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Discover Nano Oct 2023BiOCl is a potential photocatalyst in practical applications due to its excellent photostability, visible light activity, and competitive bandgap energy. However, the...
BiOCl is a potential photocatalyst in practical applications due to its excellent photostability, visible light activity, and competitive bandgap energy. However, the fast recombination of photogenerated charge carriers makes it impractical for pollution mitigation. Recently, aggregated porphyrins have emerged as photosensitizers in light-dependent applications such as photocatalysis. Although BiOCl and porphyrin can function as separate photocatalysts, their photocatalytic properties in terms of visible light adsorption, charge separation and transport, can be improved when they are combined to form heterostructure. In this study, rod-shaped aggregated 5,10,15, 20-Tetrakis (4-carboxyphenyl) porphyrin was synthesized by CTAB-assisted, self-assembly strategy and BiOCl by a facile microwave method. The porphyrin and BiOCl were combined to generate a series of x%Porphyrin@BiOCl having 0.02% wt., 0.1% wt., 0.4% wt., 1% wt. and 10% wt. as compositions of porphyrin. The materials' photocatalytic degradation efficiency was tested on Rhodamine B dye as a representative pollutant. The best and worst performances were reported for 1%Porphyrin@BiOCl and 10%Porphyrin@BiOCl, respectively, which are 3.1 and 0.5 times increases in efficiency compared to pure BiOCl. From the radical trapping experiment, electrons and superoxide were the dominant reactive species in the degradation process. The enhanced photocatalytic capability of the materials was attributed to the photosensitizing property of porphyrin and the heterojunction formation, which promotes the separation of photogenerated charge carriers. A plausible step-scheme (S-scheme) was proposed for the photocatalytic degradation mechanism. The S-scheme provided the high redox potential of the photogenerated charge carriers. The findings herein offer a new option for improving the photocatalytic performance of BiOCl for environmental applications through the photosensitization strategy.
PubMed: 37906403
DOI: 10.1186/s11671-023-03915-4 -
RSC Advances Jul 2023We report herein the surface decoration of a water-soluble free-base porphyrin, namely, 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin-tetra(-toluenesulfonate)...
We report herein the surface decoration of a water-soluble free-base porphyrin, namely, 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin-tetra(-toluenesulfonate) (HTMPyP), over three different zirconium-based metal-organic frameworks of different linker structure and functionality; namely UiO66, UiO66-NH, and MIP-202, self-assembly. The synthesized MOFs along with the resulting complexes have been characterized spectroscopic and analytical techniques (XRD, FT-IR, TEM, N adsorption/desorption, and laser scanning confocal microscopy). The self-assembly of HTMPyP with the examined three MOFs was observed by using the steady-state absorption and fluorescence, as well as the fluorescence lifetime studies. It was evident that the highest complex interaction was recorded between porphyrin and UiO-66-NH compared with the lowest interactions between porphyrin and MIP-202. This is in good agreement with the high surface area and pore volume of UiO-66 (1100 m g and 0.68 cm g) and compared to that of MIP-202 (94 m g and 0.26 cm g). The photocatalytic activities of the three porphyrin entities immobilized zirconium-based MOFs were compared toward methyl orange dye degradation from aqueous solution under visible light irradiation ( = 430 nm). The photocatalytic studies render the fabrication of the self-assembled HTMPyP@UiO-66-NH composite as a promising material for dye degradation from polluted wastewater.
PubMed: 37529362
DOI: 10.1039/d3ra02656f -
Free Radical Biology & Medicine Aug 2023Kidneys are pivotal organ in iron redistribution and can be severely damaged in the course of hemolysis. In our previous studies, we observed that induction of...
Kidneys are pivotal organ in iron redistribution and can be severely damaged in the course of hemolysis. In our previous studies, we observed that induction of hypertension with angiotensin II (Ang II) combined with simvastatin administration results in a high mortality rate or the appearance of signs of kidney failure in heme oxygenase-1 knockout (HO-1 KO) mice. Here, we aimed to address the mechanisms underlying this effect, focusing on heme and iron metabolism. We show that HO-1 deficiency leads to iron accumulation in the renal cortex. Higher mortality of Ang II and simvastatin-treated HO-1 KO mice coincides with increased iron accumulation and the upregulation of mucin-1 in the proximal convoluted tubules. In vitro studies showed that mucin-1 hampers heme- and iron-related oxidative stress through the sialic acid residues. In parallel, knock-down of HO-1 induces the glutathione pathway in an NRF2-depedent manner, which likely protects against heme-induced toxicity. To sum up, we showed that heme degradation during heme overload is not solely dependent on HO-1 enzymatic activity, but can be modulated by the glutathione pathway. We also identified mucin-1 as a novel redox regulator. The results suggest that hypertensive patients with less active HMOX1 alleles may be at higher risk of kidney injury after statin treatment.
