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91.
Selective Cytotoxicity of 1,3,4-Thiadiazolium Mesoionic Derivatives on Hepatocarcinoma Cells (HepG2)
Gustavo Jabor Gozzi Amanda do Rocio Andrade Pires Glaucio Valdameri Maria Eliane Merlin Rocha Glaucia Regina Martinez Guilhermina Rodrigues Noleto Alexandra Acco Carlos Eduardo Alves de Souza Aurea Echevarria Camilla Moretto dos Reis Attilio Di Pietro Sílvia Maria Suter Correia Cadena 《PloS one》2015,10(6)
In this work, we evaluated the cytotoxicity of mesoionic 4-phenyl-5-(2-Y, 4-X or 4-X-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride derivatives (MI-J: X=OH, Y=H; MI-D: X=NO2, Y=H; MI-4F: X=F, Y=H; MI-2,4diF: X=Y=F) on human hepatocellular carcinoma (HepG2), and non-tumor cells (rat hepatocytes) for comparison. MI-J, M-4F and MI-2,4diF reduced HepG2 viability by ~ 50% at 25 μM after 24-h treatment, whereas MI-D required a 50 μM concentration, as shown by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. The cytotoxicity was confirmed with lactate dehydrogenase assay, of which activity was increased by 55, 24 and 16% for MI-J, MI-4F and MI-2,4diF respectively (at 25 μM after 24 h). To identify the death pathway related to cytotoxicity, the HepG2 cells treated by mesoionic compounds were labeled with both annexin V and PI, and analyzed by flow cytometry. All compounds increased the number of doubly-stained cells at 25 μM after 24 h: by 76% for MI-J, 25% for MI-4F and MI-2,4diF, and 11% for MI-D. It was also verified that increased DNA fragmentation occurred upon MI-J, MI-4F and MI-2,4diF treatments (by 12%, 9% and 8%, respectively, at 25 μM after 24 h). These compounds were only weakly, or not at all, transported by the main multidrug transporters, P-glycoprotein, ABCG2 and MRP1, and were able to slightly inhibit their drug-transport activity. It may be concluded that 1,3,4-thiadiazolium compounds, especially the hydroxy derivative MI-J, constitute promising candidates for future investigations on in-vivo treatment of hepatocellular carcinoma. 相似文献
92.
Flávio Teles Tarcilo Machado da Silva Francisco Pessoa da Cruz Júnior Vitor Hugo Honorato Henrique de Oliveira Costa Ana Paula Fernandes Barbosa Sabrina Gomes de Oliveira Zenaldo Porfírio Alexandre Braga Libório Raquel Lerner Borges Camilla Fanelli 《PloS one》2015,10(1)
The pathogenic role of inflammation and oxidative stress in chronic kidney disease (CKD) is well known. Anti-inflammatories and antioxidant drugs has demonstrated significant renoprotection in experimental nephropathies. Moreover, the inclusion of natural antioxidants derived from food and herbal extracts (such as polyphenols, curcumin and lycopene) as an adjuvant therapy for slowing CKD progression has been largely tested. Brazilian propolis is a honeybee product, whose anti-inflammatory, antimicrobial and antioxidant effects have been widely shown in models of sepsis, cancer, skin irritation and liver fibrosis. Furthermore, previous studies demonstrated that this compound promotes vasodilation and reduces hypertension. However, potential renoprotective effects of propolis in CKD have never been investigated. The aim of this study was to evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP), in the 5/6 renal ablation model (Nx). Adult male Wistar rats underwent Nx and were divided into untreated (Nx) and RP-treated (Nx+RP) groups, after 30 days of surgery; when rats already exhibited marked hypertension and proteinuria. Animals were observed for 90 days from the surgery day, when Nx+RP group showed significant reduction of hypertension, proteinuria, serum creatinine retention, glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared to age-matched untreated Nx rats, which worsened progressively over time. In conclusion, RP treatment attenuated hypertension and structural renal damage in Nx model. Reduction of renal inflammation and oxidative stress could be a plausible mechanism to explain this renoprotection. 相似文献
93.
