Tissue distribution of EDTA encapsulated within liposomes of varying surface properties

Liposomes containing ethylenediaminetetraacetic acid (EDTA) were prepared with different surface properties by varying the liposomal lipid constituents. Positively charged liposomes were prepared with a mixture of phosphatidylcholine, cholesterol, and stearylamine. Negatively charged liposomes were prepared with a mixture of phosphatidylcholine, cholesterol, and phosphatidylserine. Neutral liposomes were prepared with phosphatidylcholine alone, dipalmitoyl phosphatidylcholine alone, or with a mixture of phosphatidylcholine and cholesterol. Distributions of ¹⁴C-labeled EDTA were determined in mouse tissues from 5 min to 24 h after a single intravenous injection of liposome preparation. Differences in tissue distribution were produced by the different liposomal lipid compositions. Uptake of EDTA by spleen and marrow was highest from negatively charged liposomes. Uptake of EDTA by lungs was highest from positively charged liposomes; lungs and brain retained relatively high levels of EDTA from these liposomes between 1 and 6 h after injection. Liver uptake of EDTA from positively or negatively charged liposomes was similar; the highest EDTA uptake by liver was from the neutral liposomes composed of a mixture of phosphatidylcholine and cholesterol. Liposomes composed of dipalmitoyl phosphatidylcholine produced the lowest liposomal EDTA uptake observed in liver and marrow but modrate uptake by lungs. Tissue uptake and retention of EDTA from all of the liposome preparations were greater than those of non-encapsulated EDTA. The results presented demonstrate that the tissue distribution of a molecule can be modified by encapsulation of that substance into liposomes of different surface properties. Selective delivery of liposome-encapsulated drugs to specific tissues could be effectively used in chemotherapy and membrane biochemistry.     

The Excitotoxin Quinolinic Acid Induces Tau Phosphorylation in Human Neurons

Some of the tryptophan catabolites produced through the kynurenine pathway (KP), and more particularly the excitotoxin quinolinic acid (QA), are likely to play a role in the pathogenesis of Alzheimer''s disease (AD). We have previously shown that the KP is over activated in AD brain and that QA accumulates in amyloid plaques and within dystrophic neurons. We hypothesized that QA in pathophysiological concentrations affects tau phosphorylation. Using immunohistochemistry, we found that QA is co-localized with hyperphosphorylated tau (HPT) within cortical neurons in AD brain. We then investigated in vitro the effects of QA at various pathophysiological concentrations on tau phosphorylation in primary cultures of human neurons. Using western blot, we found that QA treatment increased the phosphorylation of tau at serine 199/202, threonine 231 and serine 396/404 in a dose dependent manner. Increased accumulation of phosphorylated tau was also confirmed by immunocytochemistry. This increase in tau phosphorylation was paralleled by a substantial decrease in the total protein phosphatase activity. A substantial decrease in PP2A expression and modest decrease in PP1 expression were observed in neuronal cultures treated with QA. These data clearly demonstrate that QA can induce tau phosphorylation at residues present in the PHF in the AD brain. To induce tau phosphorylation, QA appears to act through NMDA receptor activation similar to other agonists, glutamate and NMDA. The QA effect was abrogated by the NMDA receptor antagonist memantine. Using PCR arrays, we found that QA significantly induces 10 genes in human neurons all known to be associated with AD pathology. Of these 10 genes, 6 belong to pathways involved in tau phosphorylation and 4 of them in neuroprotection. Altogether these results indicate a likely role of QA in the AD pathology through promotion of tau phosphorylation. Understanding the mechanism of the neurotoxic effects of QA is essential in developing novel therapeutic strategies for AD.     

An improved breeding method for solitarious locusts

In order to unravel the physiological, endocrine, and behavioral differences between gregarious and solitarious forms of the desert locust, Schistocerca gregaria (Forsk.) (Orthoptera, Acrididae), a constant supply of rather large numbers of solitary individuals has to be guaranteed. This represents a bottleneck, mainly because of the intensity of the labor involved and limited laboratory accommodation. The method we describe here substantially reduces the space and manpower needed. The survival rate we obtained in the solitarised population was relatively high, reaching about 55%. The optimal rearing temperature proved to be 32–36 °C. Cabbage leaves and oat flakes sufficed for feeding all year round. Special racks have been designed that enable high density stacking and easy handling. The solitarisation process was monitored over ten consecutive generations. Changes in morphometrics, eye stripes, color, and behavior were recorded, of which only morphometrics, temperature related development, and mortality are discussed. A shift towards the solitarious phase was recorded, with clear differences between gregarious, 1^st generation and 7^th to 10^th generation solitarious locusts.     

