Schisandrin B Suppresses Colon Cancer Growth by Inducing Cell Cycle Arrest and Apoptosis: Molecular Mechanism and Therapeutic Potential.

Colon cancer is among the most lethal and prevalent malignant tumors in the world, and the lack of effective therapies highlights the need for novel therapeutic approaches. Schisandrin B (Sch B), a lignan extracted from the fruit of, has been reported for its anticancer properties. However, to date, no studies have been done to characterize the exact molecular mechanisms underlying the antitumorigenic effects of Sch B in colon cancer.

Enhancing the antibacterial effect of chitosan to combat orthopaedic implant-associated infections.

The development of antibacterial resistance imposes the development of novel materials to relieve the burden of infection. Chitosan, a material of natural and sustainable origin, possesses ideal characteristics to translate into a novel biomaterial with antibacterial properties, as it already has these properties and it allows easy and scalable chemical modification to enhance its activity. The aim of the present work was that of producing low molecular weight chitosans that have higher solubility and can remain protonated at physiological pH, thus enhancing the antimicrobial action.

Harnessing the Antibacterial Properties of Fluoridated Chitosan Polymers against Oral Biofilms.

Dental caries are a worldwide endemic chronic disease affecting people of all ages. Due to the limitations of daily used oral hygiene products, there is an unmet need for new, effective, safe, and economic oral products. We have recently demonstrated that -(2(2,6-diaminohexanamide)-chitosan (CS3H Lys) has enhanced antibacterial properties against the main cariogenic bacterium, and here we investigated the effect of fluoridation of this polymer (CS3H Lys F) on its antibacterial properties and the ability to protect teeth from acid demineralization.

Comparative Phenotypic, Proteomic, and Phosphoproteomic Analysis Reveals Different Roles of Serine/Threonine Phosphatase and Kinase in the Growth, Cell Division, and Pathogenicity of .

Eukaryote-like serine/threonine kinases (STKs) and cognate phosphatases (STPs) comprise an important regulatory system in many bacterial pathogens. The complexity of this regulatory system has not been fully understood due to the presence of multiple STKs/STPs in many bacteria and their multiple substrates involved in many different physiological and pathogenetic processes. are the best materials for the study due to a single copy of the gene encoding STK and its cognate STP.

Antimicrobial compounds from an FDA-approved drug library with activity against Streptococcus suis.

Aim: Antimicrobial resistance (AMR) has become a global concern. Developing novel antimicrobials is one of the most effective approaches in tackling AMR. Considering its relatively low cost and risk, drug repurposing has been proposed as a valuable approach for novel antimicrobial discovery.

Evaluation of Antibacterial and Cytotoxicity Properties of Silver Nanowires and Their Composites with Carbon Nanotubes for Biomedical Applications.

In this work, we prepared silver nanowires (AgNWs) via the polyol method in the presence or absence of single wall carbon nanotubes (CNTs) and tested their physicochemical, antibacterial and cytotoxic properties. Results showed that the introduction of CNTs lead to the formation of AgNWs at lower temperature, but the final product characteristics of AgNWs and AgNWs-CNT were not significantly different. AgNWs exhibited antibacterial properties against all the studied bacterial species via the formation of oxygen reactive species (ROS) and membrane damage.

Antibacterial PMMA Composite Cements with Tunable Thermal and Mechanical Properties.

PMMA-based cements are the most used bone cements in vertebroplasty and total hip arthroplasty. However, they present several drawbacks, including susceptibility to bacterial infection, monomer leakage toxicity, and high polymerization temperature, which can all lead to damage to the surrounding tissues and their failure. In the present study, silver nanowires (AgNWs) have been introduced to bestow antibacterial properties; chitosan (CS) to promote porosity and to reduce the polymerization temperature, without negatively affecting the mechanical performance; and methacryloyl chitosan (CSMCC) to promote cross-linking with methyl methacrylate (MMA) and reduce the quantity of monomer required for polymerization.

