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1.
Viruses ; 13(7)2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34372590

RESUMO

Bacteriophages vB_YpeM_fEV-1 (fEV-1) and vB_YpeM_fD1 (fD1) were isolated from incoming sewage water samples in Turku, Finland, using Yersinia pestis strains EV76 and KIM D27 as enrichment hosts, respectively. Genomic analysis and transmission electron microscopy established that fEV-1 is a novel type of dwarf myovirus, while fD1 is a T4-like myovirus. The genome sizes are 38 and 167 kb, respectively. To date, the morphology and genome sequences of some dwarf myoviruses have been described; however, a proteome characterization such as the one presented here, has currently been lacking for this group of viruses. Notably, fEV-1 is the first dwarf myovirus described for Y. pestis. The host range of fEV-1 was restricted strictly to Y. pestis strains, while that of fD1 also included other members of Enterobacterales such as Escherichia coli and Yersinia pseudotuberculosis. In this study, we present the life cycles, genomes, and proteomes of two Yersinia myoviruses, fEV-1 and fD1.


Assuntos
Bacteriófagos/genética , Bacteriófagos/fisiologia , Genoma Viral , Proteoma , Yersinia pestis/virologia , Bacteriófagos/ultraestrutura , Finlândia , Especificidade de Hospedeiro , Microscopia Eletrônica de Transmissão , Esgotos , Yersinia pestis/classificação
2.
Environ Sci Pollut Res Int ; 28(40): 56319-56332, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34050519

RESUMO

Cisplatin, an anticancer drug used in treating various types of cancers, can cause reproductive toxicities during chemotherapy. Keeping this in view, the present study was designed to investigate the possible protective effects of normal vitamin C and E and vitamin C and E nanoparticles (embedded in chitosan) against cisplatin-induced reproductive toxicities. Vitamins C, E, and their nanoparticles in this regard proved to be an effective therapy. The work aimed to treat cisplatin-induced reproductive toxicities through vitamin C and E and their nanoparticles. Cisplatin exposure caused significant reduction in the weight, testosterone level, and changed lipid profile. Similarly, cisplatin induced significant widespread testicular atrophy and testicular lesions as evidenced by the gaps in the epithelium and loss of differentiating germ cells. Vitamin C and E and their nanoparticles rescued the weight, testosterone level, and testicular disturbances, which is associated with improved histological view of testicular tissues. The current study highlights evidence that designing a medication of vitamin C and E nanoparticles is useful in mitigating cisplatin-induced reproductive toxicity in cancerous male patients underlying chemotherapy.


Assuntos
Quitosana , Nanopartículas , Androgênios , Animais , Antioxidantes , Ácido Ascórbico , Cisplatino/toxicidade , Humanos , Masculino , Ratos , Testículo , Vitamina E , Vitaminas
3.
Front Microbiol ; 11: 1356, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636826

RESUMO

We report here the complete genome sequence and characterization of Yersinia bacteriophage vB_YenP_ϕ80-18. ϕ80-18 was isolated in 1991 using a Y. enterocolitica serotype O:8 strain 8081 as a host from a sewage sample in Turku, Finland, and based on its morphological and genomic features is classified as a podovirus. The genome is 42 kb in size and has 325 bp direct terminal repeats characteristic for podoviruses. The genome contains 57 predicted genes, all encoded in the forward strand, of which 29 showed no similarity to any known genes. Phage particle proteome analysis identified altogether 24 phage particle-associated proteins (PPAPs) including those identified as structural proteins such as major capsid, scaffolding and tail component proteins. In addition, also the DNA helicase, DNA ligase, DNA polymerase, 5'-exonuclease, and the lytic glycosylase proteins were identified as PPAPs, suggesting that they might be injected together with the phage genome into the host cell to facilitate the take-over of the host metabolism. The phage-encoded RNA-polymerase and DNA-primase were not among the PPAPs. Promoter search predicted the presence of four phage and eleven host RNA polymerase -specific promoters in the genome, suggesting that early transcription of the phage is host RNA-polymerase dependent and that the phage RNA polymerase takes over later. The phage tolerates pH values between 2 and 12, and is stable at 50°C but is inactivated at 60°C. It grows slowly with a 50 min latent period and has apparently a low burst size. Electron microscopy revealed that the phage has a head diameter of about 60 nm, and a short tail of 20 nm. Whole-genome phylogenetic analysis confirmed that ϕ80-18 belongs to the Autographivirinae subfamily of the Podoviridae family, that it is 93.2% identical to Yersinia phage fHe-Yen3-01. Host range analysis showed that ϕ80-18 can infect in addition to Y. enterocolitica serotype O:8 strains also strains of serotypes O:4, O:4,32, O:20 and O:21, the latter ones representing similar to Y. enterocolitica serotype O:8, the American pathogenic biotype 1B strains. In conclusion, the phage ϕ80-18 is a promising candidate for the biocontrol of the American biotype 1B Y. enterocolitica.