Topics: Mice; Animals; Heme Oxygenase-1; Angiotensin II; Mucin-1; Heme Oxygenase (Decyclizing); Simvastatin; Kidney; Iron; Hypertension; Heme; Glutathione
PubMed: 37302617
DOI: 10.1016/j.freeradbiomed.2023.05.018 -
Nature Communications Jan 2024Emerging evidence indicates that the activation of ferroptosis by glutathione peroxidase 4 (GPX4) inhibitors may be a prominent therapeutic strategy for tumor...
Emerging evidence indicates that the activation of ferroptosis by glutathione peroxidase 4 (GPX4) inhibitors may be a prominent therapeutic strategy for tumor suppression. However, the wide application of GPX4 inhibitors in tumor therapy is hampered due to poor tumor delivery efficacy and the nonspecific activation of ferroptosis. Taking advantage of in vivo self-assembly, we develop a peptide-ferriporphyrin conjugate with tumor microenvironment specific activation to improve tumor penetration, endocytosis and GPX4 inhibition, ultimately enhancing its anticancer activity via ferroptosis. Briefly, a GPX4 inhibitory peptide is conjugated with an assembled peptide linker decorated with a pH-sensitive moiety and ferriporphyrin to produce the peptide-ferriporphyrin conjugate (Gi-F-CAA). Under the acidic microenvironment of the tumor, the Gi-F-CAA self-assembles into large nanoparticles (Gi-F) due to enhanced hydrophobic interaction after hydrolysis of CAA, improving tumor endocytosis efficiency. Importantly, Gi-F exhibits substantial inhibition of GPX4 activity by assembly enhanced binding (AEB) effect, augmenting the oxidative stress of ferriporphyrin-based Fenton reaction, ultimately enabling antitumor properties in multiple tumor models. Our findings suggest that this peptide-ferriporphyrin conjugate design with AEB effect can improve the therapeutic effect via induction of ferroptosis, providing an alternative strategy for overcoming chemoresistance.
Topics: Humans; Ferroptosis; Endocytosis; Hemin; Hydrolysis; Peptides; Cell Line, Tumor; Neoplasms; Tumor Microenvironment
PubMed: 38212623
DOI: 10.1038/s41467-023-44665-2 -
Applied Microbiology and Biotechnology Dec 2024Heme is an iron-containing porphyrin compound widely used in the fields of healthcare, food, and medicine. Compared to animal blood extraction, it is more advantageous... (Review)
Review
Heme is an iron-containing porphyrin compound widely used in the fields of healthcare, food, and medicine. Compared to animal blood extraction, it is more advantageous to develop a microbial cell factory to produce heme. However, heme biosynthesis in microorganisms is tightly regulated, and its accumulation is highly cytotoxic. The current review describes the biosynthetic pathway of free heme, its fermentation production using different engineered bacteria constructed by metabolic engineering, and strategies for further improving heme synthesis. Heme synthetic pathway in Bacillus subtilis was modified utilizing genome-editing technology, resulting in significantly improved heme synthesis and secretion abilities. This technique avoided the use of multiple antibiotics and enhanced the genetic stability of strain. Hence, engineered B. subtilis could be an attractive cell factory for heme production. Further studies should be performed to enhance the expression of heme synthetic module and optimize the expression of heme exporter and fermentation processes, such as iron supply. KEY POINTS: • Strengthening the heme biosynthetic pathway can significantly increase heme production. • Heme exporter overexpression helps to promote heme secretion, thereby further promoting excessive heme synthesis. • Engineered B. subtilis is an attractive alternative for heme production.
Topics: Animals; Heme; Fermentation; Porphyrins; Anti-Bacterial Agents; Iron
PubMed: 38194135
DOI: 10.1007/s00253-023-12968-5 -
Frontiers in Immunology 2023Triple negative breast cancer (TNBC) is a subtype of breast cancer characterised by its high tumourigenic, invasive, and immunosuppressive nature. Photodynamic therapy...
INTRODUCTION
Triple negative breast cancer (TNBC) is a subtype of breast cancer characterised by its high tumourigenic, invasive, and immunosuppressive nature. Photodynamic therapy (PDT) is a focal therapy that uses light to activate a photosensitizing agent and induce a cytotoxic effect. 5-aza-2'-deoxycytidine (5-ADC) is a clinically approved immunomodulatory chemotherapy agent. The mechanism of the combination therapy using PDT and 5-ADC in evoking an anti-tumour response is not fully understood.
METHODS
The present study examined whether a single dose of 5-ADC enhances the cytotoxic and anti-tumour immune effect of low dose PDT with verteporfin as the photosensitiser in a TNBC orthotopic syngeneic murine model, using the triple negative murine mammary tumour cell line 4T1. Histopathology analysis, digital pathology and immunohistochemistry of treated tumours and distant sites were assessed. Flow cytometry of splenic and breast tissue was used to identify T cell populations. Bioinformatics were used to identify tumour immune microenvironments related to TNBC patients.
