Mechanisms of Keap1/Nrf2 modulation in bacterial infections: implications in persistence and clearance.

Pathogenic bacteria trigger complex molecular interactions in hosts that are characterized mainly by an increase in reactive oxygen species (ROS) as well as an inflammation-associated response. To counteract oxidative damage, cells respond through protective mechanisms to promote resistance and avoid tissue damage and infection; among these cellular mechanisms the activation or inhibition of the nuclear factor E2-related factor 2 (Nrf2) is frequently observed. The transcription factor Nrf2 is considered the regulator of several hundred cytoprotective and antioxidant genes.

Molecular dynamics simulations reveal efficient heavy metal ion removal by two-dimensional Cu-THQ metal-organic framework membrane.

Two-dimensional (2D) metal-organic frameworks (MOFs) have been extensively utilized across various research areas. However, the application of 2D MOF-based membranes for the removal of heavy metal ions remains largely unexplored, despite their potential as suitable candidates due to their inherent porosity. In this study, we employed molecular dynamics (MD) simulations to investigate the capacity of a typical 2D MOF, Cu-THQ, for the separation of heavy metal ions, including Cd²⁺, Cu²⁺, Hg²⁺, and Pb²⁺.

Potential toxicity of Graphene (Oxide) quantum dots to human intestinal fatty acid binding protein (HIFABP) via obstructing the protein's openings.

Graphene quantum dots (GQDs) have garnered significant attention across numerous fields due to their ultrasmall size and exceptional properties. However, their extensive applications may lead to environmental exposure and subsequent uptake by humans. Yet, conflicting reports exist regarding the potential toxicity of GQDs based on experimental investigations.

In Silico Approach: Anti-Tuberculosis Activity of Caespitate in the H37Rv Strain.

Tuberculosis is a highly lethal bacterial disease worldwide caused by (). Caespitate is a phytochemical isolated from , a plant used in African traditional medicine that shows anti-tubercular activity, but its mode of action remains unknown. It is suggested that there are four potential targets in , specifically in the H37Rv strain: InhA, MabA, and UGM, enzymes involved in the formation of 's cell wall, and PanK, which plays a role in cell growth.

Molecular Dynamic Simulations for Biopolymers with Biomedical Applications.

Computational modeling (CM) is a versatile scientific methodology used to examine the properties and behavior of complex systems, such as polymeric materials for biomedical bioengineering. CM has emerged as a primary tool for predicting, setting up, and interpreting experimental results. Integrating in silico and in vitro experiments accelerates scientific advancements, yielding quicker results at a reduced cost.

Molecular dynamics simulations suggest the potential toxicity of fluorinated graphene to HP35 protein via unfolding the α-helix structure.

Fluorinated graphene, a two-dimensional nanomaterial composed of three atomic layers, a central carbon layer sandwiched between two layers of fluorine atoms, has attracted considerable attention across various fields, particularly for its potential use in biomedical applications. Nonetheless, scant effort has been devoted to assessing the potential toxicological implications of this nanomaterial. In this study, we scrutinize the potential impact of fluorinated graphene on a protein model, HP35 by utilizing extensive molecular dynamics (MD) simulation methods.

Peptide-based allosteric inhibitor targets TNFR1 conformationally active region and disables receptor-ligand signaling complex.

Tumor necrosis factor (TNF) receptor 1 (TNFR1) plays a pivotal role in mediating TNF induced downstream signaling and regulating inflammatory response. Recent studies have suggested that TNFR1 activation involves conformational rearrangements of preligand assembled receptor dimers and targeting receptor conformational dynamics is a viable strategy to modulate TNFR1 signaling. Here, we used a combination of biophysical, biochemical, and cellular assays, as well as molecular dynamics simulation to show that an anti-inflammatory peptide (FKCRRWQWRMKK), which we termed FKC, inhibits TNFR1 activation allosterically by altering the conformational states of the receptor dimer without blocking receptor-ligand interaction or disrupting receptor dimerization.

Villin headpiece unfolding upon binding to boridene mediated by the "anchoring-perturbation" mechanism.

We employ molecular dynamics (MD) simulations to investigate the influence of boridene on the behavior of a protein model, HP35, with the aim of assessing the potential biotoxicity of boridene. Our MD results reveal that HP35 can undergo unfolding via an "anchoring-perturbation" mechanism upon adsorption onto the boridene surface. Specifically, the third helix of HP35 becomes tightly anchored to the boridene surface through strong electrostatic interactions between the abundant molybdenum atoms on the boridene surface and the oxygen atoms on the HP35 backbone.

