-
Frontiers in Microbiology 2024causes listeriosis, an infectious and potentially fatal disease of animals and humans. A diverse network of transcriptional regulators, including LysR-type catabolite...
causes listeriosis, an infectious and potentially fatal disease of animals and humans. A diverse network of transcriptional regulators, including LysR-type catabolite control protein C (CcpC), is critical for the survival of and its ability to transition into the host environment. In this study, we explored the physiological and genetic consequences of deleting and the effects of such deletion on the ability of to cause disease. We found that deletion did not impact hemolytic activity, whereas it resulted in significant reductions in phospholipase activities. Western blotting revealed that the Δ strain produced significantly reduced levels of the cholesterol-dependent cytolysin LLO relative to the wildtype F2365 strain. However, the Δ mutant displayed no significant intracellular growth defect in macrophages. Furthermore, Δ strain exhibited reduction in plaque numbers in fibroblasts compared to F2365, but plaque size was not significantly affected by deletion. In a murine model system, the Δ strain exhibited a significantly reduced bacterial burden in the liver and spleen compared to the wildtype F2365 strain. Interestingly, the deletion of this gene also enhanced the survival of under conditions of HO-induced oxidative stress. Transcriptomic analyses performed under HO-induced oxidative stress conditions revealed that DNA repair, cellular responses to DNA damage and stress, metalloregulatory proteins, and genes involved in the biosynthesis of peptidoglycan and teichoic acids were significantly induced in the deletion strain relative to F2365. In contrast, genes encoding internalin, 1-phosphatidylinositol phosphodiesterase, and genes associated with sugar-specific phosphotransferase system components, porphyrin, branched-chain amino acids, and pentose phosphate pathway were significantly downregulated in the deletion strain relative to F2365. This finding highlights CcpC as a key factor that regulates physiology and responses to oxidative stress by controlling the expression of important metabolic pathways.
PubMed: 38881664
DOI: 10.3389/fmicb.2024.1403694 -
Biochemistry. Biokhimiia May 2024Extensive skin damage requires specialized therapy that stimulates regeneration processes without scarring. The possibility of using combination of a collagen gel...
Extensive skin damage requires specialized therapy that stimulates regeneration processes without scarring. The possibility of using combination of a collagen gel application as a wound dressing and fibroblast attractant with verteporfin as an antifibrotic agent was examined in vivo and in vitro. In vitro effects of verteporfin on viability and myofibroblast markers expression were evaluated using fibroblasts isolated from human scar tissue. In vivo the collagen gel and verteporfin (individually and in combination) were applied into the wound to investigate scarring during skin regeneration: deviations in skin layer thickness, collagen synthesis, and extracellular matrix fibers were characterized. The results indicate that verteporfin reduces fibrotic phenotype by suppressing expression of the contractile protein Sm22α without inducing cell death. However, administration of verteporfin in combination with the collagen gel disrupts its ability to direct wound healing in a scarless manner, which may be related to incompatibility of the mechanisms by which collagen and verteporfin control regeneration.
Topics: Verteporfin; Humans; Collagen; Fibroblasts; Animals; Wound Healing; Antifibrotic Agents; Cells, Cultured; Tissue Scaffolds; Cicatrix; Male; Fibrosis; Skin
PubMed: 38880654
DOI: 10.1134/S0006297924050146 -
European Journal of Pharmacology Aug 2024The transcription factor nuclear factor κB (NF-κB) is activated by proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) and Toll-like receptor (TLR)...
Porphyrin derivatives inhibit tumor necrosis factor α-induced gene expression and reduce the expression and increase the cross-linked forms of cellular components of the nuclear factor κB signaling pathway.
