IL-2-mTORC1 signaling coordinates the STAT1/T-bet axis to ensure Th1 cell differentiation and anti-bacterial immune response in fish.

Utilization of specialized Th1 cells to resist intracellular pathogenic infection represents an important innovation of adaptive immunity. Although transcriptional evidence indicates the potential presence of Th1-like cells in some fish species, the existence of CD3+CD4+IFN-γ+ T cells, their detailed functions, and the mechanism determining their differentiation in these early vertebrates remain unclear. In the present study, we identified a population of CD3+CD4-1+IFN-γ+ (Th1) cells in Nile tilapia upon T-cell activation in vitro or Edwardsiella piscicida infection in vivo. By depleting CD4-1+ T cells or blocking IFN-γ, Th1 cells and their produced IFN-γ were found to be essential for tilapia to activate macrophages and resist the E. piscicida infection. Mechanistically, activated T cells of tilapia produce IL-2, which enhances the STAT5 and mTORC1 signaling that in turn trigger the STAT1/T-bet axis-controlled IFN-γ transcription and Th1 cell development. Additionally, mTORC1 regulates the differentiation of these cells by promoting the proliferation of CD3+CD4-1+ T cells. Moreover, IFN-γ binds to its receptors IFNγR1 and IFNγR2 and further initiates a STAT1/T-bet axis-mediated positive feedback loop to stabilize the Th1 cell polarization in tilapia. These findings demonstrate that, prior to the emergence of tetrapods, the bony fish Nile tilapia had already evolved Th1 cells to fight intracellular bacterial infection, and support the notion that IL-2-mTORC1 signaling coordinates the STAT1/T-bet axis to determine Th1 cell fate, which is an ancient mechanism that has been programmed early during vertebrate evolution. Our study is expected to provide novel perspectives into the evolution of adaptive immunity.

Antigenotoxic potential of the fermentation broth produced by Paenibacillus polymyxa RNC-D in vitro.

Aim: Evaluate the chemopreventive potential of the extract from P. polymyxa RNC-D. Methods: Concentrations of P. polymyxa RNC-D extract were tested in HepG2/C3A cells to assess their genotoxic (comet assay), mutagenic (micronucleus test) and antigenotoxic potential (comet assay) in vitro. Results: 400 and 40 µg/ml concentrations induced DNA lesions, whereas the 4 µg/ml induced a desmutagenic effect. Complementary tests indicated that the extract minimized the formation of reactive oxygen species induced by methyl methanesulfonate and normalized the loss of membrane potential. The quantification of cytokines indicated that TNF-α was immunostimulated by the extract. However, when administered in conjunction with the methyl methanesulfonate, the extract blocked the TNF-α release. Conclusion: The fermentation broth from P. polymyxa RNC-D showed an antigenotoxic effect, and thus the potential to be used as chemopreventive compound.

An endophytic Penicillium oxalicum isolated from Citrus limon possesses antioxidant and genoprotective potential.

AIMS: This study aimed at isolating endophytic fungi from Citrus limon (L.) possessing antioxidative and genoprotective potential. METHODS AND RESULTS: Endophytic fungi were screened for antioxidant activity using 2,2-diphenyl,1-picryl hydrazyl radical scavenging assay and maximum activity (79·70%) was exhibited by culture MP1 identified to be Penicillium oxalicum on the basis of morphological and molecular characteristics. The ethyl acetate extract of MP1 was subjected to silica column chromatography followed by LH 20 column chromatography for purification of active metabolites. The partially purified active fraction of P. oxalicum MP1 possessed good antioxidant activity as detected using various assays. It also exhibited a strong DNA damage protection potential on pUC19 plasmid DNA treated with Fenton reagent. On exposure to active fraction of MP1 significant reduction (P < 0·05) in nuclear deformities (like nuclear buds, micronuclei, nuclear ridges and binucleated cells) was observed in human lymphocytes pretreated with a toxic concentration of H2 O2 . In vivo genoprotectivity studies were conducted in fresh water fish Channa punctatus pretreated with a damaging compound 4-nonyl phenol. The active fraction of P. oxalicum MP1 caused a reduction of 94·7 and 66·60% in micronuclei and aberrant cell formation, respectively. A significant reduction (P < 0·05) in tail length and tail DNA parameters was also observed in comet assay. CONCLUSION: The endophytic P. oxalicum isolated in this study has the potential to produce metabolites possessing antioxidant and genoprotective activities. SIGNIFICANCE AND IMPACT OF THE STUDY: The isolated culture can be exploited in the field of therapeutics by virtue of its in vitro and in vivo genoprotective potential.

