Sentences with phrase «hoechst efflux»

Prolonged oral administration of a pan-retinoic acid receptor antagonist inhibits spermatogenesis in mice with a rapid recovery and changes in the expression of influx and efflux transporters.

Fortunately, efflux pumps require a source of chemical energy to perform their function.

To address this challenge, our research group is using nanoparticles not only to deliver more chemotherapy drugs to the target site within cancer cells, but also to compromise the function of the efflux pumps and thereby significantly improve safety and efficacy of cancer therapy.»

Recognizing this, He and his research team developed a way to reduce the amount of chemical energy — adenosine triphosphate (ATP)-- available to the efflux pumps in cancer cells.

The AcrA - PPMO also was effective against the human pathogens Klebsiella pneumoniae and Salmonella enterica, since those bacteria contain the same efflux pump with a matching gene sequence, Dr. Greenberg said.

The UTSW experiment focused on Escherichia coli (E. coli) and bacterial pathogens with genetically similar efflux pump complexes.

Bacteria that use these «efflux pumps» and that are treated with the new compound become sensitive to antibiotics they were previously resistant to.

Studies have revealed that the drug also inhibits bacterial efflux pumps that permit bacteria to survive within cells.

The findings, published November 28 in Scientific Reports, offer a better understanding of the motions and functions of efflux pumps.

If a pathogenic strain of bacteria acquires a gene encoding one of these efflux pumps, then it will suddenly become resistant to multiple antibacterial drugs.

«There are two scenarios for how an ADEP efflux pump could operate,» Sello said.

The efflux pumps are kept busy pumping out the fragments while the antimicrobial agents are able to stay inside the cell.

We thought, if the latter scenario is operative, then a molecule comprising the minimal portion of the ADEP that is recognized by the pump could competitively interfere with efflux of the ADEP.»

One type of efflux pump, which until recently had only been studied in parts, was recently modeled in its entirety and simulated using supercomputers at Los Alamos National Laboratory.

Sello and a team of researchers from Brown have come up with a new strategy that may help sneak drugs past the efflux guards.

Application of these computational techniques to the multitude of efflux pumps found in different Gram - negative pathogens should allow scientists to elucidate if general mechanisms are shared among different pumps or are pump - specific.

«There are efflux pumps that can export multiple drugs that have different structures and mechanisms of action.

Bacterial efflux pumps, such as the P. aeruginosa MexAB - OprM pump shown here, are one of the dominant molecular mechanisms available to Gram - negative pathogens for removing toxins, including antibiotics.

For this study, the researchers focused on efflux pumps inside the bacteria Pseudomonas aeruginosa, which can cause serious illnesses such as pneumonia and sepsis.

«We study a lot of efflux pumps to understand antibiotic resistance,» said Yu, an Iowa State professor with appointments in physics and astronomy; chemistry; biochemistry, biophysics and molecular biology; and the U.S. Department of Energy's Ames Laboratory.

New supercomputer simulations have revealed the role of transport proteins called efflux pumps in creating drug - resistance in bacteria, research that could lead to improving the drugs» effectiveness against life - threatening diseases and restoring the efficacy of defunct antibiotics.

In fact, the team showed that the fragment approach worked better than combining ADEPs with reserpine, a well - known efflux inhibitor.

It had been reported that the ADEP resistance of M. tuberculosis was due to the presence of one or perhaps more efflux pumps.

Since an efflux pump could compromise the potency of even a newly developed antibacterial drug, we need to think about ways to circumvent these efflux pumps.»

One trick used by some bacteria is to eject antibiotics through so - called efflux pumps embedded in their cellular membranes.

Some coded for multi-drug efflux pumps, which are multi-drug resistance mechanisms embedded in the bacterial membrane that pump specific antibiotics out of the bacteria.

Another supplied a plant compound (diosmetin) known to disable efflux pumps in other bacteria.

The Solution: Working with pathogenic bacteria would be far too dangerous in a school setting, so Delgado focused on disabling an efflux pump in the common bacterium E. coli.

Heterogeneity in a bacterial population that arises through a mechanism of biased partitioning of drug efflux pumps, as we identified in our study, could be a stepping - stone on the path of bacterial populations towards antibiotic resistance.»

Saint Louis University researchers then synthesized structural analogs of the discovered efflux pump inhibitors and identified properties essential for their activities.

