The Effect of Non-Thermal Plasma on the Structural and Functional Characteristics of Human Spermatozoa

Significant antibacterial properties of non-thermal plasma (NTP) have converted this technology into a promising alternative to the widespread use of antibiotics in assisted reproduction. As substantial data available on the specific in vitro effects of NTP on male reproductive cells are currently missing, this study was designed to investigate selected quality parameters of human spermatozoa (n = 51) exposed to diffuse coplanar surface barrier discharge NTP for 0 s, 15 s, 30 s, 60 s and 90 s. Sperm motility characteristics, membrane integrity, mitochondrial activity, production of reactive oxygen species (ROS), DNA fragmentation and lipid peroxidation (LPO) were investigated immediately following exposure to NTP and 2 h post-NTP treatment. Exposure to NTP with a power input of 40 W for 15 s or 30 s was found to have no negative effects on the sperm structure or function. However, a prolonged NTP treatment impaired all the sperm quality markers in a time- and dose-dependent manner. The most likely mechanism of action of high NTP doses may be connected to ROS overproduction, leading to plasma membrane destabilization, LPO, mitochondrial failure and a subsequent loss of motility as well as DNA integrity. As such, our findings indicate that appropriate plasma exposure conditions need to be carefully selected in order to preserve the sperm vitality, should NTP be used in the practical management of bacteriospermia in the future.     

Loliolide,a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from Codium tomentosum

Parkinsons Disease (PD) is the second most common neurodegenerative disease worldwide, and is characterized by a progressive degeneration of dopaminergic neurons. Without an effective treatment, it is crucial to find new therapeutic options to fight the neurodegenerative process, which may arise from marine resources. Accordingly, the goal of the present work was to evaluate the ability of the monoterpenoid lactone Loliolide, isolated from the green seaweed Codium tomentosum, to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells and their anti-inflammatory effects in RAW 264.7 macrophages. Loliolide was obtained from the diethyl ether extract, purified through column chromatography and identified by NMR spectroscopy. The neuroprotective effects were evaluated by the MTT method. Cells’ exposure to 6-OHDA in the presence of Loliolide led to an increase of cells’ viability in 40%, and this effect was mediated by mitochondrial protection, reduction of oxidative stress condition and apoptosis, and inhibition of the NF-kB pathway. Additionally, Loliolide also suppressed nitric oxide production and inhibited the production of TNF-α and IL-6 pro-inflammatory cytokines. The results suggest that Loliolide can inspire the development of new neuroprotective therapeutic agents and thus, more detailed studies should be considered to validate its pharmacological potential.     

1,2,4-Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells,Targeting GSK3β Kinase

A new series of topsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,2,4-oxadiazole moiety, was efficiently synthesized. All derivatives were pre-screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. The five most potent compounds were further investigated in various pancreatic ductal adenocarcinoma (PDAC) cell lines, including SUIT-2, Capan-1, and Panc-1 cells, eliciting EC₅₀ values in the micromolar and sub-micromolar range, associated with significant reduction of cell migration. These remarkable results might be explained by the effects of these new topsentin analogues on epithelial-to-mesenchymal transition markers, including SNAIL-1/2 and metalloproteinase-9. Moreover, flow cytometric analysis after Annexin V-FITC and propidium iodide staining demonstrated that these derivatives enhanced apoptosis of PDAC cells. Keeping with these data, the PathScan intracellular signaling and ELISA array revealed cleavage of caspase-3 and PARP and a significant inhibition of GSK3β phosphorylation, suggesting this kinase as a potential downstream target of our novel compounds. This was further supported by a specific assay for the evaluation of GSK3β activity, showing IC₅₀ values for the most active compounds against this enzyme in the micromolar range.     

Antimicrobial and Anticancer Properties of Synthetic Peptides Derived from the Wasp Parachartergus fraternus

Agelaia-MPI and protonectin are antimicrobial peptides isolated from the wasp Parachartergus fraternus that show antimicrobial and neuroactive activities. Previously, two analogues of these peptides, neuroVAL and protonectin-F, were designed to reduce nonspecific toxicity and improve potency. Here, the three-dimensional structures of neuroVAL, protonectin and protonectin-F were determined by using circular dichroism and NMR spectroscopy. Antibacterial, antifungal, cytotoxic and hemolytic activities were tested for the parent peptides and analogues. All peptides showed moderate antimicrobial activity against Gram-positive bacteria, with agelaia-MPI being the most active. Protonectin and protonectin-F were found to be toxic to cancerous and noncancerous cell lines. Internalization experiments revealed that these peptides accumulate inside both cell types. By contrast, neuroVAL was nontoxic to all tested cells and was able to enter cells without accumulating. In summary, neuroVAL has potential as a nontoxic cell-penetrating peptide, while protonectin-F needs further modification to realize its potential as an antitumor peptide.     