4.
Front Genet ; 10: 514, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214247

RESUMO

Curcumin (a polyphenolic compound in turmeric) is famous for its potent anti-inflammatory, anti-oxidant, and anti-cancer properties, and has a great potential to act as an epigenetic modulator. The epigenetic regulatory roles of curcumin include the inhibition of DNA methyltransferases (DNMTs), regulation of histone modifications via the regulation of histone acetyltransferases (HATs) and histone deacetylases (HDACs), regulation of microRNAs (miRNA), action as a DNA binding agent and interaction with transcription factors. These mechanisms are interconnected and play a vital role in tumor progression. The recent research has demonstrated the role of epigenetic inactivation of pivotal genes that regulate human pathologies such as cancers. Epigenetics helps to understand the mechanism of chemoprevention of cancer through different therapeutic agents. In this regard, dietary phytochemicals, such as curcumin, have emerged as a potential source to reverse epigenetic modifications and efficiently regulate the expression of genes and molecular targets that are involved in the promotion of tumorigenesis. The curcumin may also act as an epigenetic regulator in neurological disorders, inflammation, and diabetes. Moreover, curcumin can induce the modifications of histones (acetylation/deacetylation), which are among the most important epigenetic changes responsible for altered expression of genes leading to modulating the risks of cancers. Curcumin is an effective medicinal agent, as it regulates several important molecular signaling pathways that modulate survival, govern anti-oxidative properties like nuclear factor E2-related factor 2 (Nrf2) and inflammation pathways, e.g., nuclear factor kappa B (NF-κB). Curcumin is a potent proteasome inhibitor that increases p-53 level and induces apoptosis through caspase activation. Moreover, the disruption of 26S proteasome activity induced by curcumin through inhibiting DYRK2 in different cancerous cells resulting in the inhibition of cell proliferation opens up a new horizon for using curcumin as a potential preventive and treatment approach in proteasome-linked cancers. This review presents a brief summary of knowledge about the mechanism of epigenetic changes induced by curcumin and the potential effects of curcumin such as anti-oxidant activity, enhancement of wound healing, modulation of angiogenesis and its interaction with inflammatory cytokines. The development of curcumin as a clinical molecule for successful chemo-prevention and alternate therapeutic approach needs further mechanistic insights.

5.
Anim Nutr ; 5(4): 340-350, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31890910

RESUMO

Heat stress induced by long periods of high ambient temperature decreases animal productivity, leading to heavy economic losses. This devastating situation for livestock production is even becoming worse under the present climate change scenario. Strategies focused to breed animals with better thermo-tolerance and climatic resilience are keenly sought these days to mitigate impacts of heat stress especially in high input livestock production systems. The 70-kDa heat shock proteins (HSP70) are a protein family known for its potential role in thermo-tolerance and widely considered as cellular thermometers. HSP70 function as molecular chaperons and have major roles in cellular thermotolerance, apoptosis, immune-modulation and heat stress. Expression of HSP70 is controlled by various factors such as, intracellular pH, cyclic adenosine monophosphate (cyclic AMP), protein kinase C and intracellular free calcium, etc. Over expression of HSP70 has been observed under oxidative stress leading to scavenging of mitochondrial reactive oxygen species and protection of pulmonary endothelial barrier against bacterial toxins. Polymorphisms in flanking and promoter regions in HSP70 gene have shown association with heat tolerance, weaning weight, milk production, fertility and disease susceptibility in livestock. This review provides insight into pivotal roles of HSP70 which make it an ideal candidate genetic marker for selection of animals with better climate resilience, immune response and superior performance.

6.
Appl Environ Microbiol ; 82(17): 5340-53, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27342557

RESUMO

UNLABELLED: Bacteriophages present huge potential both as a resource for developing novel tools for bacterial diagnostics and for use in phage therapy. This potential is also valid for bacteriophages specific for Yersinia enterocolitica To increase our knowledge of Y. enterocolitica-specific phages, we characterized two novel yersiniophages. The genomes of the bacteriophages vB_YenM_TG1 (TG1) and vB_YenM_ϕR1-RT (ϕR1-RT), isolated from pig manure in Canada and from sewage in Finland, consist of linear double-stranded DNA of 162,101 and 168,809 bp, respectively. Their genomes comprise 262 putative coding sequences and 4 tRNA genes and share 91% overall nucleotide identity. Based on phylogenetic analyses of their whole-genome sequences and large terminase subunit protein sequences, a genus named Tg1virus within the family Myoviridae is proposed, with TG1 and ϕR1-RT (R1RT in the ICTV database) as member species. These bacteriophages exhibit a host range restricted to Y. enterocolitica and display lytic activity against the epidemiologically significant serotypes O:3, O:5,27, and O:9 at and below 25°C. Adsorption analyses of lipopolysaccharide (LPS) and OmpF mutants demonstrate that these phages use both the LPS inner core heptosyl residues and the outer membrane protein OmpF as phage receptors. Based on RNA sequencing and quantitative proteomics, we also demonstrate that temperature-dependent infection is due to strong repression of OmpF at 37°C. In addition, ϕR1-RT was shown to be able to enter into a pseudolysogenic state. Together, this work provides further insight into phage-host cell interactions by highlighting the importance of understanding underlying factors which may affect the abundance of phage host receptors on the cell surface. IMPORTANCE: Only a small number of bacteriophages infecting Y. enterocolitica, the predominant causative agent of yersiniosis, have been previously described. Here, two newly isolated Y. enterocolitica phages were studied in detail, with the aim of elucidating the host cell receptors required for infection. Our research further expands the repertoire of phages available for consideration as potential antimicrobial agents or as diagnostic tools for this important bacterial pathogen.


Assuntos
Proteínas de Bactérias/metabolismo , Bacteriófagos/fisiologia , Especificidade de Hospedeiro , Porinas/metabolismo , Receptores Virais/metabolismo , Yersinia enterocolitica/virologia , Proteínas de Bactérias/genética , Bacteriófagos/classificação , Bacteriófagos/genética , Bacteriófagos/isolamento & purificação , Genoma Viral , Humanos , Filogenia , Porinas/genética , Receptores Virais/genética , Temperatura , Replicação Viral , Yersiniose/microbiologia , Yersinia enterocolitica/genética , Yersinia enterocolitica/metabolismo
7.
Pak J Pharm Sci ; 28(4 Suppl): 1523-32, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26431664

RESUMO

IL-28Rα and IL10Rß collectively construct a fully functional hetero-dimeric receptor for type III interferons (IFNs). IL-28Rα is the private chain for type III IFNs since their involvement in any other pathway has not been reported yet and they are highly expressed in response to certain viral attack or cancers. IL-28Rα is specific in their expression pattern and it expresses within few cell types only. The regulatory mechanisms governing the expression of IL-28Rα at the molecular level are not completely known yet and need to be scrutinized at primary levels. In the present study, various in-silico techniques were applied and it was observed that AP1-2, STAT 1-6, P-53, LyF-1 (lymphoid transcription factor), c-Jun, PU.1, CREB (cAMP response element-binding), PLAG (pleotropic adenoma gene), MYOD (myoblast determination protein 1), NOFL and KLFS as transcription factors that are selected with preference. Interestingly AP-2, c-Jun, LyF-1, STAT, NF-Y and P53 have also been reported in literature recently as some of the key regulatory elements as well. Based on the fact that interlinking between different interferon stimulation genes (ISGs) is also not very clear and induction of one type of interferon can affect the efficacy of the other, we found that IFN-λ4 induction can increase the expression of IL-28Rα, similar to IFN-λ3 but contrary to type I IFNs, which has either no effect on the expression of IL-28Rα or can down regulate its expression at higher concentrations (data not published).


Assuntos
Regulação da Expressão Gênica , Polimorfismo de Nucleotídeo Único , Receptores de Citocinas/genética , Sítios de Ligação , Simulação por Computador , Humanos
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