Search

Introduction : La majorité des médicaments anticancéreux actuels sont pro-apoptotiques alors que dans les cancers l’apoptose est dérégulée ou inhibée expliquant en partie leur inefficacité. C’est pourquoi, trouver des médicaments d’origine végétale activant des types de mort cellulaire autres que l’apoptose pourrait constituer une alternative prometteuse. Le présent travail vise à démontrer les propriétés anticancéreuses des extraits de Erythrina senegalensis, une plante médicinale africaine utilisée dans le traitement des infections, de l’inflammation, de la douleur, de l’asthénie et des fibromes Matériels et méthodes : L’effet cytotoxique des extraits d’écorce de tronc au dichlorométhane, au dichlorométhane / méthanol (1 :1) et au méthanol a été évalué via le test MTT et la vidéomicroscopie quantitative (VMQ). L’apoptose et de la cinétique du cycle cellulaire ont été étudiées via la technique TUNEL/PI. Les marqueurs fluorescents (acridine orange, LysoTracker, MitoTracker et ER-Tracker) ont permis de caractériser l’origine de la vacuolisation cytoplasmique. Résultats : Les extraits testés étaient cytotoxiques. La VMQ et le TUNEL/PI ont révélé une mort cellulaire non-apoptotique ni autophagique (LysoTracker (-)). La vacuolisation du cytoplasme provenait du réticulum endoplasmique (ERTracker (+)) avec gonflement de mitochondrie (MitoTracker (+)), marqueurs de la parapoptose. Conclusion : E. senegalensis induit la parapoptose sur des cellules cancéreuses multirésistantes à l’apoptose.

Two antimicrobial gels, formulated with natural biopolymers (collagen and chitosan), limonene, and an imidazole derivative, were subjected to cytotoxicity tests. In these two compositions, the limonene content was 0.4% and 0.67%. The cytotoxicity tests were performed in vitro, using MTT methodology, and a standardized human normal cells line, HUVEC type. These cells were exposed to different levels of gel concentrations in the culture media. The final concentration of each gel type in culture media was situated between (0-0.125) μL/mL. The cell viability was determined after 24, 48 and 72h of exposure. The analyses showed that after 24h of exposure, the viability of the cells is greater than 91%, after 48h the viability is greater than 80%; after 72 h of exposure, the viability of the cells is greater than 74%. These values reveal that both selected gels exhibit no cytotoxicity for the normal cell line. [ABSTRACT FROM AUTHOR]

Background: The present work is part of the exploration of new antiviral molecules to combat antimicrobial resistance. In purpose, this study determined the phytochemical analysis, cytotoxicity and antiviral activity of extracts from three Ivorian medicinal plants; Gliricidia sepium, Ocimum gratissimum and Xylopia aethiopica against poliovirus 1, a non-enveloped RNA virus. Methodology: Aqueous extract of the three plants, which were identified at the herbarium of National Floristic Center Abidjan, was done using a previously described method. The precipitation or staining technique was used to highlight the chemical groups in the three extracts while the polyphenol content of each extract was assessed by the colorimetric method. Cytotoxicity and antiviral activity tests were performed in 96-well plates. Cytotoxicity of each extract on L20B (a genetically engineered mouse cell line) was determined by observation of the cell line carpet. Antiviral activity of three extracts against poliovirus type I was determined after 72 hours using an assay that measures inhibition of the cytopathic effect on cell culture. Results: The three plant extracts contain polyterpenes, sterols and polyphenols, flavonoids, catechetical tannins, saponosides and quinones but none of the extract contains gallic tannins. With the exception of O. gratissimum, alkaloids were found in extracts from the two other plants, and extract of G. sepium was richer in polyphenol than the other two extracts. The cell carpet of L20B after 72 hours contact period with three extracts remained intact at concentrations ranging from 2 to 1000 µg/ml. The aqueous extract of G. sepium showed higher antiviral activity on poliovirus 1 (74.569%) at 2µg/ml than the extracts of O. gratissimum (45.6112%) and X. aethiopica (44.5247%) after 72 hours of incubation. Conclusion: The extract of G. sepium showed potent antiviral activity against poliovirus 1 than that of O. gratissimum and X. aethiopica. This was justified by its higher polyphenol content than the two extracts. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to develop and optimize palbociclib-loaded nanobubbles for targeted breast cancer therapy., Materials and Methods: Biocompatible poly(DL-lactide-co-glycolide) was used to create nanobubbles loaded with palbociclib. The formulation process was meticulously crafted using a three-level Box-Behnken design and a double emulsion solvent evaporation method to precisely tailor the nanobubbles' properties., Results: The Derringer's desirability method optimized variables by transforming responses into a desirability scale, resulting in a global desirability value. Optimal settings, A: 526.97mg, B: 250mg,C: 2.0% w/v, D: 6101rpm, achieved a D value of 0.949. Palbociclib nanobubbles demonstrated a smaller particle size (31.78±2.12) than plain nanobubbles (38.56±3.56). PDI values indicated a uniform size distribution. The zeta potential remained consistent, with values of -31.34±3.36 for plain and -31.56±3.12 for drug-loaded nanobubbles. Encapsulation efficiency was 70.12%, highlighting effective drug encapsulation. Palbociclib release was significantly higher from nanobubbles in pH 7.4, especially with ultrasound, releasing almost 99.34% of the drug. Hemolytic activity assays confirmed safety for injection. Fluorescent intensity analysis revealed a two-fold increase in cellular uptake of palbociclib facilitated by ultrasound. The MTT assay demonstrated enhanced cytotoxicity of palbociclib-loaded nanobubbles, especially with ultrasound, emphasizing their potential for improved therapeutic efficacy. The IC 50 values for palbociclib, without ultrasound, and with ultrasound were 98.3μM, 72.34μM, and 61.34μM, respectively., Conclusion: The significant findings of this study emphasize the potential of palbociclib-loaded nanobubbles as a promising therapeutic system for improved breast cancer treatment., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Copyright of Archives of Razi Institute is the property of Institut Razi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Satureja kermanica is a native species with a relatively wide distribution in Iran, which has been studied less. Due to the low stability of the plants, in this study, the methanolic extract of S. kermanica (MSK) along with a nanoemulsion (NEK) preparation was evaluated in terms of antioxidant and cytotoxic activity., Material and Methods: The aerial parts of S. kermanica were collected and after studying the organoleptic characteristics and quality control parameters, were extracted with methanol. Total phenolic compounds and total flavonoids of the plant were measured. A nanoemulsion preparation was prepared using ultrasonication method from S. kermanica extract. After measuring the particle size of nanoemulsion, both MSK and NEK were evaluated for their antioxidant and cytotoxic activity using DPPH scavenging assay and MTT colorimetric method on breast cancer cell line (MCF-7) respectively., Results: Phytochemical studies exhibited the presence of secondary metabolites including flavonoids, tannins, steroids and carbohydrates in the plant. Based on the histogram of the SBL nanosizer, the average diameter of nanoemulsion was determined as 37.09nm. Both MSK and NEK showed dose-dependent antioxidant and cytotoxic activity. The IC 50 value of MSK and NEK for DPPH inhibition was 30.105±2.781 58.14±0.84μg/mL and for toxicity toward MCF-7 cell line was 1251.088 and 201.745±4.554μg/mL respectively., Conclusion: MSK and NEK showed antioxidant and cytotoxic activity, but in NEK, the antioxidant and cytotoxic potential of the plant was more prominent, which may be due to the rapid release of the bioactive component from the nanoemulsion., (Copyright © 2024. Published by Elsevier Masson SAS.)

