-
ACS Omega May 2024Antibiotics are frequently used to treat, prevent, or control bacterial infections, but in recent years, infections resistant to all known classes of conventional...
Antibiotics are frequently used to treat, prevent, or control bacterial infections, but in recent years, infections resistant to all known classes of conventional antibiotics have significantly grown. The development of novel, nontoxic, and nonincursive antimicrobial methods that work more quickly and efficiently than the present antibiotics is required to combat this growing public health issue. Here, Co(II) and Zn(II) derivatives of tetrakis(1-methylpyridinium-4yl)porphyrin [HTMPyP] as a tetra(ρ-toluenesulfonate) were synthesized and purified to investigate their interactions with DNA (pH 7.40, 25 °C) using UV-vis, fluorescence techniques, and antimicrobial activity. UV-vis results showed that [HTMPyP] had a high hypochromicity (∼64%) and a substantial bathochromic shift (Δλ, 14 nm), while [Co(II)TMPyP] and [Zn(II)TMPyP] showed little hypochromicity (∼37%) and a small bathochromic shift (Δλ, 3-6 nm). Results reveal that [HTMPyP] interacts with DNA via intercalation, while Co(II)- and [Zn(II)TMPyP] interact with DNA via outside self-stacking. Fluorescence results also confirmed the interaction of [HTMPyP] and the metalloporphyrins with DNA. Results of the antimicrobial activity assay revealed that the metalloporphyrins showed inhibitory effects on Gram-positive and Gram-negative bacteria and fungi, but that neither the counterions nor [HTMPyP] exhibited any inhibitory effects. Mechanism of antimicrobial activities of metalloporphyrins are discussed.
PubMed: 38799349
DOI: 10.1021/acsomega.4c01708 -
International Journal of Molecular... May 2024Heme biosynthesis is a highly conserved pathway from bacteria to higher animals. Heme, which serves as a prosthetic group for various enzymes involved in multiple...
Heme biosynthesis is a highly conserved pathway from bacteria to higher animals. Heme, which serves as a prosthetic group for various enzymes involved in multiple biochemical processes, is essential in almost all species, making heme homeostasis vital for life. However, studies on the biological functions of heme in filamentous fungi are scarce. In this study, we investigated the role of heme in . A mutant lacking the rate-limiting enzymes in heme synthesis, coproporphyrinogen III oxidase (Cpo) or ferrochelatase (Fc), was constructed using a homologous recombination strategy. The results showed that the absence of these enzymes was lethal to , but the growth defect could be rescued by the addition of hemin, so we carried out further studies with the help of hemin. The results demonstrated that heme was required for the activity of FgCyp51, and its absence increased the sensitivity to tebuconazole and led to the upregulation of in . Additionally, heme plays an indispensable role in the life cycle of , which is essential for vegetative growth, conidiation, external stress response (especially oxidative stress), lipid accumulation, fatty acid β-oxidation, autophagy, and virulence.
Topics: Fusarium; Heme; Fungal Proteins; Stress, Physiological; Oxidative Stress; Triazoles; Gene Expression Regulation, Fungal; Fungicides, Industrial; Ferrochelatase
PubMed: 38791308
DOI: 10.3390/ijms25105268 -
Biomimetics (Basel, Switzerland) Apr 2024To inhibit the deep conversion of partial oxidation products (POX-products) in C-H bonds' functionalization utilizing O,...
Efficient Inhibition of Deep Conversion of Partial Oxidation Products in C-H Bonds' Functionalization Utilizing O via Relay Catalysis of Dual Metalloporphyrins on Surface of Hybrid Silica Possessing Capacity for Product Exclusion.