Julie Hoover-Fong Nara Sobreira Julie Jurgens Peggy Modaff Carrie Blout Ann Moser Ok-Hwa Kim Tae-Joon Cho Sung?Yoon Cho Sang?Jin Kim Dong-Kyu Jin Hiroshi Kitoh Woong-Yang Park Hua Ling Kurt?N. Hetrick Kimberly?F. Doheny David Valle Richard?M. Pauli 《American journal of human genetics》2014,94(1):105-112
94.
Rodrigo Vega Camilla Fløjgaard Andrés Lira‐Noriega Yoshinori Nakazawa Jens‐Christian Svenning Jeremy B. Searle 《Ecography》2010,33(2):260-271
The southern European peninsulas (Iberian, Italian and Balkan) are traditionally recognized as glacial refugia from where many species colonized central and northern Europe after the Last Glacial Maximum (LGM). However, evidence that some species had more northerly refugia is accumulating from phylogeographic, palaeontological and palynological studies, and more recently from species distribution modelling (SDM), but further studies are needed to test the idea of northern refugia in Europe. Here, we take a rarely implemented multidisciplinary approach to assess if the pygmy shrew Sorex minutus, a widespread Eurasian mammal species, had northern refugia during the LGM, and if these influenced its postglacial geographic distribution. First, we evaluated the phylogeographic and population expansion patterns using mtDNA sequence data from 123 pygmy shrews. Then, we used SDM to predict present and past (LGM) potential distributions using two different training data sets, two different algorithms (Maxent and GARP) and climate reconstructions for the LGM with two different general circulation models. An LGM distribution in the southern peninsulas was predicted by the SDM approaches, in line with the occurrence of lineages of S. minutus in these areas. The phylogeographic analyses also indicated a widespread and strictly northern‐central European lineage, not derived from southern peninsulas, and with a postglacial population expansion signature. This was consistent with the SDM predictions of suitable LGM conditions for S. minutus occurring across central and eastern Europe, from unglaciated parts of the British Isles to much of the eastern European Plain. Hence, S. minutus likely persisted in parts of central and eastern Europe during the LGM, from where it colonized other northern areas during the late‐glacial and postglacial periods. Our results provide new insights into the glacial and postglacial colonization history of the European mammal fauna, notably supporting glacial refugia further north than traditionally recognized. 相似文献
95.
Louise Camilla Dreyer Michael Z. Hauschild Jens Schierbeck 《The International Journal of Life Cycle Assessment》2010,15(4):385-402
Background, aim and scope
A characterisation model based on multi-criteria indicators has been developed for each of four impact categories representing the labour rights according to the conventions of the International Labour Organisation (ILO) covering: forced labour, discrimination, restrictions of freedom of association and collective bargaining and child labour (Dreyer et al., Int J Life Cycle Assess, 2010a, in press). These impact categories are considered by the authors to be among the obligatory impact categories in a Social LCA. The characterisation models combine information about the way a company manages its behaviour towards some of its important stakeholders, its employees, with information about the geographical location and branch of industry of the company and the risk of violations of these workers' rights inherent in the setting of the company. The result is an indicator score which for each impact category represents the risk that violations occur in the company. In order to test the feasibility and relevance of the developed methodology, it is tested on real cases.Materials and methods
The developed characterisation models are applied to six cases representing individual manufacturing companies from three different continents. Five of the case companies are manufacturing companies while the sixth is a knowledge company. The application involves scoring the management efforts of the case company in a multi-criteria scorecard and translating the scores into an aggregated performance score, which represents the effort of the management in order to prevent violations of the workers' rights to occur in the company. The company performance score is multiplied by a contextual adjustment score which reflects the risk of violations taking place in the context (in terms of geographical location or industrial branch or sector) of the company. The resulting indicator score represents the risk that violations take place of the labour right represented by the impact category.Results
The social impact characterisation is performed for each of the six case studies using the methodology earlier developed. The procedure and outcome are documented through all the intermediary results shown for all four obligatory impact categories for each of the six case studies.Discussion
The results are judged against the risk which was observed during visits and interviews at each of the six case companies, and their realism and relevance are discussed. They are found to be satisfactory for all four impact categories for the manufacturing companies, but there are some problems for two of the impact categories in the case company which represents knowledge work, and it is discussed how these problems may be addressed through change of the underlying scorecard or the way in which the scoring is translated into a company performance score.Conclusions
It is concluded that it is feasible to perform a characterisation of the impacts related to the four obligatory impact categories representing the labour rights according to the conventions of the ILO covering: forced labour, discrimination, restrictions of freedom of association and collective bargaining and child labour. When compared with the observed situation in the companies, the results are also found to be relevant and realistic.Recommendations and perspectives
The proposed characterisation method is rather time-consuming and cannot realistically be applied to all companies in the product system. It must therefore be combined with less time-requiring screening methods which can help identify the key companies in the life cycle for which a detailed analysis is required. The possibility to apply country- or industry sector-based information is discussed, and while it is found useful to identify low-risk companies and eliminate them from more detailed studies, the ability of the screening methods to discriminate between companies located in medium and high-risk contexts is questionable. 相似文献96.