Copyright of Phytothérapie is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Résumé: Dans le rapport de l'Organisation de coopération et de développement économiques (OCDE) de 2016 intitulé Nanomaterials in waste streams , 30 % des déchets sont incinérés. Ce processus peut affecter fortement les caractéristiques physico-chimiques de nanoparticules, éventuellement présentes dans ces déchets, induisant une modification potentielle de leur toxicité initiale. La répartition des nanoparticules dans les sous-produits formés (fumées et résidus provenant de l'incinération des nanocomposites) reste incertaine. Dans le projet Nano Tox'in, des nanocomposites ont été incinérés à l'échelle de laboratoire. Les objectifs étaient de faire une étude complète des propriétés physico-chimiques et des sous-produits associés et d'évaluer l'impact sur la toxicité in vitro de la transformation des nanoparticules initiales des nanocomposites en particules libérées (particles matter [PM]) dans les aérosols et dans les résidus (mâchefers). Nous avons pu montrer que les nanoparticules étaient principalement concentrées dans les mâchefers. Nos résultats ont également confirmé que le profil toxicologique des PM est directement régi par la toxicité de la matrice polymère hôte, tandis que celui des mâchefers semble directement lié à la toxicité intrinsèque des nanoparticules. La taille, la chimie et le taux des nanoparticules ainsi que la nature de la matrice ont donc un impact sur la toxicité in vitro. Le nouveau projet, NanoDetox, va nous permettre d'étudier l'impact des mélanges de déchets (représentatif de flux de déchets) et d'évaluer les transformations physico-chimiques ainsi que les effets de synergies/antagonismes liés aux nanoparticules sur la toxicité in vitro des suies et/ou les mâchefers. According to the 2016 OECD report "Nanomaterials in waste streams", 30 % of waste is incinerated. This process can strongly affect the physical and chemical properties of any nanoparticles in the waste matter, possibly modifying their initial toxicity. Little is known about the spread of nanoparticles in the resulting by-products (smoke and residues from the incineration of the nanomaterials). In the Nano Tox'in project, nanomaterials were incinerated in a laboratory with a two-fold aim: to study their physical and chemical properties and their by-products in detail, and to assess the impact on the in vitro toxicity of the transformation of the nanomaterials' initial nanoparticles into released particulate matter (PM) in aerosols and in the residues (ash). We showed that the nanoparticles were mainly concentrated in the ash. Our results also confirmed that the toxicological profile of the PM is directly related to the toxicity of the polymer matrix host, while that of the ash seems directly linked to the intrinsic toxicity of the nanoparticles. The size, chemistry, and rate of nanoparticles along with the nature of the matrix therefore affect the in vitro toxicity. The new project, NanoDetox, will enable us to study the impact of mixed waste (representing the waste streams) and assess the physical and chemical transformations and the effects of synergies and antagonisms of nanoparticles on the in vitro toxicity of soot and/or ash. [ABSTRACT FROM AUTHOR]

