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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 -
Chemical Science May 2024Ring-contracted porphyrin analogues, such as subporphyrins and calix[3]pyrroles, have recently attracted considerable attention not only as challenging synthetic targets... (Review)
Review
Ring-contracted porphyrin analogues, such as subporphyrins and calix[3]pyrroles, have recently attracted considerable attention not only as challenging synthetic targets but also as functional macrocyclic compounds. Although canonical porphyrins and calix[4]pyrrole are selectively generated acid-catalyzed condensation reactions of pyrrole monomers, their tripyrrolic analogues are always missing under similar conditions. Recent progress in synthesis has shown that strain-controlled approaches using boron(iii)-templating, core-modification, or ring tightening provide access to various contracted porphyrins. The tripyrrolic macrocycles are a new class of functional macrocycles exhibiting unique ring-contraction effects, including strong boron chelation and strain-induced ring expansion. This Perspective reviews recent advances in synthetic strategies and the novel ring-contraction effects of subporphyrins, triphyrins(2.1.1), calix[3]pyrroles, and their analogous.
PubMed: 38756809
DOI: 10.1039/d4sc02028f -
Chemical Science May 2024Energy-efficient separation of CH/CH is a great challenge, for which adsorptive separation is very promising. CH-selective adsorption has big implications, while the...
Energy-efficient separation of CH/CH is a great challenge, for which adsorptive separation is very promising. CH-selective adsorption has big implications, while the design of CH-sorbents with ideal adsorption capability, particularly with the CH/CH-selectivity exceeded 2.0, is still challenging. Instead of the current strategies such as chemical modification or pore space modulation, we propose a new methodology for the design of CH-sorbents. With a Cu-TCPP [TCPP = 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin] framework dispersed onto a microporous carbon and a hierarchical-pore carbon, two composite sorbents are fabricated. The composite sorbents exhibit enhanced CH-selective adsorption capabilities with visible light, particularly the composite sorbent based on the hierarchical-pore carbon, whose CH and CH adsorption capacities (0 °C, 1 bar) are targetedly increased by 27% and only 1.8% with visible light, and therefore, an CH-selectivity (CH/CH = 10/90, v/v) of 4.8 can be realized. With visible light, the adsorption force of the CH molecule can be asymmetrically enhanced by the excitation enriched electron density over the adsorption sites formed the close interaction between the Cu-TCPP and the carbon layer, whereas that of the CH molecule is symmetrically altered and the forces cancelled each other out. This strategy may open up a new route for energy-efficient adsorptive separation of CH/CH with light.
PubMed: 38756801
DOI: 10.1039/d4sc00898g -
EMBO Molecular Medicine Jun 2024Although protein subunit vaccines generally have acceptable safety profiles with precise antigenic content, limited immunogenicity can lead to unsatisfactory humoral and...
Although protein subunit vaccines generally have acceptable safety profiles with precise antigenic content, limited immunogenicity can lead to unsatisfactory humoral and cellular immunity and the need for vaccine adjuvants and delivery system. Herein, we assess a vaccine adjuvant system comprising Quillaja Saponaria-21(QS-21) and cobalt porphyrin polymeric micelles that enabling the display of His-tagged antigen on its surface. The nanoscale micelles promote antigen uptake and dendritic cell activation to induce robust cytotoxic T lymphocyte response and germinal center formation. Using the recombinant protein antigens from influenza A and rabies virus, the micelle adjuvant system elicited robust antiviral responses and protected mice from lethal challenge. In addition, this system could be combined with other antigens to induce high titers of neutralizing antibodies in models of three highly pathogenic viral pathogens: Ebola virus, Marburg virus, and Nipah virus. Collectively, our results demonstrate this polymeric micelle adjuvant system can be used as a potent nanoplatform for developing antiviral vaccine countermeasures that promote humoral and cellular immunity.
Topics: Animals; Mice; Viral Vaccines; Micelles; Adjuvants, Vaccine; Adjuvants, Immunologic; Antibodies, Viral; Rabies virus; Dendritic Cells; Polymers; Female; Mice, Inbred C57BL; Influenza A virus; Mice, Inbred BALB C
PubMed: 38750307
DOI: 10.1038/s44321-024-00076-4 -
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 2024Obesity has emerged as a prominent risk factor for the development of malignant tumors. However, the existing literature on the role of adipocytes in the tumor...