To inhibit the deep conversion of partial oxidation products (POX-products) in C-H bonds' functionalization utilizing O, 5-(4-(chloromethyl)phenyl)-10,15,20-tris(perfluorophenyl)porphyrin cobalt(II) and 5-(4-(chloromethyl)phenyl)-10,15,20-tris(perfluorophenyl)porphyrin copper(II) were immobilized on the surface of hybrid silica to conduct relay catalysis on the surface. Fluorocarbons with low polarity and heterogeneous catalysis were devised to decrease the convenient accessibility of polar POX-products to catalytic centers on the lower polar surface. Relay catalysis between Co and Cu was designed to utilize the oxidation intermediates alkyl hydroperoxides to transform more C-H bonds. Systematic characterizations were conducted to investigate the structure of catalytic materials and confirm their successful syntheses. Applied to C-H bond oxidation, not only deep conversion of POX-products was inhibited but also substrate conversion and POX-product selectivity were improved simultaneously. For cyclohexane oxidation, conversion was improved from 3.87% to 5.27% with selectivity from 84.8% to 92.3%, which was mainly attributed to the relay catalysis on the surface excluding products. The effects of the catalytic materials, product exclusion, relay catalysis, kinetic study, substrate scope, and reaction mechanism were also investigated. To our knowledge, a practical and novel strategy was presented to inhibit the deep conversion of POX-products and to achieve efficient and accurate oxidative functionalization of hydrocarbons. Also, a valuable protocol was provided to avoid over-reaction in other chemical transformations requiring high selectivity.
PubMed: 38786482
DOI: 10.3390/biomimetics9050272 -
RSC Advances May 2024Porphyrin and porphyrinoid derivatives have been extensively studied in the assembly of catalysts and sensors, seeking biomimetic and bioinspired activity. In...
Porphyrin and porphyrinoid derivatives have been extensively studied in the assembly of catalysts and sensors, seeking biomimetic and bioinspired activity. In particular, Fe and Ni porphyrins can be used for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) by immobilization of these molecular catalysts on semiconductor materials. In this study, we designed a hybrid material containing a crystalline mesoporous TiO thin film in which the catalytic centres are Ni-porphyrin (NiP), Fe-porphyrin (FeP), and a NiP/FeP bimetallic system to assess whether the coexistence of both metalloporphyrins improves the OER activity. The obtained photoelectrodes were physicochemically and morphologically characterized through high-resolution FE-SEM images, UV-vis and Raman spectroscopies, cyclic voltammetry, and impedance measurements. The results show a differential behavior of the mono- and bimetallic porphyrin systems, where the Fe(iii) centre in FeP may increase the acidity and lower the reduction potential of the Ni couple when co-deposited with NiP leading to an improved photoelectrochemical water-oxidation performance. We have validated the cooperative effect of both metal complexes within this novel system, where the μ-peroxo-bridged interaction between Fe and Ni is integrated into a supramolecular heterometallic structure of porphyrins.
PubMed: 38756854
DOI: 10.1039/d3ra08047a -
Skin Research and Technology : Official... May 2024Androgenic alopecia (AGA) is the most common non-scarring alopecia disorder. Given its increasing incidence and onset during adolescence, AGA significantly impacts both...
BACKGROUND
Androgenic alopecia (AGA) is the most common non-scarring alopecia disorder. Given its increasing incidence and onset during adolescence, AGA significantly impacts both the physical and psychological well-being of affected individuals. Emerging evidence suggests a pivotal role of metabolites in AGA. This study aims to elucidate the causal relationship between metabolites and AGA using Mendelian randomization (MR) analysis.
METHODS
We conducted a two-sample Mendelian randomization (TSMR) analysis based on a genome-wide association study (GWAS) to assess the causality of 452 metabolites on AGA. The main approach employed for inferring causal effects was inverse variance weighted (IVW), which was complemented by MR-Egger regression, weighted median, as well as MR pleiotropy residual sum and outlier (MR-PRESSO) approaches. Additionally, sensitivity analyses were performed to ensure result robustness. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) in GWAS dataset comprising 452 metabolites.
RESULTS
Notably, we identified Scyllo-inositol and Alpha-ketoglutarate as the most potent protective factors against AGA, while Heme* and 2-palmitoylglycerophosphocholine* emerged as significant risk factors for AGA. Furthermore, sensitivity analysis revealed no heterogeneity in these findings.
CONCLUSIONS
Overall, our research suggests a potential causal link between metabolites and AGA, offering a more comprehensive insight into the pathogenesis of AGA and present additional strategies for prevention and treatment.