New furan and thiophene derivatives of aldimines o -HO-C 6 H 4 N CHC 4 H 4 X(R) (X = O, S; R = H, SiMe 3 , SiEt 3 , GeMe 3 , GeEt 3) were synthesized by condensation of o -aminophenol with the substituted aldehyde precursor. Their structure, electrochemical reduction/oxidation (in CH 3 CN/0.1 M Bu 4 NPF 6), frontier orbital energies, and cytotoxicity have been studied. Their electrochemical redox potentials E p show good correlation with the corresponding orbital energies and the difference E p ox – E p red corresponds well to their orbital hardness. These new compounds have a pronounced cytotoxicity toward cancer cells of human fibrosarcoma HT-1080 and mouse hepatoma MG-22A (IC 50 ≅ 1–8 μg ml−1) that can be modulated by introducing a Me 3 M substituent into the fifth position of the heterocycle (e.g., IC 50 (Me 3 Si)/IC 50 (H) ≥ 50). R 3 M-substitution reduces the orbital hardness of the aldimines studied and facilitates oxidation, promoting their oxidative metabolism. The neighboring group effect in the α-Me 3 Si-substituted thiophene derivative favors S-oxidation, which supposedly makes its metabolic mechanism different compared to R 3 M-substituted furan series (or for M = Ge in the thiophene series). Interestingly, SiMe 3 and GeMe 3 groups in both heterocyclic series (furan and thiophene) cause opposite trends in cytotoxicity, while the silyl group increases it, the germyl group decreases it. [ABSTRACT FROM AUTHOR]

Dried bulbs and leaves of Allium reuterianum were extracted with different solvents and evaluated for antioxidant, antibacterial, insecticidal, in vitro cytotoxic activities. The obtained results indicated that the highest compound 3, 4-dihidroksi benzoic acid with 166.2 µg/g in extracts. The ethanolic extracts had the highest phenolic content and acetone extracts had the lowest fenolic content. In the β-carotene-linoleic acid test system, bulb methanol (ABM) and leaf methanol (ALM) extracts showed the highest antioxidant activity. The mean antioxidant activity of ABM and ALM were 75.76±1.22% and 73.42±1.03%, respectively. The highest ferric-reducing power of extract (ABM) was determined 12.75±0.010 trolox equivalent (mg/g). Methanolic extract (ALM) exhibited a dose-dependent scavenging of DPPH and ABTS radicals with IC50 values of 0.512±0.003 mg/mL and 0.378±0.002 mg/mL respectively. Very strong reduction of gram-positive Staphylococcus aureus growth were observed during incubation of bacteria in bulb extracts (MIC was 20±1.01 μg/mL). The brine shrimp lethality assay of bulb extract has showed good toxic to brine shrimp nauplii, with LC50 of 3.987 μg/mL. The bulb extract of A. reuterianum showed highest larvicidal activity against Cx. pipiens with value LC50 (6.4129 μg/mL). The results suggest that these plants could be used as a source of natural antioxidant and antibacterial agents. [ABSTRACT FROM AUTHOR]

La bléomycine est un antibiotique antitumoral. Elle peut être responsable d'effets secondaires variables en particulier cutanés et pulmonaires. Certains sont rares, mais spécifiques de la bléomycine. Nous rapportons l'observation de deux malades âgés respectivement de 35 et 38 ans ayant présentés une toxidermie à la bléomycine a type d'érythème flagellé après administration de bléomycine pour un choriocarcinome et un lymphome malin non hodgkinien L'érythème flagellé est spécifique de la bléomycine, il complique 10 à 30% des traitements dans un délai de quelques heures à 9 semaines. Il est indépendant de la dose, de la voie d'administration et de la nature de la lésion traitée. Ces lésions apparaissent après une dose cumulative de 90 à 285 mg. Cliniquement, il s'agit de bandes linéaires avec un aspect flagellé prédominantes sur tout le tronc et les parties proximales des membres. L'éthiopathogénie est incertaine. L'évolution est marquée par une résolution spontanée des lésions à l'arrêt du traitement parfois au prix d'une pigmentation linéaire cicatricielle, ou une sclérose résiduelle.

Résumé Les plantes carnivores sont des végétaux insolites qui ont toujours intrigué les scientifiques. Leur principal emploi en thérapeutique concerne l'homéopathie, mais depuis plusieurs années, de nouvelles approches commencent à émerger. Summary Carnivorous plants are unusual plants that have always intrigued scientists. Their main therapeutic use is in homeopathy, but over the past several years, new approaches have emerged. [ABSTRACT FROM AUTHOR]

The jadomycin family of natural products was first identified and characterized by Vining and co-workers at Dalhousie University in the 1990s. Herein, we report findings from a recently developed co-amino acid supplementation culture method with S. venezuelae ISP5230 using 8-aminooctanoic acid, where the major natural product was a jadomycin variant omitting an E-ring ( 1). These results reinforce that the 3a position is susceptible to nucleophilic addition by cellular metabolites in jadomycin biosynthesis when intramolecular cyclization is unfavorable. Further, the cytotoxicity data for several unsubstituted E-ring jadomycins are reported and discussed. [ABSTRACT FROM AUTHOR]

