, and ascorbyl tocopheryl phosphate) and one oxidant (hydrogen peroxide, H₂O₂) were used. The number of differentiated cells was determined by counting the viable cells, the intracellular triglyceride (TG) level was determined by separation and quantification by HPTLC, and the superoxide anion radical scavenging rate, nitric oxide scavenging rate, and H₂O₂ scavenging rate were also investigated. Adding various antioxidants decreased the differentiated cell number and TG content in the hamster sebaceous gland cells. Meanwhile, adding an oxidant (H₂O₂) increased the differentiated cell number and cellular TG. Pretreatment with antioxidants also prevented the oxidants from increasing the differentiated cell number and TG level. A strong correlation between the intracellular TG content and the H₂O₂ scavenging rate was identified. These results indicate that radical generation and scavenging are involved in sebum production in hamster sebaceous gland cells, and that the scavenging rate of H₂O₂ may be particularly important. Full article

Cancer stem cells (CSCs) play a key role in non-small cell lung cancer (NSCLC) chemoresistance and metastasis. In this study, we used two NSCLC cell lines to investigate the regulating effect of hypoxia in the induction and maintenance of CSC traits. Our study demonstrated hypoxia-induced stemness and chemoresistance at levels comparable to those in typical CSC sphere culture. Activation of the NF-κB pathway (by transfection of NF-κB-p65) plays a key role in NSCLC CSCs and chemoresistance. Disulfiram (DS), an anti-alcoholism drug, showed a strong in vitro anti-CSC effect. It blocked cancer cell sphere reformation and clonogenicity, synergistically enhanced the cytotoxicity of four anti-NSCLC drugs (doxorubicin, gemcitabine, oxaliplatin and paclitaxel) and reversed hypoxia-induced resistance. The effect of DS on CSCs is copper-dependent. A very short half-life in the bloodstream is the major limitation for the translation of DS into a cancer treatment. Our team previously developed a poly lactic-co-glycolic acid (PLGA) nanoparticle encapsulated DS (DS-PLGA) with a long half-life in the bloodstream. Intra venous injection of DS-PLGA in combination with the oral application of copper gluconate has strong anticancer efficacy in a metastatic NSCLC mouse model. Further study may be able to translate DS-PLGA into cancer applications. Full article

In this work, a biological recovery of metals (copper and gold) from computer printed circuit board (PCB) waste was carried out by bioleaching using Aspergillus niger. Three bioleaching methods comprising one or two steps or using spent medium were tested in an incubator shaker at 30 °C and 160 rpm with different PCB waste concentrations (2.5 to 10 g/L). Glucose was used as the carbon source. The best condition evaluated was carried out in a stirred tank reactor. The FTIR spectrum confirmed the presence of oxalic, citric, and gluconic acids. A. niger showed an efficiency of bioleaching of up to 100% and 42.5% for copper and gold, respectively, using the two-step method with 2.5 g/L PCB waste after 14 days of the process. The efficiency of bioleaching in a stirred tank reactor was 83% for copper and 24% for gold. The mean metallic particle size obtained after bioleaching varied according to the PCB waste concentration (2.5–10 g/L) added in the experiments. A transmission electron microscope analysis confirmed the synthesis of metallic nanoparticles with spherical morphology. The results indicated that the PCBs bioleaching process with A. niger can be an environmentally friendly alternative to current mechanical and metallurgical processes for metal leaching. Full article

The efficacy of using a synthetic (azoxystrobin + difenoconazole), copper-based (copper oxychloride) and low-content copper compound (copper complexed with gluconate and lignosulphonate) fungicides for controlling Venturia oleaginea, the causal agent of olive spot disease, was evaluated in an olive (cv. Nabali) orchard located in the Kafr Qud area (Palestine) in 2017–2018. Treatments were applied at three different times (February, April, and August). In January 2017, at the beginning of the experiment, about 90% of the leaves grown in 2016 were infected. Defoliation was determined by counting the leaves on the labeled branches initially and then periodically. It increased gradually in both the control and treated trees, but those treated with azoxystrobin + difenoconazole or with copper complexed with gluconate and lignosulphonate showed a slower defoliation rate. During 2017, new shoots grew and new leaves developed. All treatments reduced the drop of new leaves with respect to the control, with positive effects on the reproductive activity (inflorescence growth and yield). Overall, all treatments significantly reduced the disease, thus indicating the possibility of greatly reducing infections if treatments are regularly applied each year, also with traditional (copper-based) fungicides. Due to their capability of penetrating inside the vegetative tissue, azoxystrobin + difenoconazole or copper complexed with gluconate and lignosulphonate reduced/slowed down the drop of infected leaves. The use of these fungicides is therefore particularly recommended when olive leaf spot disease is severe. The use of low-content copper compounds allows the amount of metallic copper used for the treatments against V. oleaginea to be greatly reduced. Full article