Sustained Release from Injectable Composite Gels Loaded with Silver Nanowires Designed to Combat Bacterial Resistance in Bone Regeneration Applications.

One-dimensional nanostructures, such as silver nanowires (AgNWs), have attracted considerable attention owing to their outstanding electrical, thermal and antimicrobial properties. However, their application in the prevention of infections linked to bone tissue regeneration intervention has not yet been explored. Here we report on the development of an innovative scaffold prepared from chitosan, composite hydroxyapatite and AgNWs (CS-HACS-AgNWs) having both bioactive and antibacterial properties.

Tuning Chemoreceptor Signaling by Positioning Aromatic Residues at the Lipid-Aqueous Interface.

Aromatic tuning facilitates stimulus-independent modulation of receptor output. The methodology is based upon the affinity of amphipathic aromatic residues, namely Trp and Tyr, for the polar-hydrophobic interfaces found within biological membranes. Here, we describe the application of aromatic tuning within the aspartate chemoreceptor of Escherichia coli (Tar).

A Modular High-Throughput In Vivo Screening Platform Based on Chimeric Bacterial Receptors.

Multidrug resistance (MDR) is a globally relevant problem that requires novel approaches. Two-component systems are a promising, yet untapped target for novel antibacterials. They are prevalent in bacteria and absent in mammals, and their activity can be modulated upon perception of various stimuli.

Identification of transmembrane helix 1 (TM1) surfaces important for EnvZ dimerisation and signal output.

The Escherichia coli sensor kinase EnvZ modulates porin expression in response to various stimuli, including extracellular osmolarity, the presence of procaine and interaction with an accessory protein, MzrA. Two major outer membrane porins, OmpF and OmpC, act as passive diffusion-limited pores that allow compounds, including certain classes of antibiotics such as β-lactams and fluoroquinolones, to enter the bacterial cell. Even though the mechanisms by which EnvZ detects and processes the presence of various stimuli are a fundamental component of microbial physiology, they are not yet fully understood.

Employing aromatic tuning to modulate output from two-component signaling circuits.

Two-component signaling circuits (TCSs) govern the majority of environmental, pathogenic and industrial processes undertaken by bacteria. Therefore, controlling signal output from these circuits in a stimulus-independent manner is of central importance to synthetic microbiologists. Aromatic tuning, or repositioning the aromatic residues commonly found at the cytoplasmic end of the final TM helix has been shown to modulate signal output from the aspartate chemoreceptor (Tar) and the major osmosensor (EnvZ) of Escherichia coli.

Differential repositioning of the second transmembrane helices from E. coli Tar and EnvZ upon moving the flanking aromatic residues.

Aromatic tuning, i.e. repositioning aromatic residues found at the cytoplasmic end of transmembrane (TM) domains within bacterial receptors, has been previously shown to modulate signal output from the aspartate chemoreceptor (Tar) and the major osmosensor EnvZ of Escherichia coli.

Forcing the issue: aromatic tuning facilitates stimulus-independent modulation of a two-component signaling circuit.

Two-component signaling circuits allow bacteria to detect and respond to external stimuli. Unfortunately, the input stimulus remains unidentified for the majority of these circuits. Therefore, development of a synthetic method for stimulus-independent modulation of these circuits is highly desirable because particular physiological or developmental processes could be controlled for biotechnological purposes without the need to identify the stimulus itself.

Residues at the cytoplasmic end of transmembrane helix 2 determine the signal output of the TarEc chemoreceptor.

Baseline signal output and communication between the periplasmic and cytoplasmic domains of the Escherichia coli aspartate chemoreceptor Tar(Ec) are both strongly influenced by residues at the C-terminus of transmembrane helix 2 (TM2). In particular, the cytoplasmic aromatic anchor, composed of residues Trp-209 and Tyr-210 in wild-type Tar(Ec), is important for determining the CheA kinase-stimulating activity of the receptor and its ability to respond to chemoeffector-induced stimuli. Here, we have studied the effect on Tar(Ec) function of the six-residue sequence at positions 207-212.