The bléomycine is an antitumor antibiotic. It can be responsible for in particular cutaneous and pulmonary variable side effects. Some are rare, but specific of the bléomycine. We report the observation of two patients aged respectively of 35 and 38 years old, having presented a toxidermy at the bléomycine has standard erythema whipped after administration of bléomycine for a choriocarcinomist and a malignant lymphoma not hodgkinien the whipped erythema is specific of bléomycine, it complicates 10 to 30% of the treatments within a few hours to 9 weeks. It is independent of the amount, the route of administration and the nature of the treated lesion. These lesions appear after a cumulative amount from 90 to 285 Mg. Clinically, they are linear bands with an aspect whipped prevalent on all the trunk and the proximales parts of the members. The éthiopathogénie is dubious. The evolution is marked by a spontaneous resolution of the lesions to the stop of the treatment sometimes the price of a cicatricial linear pigmentation, or a residual sclerosis. [ABSTRACT FROM AUTHOR]

Nanotechnology has been applied to many aspects of human life. Meanwhile, concerns regarding the toxicity of engineered nanomaterials to the environment have also been growing. Herein, an economic and convenient approach based on quantitative structure-activity relationship for nanomaterials (nano-QSAR) was proposed to evaluate the cytotoxicity of metal oxide nanoparticles (MONPs) to E. coli. Six molecular descriptors of 17 MONPs were selected and calculated using Gaussian98 software and DFT-B3LYP method on the LANL2DZ basis set. Two multivariable models, linear and nonlinear, were built based on the calculated molecular descriptors using multiple linear regression (MLR) and support vector machine (SVM) methods, respectively. Results demonstrated that both models presented high reliability, good predictive performance, and fine generalization ability, with all R2 values greater than 0.84. It was also revealed that the lowest unoccupied molecular orbital (LUMO) and molar heat capacity ( Cp) were the two key descriptors influencing the cytotoxicity of MONPs. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Razi Institute is the property of Institut Razi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper reports on the results of chemical synthesis and biological assays performed on several new analogues of noscapine. We have successfully synthesized four noscapine analogues called 1a-4a, as well as their four corresponding enantiomers called 1b-4b. The chemical pathway consisted of three steps with yields in excess of 60% in each step. Subsequently, we have performed biological activity assays intended to reveal the mode of action of these compounds on microtubules in buffer and in cancer cell lines. We have assayed fluorescence quenching effects in microtubule polymerization experiments, cytotoxicity evaluation in breast cancer cell lines, as well as microtubule dynamicity assessments, for each of the synthesized compounds. Finally, we performed computational docking simulations to two binding sites on β-tubulin: ( a) the colchicine binding site and ( b) the noscapine binding site. Our results indicate that these compounds have relatively low cytotoxicity profile and less pronounced effects on microtubule dynamics compared with noscapine. Our computational results indicate that these compounds bind to both putative binding sites but have higher affinity for the colchicine site. [ABSTRACT FROM AUTHOR]

Pyrazoline is an important 5-membered nitrogen heterocycle that has been extensively researched. Ten derivatives were synthesized and tested for antileukemic effects on 2 human acute leukemia cell lines, K562 and Jurkat. The most cytotoxic of these derivatives, compound 21, was chosen for investigation of cytotoxicity mechanisms. The results obtained with selectivity calculations revealed that compound 21 is more selective for acute leukemia (K562 and Jurkat cell lines) than for other tumor cell lines. Moreover, compound 21 was not cytotoxic to normal cell lines, indicating a potential use in clinical tests. Compound 21 caused a significant cell cycle arrest in the S-phase in Jurkat cells and increased the proportion of cells in the sub G0/G1 phase in both cell lines. Cells treated with compound 21 demonstrated morphological changes characteristic of apoptosis in the EB/AO assay, confirmed by externalization of phosphatidylserine by the annexin V - fluorescein isothiocyanate method and by DNA fragmentation. An investigation of cytotoxicity mechanisms suggests the involvement of an intrinsic apoptosis pathway due to mitochondrial damage and an increase in the ratio of mitochondrial Bax/Bcl2. Pyrazoline 21 obeyed Lipinski's 'rule of five' for drug-likeness. Based on these preliminary results, the antileukemic activity of compound 21 makes it a potential anticancer agent. [ABSTRACT FROM AUTHOR]