The transcription factor nuclear factor κB (NF-κB) is activated by proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) and Toll-like receptor (TLR) ligands. Screening of NPDepo chemical libraries identified porphyrin derivatives as anti-inflammatory compounds that strongly inhibited the up-regulation of intercellular adhesion molecule-1 (ICAM-1) expression induced by TNF-α, interleukin-1α, the TLR3 ligand, and TLR4 ligand in human umbilical vein endothelial cells. In the present study, the mechanisms of action of porphyrin derivatives were further elucidated using human lung adenocarcinoma A549 cells. Porphyrin derivatives, i.e., dimethyl-2,7,12,18-tetramethyl-3,8-di(1-methoxyethyl)-21H,23H-porphine-13,17-dipropionate (1) and pheophorbide a (2), inhibited TNF-α-induced ICAM-1 expression and decreased the TNF-α-induced transcription of ICAM-1, vascular cell adhesion molecule-1, and E-selectin genes. 1 and 2 reduced the expression of the NF-κB subunit RelA protein for 1 h, which was not rescued by the inhibition of proteasome- and lysosome-dependent protein degradation. In addition, 1 and 2 decreased the expression of multiple components of the TNF receptor 1 complex, and this was accompanied by the appearance of their cross-linked forms. As common components of the NF-κB signaling pathway, 1 and 2 also cross-linked the α, β, and γ subunits of the inhibitor of NF-κB kinase complex and the NF-κB subunits RelA and p50. Cellular protein synthesis was prevented by 2, but not by 1. Therefore, the present results indicate that porphyrin derivative 1 reduced the expression and increased the cross-linked forms of cellular components required for the NF-κB signaling pathway without affecting global protein synthesis.
Topics: Humans; Signal Transduction; Tumor Necrosis Factor-alpha; Intercellular Adhesion Molecule-1; NF-kappa B; Porphyrins; A549 Cells; E-Selectin; Gene Expression Regulation
PubMed: 38880218
DOI: 10.1016/j.ejphar.2024.176747 -
Analytica Chimica Acta Aug 2024Non-invasive indirect blood glucose monitoring can be realized by detecting low concentrations of glucose (0.05-5 mM) in tears, but sensitive optical indicators are...
BACKGROUND
Non-invasive indirect blood glucose monitoring can be realized by detecting low concentrations of glucose (0.05-5 mM) in tears, but sensitive optical indicators are required. The intensity of the phosphorescence of a candidate optical indicator, palladium hematoporphyrin monomethyl ether (Pd-HMME), is increased by oxygen consumption under sealed conditions in the presence of glucose and glucose oxidase. However, the glucose detection limit based on this mechanism is high (800 μM) because the phosphorescence is completely quenched under ambient oxygen conditions and hence a large amount of glucose is required to reduce the oxygen levels such that the phosphorescence signal is detectable.
RESULTS
To improve the glucose detection limit of Pd-HMME phosphorescence-based methods, the triplet protector imidazole was introduced, and strong phosphorescence was observed under ambient oxygen conditions. Detectable phosphorescence enhancement occurred at low glucose concentrations (<200 μM). Linear correlation between the phosphorescence intensity and glucose concentration was observed in the range of 30-727 μM (R = 99.9 %), and the detection limit was ∼10 μM. The glucose sensor has a fast response time (∼90 s) and excellent selectivity for glucose.
SIGNIFICANCE AND NOVELTY
These results indicate the potential of the developed optical indicator for fast, selective, and reliable low-concentration glucose sensing.
Topics: Limit of Detection; Luminescent Measurements; Hematoporphyrins; Palladium; Glucose; Glucose Oxidase; Blood Glucose; Imidazoles; Biosensing Techniques; Oxygen; Humans
PubMed: 38879210
DOI: 10.1016/j.aca.2024.342825 -
Journal of Inorganic Biochemistry Sep 2024Bacteria use the second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) to control biofilm formation and other key phenotypes in response to environmental...
Bacteria use the second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) to control biofilm formation and other key phenotypes in response to environmental signals. Changes in oxygen levels can alter c-di-GMP signaling through a family of proteins termed globin coupled sensors (GCS) that contain diguanylate cyclase domains. Previous studies have found that GCS diguanylate cyclase activity is controlled by ligand binding to the heme within the globin domain, with oxygen binding resulting in the greatest increase in catalytic activity. Herein, we present evidence that heme-edge residues control O-dependent signaling in PccGCS, a GCS protein from Pectobacterium carotovorum, by modulating heme distortion. Using enzyme kinetics, resonance Raman spectroscopy, small angle X-ray scattering, and multi-wavelength analytical ultracentrifugation, we have developed an integrated model of the full-length PccGCS tetramer and have identified conformational changes associated with ligand binding, heme conformation, and cyclase activity. Taken together, these studies provide new insights into the mechanism by which O binding modulates activity of diguanylate cyclase-containing GCS proteins.