Topics: Humans; Alopecia; Mendelian Randomization Analysis; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Male; Heme; Female
PubMed: 38747971
DOI: 10.1111/srt.13732 -
Nature Communications May 2024Bleeding and thrombosis are known as common complications of polycythemia for a long time. However, the role of coagulation system in erythropoiesis is unclear. Here, we...
Bleeding and thrombosis are known as common complications of polycythemia for a long time. However, the role of coagulation system in erythropoiesis is unclear. Here, we discover that an anticoagulant protein tissue factor pathway inhibitor (TFPI) plays an essential role in erythropoiesis via the control of heme biosynthesis in central macrophages. TFPI levels are elevated in erythroblasts of human erythroblastic islands with JAK2 mutation and hypoxia condition. Erythroid lineage-specific knockout TFPI results in impaired erythropoiesis through decreasing ferrochelatase expression and heme biosynthesis in central macrophages. Mechanistically, the TFPI interacts with thrombomodulin to promote the downstream ERK1/2-GATA1 signaling pathway to induce heme biosynthesis in central macrophages. Furthermore, TFPI blockade impairs human erythropoiesis in vitro, and normalizes the erythroid compartment in mice with polycythemia. These results show that erythroblast-derived TFPI plays an important role in the regulation of erythropoiesis and reveal an interplay between erythroblasts and central macrophages.
Topics: Polycythemia; Erythroblasts; Erythropoiesis; Heme; Humans; Animals; Lipoproteins; Macrophages; Mice; GATA1 Transcription Factor; Janus Kinase 2; Thrombomodulin; Mice, Knockout; Ferrochelatase; Male; MAP Kinase Signaling System; Mice, Inbred C57BL; Female
PubMed: 38729948
DOI: 10.1038/s41467-024-48328-8 -
Chemical Science May 2024The understanding of electron transfer pathways and orbital interactions between analytes and adsorption sites in gas-sensitive studies, especially at the atomic level,...
The understanding of electron transfer pathways and orbital interactions between analytes and adsorption sites in gas-sensitive studies, especially at the atomic level, is currently limited. Herein, we have designed eight isoreticular catechol-metalloporphyrin scaffolds, FeTCP-M and InTCP-M (TCP = 5,10,15,20-tetrakis-catechol-porphyrin, M = Fe, Co, Ni and Zn) with adjustable charge transfer schemes in the coordination microenvironment and precise tuning of orbital interactions between analytes and adsorption sites, which can be used as models for exploring the influence of these factors on gas sensing. Our experimental findings indicate that the sensitivity and selectivity can be modulated using the type of metals in the metal-catechol chains (which regulate the electron transfer routes) and the metalloporphyrin rings (which fine-tune the orbital interactions between analytes and adsorption sites). Among the isostructures, InTCP-Co demonstrates the highest response and selectivity to NO under visible light irradiation, which could be attributed to the more favorable transfer pathway of charge carriers in the coordination microenvironment under visible light illumination, as well as the better electron spin state compatibility, higher orbital overlap and orbital symmetry matching between the N-2s2p hybrid orbital of NO and the Co-3d orbital of InTCP-Co.
PubMed: 38725503
DOI: 10.1039/d3sc06909e -
Analytical Chemistry May 2024Given its pivotal role in modulating various pathological processes, precise measurement of nitric oxide (NO) levels in physiological solutions is imperative. The key...
Given its pivotal role in modulating various pathological processes, precise measurement of nitric oxide (NO) levels in physiological solutions is imperative. The key techniques include the ozone-based chemiluminescence (CL) reactions, amperometric NO sensing, and Griess assay, each with its advantages and drawbacks. In this study, a hemin/HO/luminol CL reaction was employed for accurately detecting NO in diverse solutions. We investigated how the luminescence kinetics was influenced by NO from two donors, nitrite and peroxynitrite, while also assessing the impact of culture medium components and reactive species quenchers. Furthermore, we experimentally and theoretically explored the mechanism of hemin oxidation responsible for the initiation of light generation. Although both hemin and NO enhanced the HO/luminol-based luminescence reactions with distinct kinetics, hemin's interference with NO/peroxynitrite modulated their individual effects. Leveraging the propagated signal due to hemin, the NO levels in solution were estimated, observing parallel changes to those detected via amperometric detection in response to varying concentrations of the NO-donor. The examined reactions aid in comprehending the mechanism of NO/hemin/HO/luminol interactions and how these can be used for detecting NO in solution with minimal sample size demands. Moreover, the selectivity across different solutions can be improved by incorporating certain quenchers for reactive species into the reaction.