The team focused on one efflux pump protein, known as AcrA, which connects two other proteins in a tunnel shape through the bacterial cell envelope.

«After more extensive analysis, we narrowed down our list to predict which molecules were most likely to disrupt the function of the efflux pump.»

«As a first in this field, we proposed the approach of essentially «screwing up» the efflux pump's protein assembly, and this led to the discovery of molecules with a new type of antibacterial activity,» said co-author Jeremy Smith, who serves as a UT - ORNL Governor's Chair and director of the UT - ORNL Center for Molecular Biophysics.

The researchers found four new chemicals that seek out and disrupt bacterial proteins called «efflux pumps,» known to be a major cause of antibiotic resistance.

They plan to leverage a recently awarded Innovative and Novel Computational Impact on Theory and Experiment (INCITE) allocation from DOE to perform larger simulations on the Titan supercomputer to gain deeper understanding of how bacterial efflux pumps function, identify more potent efflux pump inhibitors and optimize the best antibiotic - plus - inhibitor combinations to make them suitable for clinical trials.

This picture was suddenly complicated in 1999, when Gerd Jürgens and his colleagues at the University of Tübingen in Germany discovered a mutant of the model plant Arabidopsis with efflux pumps everywhere in the cell.

The TB bacteria use efflux pumps as a strategy to remove drugs and other threats from the cell before they can work against the bacteria.

Our observations and models demonstrate an unexpected influence of surface - generated mesoscale eddies in the transport of hydrothermal vent efflux and of vent larvae away from the northern East Pacific Rise.

For example, up - regulated influx transporters (OCT3 and OCTN1) localized at the apical membranes of Sertoli cells could mediate the transport of the drug compound 9 from the lumen into the basolateral compartment of Sertoli cells, where the up - regulated efflux transporters (ABCB1 / p - glycoprotein, ABCB8, ABCB9, ABCC5, and ABCC10) could then transport the drug out of Sertoli cells against a concentration gradient, resulting in enhanced efficiency of recovery upon cessation of treatment.

Specifically, these investigators showed that the levels of several efflux (P - glycoprotein, MRP1, ABCG1) and influx (SLC15A1) pumps were found to increase by several fold within hours of adjudin treatment (27).

Indeed, we found that long - term drug treatments were associated with increased expression of several ABC efflux transporters and influx transporters.

To begin to explore the cellular mechanisms that might be responsible for this response, histological analysis revealed less severe disruption of spermatogenesis and gene expression studies suggested that an interplay of ATP - binding cassette (ABC) efflux transporters and solute carrier (SLC) influx transporters in the testicular cells might be involved.

Interestingly, we found that at the protein level 2 efflux transporters, namely ABCB1 and ABCC10, were up - regulated and now are also expressed in germ cells, expression that was barely detectable, if at all, in controls.

A, The expression of several ABC efflux transporters, including Abcb1a, Abcb9, Abcc5, and Abcc10, were significantly up - regulated in testes after long - term drug treatment as compared with the control.

TZDs increase systemic insulin sensitivity and adipose tissue triglyceride storage while decreasing adipose tissue fatty acid efflux (83).

Similarly in C. neoformans, Chr 1 disomy confers azole resistance because this chromosome harbors ERG11 and AFR1 (which encodes the major azole efflux pump) and aneuploidy can also influence the virulence of this pathogen [16], [20], [21].

Second, our current study suggests that after the long - term drug administration in mice, the more rapid recovery may also involve the interplay of ABC efflux transporters and SLC influx transporters in the testes.

Sanny S. W. Chung, Xiangyuan Wang, Debra J. Wolgemuth; Prolonged Oral Administration of a Pan-Retinoic Acid Receptor Antagonist Inhibits Spermatogenesis in Mice With a Rapid Recovery and Changes in the Expression of Influx and Efflux Transporters, Endocrinology, Volume 157, Issue 4, 1 April 2016, Pages 1601 — 1612, https://doi.org/10.1210/en.2015-1675

PPARγ appears to be part of a network of transcription factors coordinately regulating lipid uptake and cholesterol efflux in macrophages by transcriptionally regulating the scavenger receptor CD36 and the oxysterol receptor LXRα (liver X receptor α).

Quantitative fluorescence microscopy provides high resolution imaging of passive diffusion and P - gp mediated efflux at the < i > in vivo blood — brain barrier.