Topics: Phosphorus-Oxygen Lyases; Heme; Bacterial Proteins; Pectobacterium carotovorum; Protein Conformation; Oxygen; Cyclic GMP; Escherichia coli Proteins
PubMed: 38878680
DOI: 10.1016/j.jinorgbio.2024.112638 -
Dalton Transactions (Cambridge, England... Jul 2024Electrocatalytic hydrogen generation in alkaline medium has become widely used in a variety of sectors. However, the possibility for additional performance improvement...
Electrocatalytic hydrogen generation in alkaline medium has become widely used in a variety of sectors. However, the possibility for additional performance improvement is hampered by slow kinetics. Because of this restriction, careful control over processes such as water dissociation, hydroxyl desorption and hydrogen recombination is required. Covalent organic frameworks (COFs) based on porphyrin and polyoxometalates (POMs) show encouraging electrocatalytic performance, offering a viable route for effective and sustainable hydrogen generation. Their specific architectures lead to increased electrocatalytic activity, which makes them excellent choices for developing water electrolysis as a clean energy conversion method in the alkaline medium. In this regard, TTris@ZnPor and Lindqvist POM were coordinated to create a new eco-friendly and highly active covalent organic framework (TP@VL-COF). In order to describe TP@VL-COF, extensive structural and morphological investigations were carried out through FTIR, H NMR, elemental analysis, SEM, fluorescence, UV-visible, PXRD, CV, N-adsorption isotherm, TGA and DSC analyses. In an alkaline medium, the electrocatalytic capability of 20%C/Pt, TTris@ZnPor, Lindqvist POM and TP@VL-COF was explored and compared for the hydrogen evolution reaction (HER). The TP@VL-COF showed the best catalytic efficiency for HER in an alkaline electrolyte, requiring just a 75 mV overpotential to drive 10 mA cm and outperforming 20%C/Pt, TTris@ZnPor, Lindqvist POM and other reported catalysts. The Tafel slope value also indicates faster kinetics for TP@VL-COF (114 mV dec) than for 20%C/Pt (182 mV dec) TTris@ZnPor (116 mV dec) and Lindqvist POM (125 mV dec).
PubMed: 38874545
DOI: 10.1039/d4dt00788c -
Advanced Science (Weinheim,... Jun 2024Smart drug platforms based on spatiotemporally controlled release and integration of tumor imaging are expected to overcome the inefficiency and uncertainty of...
Smart drug platforms based on spatiotemporally controlled release and integration of tumor imaging are expected to overcome the inefficiency and uncertainty of traditional theranostic modes. In this study, a composite consisting of a thermosensitive hydrogel (polyvinyl alcohol-carboxylic acid hydrogel (PCF)) and a multifunctional nanoparticle (FeO@Au/Mn(Zn)-4-carboxyphenyl porphyrin/polydopamine (FAMP)) is developed to combine tumor immunogenic cell death (ICD)/immune checkpoint blockade (ICB) therapy under the guidance of magnetic resonance imaging (MRI) and fluorescence imaging (FI). It can not only further recognize the target cells through the folate receptor of tumor cells, but also produce thermal dissolution after exposure to near-infrared light to slowly release FAMP in situ, thereby prolonging the treatment time and avoiding tumor recurrence. As FAMP entered the tumor cells, it released FAM in a pH-dependent manner. Chemodynamic, photothermal and photodynamic therapy can cause significant ICD in cancer cells. ICB can thus be further enhanced by injecting anti-programmed cell death ligand 1, improving the effectiveness of tumor treatment. The developed PCF-FAMP composite hydrogel may represent an updated drug design approach with simple compositions for cooperative MRI/FI-guided targeted therapeutic pathways for tumors.
PubMed: 38874481
DOI: 10.1002/advs.202404172 -
Chemical Science Jun 2024The construction and application of metal-organic cages with accessible internal cavities have witnessed rapid development, however, the precise synthesis of complex...