Marble is one of the materials most susceptible to copper leaching, resulting in easily identifiable turquoise stains on the marble. This problem is particularly relevant when we are talking about marble structures of heritage value. For this reason, conservators look for cleaning materials that are specific to the structure to be treated without damaging the original surface. Materials such as agar have been studied for a long time. Agar creates a controlled water release system that adapts to the needs of conservators who seek the greatest possible cleanliness without damaging the material to be treated. To improve the cleaning, chelating agents such as EDTA are added to the agar composition. However, the microbiological growth and the damage it produces to the original material are disadvantages to take into account. In order to solve these problems, other natural materials with cleaning potential such as kudzu and konjac gels were studied in combination with other chelating agents such as citrate, oxalate, and gluconic acid. For the characterization and evaluation of copper cleaning, various analytical techniques were used, including Raman spectroscopy, colorimetry, X-ray fluorescence (XRF), and inductively coupled plasma mass spectrometry (ICP-MS). In this study, both konjac and kudzu emerged as promising alternatives to agar, revealing distinctive features such as simplified preparation methods and inherent antimicrobial properties. The EDTA chelator was found to be the most harmful for marble surfaces, as it extracted a greater amount of calcium from the marble during application of the gels doped with it. Citrate and gluconic acid have been identified as a promising substitute to prepare doped gels for the removal of copper stains. These compounds exhibit comparable or potentially superior cleaning capabilities than EDTA, with no negative side effects. Full article

The long-term use of copper (Cu) fungicides in viticulture in Europe has led to Cu accumulation in vineyard top soils. However, less is known about the accumulation of Cu in grapevine grafts after the callusing process/before planting in the nursery. This paper presents the capacity of 5BB and SO4 rootstocks to accumulate Cu, as well as the patterns of translocation in the grafts. After heat forcing (callusing), the grapevine grafts of Sauvignon Blanc on 5BB and SO4 rootstocks were grown in pots for six months in a glasshouse and exposed to various Cu formulations (Cu-oxychloride, Cu-gluconate) and concentrations in peat (50, 150, 500, and 1000 mg Cu of dry weight (DW)). In addition to monitoring the shoot growth dynamics and analyzing the copper content in graft organs, bioaccumulation (BAFs) and translocation factors (TFs) of Cu were calculated. The mean Cu concentrations were ranked as follows: roots (15–164) > rootstock trunks (8–38) > canes (5–21) mg kg⁻¹ DW. The Cu concentrations depended on the Cu formulation and concentration in the substrate. Higher Cu content was found in the roots of both rootstocks (5BB and SO4, 23–155 and 15–164 mg kg⁻¹ DW, respectively) and the lowest in the canes (less than 10 mg kg⁻¹ DW) of grafts grown in Cu-oxychloride-treated peat. Based on the BAFs and TFs, both rootstocks could be considered as Cu exclusive. A higher translocation rate was determined in systemic Cu-gluconate and SO4 rootstock. With shoot length measurements, the significant inhibitory effects of Cu on grapevine grafts growth could not be confirmed, despite the inhibitory effects that were clearly expressed in the first two months of growth. Soils containing more than 500 mg Cu/kg⁻¹ are less suitable for growing vine grafts. Full article