Obesity has emerged as a prominent risk factor for the development of malignant tumors. However, the existing literature on the role of adipocytes in the tumor microenvironment (TME) to elucidate the correlation between obesity and cancer remains insufficient. Here, we aim to investigate the formation of cancer-associated adipocytes (CAAs) and their contribution to tumor growth using mouse models harboring dysfunctional adipocytes. Specifically, we employ adipocyte-specific BECN1 KO (BaKO) mice, which exhibit lipodystrophy due to dysfunctional adipocytes. Our results reveal the activation of YAP/TAZ signaling in both CAAs and BECN1-deficient adipocytes, inducing adipocyte dedifferentiation and formation of a malignant TME. The additional deletion of YAP/TAZ from BaKO mice significantly restores the lipodystrophy and inflammatory phenotypes, leading to tumor regression. Furthermore, mice fed a high-fat diet (HFD) exhibit decreased BECN1 and increased YAP/TAZ expression in their adipose tissues. Treatment with the YAP/TAZ inhibitor, verteporfin, suppresses tumor progression in BaKO and HFD-fed mice, highlighting its efficacy against mice with metabolic dysregulation. Overall, our findings provide insights into the key mediators of CAA and their significance in developing a TME, thereby suggesting a viable approach targeting adipocyte homeostasis to suppress cancer growth.
Topics: Animals; YAP-Signaling Proteins; Adipocytes; Adaptor Proteins, Signal Transducing; Mice; Tumor Microenvironment; Mice, Knockout; Diet, High-Fat; Transcription Factors; Obesity; Humans; Verteporfin; Signal Transduction; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Disease Progression; Male; Cell Transformation, Neoplastic; Neoplasms; Cell Cycle Proteins; Lipodystrophy; Mice, Inbred C57BL; Trans-Activators
PubMed: 38744820
DOI: 10.1038/s41467-024-48179-3 -
Inorganic Chemistry May 2024Phlorins have long remained underexplored relative to their fully conjugated counterparts, such as porphyrins, hydroporphyrins, and corroles. Herein, we have attempted...
Phlorins have long remained underexplored relative to their fully conjugated counterparts, such as porphyrins, hydroporphyrins, and corroles. Herein, we have attempted to bridge that knowledge gap with a scalar-relativistic density functional theory (DFT) study of unsubstituted iridium and gold phlorin derivatives and a multitechnique experimental study of iridium-bispyridine and gold complexes of 5,5-dimethyl-10,15,20-tris(pentafluorophenyl)phlorin. Theory and experiments concur that the phlorin derivatives exhibit substantially smaller HOMO-LUMO gaps, as reflected in a variety of observable properties. Thus, the experimentally studied Ir and Au complexes absorb strongly in the near-infrared (NIR), with absorption maxima at 806 and 770 nm, respectively. The two complexes are also weakly phosphorescent with emission maxima at 950 and 967 nm, respectively. They were also found to photosensitize singlet oxygen formation, with quantum yields of 40 and 28%, respectively. The near-infrared (NIR) absorption and emission are consonants with smaller electrochemical HOMO-LUMO gaps of ∼1.6 V, compared to values of ∼2.1 V, for electronically innocent porphyrins and corroles. Interestingly, both the first oxidation and reduction potentials of the Ir complex are some 600 mV shifted to more negative potentials relative to those of the Au complex, indicating an exceptionally electron-rich macrocycle in the case of the Ir complex.
PubMed: 38743029
DOI: 10.1021/acs.inorgchem.4c00483 -
BMC Cancer May 2024YAP and TAZ, the Hippo pathway terminal transcriptional activators, are frequently upregulated in cancers. In tumor cells, they have been mainly associated with...
YAP and TAZ, the Hippo pathway terminal transcriptional activators, are frequently upregulated in cancers. In tumor cells, they have been mainly associated with increased tumorigenesis controlling different aspects from cell cycle regulation, stemness, or resistance to chemotherapies. In fewer cases, they have also been shown to oppose cancer progression, including by promoting cell death through the action of the p73/YAP transcriptional complex, in particular after chemotherapeutic drug exposure. Using HCT116 cells, we show here that oxaliplatin treatment led to core Hippo pathway down-regulation and nuclear accumulation of TAZ. We further show that TAZ was required for the increased sensitivity of HCT116 cells to oxaliplatin, an effect that appeared independent of p73, but which required the nuclear relocalization of TAZ. Accordingly, Verteporfin and CA3, two drugs affecting the activity of YAP and TAZ, showed antagonistic effects with oxaliplatin in co-treatments. Importantly, using several colorectal cell lines, we show that the sensitizing action of TAZ to oxaliplatin is dependent on the p53 status of the cells. Our results support thus an early action of TAZ to sensitize cells to oxaliplatin, consistent with a model in which nuclear TAZ in the context of DNA damage and p53 activity pushes cells towards apoptosis.