The Existence of MTH1-independent 8-oxodGTPase Activity in Cancer Cells as a Compensatory Mechanism against On-target Effects of MTH1 Inhibitors.

Investigations into the human 8-oxodGTPase, MutT Homolog 1 (MTH1), have risen sharply since the first-in-class MTH1 inhibitors were reported to be highly tumoricidal. However, MTH1 as a cancer therapeutic target is currently controversial because subsequently developed inhibitors did not exhibit similar cytotoxic effects. Here, we provide the first direct evidence for MTH1-independent 8-oxodGTPase function in human cancer cells and human tumors, using a novel ATP-releasing guanine-oxidized (ARGO) chemical probe. Our studies show that this functionally redundant 8-oxodGTPase activity is not decreased by five different published MTH1-targeting small molecules or by MTH1 depletion. Significantly, while only the two first-in-class inhibitors, TH588 and TH287, reduced cancer cell viability, all five inhibitors evaluated in our studies decreased 8-oxodGTPase activity to a similar extent. Thus, the reported efficacy of the first-in-class MTH1 inhibitors does not arise from their inhibition of MTH1-specific 8-oxodGTPase activity. Comparison of DNA strand breaks, genomic 8-oxoguanine incorporation, or alterations in cellular oxidative state by TH287 versus the noncytotoxic inhibitor, IACS-4759, contradict that the cytotoxicity of the former results solely from increased levels of oxidatively damaged genomic DNA. Thus, our findings indicate that mechanisms unrelated to oxidative stress or DNA damage likely underlie the reported efficacy of the first-in-class inhibitors. Our study suggests that MTH1 functional redundancy, existing to different extents in all cancer lines and human tumors evaluated in our study, is a thus far undefined factor which is likely to be critical in understanding the importance of MTH1 and its clinical targeting in cancer.

Anti-genotoxic and anti-mutagenic activity of Escherichia coli Nissle 1917 as assessed by in vitro tests.

Anti-genotoxic or anti-mutagenic activity has been described for a number of Gram-positive probiotic bacterial species. Here we present evidence that Gram-negative Escherichia coli Nissle 1917 (EcN) also displays anti-genotoxic/anti-mutagenic activity, as assessed in vitro by the Comet Assay and the Ames Test, respectively. This activity was demonstrated by use of the mutagens 4-nitroquinoline-1-oxide (NQO), hydrogen peroxide (H2O2) and benzo(a) pyrene (B[a]P). For both assays and all three test agents the anti-genotoxic/anti-mutagenic activity of EcN was shown to be concentration dependent. By the use of extracts of bacteria that were inactivated by various procedures (heat treatment, ultrasound sonication or ultraviolet light irradiation), mechanistic explanations could be put forward. The proposed mechanisms were enforced by treating the bacterial material with proteinase K prior to testing. The mutagen H2O2 is most likely inactivated by enzymic activity, with catalase a likely candidate, while several explanations can be put forward for inactivation of B[a]P. NQO is most likely inactivated by metabolising enzymes, since the formation of the metabolite 4-aminoquinoline could be demonstrated. In conclusion, the in vitro results presented here make a strong case for antimutagenic properties of EcN.

Phenolic compounds, antioxidant capacity and antimutagenic activity in different growth stages of in vitro raised plants of Origanum vulgare L.