Topics: Hemin; Nitric Oxide; Hydrogen Peroxide; Molecular Probes; Luminol; Solutions; Luminescent Measurements; Peroxynitrous Acid; Kinetics; Oxidation-Reduction
PubMed: 38699865
DOI: 10.1021/acs.analchem.4c01516 -
Inorganic Chemistry May 2024Ground-state and time-dependent density functional theory (TDDFT) calculations with the long-range-corrected, Coulomb-attenuating CAMY-B3LYP exchange-correlation...
Ground-state and time-dependent density functional theory (TDDFT) calculations with the long-range-corrected, Coulomb-attenuating CAMY-B3LYP exchange-correlation functional and large, all-electron STO-TZ2P basis sets have been used to examine the potential "inverse hypercorrole" character of -nitrophenyl-appended dicyanidocobalt(III) corrole dianions. The effect is most dramatic for 5,15-bis(-nitrophenyl) derivatives, where it manifests itself in intense NIR absorptions. The 10-aryl groups in these complexes play a modulatory role, as evinced by experimental UV-visible spectroscopic and electrochemical data for a series of 5,15-bis(-nitrophenyl) dicyanidocobalt(III) corroles. TDDFT (CAMY-B3LYP) calculations ascribe these features clearly to a transition from the corrole's a-like HOMO (retaining the irrep used for metalloporphyrins) to a nitrophenyl-based LUMO. The outward nature of this transition contrasts with the usual phenyl-to-macrocycle direction of charge transfer transitions in many hyperporphyrins and hypercorroles; thus, the complexes studied are aptly described as inverse hypercorroles.
PubMed: 38696617
DOI: 10.1021/acs.inorgchem.4c00344 -
ACS Nano May 2024Assessment of hypoxia, nutrients, metabolite gradients, and other hallmarks of the tumor microenvironment within 3D multicellular spheroid and organoid models represents...
Assessment of hypoxia, nutrients, metabolite gradients, and other hallmarks of the tumor microenvironment within 3D multicellular spheroid and organoid models represents a challenging analytical task. Here, we report red/near-infrared (NIR) emitting cell staining with O-sensitive nanoparticles, which enable measurements of spheroid oxygenation on a conventional fluorescence microscope. Nanosensor probes, termed "MMIR" (multimodal infrared), incorporate an NIR O-sensitive metalloporphyrin (PtTPTBPF) and deep red aza-BODIPY reference dyes within a biocompatible polymer shell, allowing for oxygen gradient quantification via fluorescence ratio and phosphorescence lifetime readouts. We optimized staining techniques and evaluated the nanosensor probe characteristics and cytotoxicity. Subsequently, we applied nanosensors to the live spheroid models based on HCT116, DPSCs, and SKOV3 cells, at rest, and treated with drugs affecting cell respiration. We found that the growth medium viscosity, spheroid size, and formation method influenced spheroid oxygenation. Some spheroids produced from HCT116 and dental pulp stem cells exhibited "inverted" oxygenation gradients, with higher core oxygen levels than the periphery. This contrasted with the frequently encountered "normal" gradient of hypoxia toward the core caused by diffusion. Further microscopy analysis of spheroids with an "inverted" gradient demonstrated metabolic stratification of cells within spheroids: thus, autofluorescence FLIM of NAD(P)H indicated the formation of a glycolytic core and localization of OxPhos-active cells at the periphery. Collectively, we demonstrate a strong potential of NIR-emitting ratiometric nanosensors for advanced microscopy studies targeting live and quantitative real-time monitoring of cell metabolism and hypoxia in complex 3D tissue models.
Topics: Humans; Spheroids, Cellular; Oxygen; Nanoparticles; Microscopy, Fluorescence; Infrared Rays; Metalloporphyrins
PubMed: 38687976
DOI: 10.1021/acsnano.3c12539