Aspirin, one of the widely used nonsteroidal anti-inflammatory drugs, is the most highly consumed pharmaceutical product in the world. However, it has several side effects in cells. This study was designed to investigate the antioxidative activity and cytoprotective effects of essential oil of Citrus limon (EOC) extracted from leaves against aspirin-induced damages in the rat small intestine epithelial cells (IEC-6). Biochemical indicators were used to assess cytotoxicity and oxidative damages caused by aspirin treatment on IEC-6. Our results showed that the chemical characterization of EOC identified 25 compounds representing 98.19% of the total oil. The major compounds from this oil were z-citral (53.21%), neryl acetate (13.06%), geranyl acetate (10.33%), and limonene (4.23%). Aspirin induced a decrease in cell viability as well as an increase in superoxide dismutase (SOD) and catalase (CAT) activities. Contrariwise, the co-exposure of cells to aspirin and EOC alleviated every above syndrome by an increase in cell survival and decrease in SOD and CAT activities. In conclusion, the essential oil of C. limon has a potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Mycology / Journal de Mycologie Médicale is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cadmium (Cd) is one of the most toxic heavy metals. It is of great environmental concern and its toxicity has been investigated in a variety of cells. In this study, we elucidated the toxic effects of Cd in cells of yeast ( Saccharomyces cerevisiae). Our results showed that Cd2+ (0.05-5.0 mmol·L−1) significantly inhibited yeast cell growth, and the inhibitory effect was positively correlated with Cd2+ concentrations. Cd2+ caused loss of yeast cell viability in a concentration- and duration-dependent manner. Intracellular reactive oxygen species (ROS) and Ca2+ levels increased in yeast cells after exposure to 5.0 mmol·L−1 Cd for 6 h. Cd2+-caused cell viability loss was blocked by antioxidants (0.5 mmol·L−1 ascorbic acid or 500 U·mL−1 catalase) or Ca2+ antagonists (0.5 mmol·L−1 ethylene glycol tetraacetic acid or 0.5 mmol·L−1 LaCl3). Moreover, a collapse of mitochondrial membrane potential (ΔΨm) was observed in Cd2+-treated yeast cells. These results indicate that Cd-induced yeast cell killing was associated with the elevation of intracellular ROS and Ca2+ levels and also the loss of ΔΨm. [ABSTRACT FROM AUTHOR]

Résumé La présence des anticorps anti-HLA dans le sérum d’un patient est la conséquence d’une réponse immunitaire produite lors d’un événement immunisant comme la transfusion, la grossesse ou la greffe. Ces anticorps peuvent être cytotoxiques en activant la voie du complément via le C1q, et risquent d’entraîner un rejet lors d’une greffe d’organe. Certains patients de sexe masculin, candidats à la transplantation rénale, présentent une recherche positive des anticorps anti-HLA alors qu’ils n’ont aucun antécédent d’événement immunisant. Ces anticorps sont qualifiés d’anticorps naturels. Notre travail consiste à évaluer la cytotoxicité des anticorps anti-HLA naturels chez les patients suivis au laboratoire d’immunologie du service de transfusion sanguine et d’hémovigilance (STSH) dans le cadre de la greffe rénale. Patients et méthodes Nous avons évalué la cytotoxicité des anticorps anti-HLA dépistés chez des patients marocains de sexe masculin, sans antécédents d’immunisation, en utilisant le réactif C1qScreen de One Lambda pour Luminex™. Résultats Le taux de positivité de la recherche des anticorps anti-HLA chez les patients hommes jamais immunisés est de 25,4 %. Ces anticorps ne sont pas cytotoxiques. Conclusion Notre étude a montré un taux de positivité des anticorps anti-HLA naturels inférieur à la littérature (25,4 % contre 63 %). Il semblerait que ces anticorps naturels ne soient pas cytotoxiques, et leur implication dans la greffe rénale reste à déterminer. The presence of anti-HLA antibodies in the serum of a patient result from an immune response produced during an immunizing event as transfusion, pregnancy or graft. These antibodies can be cytotoxic by activating the complement pathway via C1q and may cause organ rejection during the transplant. Some male patients awaiting kidney transplantation are seropositive for anti-HLA antibodies when they have no immunizing antecedent event. These antibodies are qualified as natural antibodies. Our work is to assess the cytotoxicity of natural anti-HLA antibodies in patients followed at the immunology laboratory of the blood transfusion service and hemovigilance (STSH) as part of the kidney transplant. Patients and methods We evaluated the cytotoxicity of HLA antibodies detected in male Moroccan patients without immunization history using C1qScreen One Lambda reagent for Luminex™. Results Non-immunized men were positive for HLA antibodies screening in 25.4%. These antibodies are not cytotoxic. Conclusion Our study showed a positivity rate of natural HLA antibody low than the literature (25.4% against 63%). It appears that these natural antibodies are not cytotoxic and their involvement in renal transplant remains to be determined. [ABSTRACT FROM AUTHOR]