Efficient micropropagation procedure was developed for Origanum vulgare, a high-value culinary herb, and the phytochemicals, phenolic content, antioxidant and antimutagenic activity of leaf and stem, derived from different growing stages were analyzed. The agar solidified Murashige and Skoog (MS) medium supplemented with a combination of 6-benzylaminopurine and α-naphthaleneacetic acid was optimized as best shoot-multiplication-medium. Shoots were rooted best on 1/2 strength MS medium supplemented with 50 µM indole-3-butyric acid (IBA). The plantlets were successfully acclimatized ex vitro in a soil, sand and farmyard manure mixture (2:1:1 v/v/v) with 100% survival rate in greenhouse. The total anthocyanin and total phenolic content were observed significantly higher in leaves of in vitro-raised plants. However, total tannin, flavonoid and antioxidant activity remained higher in leaves of mother plant maintained under ployhouse condition. All the plant extracts have shown significant antimutagenic activity except in vitro-growing plants. A total of 13 polyphenolic compounds were detected in different extracts using high performance liquid chromatography. Among these, catechin was detected maximum in in vitro-growing cultures and chlorogenic acid in leaves of mother plant. These findings will help the farmers, medicinal plant growers, and industries for mass multiplication and effective extraction of phytochemicals from O. vulgare.

SOS Response Inhibitory Properties by Potential Probiotic Formulations of Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933 Obtained by Solid-State Fermentation.

The ability of fermentates of two potential probiotic strains, Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933, to lower the SOS response in bacteria was evaluated using Escherichia coli-based Lux biosensors (pRecA-lux) and the tested bacilli fermentates obtained through solid-state fermentation. The SOS response was stimulated by the addition of ciprofloxacine. Preparations of both Bacillus fermentates demonstrated SOS-inhibitory activity (up to 54.21%). The strain КATMIRA1933 was characterized by higher SOS-inhibitory activity. The active components of the fermentates were stable against heating, proteinase, and RNase action.

The degradation, antioxidant and antimutagenic activity of the mucilage polysaccharide from Dioscorea opposita.

The mucilage polysaccharide was extracted from Dioscorea opposita in cold water and then degraded in two reagents hydrogen peroxide and ascorbic acid. Three low-molecular-weight-samples were prepared, and their antioxidant and antimutagenic activity were investigated. Chemical composition analysis indicated that the degradation action was in a concentration dependent manner. Total sugars content of three degraded samples were significantly higher than raw sample. The uronic acid content in the degraded sample LP3 was significantly higher than other samples. LP3 processed the higher scavenging effect on hydroxyl and superoxide radicals than other two degraded samples because of its lower molecular weight and more uronic acid. LP3 processed the excellent antimutagenic activity and higher anti-lipid peroxidation in garlic roots. There maybe a certain relationship between the two activities. The present results indicated this mucilage could be a potential candidate of the natural antimutagen.

Photoprotective and Antimutagenic Activity of Agaricus subrufescens Basidiocarp Extracts.

The photoprotective and antimutagenic activity of opened and closed basidiocarps of Agaricus subrufescens (=A. blazei; =A. brasiliensis) obtained by different extraction methods were evaluated on Aspergillus nidulans conidia submitted to ultraviolet (UV) light. The aqueous extracts were obtained by three extraction methods: maceration, infusion, and decoction, at two different extraction times. The extracts of A. subrufescens did not present toxicity for A. nidulans conidia. A suspension of A. nidulans conidia was submitted to extracts before and after the exposure to UV light. All basidiocarp extracts, regardless of the extraction method or development stage, protected A. nidulans conidia against the damaging effects of the mutagenic agent. The antimutagenic and photoprotective activity was strengthened with extracts obtained by 168-h maceration, followed by 24-h maceration and 60-min infusion and, at last, by 30-min infusion. Although the extracts presented protector effect as well as recoverer effect to the action of UV light, the preventive effect was more evident. Differences in the biological activity in function of the different development stages were detected with greater antimutagenic and photoprotective activity for the opened basidiocarps. However, the extraction method is the most important factor to be considered when compared to the basidiocarp development stage to obtain better antimutagenic and photoprotective activity of A. subrufescens basidiocarps.

Comparison of in vivo and in vitro digestion on polyphenol composition in lingonberries: potential impact on colonic health.

