Search

• A functional segment of BAX protein can be engineered to self-assemble as fluorescent nanoparticles targeted to the tumoral marker CXCR4. • Despite their CXCR4 selectivity, BAX nanoparticles do not show a tumor biodistribution and accumulate in liver and kidney. • The cocktail administration of BAX nanoparticles with equivalent PUMA and BAK constructs results in high tumor accumulation and potent antitumoral effect. • The combined administration of BAX, PUMA and BAK nanoparticles promote potent tumor cell destruction with a profile different from that of any of the single pro-apoptotic factors. A functional 29 amino acid-segment of the helix α5 from the human BAX protein has been engineered for production in recombinant bacteria as self-assembling, GFP-containing fluorescent nanoparticles, which are targeted to the tumoral marker CXCR4. These nanoparticles, of around 34 nm in diameter, show a moderate tumor biodistribution and limited antitumoral effect when systemically administered to mouse models of human CXCR4+ colorectal cancer (at 300 μg dose). However, if such BAX nanoparticles are co-administered in cocktail with equivalent nanoparticulate versions of BAK and PUMA proteins at the same total protein dose (300 μg), protein biodistribution and stability in tumor is largely improved, as determined by fluorescence profiles. This fact leads to a potent and faster destruction of tumor tissues when compared to individual pro-apoptotic factors. The analysis and interpretation of the boosted effect, from both the structural and functional sides, offers clues for the design of more efficient nanomedicines and theragnostic agents in oncology based on precise cocktails of human proteins. Several human pro-apoptotic peptides (namely BAK, BAX and PUMA) have been engineered as self-assembling protein nanoparticles targeted to the tumoral marker CXCR4. The systemic administration of the same final amounts of those materials as single drugs, or as combinations of two or three of them, shows disparate intensities of antitumoral effects in a mouse model of human colorectal cancer, which are boosted in the triple combination on a non-additive basis. The superiority of the combined administration of pro-apoptotic agents, acting at different levels of the apoptotic cascade, opens a plethora of possibilities for the development of effective and selective cancer therapies based on the precise cocktailing of pro-apoptotic nanoparticulate agents. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Protein complexes are known to play a major role in controlling cellular activity in a living being. Identifying complexes from raw protein protein interactions (PPIs) is an important area of research. Earlier work has been limited mostly to yeast. Such protein complex identification methods, when applied to large human PPIs often give poor performance. We introduce a novel method called CSC to detect protein complexes. The method is evaluated in terms of positive predictive value, sensitivity and accuracy using the datasets of the model organism, yeast and humans. CSC outperforms several other competing algorithms for both organisms. Further, we present a framework to establish the usefulness of CSC in analyzing the influence of a given disease gene in a complex topologically as well as biologically considering eight major association factors. [ABSTRACT FROM AUTHOR]

Introduction This study evaluated the bacterial and human metaproteome of root apexes and the matched inflammatory lesions from teeth with post-treatment apical periodontitis. Methods Root apexes and matched inflammatory lesions from root canal–treated teeth with apical periodontitis were obtained during periradicular surgery. All root canal fillings were rated as adequate on the basis of radiographs and cone-beam computed tomography. The specimens were cryopulverized and subjected to metaproteomic analysis for human and bacterial proteins by using a mass spectrometry platform that is based on nanoflow liquid chromatography coupled with linear ion trap quadrupole Velos Orbitrap. Results The metaproteome analyses revealed the presence of viable and metabolically active human and bacterial cells in both apexes and lesions. Several bacterial proteins of interest for pathogenicity and therapeutics were identified in both apexes and lesions, including proteins related to antibiotic resistance, proteolytic function, stress response, adhesion, and virulence. Many human proteins related to immune defense mechanisms were also detected in both root apex and lesion specimens, including immunoglobulins, complement system, and proteins linked to T-cell and B-cell activation, neutrophil microbicidal processes, antigen recognition/presentation, bone resorption, and protection against tissue damage. Conclusions Occurrence of host defense factors from the innate and adaptive immune responses and bacterial virulence, survival, and resistance proteins in matched root apexes/periradicular inflammatory lesions indicates a complex and dynamic host-pathogen interaction in teeth with post-treatment apical periodontitis. [ABSTRACT FROM AUTHOR]

Copyright of Implant Dentistry is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article presents a study on the importance of the extract of rice protein or oryza sativa for the management of periodontal diseases. It states that the extract contains a proteinaceous inhibitors against human proteins by porphyromonas gingivalis cyteine proteinases which involves arg-specific gingipain (Rgp) activity. Result shows that the extracts suppresses the porphyromonas gingivalis' growth by the inhibitory activity of bacterial proteinase.

Abstract: Ebola Virus (EBOV) presents a challenge for vaccine development because immune correlates of protection in humans are not well known. In earlier studies we developed a concept of local similarity which refers to resemblance of structural patterns of unrelated proteins as a function of their amino acid composition. The search for local similarities between human and EBOV proteins was performed. The resemblance of NP protein of EBOV to vascular endothelial growth factor and its receptor, which play a key role in the regulation of vascular permeability, was identified. A high degree of local similarity of Ebola GP protein with the tactile protein of the T-cell surface was also revealed. The similarity of the Ebola VP24 protein fragment with complement receptor type 1 (CD35 antigen) appears to be correlated with early activation of complement in lethal Ebola fever. This finding supports our prior studies indicating that VP24 determines the difference between lethal and non-lethal strains of EBOV. Several other similarities of potential significance were identified that might play an important role in the aetiology of Ebola-induced disease. In conclusion, local similarities between EBOV and human host proteins may provide a key to rational design of safe and effective filovirus vaccines. Such a vaccine must be free from epitopes that could potentially trigger Ebola-like hemorrhagic fever due to an autoimmune reaction induced by vaccination and other unanticipated adversities. [ABSTRACT FROM AUTHOR]