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Biomedicine & Pharmacotherapy =... Aug 2023Photodynamic therapy (PDT) and sonodynamic therapy (SDT) are non-invasive treatment methods with obvious inhibitory effect on tumors and have few side effects, which... (Review)
Review
Photodynamic therapy (PDT) and sonodynamic therapy (SDT) are non-invasive treatment methods with obvious inhibitory effect on tumors and have few side effects, which have been widely concerned and explored by researchers. Sensitizer is the main factor in determining the therapeutic effect of PDT and SDT. Porphyrins, a group of organic compounds widespread in nature, can be activated by light or ultrasound and produce reactive oxygen species. Therefore, porphyrins as sensitizers in PDT have been widely explored and investigated for many years. Herein, we summarize the classical porphyrin compounds and their applications and mechanisms in PDT and SDT. The application of porphyrin in clinical diagnosis and imaging is also discussed. In conclusion, porphyrins have good application prospects in disease treatment as an important part of PDT or SDT, and in clinical diagnosis and imaging.
Topics: Humans; Porphyrins; Photochemotherapy; Ultrasonic Therapy; Neoplasms; Reactive Oxygen Species
PubMed: 37236030
DOI: 10.1016/j.biopha.2023.114933 -
Gastroenterology Jan 2024
Topics: Humans; Protoporphyria, Erythropoietic; Photosensitivity Disorders; Abdominal Pain; Protoporphyrins
PubMed: 37579823
DOI: 10.1053/j.gastro.2023.07.028 -
Thrombosis Research Feb 2024Hemolysis is a known risk factor for thrombosis resulting in critical limb ischemia and microcirculatory disturbance and organ failure. Intravasal hemolysis may lead to...
BACKGROUND AND AIMS
Hemolysis is a known risk factor for thrombosis resulting in critical limb ischemia and microcirculatory disturbance and organ failure. Intravasal hemolysis may lead to life-threatening complications due to uncontrolled thrombo-inflammation. Until now, conventional antithrombotic therapies failed to control development and progression of these thrombotic events. Thus, the pathophysiology of these thrombotic events needs to be investigated to unravel underlying pathways and thereby identify targets for novel treatment strategies.
METHODS
Here we used classical experimental set-ups as well as high-end flow cytometry, metabolomics and lipidomic analysis to in-depth analyze the effects of hemin on platelet physiology and morphology.
RESULTS
Hemin does strongly and swiftly induce platelet activation and this process is modulated by the sGC-cGMP-cGKI signaling axis. cGMP modulation also reduced the pro-aggregatory potential of plasma derived from patients with hemolysis. Furthermore, hemin-induced platelet death evokes distinct platelet subpopulations. Typical cell death markers, such as ROS, were induced by hemin-stimulation and the platelet lipidome was specifically altered by high hemin concentration. Specifically, arachidonic acid derivates, such as PGE, TXB or 12-HHT, were significantly increased. Balancing the cGMP levels by modulation of the sGC-cGMP-cGKI axis diminished the ferroptotic effect of hemin.
CONCLUSION
We found that cGMP modulates hemin-induced platelet activation and thrombus formation in vitro and cGMP effects hemin-mediated platelet death and changes in the platelet lipidome. Thus, it is tempting to speculate that modulating platelet cGMP levels may be a novel strategy to control thrombosis and critical limb ischemia in patients with hemolytic crisis.
Topics: Humans; Hemin; Chronic Limb-Threatening Ischemia; Hemolysis; Microcirculation; Blood Platelets; Thrombosis
PubMed: 38171216
DOI: 10.1016/j.thromres.2023.12.008 -
Bioconjugate Chemistry Dec 2023Porphyrins have been vastly explored and applied in many cutting-edge fields with plenty of encouraging achievements because of their excellent properties. As important... (Review)
Review
Porphyrins have been vastly explored and applied in many cutting-edge fields with plenty of encouraging achievements because of their excellent properties. As important derivatives of porphyrins, porphyrin-based amphiphiles (PBAs) not only maintain the advanced properties of porphyrins (catalysis, imaging, and energy transfer) but also possess self-assembly and encapsulation capability in aqueous solution. Accordingly, PBAs and their self-assembles have had important roles in diagnosing and treating tumors and inflammation lesions , but not limited to these. In this article, we introduce the research progress of PBAs, including their constitution, structure design strategies, and performances in tumor and inflammation lesion diagnosis and treatments. On that basis, the defects of synthesized PBAs during their application and the possible effective strategies to overcome the limitations are also proposed. Finally, perspectives on PBAs exploration are updated based on our knowledge. We hope this review will bring researchers from various domains insights about PBAs.