An indole ring system is considered as a versatile scaffold in the pharmaceutical field. In this article, comparative QSAR modeling (2D-QSAR, 3D-QSAR; kNN-MFA and CoMSIA) was performed on some Knoevenagel-type cytotoxic indole derivatives to understand the structural requirements for the cytotoxic property of these compounds. The 2D-QSAR model was statistically significant and imparted high predictive ability ( nTrain = 30; R = 0.917; = 0.801; = 0.757; Q2 = 0.722; nTest = 9; = 0.799). A statistically significant 3D-QSAR kNN-MFA model (both with stepwise forward and simulated annealing model selection method) as well as a 3D-QSAR CoMSIA model was developed to identify the key chemical features associated with enhancing the cytotoxic activities of these indoles. The results suggest that the presence of bulky group in R position can cause better cytotoxic activities. Consequently, substitution with cyano group at X portion and cyano/ester/keto/sulphonyl features at Y position is favourable for the cytotoxicity. However, hydrophobic features in R′ region are unfavourable for the biological activity. The chemical and structural features identified from the study may provide important avenues to modulate the structure of these indoles to a desirable biological end point. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Animal Science is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Solvothermal chemistry was employed to produce PCN-95 starting with pyrene forming eight connected Zr6 clusters conforming to an isoreticular structure (P6/mmm). The secondary building unit was determined from polycrystals as having Zr6 center octahedral to and covering all triangular faces with eight OH and carboxylates as the framework. The polycordinated network material was characterized by electron microscopy and evaluated from its cytotoxicity against human ovarian cells. The concentration at 50% inhibition was in the low parts per million and electron micrographs showed a 'darker region' around the DNA, indicative of DNA condensation leading to fragmentation. To determine whether the observed biological effects were due to the generation of singlet oxygen or elicitation of specific death pathways, the polycordinated network with and without select inhibitors or reducing and oxidizing agents was employed against human retinal pigment epithelium in vitro and NO measured as a measure of cell health against controls cells (without any cofactors). The NO release was measured a over 3 h time period and the kinetic plots compared and contrasted with known biochemical pathways. The plots were similar to methylene blue, a known singlet oxygen generator and between hydrogen peroxide and citrate but unlike cyanide or rotenone. Collectively, the results support the hypothesis of singlet oxygen generation at the mitochondria and interaction with complex IV of the electron transport chain, facilitating the reduction of nitrite towards more NO. When the cell generates higher concentrations of NO, the apoptotic pathways are triggered resulting in cell death. [ABSTRACT FROM AUTHOR]

We synthesized 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP), characterized it by electrochemistry, spectroelectrochemistry, and electron paramagnetic resonance techniques, and evaluated its cytotoxicity to human cancer cell lines. The results revealed that HHTP has accessible higher-oxidation states, especially the tris-semiquinone monoradical. This species is stable and is formed after being stored for months. HHTP exhibited cytotoxic effects on 5 human cancer cell lines, including glioma and lung cancer cells. The cytotoxic effect was evaluated based on the decrease in cell viability, increases in the percentage of cells with fragmented DNA, and elevated numbers of annexin V-PI-positive cells after HHTP treatment. [ABSTRACT FROM AUTHOR]

Despite the interactions known to occur between various lower respiratory tract pathogens and alveolar epithelial cells (AECs), few reports examine factors influencing the interplay between Mycobacterium tuberculosis bacilli and AECs during infection. Importantly, in vitro studies have demonstrated that the M. tuberculosis hbha and esxA gene products HBHA and ESAT6 directly or indirectly influence AEC survival. In this report, we identify Rv3351c as another M. tuberculosis gene that impacts the fate of both the pathogen and AEC host. Intracellular replication of an Rv3351c mutant in the human AEC type II pneumocyte cell line A549 was markedly reduced relative to the complemented mutant and parent strain. Deletion of Rv3351c diminished the release of lactate dehydrogenase and decreased uptake of trypan blue vital stain by host cells infected with M. tuberculosis bacilli, suggesting attenuated cytotoxic effects. Interestingly, an isogenic hbha mutant displayed reductions in AEC killing similar to those observed for the Rv3351c mutant. This opens the possibility that multiple M. tuberculosis gene products interact with AECs. We also observed that Rv3351c aids intracellular replication and survival of M. tuberculosis in macrophages. This places Rv3351c in the same standing as HBHA and ESAT6, which are important factors in AECs and macrophages. Defining the mechanism(s) by which Rv3351c functions to aid pathogen survival within the host may lead to new drug or vaccine targets. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of lesions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). The excess influx of fatty acids (FAs) into the liver is recognized as a main cause of simple steatosis formation and progression to NASH. Recently, administration of lactoferrin (LF), a glycoprotein present in milk, was suggested to prevent NAFLD development. However, the effect of LF on the contribution of FA to NAFLD development remains unclear. In this study, the effects of LF on FA mixture (FAm)-induced lipotoxicity using human hepatocarcinoma G2 cells were assessed. FAm significantly decreased cell viability and increased intracellular lipid accumulation, whereas LF significantly recovered cell viability without affecting lipid accumulation. FAm-induced lactic dehydrogenase (LDH) and caspase-3/7 activities were significantly decreased by LF and SP600125, a c-Jun N-terminal kinase (JNK) specific inhibitor. We also found that LF added to FAm-treated cells induced Akt phosphorylation, which contributed to inhibition of JNK signaling pathway-dependent apoptosis. Akt inhibitor VIII, an allosteric Akt inhibitor, significantly attenuated the effect of LF on LDH activity and abrogated the ones on cell viability and caspase-3/7 activity. In summary, the present study has revealed that LF has a protective effect on FAm-induced lipotoxicity in a HepG2 model of NAFLD and identified the activation of the Akt signaling pathway as a possibly major mechanism. [ABSTRACT FROM AUTHOR]