The composition of polyphenols in ileal fluid samples obtained from an ileostomy subject after lingonberry intake was compared with lingonberry extracts obtained after simulated in vitro digestion (IVDL) and subsequent faecal fermentation (IVFL). HPLC-PDA-MS/MS analysis confirmed similar patterns of lingonberry (poly)phenolic metabolism after the in vivo and in vitro digestion, with reduced recovery of anthocyanins and a similar pattern of recovery for proanthocyanidins observed for both methods of digestion. On the other hand, the IVFL sample contained none of the original (poly)phenolic components but was enriched in simple aromatic components. Digested and fermented extracts exhibited significant (P < 0.05) anti-genotoxic (Comet assay), anti-mutagenic (Mutation Frequency assay), and anti-invasive (Matrigel Invasion assay) effects in human cell culture models of colorectal cancer at physiologically-relevant doses (0-50 µg/mL gallic acid equivalents). The ileal fluid induced significant anti-genotoxic activity (P < 0.05), but at a higher concentration (200 µg/mL gallic acid equivalents) than the IVDL. Despite extensive structural modification following digestion and fermentation, lingonberry extracts retained their bioactivity in vitro. This reinforces the need for studies to consider the impact of digestion when investigating bioactivity of dietary phytochemicals.

Naturally occurring homoisoflavonoids and their pharmacological activities.

Homoisoflavonoids, a special subclass of flavonoids, are rarely found in nature, mainly existing in Fabaceae and Asparagaceae families and being less common in Polygonaceae, Portulacaceae, Orchidaceae, and Gentianaceae families. Until now, approximately 240 natural occurring homoisoflavonoids have been identified from roots, barks, heartwood, bulbs, leaves, and seeds of the plants from the above mentioned families, which have often been used in traditional medicine. Homoisoflavonoids have been reported with a broad range of bioactivities, including anti-microbial, anti-mutagenic, anti-oxidant, immunomodulatory, anti-diabetic, cytotoxic, anti-angiogenic, vasorelaxant, and anti-inflammatory effects. To organize this review, the homoisoflavonoids were classified into five groups based on their structures: sappanin-type (I), scillascillin-type (II), brazilin-type (III), caesalpin-type (IV), and protosappanin-type (V). The structures of natural occurring homoisoflavonoids are described, and their proposed biosynthetic pathway and recent pharmacological studies are discussed. The main purpose of this review is to provide a comprehensive and up-to-date state of knowledge from phytochemical and pharmacological studies performed on homoisoflavonoids during the past decades. Homoisoflavonoids might have a large potential for further investigations of their bioactivities in order to identify important leads.

DNA-binding studies of AV-153, an antimutagenic and DNA repair-stimulating derivative of 1,4-dihydropiridine.

UNLABELLED: The ability to intercalate between DNA strands determines the cytotoxic activity of numerous anticancer drugs. Strikingly, intercalating activity was also reported for some compounds considered to be antimutagenic. The aim of this study was to determine the mode of interaction of DNA with the antimutagenic and DNA repair-stimulating dihydropyridine (DHP) AV-153. DNA and AV-153 interactions were studied by means of UV/VIS spectroscopy, fluorimetry and infrared spectroscopy. Compound AV-153 is a 1,4 dihydropyridine with ethoxycarbonyl groups in positions 3 and 5. Computer modeling of AV-153 and DNA interactions suggested an ability of the compound to dock between DNA strands at a single strand break site in the vicinity of two pyrimidines, which was confirmed in the present study. AV-153 evidently interacted with DNA, as addition of DNA to AV-153 solutions resulted in pronounced hyperchromic and bathochromic effects on the spectra. Base modification in a plasmid by peroxynitrite only minimally changed binding affinity of the compound; however, induction of single-strand breaks using Fenton's reaction greatly increased binding affinity. The affinity did not change when the ionic strength of the solution was changed from 5 to 150 mM NaCl, although it increased somewhat at 300 mM. Neither was it influenced by temperature changes from 25 to 40°C, however, it decreased when the pH of the solution was changed from 7.4 to 4.7. AV-153 competed with EBr for intercalation sites in DNA: 116 mM of the compound caused a two-fold decrease in fluorescence intensity. FT-IR spectral data analyses indicated formation of complexes between DNA and AV-153. The second derivative spectra analyses indicated interaction of AV-153 with guanine, cytosine and thymine bases, but no interaction with adenine was detected. CONCLUSIONS: The antimutagenic substance AV-153 appears to intercalate between the DNA strands at the site of a DNA nick in the vicinity of two pyrimidines.

