Porphyromonas gingivalisInduced Neuroinflammation throughout Alzheimers Disease
The possible role of anti-tumor compounds to target SOX pathway members in GC therapy is described. Moreover, SOX proteins may be used as diagnostic or prognostic biomarkers in GC.Jararhagin is a hyperalgesic metalloproteinase from Bothrops jararaca venom. In rodents, jararhagin induces nociceptive behaviors that correlate with an increase in peripheral cytokine levels. However, the role of the spinal cord glia in pain processing after peripheral stimulus of jararhagin has not been investigated. Aiming to explore this proposal, mice received intraplantar (i.pl.) injection of jararhagin and the following parameters were evaluated hyperalgesia, spinal cord TNF-α, IL-1β levels, and CX3CR1, GFAP and p-NFκB activation. The effects of intrathecal (i.t.) injection of TNF-α soluble receptor (etanercept), IL-1 receptor antagonist (IL-1Ra), and inhibitors of NFκB (PDTC), microglia (minocycline) and astrocytes (α-aminoadipate) were investigated. Jararhagin inoculation induced cytokine production (TNF-α and IL-1β) in the spinal cord, which was reduced by treatment with PDTC (40% and 50%, respectively). Jararhagin mechanical hyperalgesia and cytokine production were inhibited by treatment with etanercept (67%), IL-1Ra (60%), PDTC (70%), minocycline (60%) and α-aminoadipate (45%). Furthermore, jararhagin induced an increase in p-NFκB, CX3CR1 and GFAP detection in the spinal cord indicating activation of NFκB, microglia and astrocytes. These results demonstrate for the first time that jararhagin-induced mechanical hyperalgesia is dependent on spinal cord activation of glial cells, consequent NFκB activation, and cytokine production in mice.One novel alkali-extracted polysaccharide, CM3-SII, was obtained from the fruiting body of C. militaris via column chromatography. Its structural characteristics were investigated via chemical and spectroscopic methods. The backbone of CM3-SII was composed of →4)-β-D-Manp(1→, →6)-β-D-Manp(1→, and →6)-α-D-Manp(1→ glycosyls, and branching at the O-4 positions of →6)-β-D-Manp(1→ glycosyls with β-D-Galp, (1→2) linked-β-D-Galf, and →2,6)-α-D-Manp(1→ residues. Furthermore, O-6 and O-2 positions of the →2,6)-α-D-Manp(1→ residues were substituted with methyl and β-D-Galp, respectively. This polysaccharide significantly enhanced the intracellular protein expression of low-density lipoprotein receptor and proprotein convertase subtilisin/kexin type 9 (PCSK9) via regulating sterol regulatory element-binding protein 2 in hepatoma Huh7 cells. Of note, CM3-SII significantly decreased PCSK9 secretion at the concentration of 200 μg/mL. Collectively, CM3-SII is different from the previously reported alkali-extracted polysaccharides isolated from the fruiting body of C. militaris, and it may have potential application in hypolipidemia or as a pharmaceutical additive.The antibacterial and biocompatible films have attracted much attention due to their wide range of applications. Although a lot of work has been done in this area, research in this field is still very active and associated with the continuous development of new materials. In the present study full polysaccharide chitosan-agarose (CS-AG) films were produced by reaction of chitosan with periodate activated agarose, followed by reductive amination. Activated agarose was prepared by periodate oxidation of agarose, and then applied as a crosslinking agent to form a new polymeric network. The structure of periodate activated agarose was studied by nuclear magnetic resonances spectroscopy (1H NMR) and Fourier-transform infrared spectroscopy (FT-IR). Rheological experiments showed that the viscosity of agarose solution changes rapidly by addition of periodate to the solution. Swelling, deswelling, and gel content of the films were determined at different pH. Chitosan-agarose silver nanocomposite (CS-AG/n-Ag) films were prepared by loading silver ions and subsequent reduction. The CS-AG/n-Ag films were characterized by FT-IR, thermogravimetric analysis (TGA), and scanning electron microscopy (SEM).Transmission electron microscopy (TEM) image showed that the size of silver nanoparticles was about 2-7 nm. MRTX1257 The bactericidal capacities (MBC/MIC) of the CS-AG/Ag films for Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus) were obtained 2.0, 1.0 and 2.0, respectively. The results demonstrate that the CS-AG/n-Ag films have good antibacterial activity against both the gram-negative and the gram-positive bacteria which make them suitable for food packaging and wound healing applications.The binding mode to TAP (i.e., the peptide transporter associated with antigen processing) from a viral peptide thus far has been unknown in the field of antiviral immunity, but an interfering mode from a virus-encoded TAP inhibitor has been well documented with respect to blocking the TAP function. In the current study, we predicted the structure of the pig TAP transporter and its inhibition complex by the small viral protein ICP47 of the herpes simplex virus (HSV) encoded by the TAP inhibitor to exploit inhibition of the TAP transporter as the host's immune evasion strategy. We found that the hot spots (residues Leu5, Tyr22, and Leu51) on the ICP47 inhibitor interface tended to prevail over the favored Leu and Tyr, which contributed to significant functional binding at the C-termini recognition principle of the TAP. We further characterized the specificity determinants of the peptide transporter from the pig TAP by the ICP47 inhibitor effects and multidrug TmrAB transporter from the Thermus thermophillus and its immunity regarding its structural homolog of the pig TAP. The specialized structure-function relationship from the