A small family of organometallic platinum complexes containing a chloride, cis-cyclooctene, and a Schiff base ligand have been prepared and characterized fully. Three aliphatic amines and four aromatic amines were chosen as representative examples. All complexes were stable in air except for 7, derived from the pinacol-protected 4-aminophenylboronate ester 4-H2NC6H4Bpin (pin = 1,2-O2C2Me4), which decomposed via B-C bond cleavage. Both complexes 4 (derived from aniline) and 7 were further characterized by single-crystal X-ray diffraction studies and confirmed the square planar nature of the platinum centre whereby the chloride ligand lies trans to the deprotonated hydroxyl group of the Schiff base ligand. The imine functionality is trans to the organic cyclooctene group. Complex 3, which contained the longest aliphatic chain studied (an octyl group), was the most promising for inducing apoptosis in the malignant MB231 breast cancer cell line. Conversely, complexes 4- 6, which contained aromatic groups, were the most active against renal cell carcinoma (RCC) cell lines. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the toxicity of extracts from disposable chopsticks, toothpicks, and paper cups on L-929 cells. Methods: We followed national standards to prepare the extracts from disposable chopsticks, toothpicks, and paper cups used for the cell culture media, and the morphology of L-929 cells was observed with an optical microscope. The loss rate for adherent cells was evaluated with the trypan blue exclusion method, and cell proliferation was determined using the WST-1 assay. Results: Compared with the control group, the cells cultured in media containing the extracts showed signs of apoptosis and necrosis after culturing for 4 or 7 days, and the loss rate for adherent cells was significantly increased ( P < 0.05). An obvious decrease in cell viability was also observed ( P < 0.05). Conclusion: The extracts from disposable chopsticks, toothpicks, and paper cups can affect the growth and proliferation of L-929 cells and are potentially toxic to humans. [ABSTRACT FROM AUTHOR]

Résumé Les cellules Natural Killer (NK) sont non seulement des effecteurs cytotoxiques de la réponse immune innée dirigée contre les cellules tumorales ou infectées mais aussi d’importants immunorégulateurs. Leur activation résulte d’une balance entre signaux inhibiteurs ou activateurs issus de multiples récepteurs. La leptine, produit par les adipocytes, est un facteur métabolique majeur qui module le système immunitaire. L’hyperleptinémie est un facteur de risque de dysimmunité et de cancer en lien, notamment, avec une moindre vigilance anti-tumorale. Cette revue fait la synthèse de la littérature traitant de l’impact de la leptine sur les cellules NK. In vitro, la leptine, en concentration similaire à celle retrouvée en situation d’obésité, stimule non seulement l’activité métabolique mais aussi l’activité lytique des cellules NK. À l’inverse, in vivo, l’hyperleptinémie associée à un régime hypercalorique ou une obésité constitutive, n’est pas corrélée à la cytotoxicité des cellules NK ce qui laisse supposer l’émergence d’une leptinorésistance. Natural Killer (NK) cells are not just cytotoxic effectors of the innate immune response against tumors and infections but also important immunoregulators. They are activated by an intricate balance between signals provided by their inhibitory and activating receptors. Leptin, one major metabolic factor produced by adipocytes, appears to be strongly involved in obesity-induced dysimmunity and carcinogenesis. This paper reviews the studies investigating the effect of leptin on NK cells. Leptin, at level similar to that found in obesity, stimulate, in vitro , both the NK cell metabolic and lytic activities. In contrast, no significant association was observed, in vivo , between serum leptin and NK cytotoxicity whatever the model, diet-induced or constitutive obesity. These findings may be related to leptin resistance. [ABSTRACT FROM AUTHOR]

Résumé Le syndrome hémophagocytaire (SH) ou hémophagocytose lymphohistiocytaire est un syndrome d’hyperinflammation potentiellement fatal lié à une stimulation anarchique du système immunitaire. Ce syndrome est lié à une hyper-activation des lymphocytes et des macrophages et se caractérise par une synthèse élevée de cytokines pro-inflammatoires : IL-1, IL-6, TNF-α, IFN-γ dont les différentes actions expliquent les signes cliniques et biologiques. Le déficit génétique ou secondairement acquis et transitoire de la fonction de cytotoxicité des lymphocytes T et des cellules NK constitue le point commun et l’origine de ces perturbations biologiques. Il existe 2 groupes de SH : les SH primaires ou génétiques et les SH secondaires ou réactionnelles à des infections, des maladies auto-immunes, des cancers, des médicaments. Quelle que soit l’étiologie, la clinique est identique et peu spécifique. La biologie se caractérise par une cytopénie (2 ou 3 lignées), une hyper-triglycéridémie et hyper-ferritininémie, une hypofibrinogémie, la mise en évidence d‘une hémophagocytose dans la moelle osseuse ou dans un organe atteint signe la SH. Parmi les critères diagnostiques, des examens immunologiques plus spécifiques ont été développés à partir des mécanismes physiopathologiques : dosage du sCD25, de sCD163, numération des lymphocytes T CD8+ DR+, analyse des fonctions cytotoxiques des cellules NK, détection intracytoplasmique de la perforine. En cohérence avec les mécanismes physiopathologiques, le traitement consiste en une diminution de l’état hyperinflammatoire et de l’activation des cellules de l’immunité, associée au traitement des pathologies à l’origine de l’activation du système immunitaire et, dans les formes génétiques, la greffe de moelle osseuse. Summary Hemophagocytic lymphohistiocytosis (HLH) is the consequence of immune system hyperactivation, responsible for an hyperinflammatory state potentially fatal. Lymphocytes and histiocytes hyperactivation is characterised by a pro-inflammatory cytokine storm : massive secretion of IL-1, IL-6, TNF-α, IFN-γ by activated lymphocytes and macrophages. Cytokine hypersecretion is responsible for clinical and biological signs. Genetic (primary HLH) or acquired (secondary HLH) defect of CD8 T lymphocyte and NK cell cytotoxicity is at the origin of HLH. Secondary or acquired HLH occurred in infections, autoimmune diseases or malignancies. HLH symptoms are not specific, and diagnosis is often delayed. Biological parameters are cytopenias, hyperferritinemia, hyperetriglyceridemia, hypofibrinogenemia, hemophagocytosis in bone marrow or other involved organs. Advances in pathophysiological mechanisms understanding allow to identify perturbed immunologic parameters : sCD25 and sCD163 increased, CD8 T cell HLA-DR overexpression, NK cytotoxicity absent or decreased. Initial treatment is urgent and consists of a decrease of hyperinflammatory state. Hematopoietic cell transplantation is proposed in genetic HLH. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an opportunistic pathogen that can infect susceptible patients suffering from cystic fibrosis, immunosuppression, and severe burns. Nosocomial- and community-acquired infection is likely due to contact with water sources contaminated with P. aeruginosa. Most of what is known about the virulence properties of P. aeruginosa was derived from studies using fairly rich broths, which do not represent conditions found in water, such as low nutrient concentrations. Here, we compare biofilm production, invasion of epithelial cells, cytotoxicity, and pyocyanin production of P. aeruginosa in water with P. aeruginosa grown in rich broth. Since tap water is variable, we used a defined water medium, Fraquil, to ensure reproducibility of the results. We found that P. aeruginosa does not readily form biofilm in Fraquil. Pseudomonas aeruginosa is equally able to attach to and invade epithelial cells but is more cytotoxic after incubation in water for 30 days than when it is grown in rich broth. Moreover, P. aeruginosa produces less pyocyanin when exposed to water. Our results show that P. aeruginosa seems to have different properties when exposed to water than when grown in rich broth. [ABSTRACT FROM AUTHOR]

BACKGROUND: 1,1-dimethyl-biguanide hydrochloride (biguanide metformin) is a hypoglycemic agent that is widely used in the treatment of Type 2 diabetes. Use of metformin was found to be associated with the lower risk of cancer. It is suggested that metformin has an anticancer and antiproliferative effect and affects the apoptosis by activating the AMPK and inhibiting the mammalian target of rapamycin (mTOR). Although the effects of metformin treatment of various types of cancers are defined with many mechanisms, the literature provides only sufficient information about how it affects the SGK-1, Par-4 and Cav-1 mRNA expressions and the impact of this effect on cytotoxicity. The breast cancer is globally one of the most important causes of cancer-related mortality for women. We, therefore investigated the possible effects of metmorfin on proliferation, cytotoxicity and some unfolded protein response (UPR) genes in the breast cancer cells (MCF-7). MATERIALS AND METHODS: We administrated 0.31 mM, 2.5 mM and 10 mM of metformin alone and in combination with 2-DG to the MCF-7 cells and monitored the cell viability and proliferation with real-time cell analyzer system for 48 hours. We also measured CHOP, Cav-1, HO-1, SGK-1 and Par-4 genes mRNA expression levels using Real Time-Polymerase Chain Reaction (RT-PCR). We considered the GAPDH gene as reference gene and the control groups as calibrator. We performed an analysis for relative gene expressions of the study groups. RESULTS: Metformin caused transcriptional regulation of UPR and tumor-related genes in MCF-7 cells and inhibited the proliferation depending on the dose, resulting in cytotoxic effect. CONCLUSIONS: We consider that administration of metformin with chemotherapeutic agents could be an effective method in treatment of breast cancer through mechanisms such as reduced resistance to chemotherapy and increased cytotoxic activity. [ABSTRACT FROM AUTHOR]

Evidence has shown that individuals exposed to indoor toxic molds for extended periods of time have elevated risk of developing numerous respiratory illnesses. It is not clear at the cellular level what impact mold exposure has on the immune system. Herein, we show that 2 fungal volatiles ( E)-2-octenal and oct-1-en-3-ol have cytotoxic effects on murine bone marrow stromal cells. To further analyze alterations to the cell, we evaluated the impact these volatile organic compounds have on membrane composition and hence fluidity. Both ( E)-2-octenal and oct-1-en-3-ol exposure caused a shift to unsaturated fatty acids and lower cholesterol levels in the membrane. This indicates that the volatile organic compounds under investigation increased membrane fluidity. These vast changes to the cell membrane are known to contribute to the breakdown of normal cell function and possibly lead to death. Since bone marrow stromal cells are vital for the appropriate development and activation of immune cells, this study provides the foundation for understanding the mechanism at a cellular level for how mold exposure can lead to immune-related disease conditions. [ABSTRACT FROM AUTHOR]