Artonin E Induces Apoptosis via Mitochondrial Dysregulation in SKOV-3 Ovarian Cancer Cells

Artonin E is a prenylated flavonoid isolated from the stem bark of Artocarpus elasticus Reinw.(Moraceae). This study aimed to investigate the apoptotic mechanisms induced by artonin E in a metastatic human ovarian cancer cell line SKOV-3 in vitro. MTT assay, clonogenic assay, acridine orange and propidium iodide double staining, cell cycle and annexin V analyses were performed to explore the mode of artonin E-induced cell death at different time points. DNA laddering, activation of caspases-3, -8, and -9, multi-parametric cytotoxicity-3analysis by high-content screening, measurement of reactive oxygen species generation, and Western blot were employed to study the pathways involved in the apoptosis. MTT results showed that artonin E inhibited the growth of SKOV-3 cells, with IC₅₀ values of 6.5±0.5μg/mL after 72 h treatment, and showed less toxicity toward a normal human ovarian cell lineT1074, with IC₅₀ value of 32.5±0.5μg/mL. Results showed that artonin E induced apoptosis and cell cycle arrest at the S phase. This compound also promoted the activation of caspases-3, -8, and -9. Further investigation into the depletion of mitochondrial membrane potential and release of cytochrome c revealed that artonin E treatment induced apoptosis via regulation of the expression of pro-survival and pro-apoptotic Bcl-2 family members. The expression levels of survivin and HSP70 proteins were also down regulated in SKOV-3 cells treated with artonin E. We propose that artonin E induced an antiproliferative effect that led to S phase cell cycle arrest and apoptosis through dysregulation of mitochondrial pathways, particularly the pro- and anti-apoptosis signaling pathways.     

Evaluation of Antibacterial Activity of Lavandulapedunculata subsp. atlantica (Braun‐Blanq.) Romo Essential Oil and Selected Terpenoids against Resistant Bacteria Strains–Structure–Activity Relationships

The genus Lavandula is known for its different uses in traditional medicine. This study is interested in the chemical composition of Lavandulapedunculata subsp.atlantica (Braun‐Blanq. ) Romo as well as evaluating its antibacterial potential against multi‐resistant strains. The analysis of Lavandulaatlantica essential oil (LAEO) allows the identification of 47 components representing 93.6 % of all identified. The main constituent of LAEO was camphor (50.4 %), followed by fenchone (14.1 %) and camphene (5.6 %). The antibacterial assays revealed that LAEO was active against all the studied bacteria. A preliminary study of the relationship between certain terpenoids and antibacterial activity was also carried out in order to note the compound(s) that are responsible for LAEO's antibacterial activity. This study showed that the activity of the essential oil may be due to the presence of certain minor compounds such as carvone, considering the presence of the synergistic effect between the essential oil.     

Uncovering Atomic‐Scale Stability and Reactivity in Engineered Zinc Oxide Electrocatalysts for Controllable Syngas Production

In this study, scalable, flame spray synthesis is utilized to develop defective ZnO nanomaterials for the concurrent generation of H₂ and CO during electrochemical CO₂ reduction reactions (CO₂RR). The designed ZnO achieves an H₂/CO ratio of ≈1 with a large current density (j) of 40 mA cm^?2 during long‐term continuous reaction at a cell voltage of 2.6 V. Through in situ atomic pair distribution function analysis, the remarkable stability of these ZnO structures is explored, addressing the knowledge gap in understanding the dynamics of oxide catalysts during CO₂RR. Through optimization of synthesis conditions, ZnO facets are modulated which are shown to affect reaction selectivity, in agreement with theoretical calculations. These findings and insights on synthetic manipulation of active sites in defective metal‐oxides can be used as guidelines to develop active catalysts for syngas production for renewable power‐to‐X to generate a range of fuels and chemicals.     

Micropropagation,encapsulation, and conservation of Decalepis salicifolia,a vanillin isomer containing medicinal and aromatic plant

In Vitro Cellular & Developmental Biology - Plant - An efficient in vitro propagation and synthetic seed production protocol was established for the conservation of Decalepis salicifolia (Bedd....