Search results for "ibi"
showing 10 items of 13473 documents
Phage Therapy in Gastrointestinal Diseases
2020
Gastrointestinal tract microbiota plays a key role in the regulation of the pathogenesis of several gastrointestinal diseases. In particular, the viral fraction, composed essentially of bacteriophages, influences homeostasis by exerting a selective pressure on the bacterial communities living in the tract. Gastrointestinal inflammatory diseases are mainly induced by bacteria, and have risen due to the emergence of antibiotic resistant strains. In the lack of effective treatments, phage therapy has been proposed as a clinical alternative to restore intestinal eubiosis, thanks to its immunomodulatory and bactericidal effect against bacterial pathogens, such as Clostridioides difficile in ulce…
Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances
2016
The human microbiome is overly exposed to antibiotics, due, not only to their medical use, but also to their utilization in farm animals and crops. Microbiome composition can be rapidly altered by exposure to antibiotics, with potential immediate effects on health, for instance through the selection of resistant opportunistic pathogens that can cause acute disease. Microbiome alterations induced by antibiotics can also indirectly affect health in the long-term. The mutualistic microbes in the human body interact with many physiological processes, and participate in the regulation of immune and metabolic homeostasis. Therefore, antibiotic exposure can alter many basic physiological equilibri…
Rhodococcus aetherivorans BCP1 as cell factory for the production of intracellular tellurium nanorods under aerobic conditions
2016
Tellurite (TeO3 2−) is recognized as a toxic oxyanion to living organisms. However, mainly anaerobic or facultative-anaerobic microorganisms are able to tolerate and convert TeO3 2− into the less toxic and available form of elemental Tellurium (Te0), producing Te-deposits or Te-nanostructures. The use of TeO3 2−-reducing bacteria can lead to the decontamination of polluted environments and the development of “green-synthesis” methods for the production of nanomaterials. In this study, the tolerance and the consumption of TeO3 2− have been investigated, along with the production and characterization of Te-nanorods by Rhodococcus aetherivorans BCP1 grown under aerobic conditions. Aerobically …
Bacteriophage-Based Bacterial Wilt Biocontrol for an Environmentally Sustainable Agriculture
2017
Bacterial wilt diseases caused by Ralstonia solanacearum, R. pseudosolanacearum and R. syzygii subsp. indonesiensis (former R. solanacearum species complex) are among the most important plant diseases worldwide, severely affecting a high number of crops and ornamentals. Difficulties of bacterial wilt control by non-biological methods are related to effectiveness, bacterial resistance and environmental impact. Alternatively, a great many biocontrol strategies have been carried out, with the advantage of being environmentally friendly. Advances in bacterial wilt biocontrol include an increasing interest in bacteriophage-based treatments as a promising re-emerging strategy. Bacteriophages agai…
Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis
2019
Summary While antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive for reasons that remain unclear. Here, we show that Linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell-mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of T helper-17 cell effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondrial translation in differentiating T cells, either with RAbos or through the inhibition of mitochondrial elongation factor G1 (mEF-G1) progressi…
Addition of thiols to the double bond of dipeptide C-terminal dehydroalanine as a source of new inhibitors of cathepsin C.
2017
Addition of thiols to double bond of glycyl-dehydroalanine and phenyl-dehydroalanine esters provided micromolar inhibitors of cathepsin C. The structure-activity studies indicated that dipeptides containing N-terminal phenylalanine exhibit higher affinity towards the enzyme. A series of C-terminal S-substituted cysteines are responsible for varying interaction with S1 binding pocket of cathepsin C. Depending on diastereomer these compounds most likely act as slowly reacting substrates or competitive inhibitors. This was proved by TLC analysis of the medium in which interaction of methyl (S)-phenylalanyl-(R,S)-(S-adamantyl)cysteinate (7i) with the enzyme was studied. Molecular modeling enabl…
Bioactive triterpenes of protium heptaphyllum gum resin extract display cholesterol-lowering potential
2021
Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects. Consequently, patients with mild hypercholesterolemia prefer the use of food supplements since these are perceived to be safer. Here, we investigate the phytochemical profile and cholesterol-lowering potential of Protium heptaphyllum gum resin extract (PHE). Chemical characterization via HPLC-APCI-HRMS2 and…
Identification of estrogen receptor α ligands with virtual screening techniques.
2016
Utilization of computer-aided molecular discovery methods in virtual screening (VS) is a cost-effective approach to identify novel bioactive small molecules. Unfortunately, no universal VS strategy can guarantee high hit rates for all biological targets, but each target requires distinct, fine-tuned solutions. Here, we have studied in retrospective manner the effectiveness and usefulness of common pharmacophore hypothesis, molecular docking and negative image-based screening as potential VS tools for a widely applied drug discovery target, estrogen receptor α (ERα). The comparison of the methods helps to demonstrate the differences in their ability to identify active molecules. For example,…
Investigation on Quantitative Structure-Activity Relationships of 1,3,4-Oxadiazole Derivatives as Potential Telomerase Inhibitors.
2020
Background:Telomerase, a reverse transcriptase, maintains telomere and chromosomes integrity of dividing cells, while it is inactivated in most somatic cells. In tumor cells, telomerase is highly activated, and works in order to maintain the length of telomeres causing immortality, hence it could be considered as a potential marker to tumorigenesis.A series of 1,3,4-oxadiazole derivatives showed significant broad-spectrum anticancer activity against different cell lines, and demonstrated telomerase inhibition.Methods:This series of 24 N-benzylidene-2-((5-(pyridine-4-yl)-1,3,4-oxadiazol-2yl)thio)acetohydrazide derivatives as telomerase inhibitors has been considered to carry out QSAR studies…
The dimer-monomer equilibrium of SARS-CoV-2 main protease is affected by small molecule inhibitors
2021
AbstractThe maturation of coronavirus SARS-CoV-2, which is the etiological agent at the origin of the COVID-19 pandemic, requires a main protease Mpro to cleave the virus-encoded polyproteins. Despite a wealth of experimental information already available, there is wide disagreement about the Mpro monomer-dimer equilibrium dissociation constant. Since the functional unit of Mpro is a homodimer, the detailed knowledge of the thermodynamics of this equilibrium is a key piece of information for possible therapeutic intervention, with small molecules interfering with dimerization being potential broad-spectrum antiviral drug leads. In the present study, we exploit Small Angle X-ray Scattering (…