Topics: Humans; Porphyrins; Nanostructures; Neoplasms; Inflammation
PubMed: 37955349
DOI: 10.1021/acs.bioconjchem.3c00432 -
Journal of Inherited Metabolic Disease Nov 2023Acute intermittent porphyria (AIP) is a rare hereditary metabolic disease characterized by acute attacks and accumulation of the porphyrin precursors 5-aminolevulinic...
Acute intermittent porphyria (AIP) is a rare hereditary metabolic disease characterized by acute attacks and accumulation of the porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). Patients with AIP have a high risk of primary liver cancer (PLC). We aimed to assess the association between porphyrin precursor excretion and the risk for PLC in patients with AIP. We studied 48 patients with AIP who developed PLC between 1987 and 2015 and 140 age and sex matched controls with AIP but no PLC. Data on all available urinary PBG and ALA samples collected from 1975 until 1 year before PLC diagnosis were analyzed and compared between cases and controls using logistic regression. Porphyrin precursor excretion was higher in patients with PLC (PBG median 7.9 [IQR 4.4-21.9] mmol/mol creatinine) than in controls (3.8 [1.2-9.8]) (adjusted odds ratio 1.07, 95% confidence interval: 1.02-1.12). None of the 28 patients with all registered samples below the upper limit of normal (ULN) developed PLC, and only one of the 45 patients with all samples <2× ULN developed PLC. Among non-PLC controls, ALA and PBG levels decreased after age 50-60 while an increasing trend was observed after age 65 among those who developed PLC. Increased urinary porphyrin precursors are associated with a high risk of developing PLC. Patients with normal levels appear to have a low risk while high or increasing ALA and PBG after age 65 indicates high risk, which should be considered in surveillance decisions.
Topics: Humans; Middle Aged; Aged; Porphyria, Acute Intermittent; Case-Control Studies; Aminolevulinic Acid; Porphobilinogen; Porphyrins; Liver Neoplasms
PubMed: 37650859
DOI: 10.1002/jimd.12676 -
Molecular Genetics and Metabolism Nov 2023Acute hepatic porphyria (AHP) is a group of four rare inherited diseases, each resulting from a deficiency in a distinct enzyme in the heme biosynthetic pathway....
Acute hepatic porphyria (AHP) is a group of four rare inherited diseases, each resulting from a deficiency in a distinct enzyme in the heme biosynthetic pathway. Characterized by acute neurovisceral symptoms that may mimic other medical and psychiatric conditions, lack of recognition of the disease often leads to a delay in diagnosis and initiation of effective treatment. Biochemical testing for pathway intermediates that accumulate when the disease is active forms the basis for screening and establishing a diagnosis. Subsequent genetic analysis identifies the pathogenic variant, supporting screening of family members and genetic counseling. Management of AHP involves avoidance of known exogenous and hormonal triggers, symptomatic treatment, and prevention of recurrent attacks. Here we describe six case studies from our own real-world experience to highlight current recommendations and challenges associated with the diagnosis and long-term management of the disease.
Topics: Humans; Porphobilinogen; Porphyrias, Hepatic; Porphobilinogen Synthase; Heme
PubMed: 37542766
DOI: 10.1016/j.ymgme.2023.107670 -
Journal of Cerebral Blood Flow and... Aug 2023Spontaneous intracerebral hemorrhage (ICH) is a devastating disease with high morbidity and mortality worldwide. We have previously shown that ferroptosis contributes to...
Spontaneous intracerebral hemorrhage (ICH) is a devastating disease with high morbidity and mortality worldwide. We have previously shown that ferroptosis contributes to neuronal loss in ICH mice. The overload of iron and dysfunction of glutathione peroxidase 4 (GPx4) promote neuronal ferroptosis post-ICH. However, how epigenetic regulatory mechanisms affect the ferroptotic neurons in ICH remains unclear. In the current study, hemin was used to induce ferroptosis in N2A and SK-N-SH neuronal cells to mimic ICH. The results showed that hemin-induced ferroptosis was accompanied by an increment of global level of trimethylation in histone 3 lysine 9 (H3K9me3) and its methyltransferase Suv39h1. Transcriptional target analyses indicated that H3K9me3 was enriched at the promoter region and gene body of transferrin receptor gene 1 () and repressed its expression upon hemin stimulation. Inhibition of H3K9me3 with inhibitor or siRNA against Suv39h1 aggravated hemin- and RSL3-induced ferroptosis by upregulating expression. Furthermore, Suv39h1-H3K9me3 mediated repression of contributes to the progression of ICH in mice. These data suggest a protective role of H3K9me3 in ferroptosis post ICH. The knowledge gained from this study will improve the understanding of epigenetic regulation in neuronal ferroptosis and shed light on future clinical research after ICH.
