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1.
Int J Mol Sci ; 23(23)2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36499572

RESUMO

Diazotrophic bacteria isolated from the rhizosphere of a wild wheat ancestor, grown from its refuge area in the Fertile Crescent, were found to be efficient Plant Growth-Promoting Rhizobacteria (PGPR), upon interaction with an elite wheat cultivar. In nitrogen-starved plants, they increased the amount of nitrogen in the seed crop (per plant) by about twofold. A bacterial growth medium was developed to investigate the effects of bacterial exudates on root development in the elite cultivar, and to analyze the exo-metabolomes and exo-proteomes. Altered root development was observed, with distinct responses depending on the strain, for instance, with respect to root hair development. A first conclusion from these results is that the ability of wheat to establish effective beneficial interactions with PGPRs does not appear to have undergone systematic deep reprogramming during domestication. Exo-metabolome analysis revealed a complex set of secondary metabolites, including nutrient ion chelators, cyclopeptides that could act as phytohormone mimetics, and quorum sensing molecules having inter-kingdom signaling properties. The exo-proteome-comprised strain-specific enzymes, and structural proteins belonging to outer-membrane vesicles, are likely to sequester metabolites in their lumen. Thus, the methodological processes we have developed to collect and analyze bacterial exudates have revealed that PGPRs constitutively exude a highly complex set of metabolites; this is likely to allow numerous mechanisms to simultaneously contribute to plant growth promotion, and thereby to also broaden the spectra of plant genotypes (species and accessions/cultivars) with which beneficial interactions can occur.


Assuntos
Microbiologia do Solo , Triticum , Triticum/metabolismo , Raízes de Plantas/metabolismo , Rizosfera , Bactérias , Desenvolvimento Vegetal , Plantas , Nitrogênio/metabolismo , Exsudatos de Plantas/metabolismo
2.
Clin Case Rep ; 9(9): e04790, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34552737

RESUMO

Malignant melanomas metastatic to the thyroid gland are uncommon. Based on microscopy and DNA methylation profile, we report a rare coexistence of neoplasms in the thyroid, presumably in our case, with relapse-free condition on adjuvant therapy.

3.
Mater Sci Eng C Mater Biol Appl ; 121: 111876, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33579499

RESUMO

Device-Associated Healthcare-Associated Infections (DA-HAI) are a major threat to public health worldwide since they are associated with increased hospital stays, morbidity, mortality, financial burden, and hospital overload. A strategy to combat DA-HAI involves the use of medical devices endowed with surfaces that can kill or repel pathogens and prevent biofilm formation. We aimed to develop low-toxic protease-resistant anti-biofilm surfaces that can sensitize drug-resistant bacteria to sub-inhibitory concentrations of antibiotics. To this end, we hypothesized that polymyxin B nonapeptide (PMBN) could retain its antibiotic-enhancing potential upon immobilization on a biocompatible polymer, such as silicone. The ability of PMBN-coated silicone to sensitize a multidrug-resistant clinical isolate of Pseudomonas aeruginosa (strain Ps4) to antibiotics and block biofilm formation was assessed by viable counting, confocal microscopy and safranin uptake. These assays demonstrated that covalently immobilized PMBN enhances not only antibiotics added exogenously but also those incorporated into the functionalized coating. As a result, the functionalized surface exerted a potent bactericidal activity that precluded biofilm formation. PMBN-coated silicone displayed a high level of stability and very low cytotoxicity and hemolytic activity in the presence of antibiotics. We demonstrated for the first time that an antibiotic enhancer can retain its activity when covalently attached to a solid surface. These findings may be applied to the development of medical devices resistant to biofilm formation.