Bacterial canker, caused by Pseudomonas syringae pv. syringae and pv. morsprunorum, is one of the most important diseases of stone fruit trees (Prunus spp.). The pathogen infects buds, flowers, fruitlets, leaves and shoots, from which the disease spreads to the branches, boughs and trunks, causing necrosis and cankers. The efficacy of different chemical and biological products for the control of bacterial canker on stone fruit trees was tested in 2018–2021. The experiments were conducted in sour cherry, plum and sweet cherry orchards in central Poland. Foliar application of the tested preparations was performed three times a season. The biological efficacy of the tested products in the control of bacterial canker was evaluated on sour cherry on the basis of infected leaves and fruits and on plum and sweet cherry on the basis of infected leaves. The highest efficacy was observed for products containing various forms of copper—copper oxide, copper oxychloride and copper hydroxide—as well as fertilizers with copper gluconate and the fungicide Luna Care 71.6 WG (fluopyram and fosetyl-Al). However, the biological preparations were significantly less effective. The conducted studies showed that preparations based on copper gluconate can be a valuable alternative to typical copper fungicides. Full article

Repurposed drugs have demonstrated in vitro success against high-grade gliomas; however, their clinical success has been limited due to the in vitro model not truly representing the clinical scenario. In this study, we used two distinct patient-derived tumour fragments (tumour core (TC) and tumour margin (TM)) to generate a heterogeneous, clinically relevant in vitro model to assess if a combination of repurposed drugs (irinotecan, pitavastatin, disulfiram, copper gluconate, captopril, celecoxib, itraconazole and ticlopidine), each targeting a different growth promoting pathway, could successfully treat high-grade gliomas. To ensure the clinical relevance of our data, TC and TM samples from 11 different patients were utilized. Our data demonstrate that, at a concentration of 100µm or lower, all drug combinations achieved lower LogIC₅₀ values than temozolomide, with one of the combinations almost eradicating the cancer by achieving cell viabilities below 4% in five of the TM samples 6 days after treatment. Temozolomide was unable to stop tumour growth over the 14-day assay, while combination 1 stopped tumour growth, with combinations 2, 3 and 4 slowing down tumour growth at higher doses. To validate the cytotoxicity data, we used two distinct assays, end point MTT and real-time IncuCyte life analysis, to evaluate the cytotoxicity of the combinations on the TC fragment from patient 3, with the cell viabilities comparable across both assays. The local administration of combinations of repurposed drugs that target different growth promoting pathways of high-grade gliomas have the potential to be translated into the clinic as a novel treatment strategy for high-grade gliomas. Full article

Anemia is one of the most frequent and earliest complications of chronic kidney disease (CKD), which impacts a patient’s quality of life and increases the risk of adverse clinical outcomes. Patients’ inflammatory status is strictly related to the occurrence of functional iron deficiency anemia (IDA) because this causes an increase in hepcidin levels with the consequent inhibition of iron absorption and release from cellular stores into blood circulation. The aim of this study was to evaluate the use of the new oral formulation based on ferric sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate, and selenomethionine (Ferachel Forte^®) in patients with moderate CKD and functional IDA, analyzing the inflammatory status in addition to iron blood parameters, in comparison with oral ferrous sulfate and liposomal iron therapies. Sixty-two elderly patients were randomly allocated to one of the following oral treatments for 6 months: ferrous sulfate (Group 1; N = 20), ferric sodium EDTA in combination (Group 2; N = 22), and ferric liposomal formulation (Group 3; N = 20). The evaluated parameters included iron profile parameters of hemoglobin (Hb), sideremia, ferritin, transferrin saturation, C-reactive protein (CRP), and hepcidin. The results showed that in Group 1, there were no improvements. In Group 2, there were statistically significant (p < 0.001) improvements in all evaluated parameters. Finally, in Group 3, there were significant improvements in all evaluated parameters except for hepcidin, which was less than that of Group 2 patients. In conclusion, the findings showed the superior efficacy of the formulation based on ferric sodium EDTA over the other oral iron sources, and that this formulation can contribute to reducing the systemic inflammatory status in patients with CKD. Full article