Topics: Mice; Animals; Ferroptosis; Hemin; Epigenesis, Genetic; Cerebral Hemorrhage; Neurons
PubMed: 36960698
DOI: 10.1177/0271678X231165653 -
Ceska a Slovenska Oftalmologie :... 2024Central serous chorioretinopathy (CSC) is a disease characterized by serous detachment of the neuroretina, especially in the posterior pole of the eye. It is often... (Review)
Review
Central serous chorioretinopathy (CSC) is a disease characterized by serous detachment of the neuroretina, especially in the posterior pole of the eye. It is often accompanied by serous detachment of the retinal pigment epithelium (RPE) and associated with the leakage of fluid into the subretinal space through the defective RPE. CSC most often affects men of working age. The exact pathophysiology of the disease is not completely known. Based on indocyanine green angiography (ICG), which revealed increased permeability of choroidal vessels, and optical coherence tomography (OCT) showing increased choroidal thickness, choroidal vasculopathy is assumed to be the primary cause of CSC. In most cases, CSC has a good prognosis with spontaneous resorption of the subretinal fluid (SRF) and improvement of visual functions. However, in a small percentage of patients the disease progresses to a chronic or recurrent course, and can lead to irreversible functional and anatomical changes of the retina with a final clinical picture of diffuse retinal pigment epitheliopathy (DRPE). The optimal treatment approach for patients with CSC remains controversial. In recent decades, myriad therapeutic approaches have been used in the treatment of chronic forms of CSC (cCSC); these included for example laser photocoagulation, pharmaceutical treatment, standard photodynamic therapy (PDT) or anti-VEGF. In recent years a less destructive method, specifically PDT in reduced dose regimens, either with a reduced dose of verteporfin or the laser beam energy used, has been preferred in the treatment of cCSC. Comparable efficacy and safety has been demonstrated using reduced-dose or reduced-fluence PDT regimens in patients with cCSC, with an improvement in best-corrected visual acuity and reduction of SRF.
Topics: Male; Humans; Central Serous Chorioretinopathy; Photosensitizing Agents; Photochemotherapy; Visual Acuity; Fluorescein Angiography; Tomography, Optical Coherence; Retrospective Studies; Porphyrins
PubMed: 38531681
DOI: 10.31348/2023/27 -
Nature Chemical Biology Oct 2023Despite wide appreciation of the biological role of nitric oxide (NO) synthase (NOS) signaling, questions remain about the chemical nature of NOS-derived bioactivity....
Despite wide appreciation of the biological role of nitric oxide (NO) synthase (NOS) signaling, questions remain about the chemical nature of NOS-derived bioactivity. Here we show that NO-like bioactivity can be efficiently transduced by mobile NO-ferroheme species, which can transfer between proteins, partition into a hydrophobic phase and directly activate the sGC-cGMP-PKG pathway without intermediacy of free NO. The NO-ferroheme species (with or without a protein carrier) efficiently relax isolated blood vessels and induce hypotension in rodents, which is greatly potentiated after the blockade of NOS activity. While free NO-induced relaxations are abolished by an NO scavenger and in the presence of red blood cells or blood plasma, a model compound, NO-ferroheme-myoglobin preserves its vasoactivity suggesting the physiological relevance of NO-ferroheme species. We conclude that NO-ferroheme behaves as a signaling entity in the vasculature.
Topics: Nitric Oxide; Erythrocytes; Heme; Signal Transduction
PubMed: 37710073
DOI: 10.1038/s41589-023-01411-5 -
Life Science Alliance Jul 2024All cancer cells reprogram metabolism to support aberrant growth. Here, we report that cancer cells employ and depend on imbalanced and dynamic heme metabolic pathways,...
All cancer cells reprogram metabolism to support aberrant growth. Here, we report that cancer cells employ and depend on imbalanced and dynamic heme metabolic pathways, to accumulate heme intermediates, that is, porphyrins. We coined this essential metabolic rewiring "porphyrin overdrive" and determined that it is cancer-essential and cancer-specific. Among the major drivers are genes encoding mid-step enzymes governing the production of heme intermediates. CRISPR/Cas9 editing to engineer leukemia cell lines with impaired heme biosynthetic steps confirmed our whole-genome data analyses that porphyrin overdrive is linked to oncogenic states and cellular differentiation. Although porphyrin overdrive is absent in differentiated cells or somatic stem cells, it is present in patient-derived tumor progenitor cells, demonstrated by single-cell RNAseq, and in early embryogenesis. In conclusion, we identified a dependence of cancer cells on non-homeostatic heme metabolism, and we targeted this cancer metabolic vulnerability with a novel "bait-and-kill" strategy to eradicate malignant cells.
Topics: Humans; Heme; Porphyrins; Cell Line, Tumor; CRISPR-Cas Systems; Neoplasms; Metabolic Networks and Pathways; Cell Differentiation; Gene Editing; Animals; Mice
PubMed: 38649187
DOI: 10.26508/lsa.202302547