Assuntos
Preparações Farmacêuticas , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Biofilmes , Testes de Sensibilidade Microbiana , Silicones
4.
Genomics ; 113(1 Pt 2): 892-895, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33091548

RESUMO

Recently the first genome sequences for 11 SARS-CoV-2 isolates from Lebanon became available. Here, we report the detection of variants within the genome of these strains. Pairwise alignment analysis using blastx was performed between these sequences and the UniProtKB data for the SARS-CoV-2 coronavirus to identify amino acid variations. Variants analysis was performed using multiple Bioinformatics tools. We noticed for the first time 18 mutations that have never been reported before. Among those, a frame shift (8651A>) in NSP4, a stop codon 6887A > T in NSP3 and two missense mutations in spike S2 were found. In addition, we found 28 variants in ORF1ab alone. A previously reported variant, 23403A > G, in the spike protein S2 was mostly seen. Two other known mutations 25563G > T in ORF3a and 14408C > T in ORF1ab were detected respectively in 6 and 8 out of the 11 isolates. Our results may help to prognose forthcoming infections in this region.


Assuntos
COVID-19/virologia , Variação Genética , Genoma Viral , Mutação , SARS-CoV-2/genética , COVID-19/epidemiologia , Teste de Ácido Nucleico para COVID-19 , Códon de Terminação , Evolução Molecular , Mutação da Fase de Leitura , Humanos , Líbano/epidemiologia , Mutação de Sentido Incorreto , Pandemias , SARS-CoV-2/isolamento & purificação , Alinhamento de Sequência , Glicoproteína da Espícula de Coronavírus/genética
5.
Pak J Pharm Sci ; 33(1): 199-206, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32122849

RESUMO

Scorzonera have been confirmed to have potent bioactivity. Scorzonera mackmeliana (Asteraceae), the endemic plant to Lebanon, has not yet been investigated. In the present study, we assessed the antibacterial activity of S. mackmeliana extracts against referenced bacterial strains. Extracts from different parts of the plant were evaluated against Staphylococcus, Enterococcus, Escherichia and Pseudomonas species. Phytochemical screening was done by standard biochemical tests and minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and minimal biofilm eradication concentration (MBEC) were determined by micro dilution method. The extracts possessed mainly alkaloids, phenols, flavonoids and coumarins. Gram-negative bacteria were most sensitive, whose MICs ranged between 48.98 and 341.85 mg/ml. Water stems extract, rich in phenols, was the most active with an MIC of 48.98 mg/ml. MBC was only recorded for water flowers extract, rich in resins, against P. aeruginosa and ethanolic roots extract, rich in terpenoids, against S. epidermidis with values of 160.85 mg/ml and 284.35 mg/ml, respectively. Furthermore, antibiofilm activity showed that the lowest MBEC was 0.1 mg/ml for water stems extract with an eradication ability of 91% (p <0.0001). Hence, this study suggests S. mackmeliana as a promising candidate for future investigations to elucidate the major bioactive compound behind the antibacterial and antibiofilm effect.


Assuntos
Biofilmes/efeitos dos fármacos , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Extratos Vegetais/farmacologia , Scorzonera/química , Antibacterianos/química , Antibacterianos/farmacologia , Flores/química , Extratos Vegetais/química , Folhas de Planta/química , Raízes de Plantas/química , Caules de Planta/química , Plantas/química
6.
Adv Exp Med Biol ; 1117: 257-279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30980362

RESUMO

Microbial cells show a strong natural tendency to adhere to surfaces and to colonize them by forming complex communities called biofilms. In this growth mode, biofilm-forming cells encase themselves inside a dense matrix which efficiently protects them against antimicrobial agents and effectors of the immune system. Moreover, at the physiological level, biofilms contain a very heterogeneous cell population including metabolically inactive organisms and persisters, which are highly tolerant to antibiotics. The majority of human infectious diseases are caused by biofilm-forming microorganisms which are responsible for pathologies such as cystic fibrosis, infective endocarditis, pneumonia, wound infections, dental caries, infections of indwelling devices, etc. AMPs are well suited to combat biofilms because of their potent bactericidal activity of broad spectrum (including resting cells and persisters) and their ability to first penetrate and then to disorganize these structures. In addition, AMPs frequently synergize with antimicrobial compounds and were recently reported to repress the molecular pathways leading to biofilm formation. Finally, there is a very active research to develop AMP-containing coatings that can prevent biofilm formation by killing microbial cells on contact or by locally releasing their active principle. In this chapter we will describe these strategies and discuss the perspectives of the use of AMPs as anti-biofilm agents for human therapy and prophylaxis.