RESULTS
Functional experiments showed that PDT was most effective when used in combination with 5-ADC to optimize its efficacy. 5-ADC/PDT combination therapy elicited a synergistic effect and was significantly more cytotoxic than monotherapies on 4T1 tumour cells. For tumour therapy, all types of treatments demonstrated histopathologically defined margins of necrosis, increased T cell expression in the spleen with absence of metastases or distant tissue destruction. Flow cytometry and digital pathology results showed significant increases in CD8 expressing cells with all treatments, whereas only the 5-ADC/PDT combination therapy showed increase in CD4 expression. Bioinformatics analysis of in silico publicly available TNBC data identified BCL3 and BCL2 as well as the following anti-tumour immune response biomarkers as significantly altered in TNBC compared to other breast cancer subtypes: GZMA, PRF1, CXCL1, CCL2, CCL4, and CCL5. Interestingly, molecular biomarker assays showed increase in anti-tumour response genes after treatment. The results showed concomitant increase in BCL3, with decrease in BCL2 expression in TNBC treatment. In addition, the treatments showed decrease in PRF1, CCL2, CCL4, and CCL5 genes with 5-ADC and 5-ADC/PDT treatment in both spleen and breast tissue, with the latter showing the most decrease.
DISCUSSION
To our knowledge, this is the first study that shows which of the innate and adaptive immune biomarkers are activated during PDT related treatment of the TNBC 4T1 mouse models. The results also indicate that some of the immune response biomarkers can be used to monitor the effectiveness of PDT treatment in TNBC murine model warranting further investigation in human subjects.
Topics: Humans; Animals; Mice; Verteporfin; Triple Negative Breast Neoplasms; Decitabine; Disease Models, Animal; Photosensitizing Agents; Antineoplastic Agents; Photochemotherapy; Biomarkers; Proto-Oncogene Proteins c-bcl-2; Tumor Microenvironment
PubMed: 38022682
DOI: 10.3389/fimmu.2023.1188087 -
Scientific Reports Sep 2023Maintaining life (respiration), cell death (apoptosis), oxygen transport and immunity are main biological functions of heme containing proteins. These functions are...
Maintaining life (respiration), cell death (apoptosis), oxygen transport and immunity are main biological functions of heme containing proteins. These functions are controlled by the axial ligands and the redox status of the iron ion (oscillations between Fe and Fe) in the heme group. This paper aims to evaluate the current state of knowledge on oxidation and oxygenation effects in heme proteins. We determined the redox status of the iron ion in whole blood (without and with anticoagulant), hemoglobin in erythrocytes, in isolated cytochrome c and cytochrome c in mitochondria of the human lung cancer cells using UV-VIS electronic absorption spectroscopy, Raman spectroscopy and Raman imaging. Here we discussed the mechanism responsible for the Q electronic absorption band spectral behavior, i.e., its splitting, and its change in extinction coefficient, as well as vibrational modifications upon oxygenation and oxidation. We compared the redox status of heme in hemoglobin of human erythrocytes and cytochrome c in mitochondria of human lung cancer cells. Presented results allow simultaneous identification of oxy- and deoxy-Hb, where 1547 and 1604 cm vibrations correspond to deoxygenated hemoglobin, while 1585 and 1638 cm correspond to oxyhemoglobin, respectively. Our results extend knowledge of oxidation and oxygenation effects in heme proteins. We demonstrated experimentally the mechanism of electronic-vibrational coupling for the Q band splitting. Presented results extend knowledge on oxidation and oxygenation effects in heme proteins and provide evidence that both processes are strongly coupled. We showed that retinoic acid affects the redox state of heme in cytochrome c in mitochondria. The change of the redox status of cytochrome c in mitochondria from the oxidized form to the reduced form has very serious consequences in dysfunction of mitochondria resulting in inhibition of respiration, apoptosis and cytokine induction.