The construction and application of metal-organic cages with accessible internal cavities have witnessed rapid development, however, the precise synthesis of complex metal-organic capsules with multiple cavities and achievement of multi-guest encapsulation, and further in-depth comprehension of host-multi-guest recognition remain a great challenge. Just like building LEGO blocks, herein, we have constructed a series of high-order layered metal-organic architectures of generation ( = 1/2/3/4 is also the number of cavities) by multi-component coordination-driven self-assembly using porphyrin-containing tetrapodal ligands (like plates), multiple parallel-podal ligands (like clamps) and metal ions (like nodes). Importantly, these high-order assembled structures possessed different numbers of rigid and separate cavities formed by overlapped porphyrin planes with specific gaps. The host-guest experiments and convincing characterization proved that these capsules G2-G4 could serve as host structures to achieve multi-guest recognition and unprecedentedly encapsulate up to four C molecules. More interestingly, these capsules revealed negative cooperation behavior in the process of multi-guest recognition, which provides a new platform to further study complicated host-multi-guest interaction in the field of supramolecular chemistry.
PubMed: 38873050
DOI: 10.1039/d4sc01204f -
Chemistry (Weinheim An Der Bergstrasse,... Jun 2024Sustainable alternatives for the energy intensive synthesis of H2O2 are necessary. Molecular cobalt catalysts show potential but are typically restricted by undesired...
Sustainable alternatives for the energy intensive synthesis of H2O2 are necessary. Molecular cobalt catalysts show potential but are typically restricted by undesired bimolecular pathways leading to the breakdown of both H2O2 and the catalyst. The confinement of cobalt porphyrins in the PCN-224 metal-organic framework leads to an enhanced selectivity towards H2O2 and stability of the catalyst. Consequently, oxygen can now be selectively reduced to hydrogen peroxide with a stable conversion for at least 5 h, illustrating the potential of catalysts confined in MOFs to increase the selectivity and stability of electrocatalytic conversions.
PubMed: 38872486
DOI: 10.1002/chem.202401339 -
Biomedical Materials (Bristol, England) Jun 2024Recently, cytokine-induced killer (CIK) cells have a broad application prospect in the comprehensive diagnosis and treatment of tumors owing to their unique...
Recently, cytokine-induced killer (CIK) cells have a broad application prospect in the comprehensive diagnosis and treatment of tumors owing to their unique characteristics of killing and targeting malignant tumors. Herein, we report a facile strategy for synthesis of monodisperse gold nanostars (GNSs) based on PEGylation and co-loaded with the photosensitizer chlorin e6 (Ce6) to form GNSs-PEG@Ce6 NPs. Then employing CIK cells loading the as-prepared GNSs-PEG@Ce6 NPs to fabricate a CIK cells-based drug delivery system (GNSs-PEG@Ce6-CIK) for lung cancer. Among them, GNSs was functioned as transport media, Ce6 acted as the near-infrared (NIR) fluorescence imaging agent and photodynamic therapy (PDT), and CIK cells served as targeting vectors for immunotherapy, which can increase the efficiency of tumor enrichment and treatment effect. The results of cellular experiments demonstrated that GNSs-PEG@Ce6 NPs had good dispersibility, water solubility and low toxicity under physiological conditions, and the cultured CIK cells had strong anti-tumor properties. Subsequently, GNSs-PEG@Ce6-CIK could effectively inhibit the growth of A549 cells under the exposure of 633 nm laser, which showed stronger killing effect than that of GNSs-PEG@Ce6 NPs or CIK cells. In addition, they showed good tumor targeting and tumor synergistic killing activity. Therefore, GNSs-PEG@Ce6-CIK was constructed for targeted NIR fluorescence imaging, enhanced PDT and immunotherapy of lung cancer.
Topics: Gold; Chlorophyllides; Photochemotherapy; Lung Neoplasms; Humans; Animals; Porphyrins; Cytokine-Induced Killer Cells; Photosensitizing Agents; Metal Nanoparticles; Mice; Immunotherapy; Cell Line, Tumor; Drug Delivery Systems; Polyethylene Glycols; A549 Cells; Optical Imaging; Mice, Nude
PubMed: 38870927
DOI: 10.1088/1748-605X/ad580c