Production of human tetraspanin proteins in Escherichia coli.

Tetraspanins are found in multicellular eukaryotes and are generally thought to act as scaffolding proteins, localizing multiple proteins to a specific region of the cell membrane. Activities for tetraspanins have been identified in several fundamental processes such as motility, cell adhesion, proliferation and viral entry. Tetraspanins are also key players in cancer development and progression.

The residue composition of the aromatic anchor of the second transmembrane helix determines the signaling properties of the aspartate/maltose chemoreceptor Tar of Escherichia coli.

Repositioning of the tandem aromatic residues (Trp-209 and Tyr-210) at the cytoplasmic end of the second transmembrane helix (TM2) modulates the signal output of the aspartate/maltose chemoreceptor of Escherichia coli (Tar(Ec)). Here, we directly assessed the effect of the residue composition of the aromatic anchor by studying the function of a library of Tar(Ec) variants that possess all possible combinations of Ala, Phe, Tyr, and Trp at positions 209 and 210. We identified three important properties of the aromatic anchor.

Structural characterization of AS1-membrane interactions from a subset of HAMP domains.

HAMP domains convert an extracellular sensory input into an intracellular signaling response in a wide variety of membrane-embedded bacterial proteins. These domains are almost invariably found adjacent to the inner leaflet of the cell membrane. We therefore examined the interaction of peptides corresponding to either AS1 or AS2 of four different, well-characterized HAMP domains with several membrane model systems.

Mutational analysis of the transmembrane helix 2-HAMP domain connection in the Escherichia coli aspartate chemoreceptor tar.

Transmembrane helix 2 (TM2) of the Tar chemoreceptor undergoes an inward piston-like displacement of 1 to 3 Å upon binding aspartate. This signal is transmitted to the kinase-control module via the HAMP domain. Within Tar, the HAMP domain forms a parallel four-helix bundle consisting of a dimer of two amphipathic helices connected by a flexible linker.

The region preceding the C-terminal NWETF pentapeptide modulates baseline activity and aspartate inhibition of Escherichia coli Tar.

The Tar chemoreceptor-CheA-CheW ternary complex of Escherichia coli is a transmembrane allosteric enzyme in which binding of ligands to the periplasmic domain modulates the activity of CheA kinase. Kinase activity is also affected by reversible methylation of four glutamyl residues in the cytoplasmic domain of the receptor. E.

Tuning Escherichia coli for membrane protein overexpression.

A simple generic method for optimizing membrane protein overexpression in Escherichia coli is still lacking. We have studied the physiological response of the widely used "Walker strains" C41(DE3) and C43(DE3), which are derived from BL21(DE3), to membrane protein overexpression. For unknown reasons, overexpression of many membrane proteins in these strains is hardly toxic, often resulting in high overexpression yields.

Tuning a bacterial chemoreceptor with protein-membrane interactions.

Chemoreceptors in Escherichia coli are homodimeric transmembrane proteins that convert environmental stimuli into intracellular signals controlling flagellar motion. Chemoeffectors bind to the extracellular (periplasmic) domain of the receptors, whereas their cytoplasmic domain mediates signaling and adaptation. The second transmembrane helix (TM2) connects these two domains.

Cooperative signaling among bacterial chemoreceptors.

Four chemoreceptors in Escherichia coli mediate responses to chemicals in the environment. The receptors self-associate and localize to the cell poles. This aggregation implies that interactions among receptors are important parameters of signal processing during chemotaxis.

Tryptophan residues flanking the second transmembrane helix (TM2) set the signaling state of the Tar chemoreceptor.

The chemoreceptors of Escherichia coli are homodimeric membrane proteins that cluster in patches near the cell poles. They convert environmental stimuli into intracellular signals that control flagellar rotation. The functional domains of a receptor are physically separated by the cell membrane.