Assuntos
Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Biofilmes , Humanos
7.
BMC Infect Dis ; 16: 234, 2016 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-27233894

RESUMO

BACKGROUND: We report herein a case of fecal microbiota transplantation (FMT) used for severe Clostridium difficile infection for a 65-year-old Lebanese man who underwent left ventricular assist device implantation. To the best of our knowledge this is the first case report from Lebanon and the region presenting such technique. CASE PRESENTATION: The patient experienced diarrhea and rectal bleeding and was diagnosed of pseudomembranous colitis (PMC). His condition failed to improve on maximal pharmacological therapy. Protocolectomy, an invasive operation consisting in resection of the entire colon and rectum seemed to be the last resort before the patient responded to FMT given through gastroscopy. CONCLUSION: Despite the increasing experience with FMT for C. difficile infection, published evidence in severe related cases from this region is very limited. Hence, we promote adjunctive FMT, an effective noninvasive method, to be considered as a promising early treatment option in severe C. difficile infection.


Assuntos
Clostridioides difficile , Infecções por Clostridium/terapia , Enterocolite Pseudomembranosa/terapia , Transplante de Microbiota Fecal , Coração Auxiliar/microbiologia , Implantação de Prótese/efeitos adversos , Idoso , Estudos de Casos e Controles , Clostridioides difficile/crescimento & desenvolvimento , Infecções por Clostridium/microbiologia , Diarreia/microbiologia , Diarreia/terapia , Enterocolite Pseudomembranosa/microbiologia , Fezes/microbiologia , Hemorragia Gastrointestinal/microbiologia , Hemorragia Gastrointestinal/terapia , Coração Auxiliar/efeitos adversos , Humanos , Líbano , Masculino , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/terapia
8.
Sci Rep ; 5: 8996, 2015 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-25757575

RESUMO

Defect in apoptosis has been implicated as a major cause of resistance to chemotherapy observed in B cell chronic lymphocytic leukaemia (B CLL). This study evaluated the pro-apoptotic effect of an anthocyanin-rich dietary bilberry extract (Antho 50) on B CLL cells from 30 patients and on peripheral blood mononuclear cells (PBMCs) from healthy subjects, and determined the underlying mechanism. Antho 50 induced concentration- and time-dependent pro-apoptotic effects in B CLL cells but little or no effect in PBMCs. Among the main phenolic compounds of the bilberry extract, delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside induced a pro-apoptotic effect. Antho 50-induced apoptosis is associated with activation of caspase 3, down-regulation of UHRF1, a rapid dephosphorylation of Akt and Bad, and down-regulation of Bcl-2. Antho 50 significantly induced PEG-catalase-sensitive formation of reactive oxygen species in B CLL cells. PEG-catalase prevented the Antho 50-induced induction of apoptosis and related signaling. The present findings indicate that Antho 50 exhibits strong pro-apoptotic activity through redox-sensitive caspase 3 activation-related mechanism in B CLL cells involving dysregulation of the Bad/Bcl-2 pathway. This activity of Antho 50 involves the glucoside and rutinoside derivatives of delphinidin. They further suggest that Antho 50 has chemotherapeutic potential by targeting selectively B CLL cells.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Oxirredução , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vaccinium myrtillus/química , Proteína de Morte Celular Associada a bcl/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antocianinas/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Feminino , Glucosídeos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Espécies Reativas de Oxigênio/metabolismo
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