Moderate binding of villin headpiece protein to CN nanosheet reveals the suitable biocompatibility of this nanomaterial.

Since its recent successful synthesis and due to its promising physical and chemical properties, the carbon nitrite nanomaterial, CN, has attracted considerable attention in various scientific areas. However, thus far, little effort has been devoted to investigating the structural influence of the direct interaction of this 2D nanomaterial and biomolecules, including proteins and biomembranes so as to understand the physical origin of its bio-effect, particularly from the molecular landscape. Such information is fundamental to correlate to the potential nanotoxicology of the CN nanomaterial.

Robust Mechanical Destruction to the Cell Membrane of Carbon Nitride Polyaniline (CN): A Molecular Dynamics Simulation Study.

The drug-resistant bacteria, particularly multidrug-resistant bacteria, has emerged as a major global public health concern posing serious threats to human life and survival. Nanomaterials, including graphene, have shown promise as effective antibacterial agents owing to their unique antibacterial mechanism compared with traditional drugs. Despite the structural similarity to graphene, the potential antibacterial activity of carbon nitride polyaniline (CN) remains unexplored.

Reversible Thermo-Optical Response Nanocomposites Based on RAFT Symmetric Triblock Copolymers (ABA) of Acrylamide and -Isopropylacrylamide and Gold Nanoparticles.

The development of composite materials with thermo-optical properties based on smart polymeric systems and nanostructures have been extensively studied. Due to the fact of its ability to self-assemble into a structure that generates a significant change in the refractive index, one of most attractive thermo-responsive polymers is poly(-isopropylacrylamide) (PNIPAM), as well as its derivatives such as multiblock copolymers. In this work, symmetric triblock copolymers of polyacrylamide (PAM) and PNIPAM (PAM--PNIPAM--PAM) with different block lengths were prepared by reversible addition-fragmentation chain-transfer polymerization (RAFT).

The single-atom catalytic activity of the hydrogen evolution reaction of the experimentally synthesized boridene 2D material: a density functional theory study.

Context: Previous theoretical studies have suggested that two-dimensional (2D) MBene materials might display adequate monatomic catalytic activity for the hydrogen evolution reaction (HER). Recently, a study reported the experimental synthesis of a 2D MBene (MoB), re-defined as boridene, albeit no effort has been devoted to explore the single-atom catalytic activity for HER of this experimentally synthesized 2D material. Therefore, we herein investigate the single-atom HER performance of the boridene.

Hydrolyzed Polyacrylamide as an In Situ Assistant in the Nucleation and Growth of Gold Nanoparticles.

The modulation of nanoparticles' size, shape, and dispersion by polymers has attracted particular attention in different fields. Nevertheless, there is a lack of information regarding the use of charged macromolecules as assistants in the nanostructures' nucleation and growth processes. Prompted by this, the in situ synthesis of gold nanoparticles (AuNPs) aided by hydrolyzed polyacrylamides (HPAM), with different chemical structures, was developed.

Single-layered fluorinated graphene nanopores for H/CH and H/CO separation with high efficiency and selectivity.

The utilization of hydrogen gas (H) as an energy resource is a critical alternative to relieve the current greenhouse effect exacerbated by the excessive use of fossil fuels. The production of pure H is usually achieved by its separation from H/CH and H/CO mixtures; however, such process still represents a great challenge due to the inevitable contamination that occurs after the membrane sieving. Here, we investigate the ability of a 2-dimensional material, a nanoporous fluorinated graphene (F-GRA), to perform the separation of H/CH and H/CO using molecular dynamics simulations.

Identification of Molecular Determinants in iRhoms1 and 2 That Contribute to the Substrate Selectivity of Stimulated ADAM17.

The metalloprotease ADAM17 is a key regulator of the TNFα, IL-6R and EGFR signaling pathways. The maturation and function of ADAM17 is controlled by the seven-membrane-spanning proteins iRhoms1 and 2. The functional properties of the ADAM17/iRhom1 and ADAM17/iRhom2 complexes differ, in that stimulated shedding of most ADAM17 substrates tested to date can be supported by iRhom2, whereas iRhom1 can only support stimulated shedding of very few ADAM17 substrates, such as TGFα.

Development of Novel Recombinant Antigens of Nucleoprotein and Matrix Proteins of Antigenicity and Structural Prediction.

Blue eye disease (BED) is a swine viral infection that affects the pork industry of Mexico. (PRV) is the etiological agent, and the hemagglutinin-neuraminidase protein (HN) is characterized as the best antigen for serological tests, although other structural proteins, including the nucleoprotein (NP) and the matrix (M) protein, have been investigated during the infection of members of the family, generating promising results. Herein, for the first time, we successfully produced and characterized both the NP and M proteins of PRV by using a recombinant strategy in the heterologous system.

Intrapallidal injection of cannabidiol or a selective GPR55 antagonist decreases motor asymmetry and improves fine motor skills in hemiparkinsonian rats.

Cannabidiol (CBD) presents antiparkinsonian properties and neuromodulatory effects, possibly due to the pleiotropic activity caused at multiple molecular targets. Recently, the GPR55 receptor has emerged as a molecular target of CBD. Interestingly, GPR55 mRNA is expressed in the (GPe) and striatum, hence, it has been suggested that its activity is linked to motor dysfunction in Parkinson's disease (PD).

Interacting binding insights and conformational consequences of the differential activity of cannabidiol with two endocannabinoid-activated G-protein-coupled receptors.

Cannabidiol (CBD), the major non-psychoactive phytocannabinoid present in the plant has displayed beneficial pharmacological effects in the treatment of several neurological disorders including, epilepsy, Parkinson's disease, and Alzheimer's disease. In particular, CBD is able to modulate different receptors in the endocannabinoid system, some of which belong to the family of G-protein-coupled receptors (GPCRs). Notably, while CBD is able to antagonize some GPCRs in the endocannabinoid system, it also seems to activate others.

Conceptual DFT, QTAIM, and Molecular Docking Approaches to Characterize the T-Type Calcium Channel Blocker Anandamide.

The anandamide is a relevant ligand due to its capacity of interacting with several proteins, including the T-type calcium channels, which play an important role in neuropathic pain and depression disorders. Hence, a detailed characterization of the chemical properties and conformational stability of anandamide may provide valuable information to understand its behavior in a biological context. Herein, conceptual DFT and QTAIM analyses were performed to theoretically characterize the chemical reactivity properties and the structural stability of conformations of anandamide, using the BP86/cc-pVTZ level of theory.

Possible Co-Evolution of Polyglutamine and Polyproline in Huntingtin Protein: Proline-Rich Domain as Transient Folding Chaperone.

Huntington's disease is an inherited neurodegenerative disorder caused by the overduplication of CAG repeats in the Huntingtin gene. Recent findings revealed that among the orthologs, the expansion of CAG repeats (polyQ) in the Huntingtin gene occurs in tandem with the duplication of CCG repeats (polyP). However, the molecular mechanism of this possible co-evolution remains unknown.

Fluorinated graphene nanomaterial causes potential mechanical perturbations to a biomembrane.

Fluorinated graphene (F-GRA) has attracted great interest in biomedical applications. In this context, the direct interaction between F-GRA and various biomolecules is a vital process guiding the bio-function of this nanomaterial. Nevertheless, information regarding the interaction of F-GRA with biomolecules is scarce, particularly at the molecular level.

Theoretical Study of the Structural Stability, Chemical Reactivity, and Protein Interaction for NMP Compounds as Modulators of the Endocannabinoid System.

The cannabinoid receptors (CB1/CB2) and the T-type calcium channels are involved in disorders associated with both physiological pain and depressive behaviors. Valuable pharmacological species carbazole derivatives such as the NMP-4, NMP-7, and NMP-181 (Neuro Molecular Production) regulate both biological entities. In this work, DFT calculations were performed to characterize theoretically their structural and chemical reactivity properties using the BP86/cc-pVTZ level of theory.

Polymers as Versatile Players in the Stabilization, Capping, and Design of Inorganic Nanostructures.

The integration of simple components to generate sophisticated hybrid materials with fine-tuned properties represents a significant scientific challenge. Herein, we present recent advances in the use of polymers to control the synthesis and properties of three of the most relevant inorganic nanoparticles, namely, quantum dots (QDs), magnetic nanoparticles (MNPs), and noble metal nanoparticles (NMNPs). We show relevant examples of how polymeric structures synthesized by techniques such as ATRP, RAFT, and living cationic polymerization are used to aid in the synthesis and stabilization of the nanostructures to generate nanocomposites with outstanding capabilities.

Novel variants of engineered water soluble mu opioid receptors with extensive mutations and removal of cysteines.

We have shown that water-soluble variants of the human mu opioid receptor (wsMOR) containing a reduced number of hydrophobic residues at the lipid-facing residues of the transmembrane (TM) helices can be expressed in E. coli. In this study, we tested the consequences of increasing the number of mutations on the surface of the transmembrane domain on the receptor's aqueous solubility and ligand binding properties, along with mutation of 11 cysteine residues regardless of their solvent exposure value and location in the protein.