The high level of copper (Cu) accumulation in the soil, the risk of surface water contamination, and the potential public health problems due to Cu entering the food chain have raised concerns on the use of Cu compounds in agriculture, including olive growing. As a consequence, there is worldwide regulatory pressure on agricultural systems to limit the use of Cu compounds. Hence, a field trial was carried out to evaluate the effectiveness of low copper containing chemicals to control olive leaf spot (OLS) disease caused by Venturia oleaginea. The trial was conducted in 2021 in an olive (cv. Nabali Baladi) grove in Palestine. Copper complexed with lignosulphonate and gluconate (Disper Cu Max^®) and the self-defense inducer Disper Broton GS^® were evaluated and compared to dodine and the traditionally and frequently used copper hydroxide. In addition, untreated trees were used as the control. Treatments were made in March, July, and August. In March 2021, leaves grown in 2020 were present and 100% infected. V. oleaginea infections caused defoliation in untreated and treated olive trees with varying degrees of intensity: the Control had the most defoliation, followed by copper hydroxide and Disper Cu Max^®, whereas dodine and, in particular, Disper Broton GS^® had the least. All treatments reduced symptomatic leaves but their efficacy varied significantly: copper hydroxide was the least effective, Disper Cu Max^® was intermediate, dodine and, mainly, Disper Broton GS^® were the most effective. Overall, the results are promising since Disper Cu Max^® and Disper Broton GS^® were able to significantly reduce OLS damage and the amount of copper used for treatments. Full article

Growth in the human population and intensive, large-scale farming results in a lowering in the quality of nutrition. An oversupply of food energy is often accompanied with a deficiency in micronutrients. To address this problem, the food industry provides products enriched with bioactive substances. The main challenge of this technology is the even distribution of micronutrients in the matrix of the fortified food. A possible solution to this challenge is to use stable and effective carriers. The aim of this work was to verify the applicability of native potato starch and modified starches (commonly used in the food industry) as carriers for microelements. Adsorptions were carried out in starch suspensions at a temperature below gelatinisation. The native potato starch and the modified starches (E 1404, E 1412, E 1420, and E 1422) were assessed for their effectiveness in adsorbing copper, iron, and zinc sulphates or gluconates. Pasting characteristics were analysed using a Brabender viscograph and light microscopy. Furthermore, texture profile analysis of starch-based desserts was carried out with the use of the tested carriers. Starch in both its native and modified forms was able to effectively adsorb copper, iron, and zinc ions. Adsorption was more efficient when using modified starches containing hydrophilic carboxyl groups. The effectiveness of adsorption with oxidised starches increased with an increase in the degree of substitution. Starches containing more hydrophobic acetyl groups were less effective as adsorbents of microelements. The cation adsorption efficiency decreased in the order copper > iron > zinc, and sulphates were better adsorbed than gluconates. Copper ions influenced the pasting characteristics of the oxidised starches, and these effects were dependent on the degree of substitution with carboxyl groups. As observed by light microscopy, the presence of copper ions changes the interaction between the starch macromolecules and water. However, the above-mentioned changes did not significantly affect the texture of traditional sweet desserts. Starch, particularly its oxidised derivatives containing hydrophilic oxidised groups, can be recommended as a carrier of microelements for food fortification. The use of modified starches containing relatively hydrophobic acetyl groups is not appropriate because they absorb microelements less efficiently than native starch. Full article

Despite the medical urgency presented by cubozoan envenomations, ineffective and contradictory first-aid management recommendations persist. A critical barrier to progress has been the lack of readily available and reproducible envenomation assays that (1) recapitulate live-tentacle stings; (2) allow quantitation and imaging of cnidae discharge; (3) allow primary quantitation of venom toxicity; and (4) employ rigorous controls. We report the implementation of an integrated array of three experimental approaches designed to meet the above-stated criteria. Mechanistically overlapping, yet distinct, the three approaches comprised (1) direct application of test solutions on live tentacles (termed tentacle solution assay, or TSA) with single image- and video-microscopy; (2) spontaneous stinging assay using freshly excised tentacles overlaid on substrate of live human red blood cells suspended in agarose (tentacle blood agarose assays, or TBAA); and (3) a “skin” covered adaptation of TBAA (tentacle skin blood agarose assay, or TSBAA). We report the use and results of these assays to evaluate the efficacy of topical first-aid approaches to inhibit tentacle firing and venom activity. TSA results included the potent stimulation of massive cnidae discharge by alcohols but only moderate induction by urine, freshwater, and “cola” (carbonated soft drink). Although vinegar, the 40-year field standard of first aid for the removal of adherent tentacles, completely inhibited cnidae firing in TSA and TSBAA ex vivo models, the most striking inhibition of both tentacle firing and subsequent venom-induced hemolysis was observed using newly-developed proprietary formulations (Sting No More™) containing copper gluconate, magnesium sulfate, and urea. Full article