Topics: Humans; Cytochromes c; Hemoglobins; Erythrocytes; Lung Neoplasms; Oxidation-Reduction; Hemeproteins; Heme; Lung
PubMed: 37679473
DOI: 10.1038/s41598-023-41858-z -
Biophysical Reviews Aug 2023The unbridled use of antimicrobial drugs over the last decades contributed to the global dissemination of drug-resistant pathogens and increasing rates of... (Review)
Review
The unbridled use of antimicrobial drugs over the last decades contributed to the global dissemination of drug-resistant pathogens and increasing rates of life-threatening infections for which limited therapeutic options are available. Currently, the search for safe, fast, and effective therapeutic strategies to combat infectious diseases is a worldwide demand. Antimicrobial photodynamic therapy (APDT) rises as a promising therapeutic approach against a wide range of pathogenic microorganisms. APDT combines light, a photosensitizing drug (PS), and oxygen to kill microorganisms by oxidative stress. Since the APDT field involves branches of biology and physics, the strengthening of interdisciplinary collaborations under the aegis of biophysics is welcome. Given this scenario, Brazil is one of the global leaders in the production of APDT science. In this review, we provide detailed reports of APDT studies published by the Laboratory of Optical Therapy (IPEN-CNEN), Group of Biomedical Nanotechnology (UFPE), and collaborators over the last 10 years. We present an integrated perspective of APDT from basic research to clinical practice and highlight its promising use, encouraging its adoption as an effective and safe technology to tackle important pathogens. We cover the use of methylene blue (MB) or Zn(II) porphyrins as PSs to kill bacteria, fungi, parasites, and pathogenic algae in laboratory assays. We describe the impact of MB-APDT in Dentistry and Veterinary Medicine to treat different infectious diseases. We also point out future directions combining APDT and nanotechnology. We hope this review motivates further APDT studies providing intuitive, vivid, and insightful information for the readers.
PubMed: 37681106
DOI: 10.1007/s12551-023-01066-5 -
Pharmaceutics Aug 2023Malignant melanoma poses a significant global health burden. It is the most aggressive and lethal form of skin cancer, attributed to various risk factors such as UV... (Review)
Review
Malignant melanoma poses a significant global health burden. It is the most aggressive and lethal form of skin cancer, attributed to various risk factors such as UV radiation exposure, genetic modifications, chemical carcinogens, immunosuppression, and fair complexion. Photodynamic therapy is a promising minimally invasive treatment that uses light to activate a photosensitizer, resulting in the formation of reactive oxygen species, which ultimately promote cell death. When selecting photosensitizers for melanoma photodynamic therapy, the presence of melanin should be considered. Melanin absorbs visible radiation similar to most photosensitizers and has antioxidant properties, which undermines the reactive species generated in photodynamic therapy processes. These characteristics have led to further research for new photosensitizing platforms to ensure better treatment results. The development of photosensitizers has advanced with the use of nanotechnology, which plays a crucial role in enhancing solubility, optical absorption, and tumour targeting. This paper reviews the current approaches (that use the synergistic effect of different photosensitizers, nanocarriers, chemotherapeutic agents) in the photodynamic therapy of melanoma.
PubMed: 37631339
DOI: 10.3390/pharmaceutics15082124 -
Maintenance of heme homeostasis in through post-translational regulation of glutamyl-tRNA reductase.Journal of Bacteriology Sep 2023is an important human pathogen responsible for a variety of infections including skin and soft tissue infections, endocarditis, and sepsis. The combination of...
is an important human pathogen responsible for a variety of infections including skin and soft tissue infections, endocarditis, and sepsis. The combination of increasing antibiotic resistance in this pathogen and the lack of an efficacious vaccine underscores the importance of understanding how maintains metabolic homeostasis in a variety of environments, particularly during infection. Within the host, must regulate cellular levels of the cofactor heme to support enzymatic activities without encountering heme toxicity. lutamyl NA eductase (GtrR), the enzyme catalyzing the first committed step in heme synthesis, is an important regulatory node of heme synthesis in Bacteria, Archaea, and Plantae. In many organisms, heme status negatively regulates the abundance of GtrR, controlling flux through the heme synthesis pathway. We identified two residues within GtrR, H32 and R214, that are important for GtrR-heme binding. However, in strains expressing either GtrR or GtrR, heme homeostasis was not perturbed, suggesting an alternative mechanism of heme synthesis regulation occurs in . In this regard, we report that heme synthesis is regulated through phosphorylation and dephosphorylation of GtrR by the serine/threonine kinase Stk1 and the phosphatase Stp1, respectively. Taken together, these results suggest that the mechanisms governing staphylococcal heme synthesis integrate both the availability of heme and the growth status of the cell. IMPORTANCE represents a significant threat to human health. Heme is an iron-containing enzymatic cofactor that can be toxic at elevated levels. During infection, must control heme levels to replicate and survive within the hostile host environment. We identified residues within a heme biosynthetic enzyme that are critical for heme binding however, abrogation of heme binding is not sufficient to perturb heme homeostasis within . This marks a divergence from previously reported mechanisms of heme-dependent regulation of the highly conserved enzyme glutamyl tRNA reductase (GtrR). Additionally, we link cell growth arrest to the modulation of heme levels through the post-translational regulation of GtrR by the kinase Stk1 and the phosphatase Stp1.
Topics: Humans; Heme; Staphylococcus aureus; Bacterial Proteins; Homeostasis; Phosphoric Monoester Hydrolases; Staphylococcal Infections
PubMed: 37655914
DOI: 10.1128/jb.00171-23