Camilla L. Nesb? Rajkumari Kumaraswamy Marlena Dlutek W. Ford Doolittle Julia Foght 《Applied and environmental microbiology》2010,76(14):4896-4900
All cultivated Thermotogales are thermophiles or hyperthermophiles. However, optimized 16S rRNA primers successfully amplified Thermotogales sequences from temperate hydrocarbon-impacted sites, mesothermic oil reservoirs, and enrichment cultures incubated at <46°C. We conclude that distinct Thermotogales lineages commonly inhabit low-temperature environments but may be underreported, likely due to “universal” 16S rRNA gene primer bias.Thermotogales, a bacterial group in which all cultivated members are anaerobic thermophiles or hyperthermophiles (5), are rarely detected in anoxic mesothermic environments, yet their presence in corresponding enrichment cultures, bioreactors, and fermentors has been observed using metagenomic methods and 16S rRNA gene amplification (6) (see Table S1 in the supplemental material). The most commonly detected lineage is informally designated here “mesotoga M1” (see Table S1 in the supplemental material). PCR experiments indicated that mesotoga M1 sequences amplified inconsistently using “universal” 16S rRNA gene primers, perhaps explaining their poor detection in DNA isolated from environmental samples (see text and Table S2 in the supplemental material). We therefore designed three 16S rRNA PCR primer sets (Table (Table1)1) targeting mesotoga M1 bacteria and their closest cultivated relative, Kosmotoga olearia. Primer set A was the most successful set, detecting a wider diversity of Thermotogales sequences than set B and being more Thermotogales-specific than primer set C (Table (Table22).
Open in a separate windowaHeterogeneity hot spots identified in reference 1.
Open in a separate windowaSee the supplemental material for site and methodological details. NA, not applicable; ND, not determined.bThe number of OTUs observed at a 0.01 distance cutoff is given for each primer set. The numbers of clones with Thermotogales sequences are in parentheses. —, PCR was attempted but no Thermotogales sequences were obtained or the PCR consistently failed.c+, sequence(s) detected; −, not detected. For more information on the enrichments, see the text and Table S3 in the supplemental material.dFrom April to May 2004, the temperature at the depth where the sample was taken was 12°C (7).eThere were no water samples from DWH and HSAT available for enrichment cultures, and no DNA was available from HWH.fThis reservoir has been treated with biocides; moreover, at this site, the water is filtered before being reinjected into the reservoir.gTemperatures of the oil pool where the water sample was obtained. The HSAT facility receives water from two oil pools, one at 41°C and one at 50°C.hWe screened DNA from samples taken in 2006 and 2008 but detected the same sequences in both, so sequences from the two samples were pooled.iThe mesotoga M1 and Kosmotoga sequences from DWH and DF were >99% similar and were assembled into one sequence in Fig. Fig.11.jThis reservoir has been injected with water from a neighboring oil reservoir.Since the putative mesophilic Thermotogales have been overwhelmingly associated with polluted and hydrocarbon-impacted environments and mesothermic oil reservoirs are the only natural environments where mesotoga M1 sequences previously were detected (see Table S1 in the supplemental material), we selected four oil reservoirs with in situ temperatures of 14°C to 53°C and two temperate, chronically hydrocarbon-impacted sites for analysis (Table (Table2).2). Total community DNA was extracted, the 16S rRNA genes were amplified, cloned, and sequenced as described in the supplemental material. 相似文献
TABLE 1.