In vitro and in vivo models of colorectal cancer: antigenotoxic activity of berries.

The etiology of colorectal cancer (CRC), a common cause of cancer-related mortality globally, has strong associations with diet. There is considerable epidemiological evidence that fruits and vegetables are associated with reduced risk of CRC. This paper reviews the extensive evidence, both from in vitro studies and animal models, that components of berry fruits can modulate biomarkers of DNA damage and that these effects may be potentially chemoprotective, given the likely role that oxidative damage plays in mutation rate and cancer risk. Human intervention trials with berries are generally consistent in indicating a capacity to significantly decrease oxidative damage to DNA, but represent limited evidence for anticarcinogenicity, relying as they do on surrogate risk markers. To understand the effects of berry consumption on colorectal cancer risk, future studies will need to be well controlled, with defined berry extracts, using suitable and clinically relevant end points and considering the importance of the gut microbiota.

The position of imidazopyridine and metabolic activation are pivotal factors in the antimutagenic activity of novel imidazo[1,2-a]pyridine derivatives.

The antimutagenic activity of eight novel imidazo[1,2-a]pyridine derivatives (I-VIII) against sodium azide (NaN3) and benzo[a]pyrene (B[a]P) was evaluated using the Salmonella reverse mutation assay. At non-toxic concentrations (12.5-50 µM), imidazopyridines I, II, III, and V with a terminal imidazopyridine group were mutagenic, while derivatives VII and VIII with a central imidazopyridine group were not mutagenic. Compounds IV, VII, and VIII exerted a moderate antimutagenic activity against NaN3 under pre-exposure conditions, and a strong activity (>40%) against B[a]P in the presence of S9 under both pre- and co-exposure conditions and mostly independent on the dose. Imidazopyridines possibly inhibited the microsomal-dependent activation of B[a]P. The demethylated derivative VII was the most active antimutagen. All imidazopyridines had a low to moderate antioxidant activity. The antibacterial activity of imidazopyridines was sporadic and moderate probably due to the failure of bacteria to convert imidazopyridines into active metabolites. The position of imidazopyridine was a pivotal factor in the mutagenic/antimutagenic activity. The strong antimutagenic compounds were dicationic planar compounds with a centered imidazo[1,2-a]pyridine spacer. With LD50 of 60 mg/kg in mice for both derivatives VII and VIII, it is safe to investigate the anticancer activity of these derivatives in animal models.

In vitro evaluation of the protective effects of 4-thujanol against mitomycin-C and cyclophosphamide-induced genotoxic damage in human peripheral lymphocytes.

4-Thujanol (sabinene hydrate), a bicyclic monoterpene alcohol, is found in the essential oils of many aromatic and medicinal plants and is widely used as a fragrance and flavouring agent in many different products. The aim of this study was to evaluate the protective effects of 4-thujanol against the genotoxic effects induced by mitomycin C (MMC) and cyclophosphamide (CP) in human lymphocytes, using the chromosome aberrations, sister chromatid exchanges, and micronucleus tests, in the absence and in the presence of S9 mix, respectively. The cells were treated with 0.25 µg/mL MMC and 28 µg/mL CP as alone and cotreated with 13 + 0.25, 26 + 0.25, and 52 + 0.25 µg/mL 4-thujanol + MMC and with 13 + 28, 26 + 28, and 52 + 28 µg/mL 4-thujanol + CP as a mixture. The present study showed that 4-thujanol was unable to reduce the genetic damage induced by MMC, in the absence of S9 mix. On the other hand, probably the metabolites of 4-thujanol act as an antagonist and markedly antagonize CP-induced genotoxicity, in the presence of S9 mix. In general, 4-thujanol + MMC and 4-thujanol + CP decreased the mitotic index, proliferation index and nuclear division index to the same extent or more than those of individual exposure of MMC or CP. In conclusion, 4-thujanol significantly reduced (p < 0.001) the genotoxic damage induced by CP but not MMC when compared with the respective positive control alone. We can suggest that 4-thujanol may improve the chemopreventive effects and may also reduce the harmful side effects of CP, which is widely used in chemotherapy against cancer, without reducing its antiproliferative activities.

Antioxidant capacity and antimutagenic activity of anthocyanin and carotenoid extracts from nixtamalized pigmented Creole maize races (Zea mays L.).

Nixtamalization process is the first step to obtain maize based products, like tortillas; however, in both the traditional and commercial processes, white grain is generally preferred. Creole maize races, mainly pigmented varieties, have increasingly attention since these are rich in anthocyanins and carotenoids. The aim of this investigation was to evaluate the antioxidant and antimutagenic activity of rich anthocyanins and carotenoids extracts from creole maize races before (grain) and after (masa and tortilla) the nixtamalization process. Most anthocyanins and carotenoids were lost during nixtamalization. Before nixtamalization, blue and red genotypes contained either higher antioxidant capacity and anthocyanin contents (963 ± 10.0 and 212.36 ± 0.36 mg of cyanidin-3-glucoside eq/100 g, respectively) than the white and yellow genotypes. However, the highest carotenoid levels were displayed by red grains (1.01 ± 0.07 to 1.14 ± 0.08 µg of ß-carotene eq/g extract). Anthocyanins losses were observed when the blue grains were processed into masa (83 %) and tortillas (64 %). Anthocyanins content correlated with antiradical activity (r = 0.57) and with 2-aminoanthracene -induced mutagenicity inhibition on TA98 and TA100 (r = -0.62 and r = -0.44, respectively). For white grains, nixtamalization also reduced carotenoids (53 to 56 %), but not antioxidant activity and 2-Aa-induced mutagenicity. Throughout the nixtamalization process steps, all the extracts showed antimutagenic activity against 2-aminoanthracene-induced mutagenicity (23 to 90 %), displaying higher potential to inhibit base changes mutations than frameshift mutations in the genome of the tasted microorganism (TA100 and TA98, respectively). The results suggest that even though there were pigment losses, creole maize pigments show antioxidant and antimutagenic activities after nixtamalization process.

In vitro fermented nuts exhibit chemopreventive effects in HT29 colon cancer cells.

It is proven that nuts contain essential macro- and micronutrients, e.g. fatty acids, vitamins and dietary fibre (DF). Fermentation of DF by the gut microflora results in the formation of SCFA which are recognised for their chemopreventive potential, especially by influencing cell growth. However, little is known about cellular response to complex fermentation samples of nuts. Therefore, we prepared and analysed (pH, SCFA, bile acids, tocopherol, antioxidant capacity) fermentation supernatant (fs) fractions of nuts (almonds, macadamias, hazelnuts, pistachios, walnuts) after in vitro fermentation and determined their effects on growth of HT29 cells as well as their genotoxic/anti-genotoxic potential. The fermented nut samples contained 2- to 3-fold higher amounts of SCFA than the faeces control, but considerable reduced levels of bile acids. While most of the investigated native nuts comprised relatively high amounts of tocopherol (α-tocopherol in almonds and hazelnuts and γ- and δ-tocopherol in pistachios and walnuts), rather low concentrations were found in the fs. All nut extracts and nut fs showed a strong antioxidant potential. Furthermore, all fs, except the fs pistachio, reduced growth of HT29 cells significantly. DNA damage induced by H2O2 was significantly reduced by the fs of walnuts after 15 min co-incubation of HT29 cells. In conclusion, this is the first study which presents the chemopreventive effects (reduction of tumour-promoting desoxycholic acid, rise in chemopreventive SCFA, protection against oxidative stress) of different nuts after in vitro digestion and fermentation, and shows the potential importance of nuts in the prevention of colon cancer.

Antimutagenic and free radical scavenger effects of leaf extracts from Accacia salicina.

BACKGROUND: Three extracts were prepared from the leaves of Accacia salicina; ethyl acetate (EA), chloroform (Chl) and petroleum ether (PE) extracts and was designed to examine antimutagenic, antioxidant potenty and oxidative DNA damage protecting activity. METHODS: Antioxidant activity of A. salicina extracts was determined by the ability of each extract to protect against plasmid DNA strand scission induced by hydroxyl radicals. An assay for the ability of these extracts to prevent mutations induced by various oxidants in Salmonella typhimurium TA102 and TA 104 strains was conducted. In addition, nonenzymatic methods were employed to evaluate anti-oxidative effects of tested extracts. RESULTS: These extracts from leaf parts of A. salicina showed no mutagenicity either with or without the metabolic enzyme preparation (S9). The highest protections against methylmethanesulfonate induced mutagenicity were observed with all extracts and especially chloroform extract. This extract exhibited the highest inhibitiory level of the Ames response induced by the indirect mutagen 2- aminoanthracene. All extracts exhibited the highest ability to protect plasmid DNA against hydroxyl radicals induced DNA damages. The ethyl acetate (EA) and chloroform (Chl) extracts showed with high TEAC values radical of 0.95 and 0.81 mM respectively, against the ABTS(.+). CONCLUSION: The present study revealed the antimutagenic and antioxidant potenty of plant extract from Accacia salicina leaves.

Spectroscopic studies on interaction and sonodynamic damage of metallochlorophyllin (Chl-M (M=Fe, Zn and Cu)) to protein under ultrasonic irradiation.

In this paper, the chlorophyll derivatives, metallochlorophyllin (Chl-M) (M=Fe, Zn and Cu) including chlorophyllin iron (Chl-Fe), chlorophyllin zinc (Chl-Zn) and chlorophyllin copper (Chl-Cu), were adopted as sonosensitizers to combine with ultrasonic irradiation, and the sonodynamic damage of bovine serum albumin (BSA) was investigated. At first, the interaction of Chl-M with BSA was studied by fluorescence spectroscopy. The results show that the quenching mechanism belongs to a static process and among them the affinity of Chl-Fe to BSA is the most obvious. Then, some influence factors on the sonodynamic damage of BSA molecules in the presence of Chl-M under ultrasonic irradiation were also studied. Synchronous fluorescence spectra show that the binding and damage sites of Chl-M to BSA molecule are mainly on the tryptophan (Trp) residues. The generation of ROS in Chl-M sonodynamic process is estimated by the method of Oxidation-Extraction Spectrometry (OEP). This paper may offer some valuable references for the study of the sonodynamic activity of Chl-M and the effect of the central metals. Synchronously, it contributes to the application of Chl-M in SDT for tumor treatment.

Kick-starting the ratchet: the fate of mutators in an asexual population.

Muller's ratchet operates in asexual populations without intergenomic recombination. In this case, deleterious mutations will accumulate and population fitness will decline over time, possibly endangering the survival of the species. Mutator mutations, i.e., mutations that lead to an increased mutation rate, will play a special role for the behavior of the ratchet. First, they are part of the ratchet and can come to dominance through accumulation in the ratchet. Second, the fitness-loss rate of the ratchet is very sensitive to changes in the mutation rate and even a modest increase can easily set the ratchet in motion. In this article we simulate the interplay between fitness loss from Muller's ratchet and the evolution of the mutation rate from the fixation of mutator mutations. As long as the mutation rate is increased in sufficiently small steps, an accelerating ratchet and eventual extinction are inevitable. If this can be countered by antimutators, i.e., mutations that reduce the mutation rate, an equilibrium can be established for the mutation rate at some level that may allow survival. However, the presence of the ratchet amplifies fluctuations in the mutation rate and, even at equilibrium, these fluctuations can lead to dangerous bursts in the ratchet. We investigate the timescales of these processes and discuss the results with reference to the genome degradation of the aphid endosymbiont Buchnera aphidicola.