pig TAP exporter could provide insight into substrate specificity of the unique immunological properties from the host organism. The TAP disarming capacity from all five viral inhibitors (i.e., the five virus-encoded TAP inhibitors of ICP47, UL49.5, U6, BNLF2a, and CPXV012 proteins) was linked to the infiltration of the TAP functional structure in an unstable conformation and the mounting susceptibility caused by the host's TAP polymorphism. It is anticipated that the functional characterization of the pig TAP transporter based on the pig genomic variants will lead to additional insights into the genotype and single nucleotide polymorphism (SNP) in relation to antiviral resistance and disease susceptibility.Globally, SARS-CoV-2 has emerged as threat to life and economy. Researchers are trying to find a cure against this pathogen but without much success. Several attempts have been made to understand the atomic level details of SARS-CoV-2 in the past few months. However, one review with all structural details for drug and vaccine development has been missing. Hence, this review aims to summarize key functional roles played by various domains of SARS-CoV-2 genome during its entry into the host, replication, repression of host immune response and overall viral life cycle. Additionally, various proteins of SARS-CoV-2 for finding a potent inhibitor have also been highlighted. To mitigate this deadly virus, an understanding of atomic level information, pathogenicity mechanisms and functions of different proteins in causing the infection is imperative. Thus, these structural details would finally pave the way for development of a potential drug/vaccine against the disease caused by SARS-CoV-2.Recently, cellulose-based stimuli-responsive nanomaterials have received significant attention because of its natural source and biocompatibility. In this study, cellulose-graft-poly(nisopropylacrylamide)-co-2-methyl-acrylic acid 2-carbazol-9-yl-ethyl ester (cellulose-g-(PNIPAAm&PCz)) block polymers were successfully synthesized by homogeneous atom transfer radical polymerization (ATRP) in LiCl/N,N-dimethylacetamide (DMAc) dissolution system. The block polymers showed different properties due to the different PCz content. The block polymer with low PCz content (cellulose-g-(PNIPAAm&PCz)1) was dispersed in water at 25 °C and self-assembled into micelles at 37 °C. On the other hand, the block polymer with high PCz content (cellulose-g-(PNIPAAm&PCz)2) was dissolved in DMF, THF, DMSO firstly, and dialyzed at 25 °C, 37 °C and 60 °C respectively to obtain the micelles. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) indicated that the distribution range of micelles formed by cellulose-g-(PNIPAAm&PCz)1 was narrower than cellulose-g-(PNIPAAm&PCz)2. And the sizes of the micelles formed by cellulose-g-(PNIPAAm&PCz)2 had little difference under different solvents, but became bigger with the temperature increased. The micelles displayed thermo-enhanced fluorescence due to the thermal-driven chain dehydration of the grafted PNIPAAm brushes, which is contrary to the decrease of the fluorescence of the monomer when the temperature increased. The results provided a potential for the application of cellulose-based stimuli-responsive micelles in the field of drug delivery and fluorescent probes.Polymer-clay nanocomposite hydrogel films (PCNCHFs) were prepared from caboxymethyl cellulose, polyvinylpyrrolidone, agar and nanosepiolite clay (0, 0.3, 0.5, 0.7, 0.9 and 1.5% reinforcement) by treating thermally in a simple, rapid, and inexpensive route. The PCNCHFs and its 5-fluorouracil (FU)-loaded composites (PCNCHFs@FU) were tested for FU release and characterized by FTIR, XRD, FE-SEM, EDX, DSC, and TGA analyses to investigate their structural, morphological, and thermal properties. The nanosepiolite-loaded polymer composites (PCNCHF1 to PCNCHF5) exhibited higher tensile strength than the pristine polymer hydrogel (PCNCHF0); consequently, the thermal properties (glass- and melting-transition) were improved. The PCNCHFs@FU demonstrated prolonged FU release at pH 7.4 for 32 h. The biocompatibility of PCNCHFs was tested against human skin fibroblast (CCDK) cells. The viability of cells exposed to all PCNCHFs was >95% after 72 h of culture. The live/dead assay show the proliferation of fibroblast cells, confirming the biocompatibility of the hydrogels. The pH-sensitive PCNCHFs@FU release could be suitable for drug release in cancer therapy, and the developed PCNCHFs may also be useful for tissue engineering, food packaging, and other biological applications.Amyloid proteins were recognized as the crucial cause of many senile diseases. In this study, the inhibitory effects of Sennoside A (SA) and Sennoside C (SC) on amyloid fibrillation were evaluated by the combination of biophysical approaches and molecular docking tool using human lysozyme (HL) as amyloid-forming model. The results of thioflavin-T (ThT), 8-anilino-1-naphthalenesulfonic acid (ANS) and congo red (CR) assays indicated that both SA and SC could inhibit the amyloid fibrillation of HL in a dose-dependent manner. The IC50 value of SA and SC on HL fibrillation was 200.09 μM and 186.20 μM, respectively. These findings were further verified by transmission electron microscopy (TEM) and atomic force microscopy (AFM), which showed that the addition of SA or SC could sharply reduce the amyloid fibrillation of HL. Additionally, the interactions of HL with SA and SC were investigated by steady-state fluorescence spectra and molecular docking studies. The results suggested that both SA and SC could bind to the binding pocket of HL and form a stable complex mainly via hydrogen bonds, van-der-Waals forces and hydrophobic interactions.