Topics: Humans; Oxaliplatin; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Tumor Suppressor Protein p53; Colonic Neoplasms; Trans-Activators; Transcription Factors; Hippo Signaling Pathway; HCT116 Cells; Signal Transduction; Protein Serine-Threonine Kinases; Organoplatinum Compounds; Antineoplastic Agents; Intracellular Signaling Peptides and Proteins; Drug Resistance, Neoplasm; Tumor Suppressor Proteins; Adaptor Proteins, Signal Transducing; Verteporfin; Cell Line, Tumor; Tumor Protein p73; YAP-Signaling Proteins; Porphyrins; Nuclear Proteins; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Apoptosis
PubMed: 38741073
DOI: 10.1186/s12885-024-12316-4 -
Photodiagnosis and Photodynamic Therapy Jun 2024Protoporphyrin IX (PPIX) is the final precursor of heme, forming heme when iron is inserted. Individuals with erythropoietic protoporphyrias (EPP) have accumulation of... (Review)
Review
BACKGROUND
Protoporphyrin IX (PPIX) is the final precursor of heme, forming heme when iron is inserted. Individuals with erythropoietic protoporphyrias (EPP) have accumulation of PPIX, causing photosensitivity and increased liver disease risk. Many also have iron deficiency and anemia. We investigated outcomes of oral iron supplements in individuals with EPP.
METHODS
A systematic review identified literature on oral iron supplements in EPP patients. Subsequently, we administered iron supplements to EPP patients with iron deficiency. The primary outcome was impact on PPIX level. Secondary outcomes were adverse events and relative differences in hemoglobin and iron parameters.
RESULTS
The systematic review found 13 case reports and one uncontrolled clinical trial with uncertain results. From our department 10 patients with EPP and iron deficiency took daily dosages of 330 mg of ferrous fumarate for two months. Five of our patients had anemia at baseline. After 2 months of supplementation seven patients had increased PPIX level compared to baseline, two had decrease, one remained unchanged. The administration of iron led to a rise in ferritin, and in four of the anemic patients also to an improvement in blood hemoglobin. A small transiently elevation in plasma alanine transaminase concentration was observed during supplementation.
CONCLUSIONS
Overall, iron supplementation in EPP patients replenished iron stores and elevated erythrocyte PPIX and plasma alanine transaminase. For anemic patients, there was some degree of normalization of the hemoglobin level. If iron therapy is needed for EPP patients, monitoring of photosensitivity, PPIX, hemoglobin, and plasma liver enzymes is advisable.
Topics: Humans; Protoporphyria, Erythropoietic; Protoporphyrins; Dietary Supplements; Male; Female; Adult; Iron; Anemia, Iron-Deficiency; Middle Aged; Treatment Outcome
PubMed: 38734198
DOI: 10.1016/j.pdpdt.2024.104211 -
Molecules (Basel, Switzerland) May 2024-Tetrahexylporphyrin was converted to its corresponding 7,8-dihydroxychlorin using an osmium tetroxide-mediated dihydroxylation strategy. Its diol moiety was shown to be...
-Tetrahexylporphyrin was converted to its corresponding 7,8-dihydroxychlorin using an osmium tetroxide-mediated dihydroxylation strategy. Its diol moiety was shown to be able to undergo a number of subsequent oxidation reactions to form a chlorin dione and porpholactone, the first -alkylporphyrin-based porphyrinoid containing a non-pyrrolic building block. Further, the diol chlorin was shown to be susceptible to dehydration, forming the porphyrin enol that is in equilibrium with its keto-chlorin form. The -hexylchlorin dione could be reduced and it underwent mono- and bis-methylation reactions using methyl-Grignard reagents, and trifluoromethylation using the Ruppert-Prakash reagent. The optical and spectroscopic properties of the products are discussed and contrasted to their corresponding -aryl derivatives (where known). This contribution establishes -tetrahexyl-7,8-dihydroxychlorins as a new and versatile class of chlorins that is susceptible to a broad range of conversions to generate functionalized chlorins and a pyrrole-modified chlorin analogue.
PubMed: 38731635
DOI: 10.3390/molecules29092144