Primers targeting mesotoga M1 bacteria constructed and used in this studyPrimer | Sequence (5′ to 3′) | Position in mesotoga 16S rRNA gene | No. of heterogeneity hot spotsa | Potential primer match in other Thermotogales lineages |
---|---|---|---|---|
Primer set A | 1 (helix 17) | |||
NMes16S.286F | CGGCCACAAGGAYACTGAGA | 286 | Perfect match in Kosmotoga olearia. The last 7 or 8 nucleotides at the 3′ end are conserved in other Thermotogales lineages. | |
NMes16S.786R | TGAACATCGTTTAGGGCCAG | 786 | One 5′ mismatch in Kosmotoga olearia and Petrotoga mobilis; 2-4 internal and 5′ mismatches in other lineages | |
Primer set B | None | |||
BaltD.42F | ATCACTGGGCGTAAAGGGAG | 540 | Perfect match in Kosmotoga olearia; one or two 3′ mismatches in most other Thermotogales lineages | |
BaltD.494R | GTGGTCGTTCCTCTTTCAAT | 992 | No match in other Thermotogaleslineages. The primer is located in heterogeneity hot spot helices 33 and 34. This primer also fails to amplify some mesotoga M1 sequences. | |
Primer set C | 9 (all 9 regions) | |||
TSSU-3F | TATGGAGGGTTTGATCCTGG | 3 | Perfect match in Thermotoga spp., Kosmotoga olearia, and Petrotoga mobilis; two or three 5′ mismatches in other Thermotogales lineages; one 5′ mismatch to mesotoga M1 16S rRNA genes | |
Mes16S.R | ACCAACTCGGGTGGCTTGAC | 1390 | One 5′ mismatch in Kosmotoga olearia; 1-3 internal or 5′ mismatches in other Thermotogales lineages |
TABLE 2.
Mesotoga clade sequences detected in environmental samples and enrichment cultures screened in this studyaSite (abbreviation) | Temp in situ(°C) | Waterflooded | Environmental samplesb | Enrichment cultures | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Primer set A | Primer set B | Primer set C | Thermotogalesdetected by primer setc: | Lineage(s) detected | ||||||||
No. of OTUs (no. of clones) | Lineage | No. of OTUs (no. of clones) | Lineage | No. of OTUs (no. of clones) | Lineage | A | B | C | ||||
Sidney Tar Ponds sediment (TAR) | Temperate | NA | 1 (5) | M1 | 1 | M1 | — | — | + | + | + | M1, M2, M5 |
Oil sands settling basin tailings (05mlsb) | ∼12d | NA | — | — | 1 (6) | M1 | — | — | − | + | − | M1 |
Grosmont A produced water (GrosA) | 20 | No | 1 (15) | M1 | 1 (22) | M1 | 2 (14) | M1 | + | + | + | M1 |
Foster Creek produced water (FC) | 14 | No | 1 (21) | M1 | 1 (23) | M1 | 1 (1) | M1 | + | ND | − | M1 |
Oil field D wellhead water (DWH)e,f | 52-53g | Yes | 1 (14) | Kosmotogai | 1 (6) | M1i | 1 (1) | Kosmotogai | NA | NA | NA | NA |
Oil field D FWKO water (DF)f,h | 20-30 | Yes | 1 (45) | Kosmotogai | 1 (17) | M1i | — | — | + | + | − | M1, Kosmotoga, Petrotoga |
Oil field H FWKO water (HF)j | 30-32 | Yes | 7 (59) | M1, M2, M3, M4, Kosmotoga | 1 (29) | M1 | — | — | + | + | − | M1, Petrotoga |
Oil field H satellite water (HSAT)e,j | 41 and 50g | Yes | 1 (8) | M1 | — | — | 2 (16) | Kosmotoga, Thermotoga | NA | NA | NA | NA |
Oil field H wellhead water (HWH)e,j | 41 and 50g | Yes | NA | — | — | NA | NA | NA | + | + | + | M1, Petrotoga |
97.