Antibacterial activity of V- doped rod-like MgO crystals decorated with nanoflake layer

In present study, we report a V doping fabrication method for obtaining rod-like MgO crystals decorated with a nanoflake layer. This novel structure has only been minimally reported in literature. Pure MgO and Mg₂V₂O₇–MgO composite materials were obtained by precipitation and impregnation methods, with vanadium added concentrations of 0–9%. The influence of V doping on crystal structure and particle morphology of MgO was investigated by scanning electron microscopy (SEM). X-ray diffraction (XRD) analysis demonstrated that MgO has a cubic structure, while X-ray photoelectron spectroscopy (XPS) revealed that V⁵⁺ exists on the surface of MgO. The specific surface areas and pore sizes of MgO composites were calculated by BET and BJH analysis. These techniques revealed that specific surface area and pore size of MgO increased due to vanadium doping. The antibacterial effects of Mg₂V₂O₇–MgO composite materials against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were assessed using a bacterial killing/colony-forming unit (CFU) assay and bacteriostatic ring method. Our results demonstrate that V doping dramatically improved antimicrobial properties of MgO, with 7 mol% doping inducing the best antibacterial activity. The antibacterial mechanisms of Mg₂V₂O₇–MgO composite material were also proposed.     

Microwave-assisted combustion synthesis of ZnAl2O4 and ZnO nanostructure particles for photocatalytic wastewater treatment

ZnAl₂O₄ and ZnO nanostructure particles and in situ crystallization of zinc aluminate and zinc oxide coating layers on sintered α-Al₂O₃ and γ-Al₂O₃ granules by the microwave-assisted combustion method were investigated. For powders, the effects of solution pH value and for coated samples the influence of support type on the structure, microstructure, and photocatalytic activity of powders were studied. Results showed that variation of synthesis pH value caused to considerable change in agglomeration, specific surface area, obtaining up to 88 and 92% yields for zinc aluminate and zinc oxide nanoparticles, respectively. γ-alumina granules were more appropriate supports than the α-alumina ones because of the better photocatalytic activities and lower extent of the attritions for both zinc aluminate and zinc oxide coating layers.     

Studying the effect of particle size on the antibacterial activity of some N-nicotinyl phosphoric triamides

Using ultrasonic top-to-down method, nanoparticles of two N-nicotinyl phosphoric triamides: C₅H₄NC(O)NHP(O)R, R?=?4-CH₃-NC₅H₁₀ (1), (CH₃)₃CNH₂ (2) were prepared for the first time and characterized by ³¹P, ¹³C, ¹H NMR, FTIR, scanning electron microscopy, energy dispersive X-ray. The average particle size of 1 and 2 were 60–70 and 40–50?nm, respectively, and the morphology was spherical for 1 and rod for 2. Solid state (powder) antibacterial effect of these compounds and two other similar reported ones, in their macro- and nanosizes, were evaluated with colony counting method on one Gram-positive (Staphylococcus aureus) and one Gram-negative (Escherichia coli) bacteria in Brain–Heart infusion culture medium. Results showed that all the macro- and nanosized compounds, except macrosized 1, were antibacterial and all nanoscaled ones had stronger antibacterial activity than their macroscaled analogues. The most effect of the particle size was observed for 1: by decreasing the particle sizes, the antibacterial activity state of 1 was changed from inactive (for macro) to potent (for nano).     

Development of Biarylalkyl Carboxylic Acid Amides with Improved Anti-schistosomal Activity

The parasitic disease schistosomiasis is the cause of more than 200 000 human deaths per year. Although the disease is treatable, there is one major shortcoming: praziquantel has been the only drug used to combat these parasites since 1977. The risk of the emergence of resistant schistosomes is known to be increasing, as a reduced sensitivity of these parasites toward praziquantel has been observed. We developed a new class of substances, which are derived from inhibitors of human aldose reductase, and which showed promising activity against Schistosoma mansoni couples in vitro. Further optimisation of the compounds led to an increase in anti-schistosomal activity with observed phenotypes such as reduced egg production, vitality, and motility as well as tegumental damage and gut dilatation. Here, we performed structure–activity relationship studies on the carboxylic acid moiety of biarylalkyl carboxylic acids. Out of 82 carboxylic acid amides, we identified 10 compounds that are active against S. mansoni at 25 μm . The best five compounds showed an anti-schistosomal activity up to 10 μm and induced severe phenotypes. Cytotoxicity tests in human cell lines showed that two derivatives had no cytotoxicity at 50 or 100 μm . These compounds are promising candidates for further optimisation toward the new anti-schistosomal agents.     

Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 [trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents.