Inhibitory effect of essential oil on aflatoxin activities

Aflatoxins, which are well-known to be mutagenic, carcinogenic, teratogenic, hepatotoxic and immunosuppressive, also inhibit several metabolic systems. Aflatoxins are biologically active secondary metabolites produced by certain strains of Aspergillus parasiticus, Aspergillus nominus and Aspergillus flavus. Many different substances, such as essantial oils, flavanoids, could inhibit theaflatoxin production and growth of Aspergillus. In this study, aflatoxins biosyntesis, aflatoxins damaged and aflatoxins with essential oils interaction are evaluated

Antioxidant and antimutagenic activities of Viscum album fruit ethanolic extract in human lymphocytes

Polyphenolic compounds are widely distributed in plants and known to be excellent antioxidants in vitro. They have the capacity to reduce free-radical formation by scavenging free-radicals. In this studywe have evaluated the antioxidant and antimutagenic potencies of polyphenolic compounds of Viscum album against trichloroethylene (TCE)-induced oxidative and genotoxic damage. V. album extract (VAE0.5 g/ml) protected human lymphocytes against TCE. In chromosomal aberration (CA) analysis, no significant increase in total aberrations were found after treatment with TCE and all VAE concentrations. The mitotic index (MI) showed significant increase in 0.5 ìg/ml VAE samples whencompared with TCE-treated (2 ìM) group. VAE (0.5 ìg/ml) reduced the levels of malondialdehyde (MDA) significantly wherease VAE (1.0 and 2.0 ìg/ml) samples increased MDA concentrations significantly. We have also shown that the various DNA effects of TCE treatment seem to be DNA damages, but not mutations as TCE treated profiles were reverted back to the control like profiles by most probably DNA repair mechanisms in VAE 0.5 g/ml treated group

Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy

<p>Abstract</p> <p>Background</p> <p>The Toll-like receptors (TLRs) mediate innate immunity to various pathogens. A mutation (S180L) in the TLR downstream signal transducer <it>TIRAP </it>has recently been reported to be common in Europeans and Africans and to roughly half the risks of heterogeneous infectious diseases including malaria, tuberculosis, bacteremia, and invasive pneumococal disease in heterozygous mutation carriers.</p> <p>Methods</p> <p>We assessed the <it>TIRAP </it>S180L variant by melting curve and RFLP analysis in 1095 delivering women from malaria-endemic Ghana, as well as in a further 1114 individuals participating in case control studies on sepsis and leprosy in Germany, Turkey and Bangladesh.</p> <p>Results</p> <p>In Ghana, the <it>TIRAP </it>S180L polymorphism was virtually absent. In contrast, the mutation was observed among 26.6%, 32.9% and 12% of German, Bangladesh and Turkish controls, respectively. No significant association of the heterozygous genotype with sepsis or leprosy was observed. Remarkably, homozygous <it>TIRAP </it>180L tend to increase the risk of sepsis in the German study (<it>P </it>= 0.04).</p> <p>Conclusion</p> <p>A broad protective effect of <it>TIRAP </it>S180L against infectious diseases <it>per se </it>is not discernible.</p

Thrombosis in vasculitis: from pathogenesis to treatment

In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet’s syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet’syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet’s syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

Genome-wide studies reveal the essential and opposite roles of ARID1A in controlling human cardiogenesis and neurogenesis from pluripotent stem cells

Background Early human heart and brain development simultaneously occur during embryogenesis. Notably, in human newborns, congenital heart defects strongly associate with neurodevelopmental abnormalities, suggesting a common gene or complex underlying both cardiogenesis and neurogenesis. However, due to lack of in vivo studies, the molecular mechanisms that govern both early human heart and brain development remain elusive. Results Here, we report ARID1A, a DNA-binding subunit of the SWI/SNF epigenetic complex, controls both neurogenesis and cardiogenesis from human embryonic stem cells (hESCs) through distinct mechanisms. Knockout-of-ARID1A (ARID1A−/−) leads to spontaneous differentiation of neural cells together with globally enhanced expression of neurogenic genes in undifferentiated hESCs. Additionally, when compared with WT hESCs, cardiac differentiation from ARID1A −/− hESCs is prominently suppressed, whereas neural differentiation is significantly promoted. Whole genome-wide scRNA-seq, ATAC-seq, and ChIP-seq analyses reveal that ARID1A is required to open chromatin accessibility on promoters of essential cardiogenic genes, and temporally associated with key cardiogenic transcriptional factors T and MEF2C during early cardiac development. However, during early neural development, transcription of most essential neurogenic genes is dependent on ARID1A, which can interact with a known neural restrictive silencer factor REST/NRSF. Conclusions We uncover the opposite roles by ARID1A to govern both early cardiac and neural development from pluripotent stem cells. Global chromatin accessibility on cardiogenic genes is dependent on ARID1A, whereas transcriptional activity of neurogenic genes is under control by ARID1A, possibly through ARID1A-REST/NRSF interaction

Antimutagenic compounds and their possible mechanisms of action

Mutagenicity refers to the induction of permanent changes in the DNA sequence of an organism, which may result in a heritable change in the characteristics of living systems. Antimutagenic agents are able to counteract the effects of mutagens. This group of agents includes both natural and synthetic compounds. Based on their mechanism of action among antimutagens, several classes of compounds may be distinguished. These are compounds with antioxidant activity; compounds that inhibit the activation of mutagens; blocking agents; as well as compounds characterized with several modes of action. It was reported previously that several antitumor compounds act through the antimutagenic mechanism. Hence, searching for antimutagenic compounds represents a rapidly expanding field of cancer research. It may be observed that, in recent years, many publications were focused on the screening of both natural and synthetic compounds for their beneficial muta/antimutagenicity profile. Thus, the present review attempts to give a brief outline on substances presenting antimutagenic potency and their possible mechanism of action. Additionally, in the present paper, a screening strategy for mutagenicity testing was presented and the characteristics of the most widely used antimutagenicity assays were described

Superparamagnetic Iron Oxide Nanoparticles (SPION) Functionalized by Caffeic Acid (CFA)

In this research, we synthesized a novel caffeic acid-functionalized iron oxide nanoparticles (CFA-functionalized SPION) L929 (mouse fibroblast cell), U87 (glioblastoma brain cancer cell), MCF-7 (breast cancer cell), HeLa (cervix cancer cell), and A549 (human lung cancer cell) cell lines. Thermal decomposition and Stober methods were used to prepare APTES-capped SPION, respectively. The carboxylated polyethylene glycol (PEG-COOH), folic acid (FA), and caffeic acid (CFA) were attached to the surface of SPION via carboxylic/amine groups. Structural analysis (Rietveld analysis) confirmed the phase purity of the product. The conjugation of organics to the surface of SPION was followed with FT-IR spectroscopy and thermal gravimetric analysis (TGA). SEM analysis presented the spherical morphology of product with 13 +/- 3 nm particle size. And also, superparamagnetic property of product was deduced from VSM analysis. Uptake of CFA-functionalized SPION from the cell and release of CFA from CFA-functionalized SPION has been studied by using Prussian blue staining and spectrophotometer, respectively. Also, cell viability and cytotoxicity was tested by MTT and LDH assays. The uptake of CFA-functionalized SPION by HeLa, MCF-7, and U87 was higher than A549 and L929 cells. Also, caffeic acid release from CFA-functionalized SPION increased at an acidic environment (pH 4.4). A newly synthesized CFA-functionalized SPION in all used concentrations decreased cell viability and increased cytotoxicity at 24th and 48th hours. The results showed that the CFA-functionalized SPION is a potential anticancer agent for cancer therapy

Antagonistic effects of Satureja hortensis essential oil against AFB₁ on human lymphocytes in vitro

Satureja hortensis L. (Lamiaceae) используется как народное средство для лечения разных заболеваний, таких как спазмы, мышечные боли, тошнота, нарушения пищеварения, диарея и инфекционные заболевания. В настоящей работе на примере лимфоцитов человека in vitro изучали антагонистическое действие эфирного масла S. hortensis (SHE) на афлатоксины B₁ (AFB₁). Анализ эфирных масел проводился с помощью газовой хроматографии – масс-спектрометрии (GC-MS). Антигенотоксический эффект SHE был оценен на основании изучения обмена сестринских хроматид (SCE) и микроядерного теста против AFB₁. Кроме того, для оценки антиоксидативных эффектов SHE использовали уровень активностей малоновых диальдегидов (MDA), супероксиддисмутазы (SOD) и глютатионпероксидазы (GPx). Показано, что AFB₁ (5 µM) увеличивает частоту SCE, MN и уровень MDA. AFB₁ в той же концентрации снижает активность SOD и GPx. Однако различные концентрации SHE с AFB₁ снижали частоту SCE, MN и уровень MDA, а также существенно увеличивали активность SOD и GPx. Концентрации SHE 1.0, 1.5, 2.0 µL были наиболее эффективными. Результаты работы четко показали, что SHE имеет сильный антиоксидативный и анти-генотоксический эффект. Такая биологическая активность определяется химическим составом SHE.Satureja hortensis L. (Lamiaceae) has been used as a folk remedy to treat various such as cramps, muscle pains, nausea, indigestion, diarrhea, and infectious diseases. In this study, the antagonistic effects of essential oil of S. hortensis (SHE) were studied against aflatoxin B₁ (AFB₁) in human lymphocytes in vitro. The analysis of the essential oil was performed by using Gas chromatography-mass spectrometry (GC-MS). Anti-genotoxic effects of the SHEs was evaluated using sister chromatid exchange (SCE), micronuclei (MN) tests against AFB₁. Also level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities used to determine the anti-oxidative effects of the SHEs. This result showed AFB₁ (5 μM) increased the frequencies of SCE, MN and the level of MDA. AFB₁ at the same concentration decreased the activities of SOD and GPx. However, different concentrations of SHE with AFB₁ decreased the frequency of SCE and MN and level of MDA and also increased the activities of SOD and GPx significantly. Especially, the 1.0, 1.5, 2.0 μL dose of SHE are more effective than other doses. The results of this experiment have clearly shown that SHE has strong antioxidative and antigenotoxic effects, these biological activities of SHEs can be due to its component