Ann-Charlotte Karlsson Stefan Alenius Camilla Björkman Ylva Persson Stina Englund 《Acta veterinaria Scandinavica》2010,52(1):1-4
Background
Reproductive disorders associated with chlamydial infection have been reported worldwide in cattle and there are indications of potential venereal transmission.Methods
Semen samples from 21 dairy bulls and cauda epididymidis tissue samples from 43 beef bulls were analysed for chlamydial agent by real-time polymerase chain reaction (PCR) including an internal amplification control (mimic). Additionally, presence of antibodies against Chlamydophila (Cp.) abortus among the bulls was investigated with the commercial Pourquier® ELISA Cp. abortus serum verification kit.Results
No chlamydial agent was detected by PCR in either the semen samples or in the tissue samples. Additionally, no antibodies against Cp. abortus were detected.Conclusions
The results suggest that Cp. abortus is very rare, or absent in Swedish bulls and thus the risk for venereal transmission of chlamydial infection through their semen is low. However, because Chlamydophila spp. infection rates seem to differ throughout the world, it is essential to clarify the relative importance of transmission of the infection through semen on cattle fertility. 相似文献98.
Camilla Luni Jason E Shoemaker Kevin R Sanft Linda R Petzold Francis J DoyleIII 《BMC systems biology》2010,4(1):161
Background
Robustness is a recognized feature of biological systems that evolved as a defence to environmental variability. Complex diseases such as diabetes, cancer, bacterial and viral infections, exploit the same mechanisms that allow for robust behaviour in healthy conditions to ensure their own continuance. Single drug therapies, while generally potent regulators of their specific protein/gene targets, often fail to counter the robustness of the disease in question. Multi-drug therapies offer a powerful means to restore disrupted biological networks, by targeting the subsystem of interest while preventing the diseased network from reconciling through available, redundant mechanisms. Modelling techniques are needed to manage the high number of combinatorial possibilities arising in multi-drug therapeutic design, and identify synergistic targets that are robust to system uncertainty. 相似文献99.
Jon Nissen-Meyer Camilla Oppegård Per Rogne Helen Sophie Haugen Per Eugen Kristiansen 《Probiotics and antimicrobial proteins》2010,2(1):52-60
This review focuses on the structure and mode-of-action of the two-peptide (class-IIb) bacteriocins that consist of two different peptides whose genes are next to each other in the same operon. Optimal antibacterial activity requires the presence of both peptides in about equal amounts. The two peptides are synthesized as preforms that contain a 15–30 residue double-glycine-type N-terminal leader sequence that is cleaved off at the C-terminal side of two glycine residues by a dedicated ABC-transporter that concomitantly transfers the bacteriocin peptides across cell membranes. Two-peptide bacteriocins render the membrane of sensitive bacteria permeable to a selected group of ions, indicating that the bacteriocins form or induce the formation of pores that display specificity with respect to the transport of molecules. Based on structure–function studies, it has been proposed that the two peptides of two-peptide bacteriocins form a membrane-penetrating helix–helix structure involving helix–helix-interacting GxxxG-motifs that are present in all characterized two-peptide bacteriocins. It has also been suggested that the membrane-penetrating helix–helix structure interacts with an integrated membrane protein, thereby triggering a conformational alteration in the protein, which in turn causes membrane-leakage. This proposed mode-of-action is similar to the mode-of-action of the pediocin-like (class-IIa) bacteriocins and lactococcin A (a class-IId bacteriocin), which bind to a membrane-embedded part of the mannose phosphotransferase permease in a manner that causes membrane-leakage and cell death. 相似文献
100.