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In vulnerable atherosclerotic plaques, intraplaque hemorrhages (IPH) result in hemolysis of red blood cells and release of hemoglobin and free hemin. Hemin activates platelets and leads to thrombosis. Agonism of the inhibitory platelet receptor ACKR3 inhibits hemin‐dependent platelet activation and thrombus formation. To characterize the effect of hemin and ACKR3 agonism on isolated human platelets, multi‐color flow cytometry and classical experimental setup such as light transmission aggregometry and a flow chamber assay were used. Hemin induces platelet aggregation and ex vivo platelet‐dependent thrombus formation on immobilized collagen under a low shear rate of 500 s−1, indicating that free hemin is a strong activator of platelet‐dependent thrombosis. Recently, we described that ACKR3 is a prominent inhibitory receptor of platelet activation. Specific ACKR3 agonists but not conventional antiplatelet compounds such as COX‐1 inhibitor (indometacin), ADP‐receptor blocker (cangrelor), or PAR1 inhibitor (ML161) inhibit both hemin‐dependent aggregation and thrombus formation. To further characterize the effect of hemin on platelet subpopulations, we established a multi‐color flow cytometry assay. We found that hemin induces procoagulant (CD42bpos/PAC‐1neg/AnnexinVpos), aggregatory (CD42bpos/PAC‐1pos/AnnexinVneg), and inflammatory (CD42bpos/CXCR4pos/ACKR3pos/AnnexinVpos) platelet subpopulations. Treatment with ACKR3 agonists significantly decreased the formation of procoagulant and ACKR3pos platelets in response to hemin. We conclude that hemin is a strong activator for the formation of procoagulant platelets and thrombus formation which is dependent on the function of ACKR3. Activation of ACKR3 using specific agonists may offer a therapeutic strategy to regulate the vulnerability of atherosclerotic plaques in areas of IPH. [ABSTRACT FROM AUTHOR]

Hemin is an important iron‐containing porphyrin that has important therapeutic properties to control the symptoms of porphyria attacks that include pain, high blood pressure, rapid heartbeat, mental changes, and so forth. Lysozyme has many applications, which include from therapeutic to preservation of foods. The interaction of hemin with an important model protein, hen egg white lysozyme (HEWL), has been observed in this study through hybrid in silico with biophysical studies. There was a strong 1:1 cooperative binding between hemin and HEWL, which was revealed from the strong quenching of the latter by the former. The binding was favored by the decrease in temperature, which is due to the involvement of static type of quenching mechanism in the interaction. Experimental analyses suggested that the major forces involved in the binding were polar ones, and there was an efficient energy transfer from the fluorophore to the ligand. The combination of far‐UV CD spectroscopy and Rayleigh light scattering experiments established that hemin has the strong tendency to unfold HEWL. An extensive molecular docking investigation involving 2000 docking runs recognized the preferred binding site of hemin within HEWL, and also suggested that apart from the polar forces, hydrophobic interactions have also played an important role in the binding. [ABSTRACT FROM AUTHOR]

Background: Acute hepatic porphyria is a group of multisystem disorders of which acute intermittent porphyria is the most common subtype. Givosiran, a subcutaneously administered RNA interference therapeutic targeting liver ALAS mRNA, is approved for treating these disorders. This Phase 1/2 open-label extension study (NCT02949830) evaluated the long-term safety and efficacy of givosiran in adults with acute intermittent porphyria, with follow-up of up to 48 months, which is the longest follow-up of givosiran treatment to date. Participants were adults aged 18–65 years who completed part C of the Phase 1 givosiran study (NCT2452372). Methods: Enrollees received givosiran for up to 48 months. Primary and secondary endpoints included the incidence of adverse events, changes in urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels, annualized rate of porphyria attacks, and annualized hemin use. Quality of life was assessed using the EQ-5D-5L instrument as an exploratory endpoint. Results: Sixteen patients (median age: 39.5 years) participated. Common adverse events included abdominal pain, nasopharyngitis, and nausea (50% each), with injection-site erythema (38%) and injection-site pruritus (25%) noted as frequent treatment-related reactions. Givosiran therapy reduced annualized rates of porphyria attacks and hemin use by 97% and 96%, respectively. From months > 33 to 48, all patients were free from attacks requiring significant medical intervention and did not use hemin. There were substantial reductions in median urinary ALA and PBG of 95% and 98%, respectively. Additionally, a clinically meaningful improvement in quality of life was observed. Conclusions: In the longest follow-up of givosiran-treated patients reported to date, the therapy maintained an acceptable safety profile and demonstrated sustained improvements in clinical outcomes over 4 years in patients with acute intermittent porphyria. [ABSTRACT FROM AUTHOR]

The antioxidant activity of carnosine and of carnosine dinitrosyl iron complexes (DNICs) was studied. A system with metmyoglobin (metMb) or hemin in combination with tert-butyl hydroperoxide (t-BOOH) was used as an experimental model. Using the luminol-dependent chemiluminescence method, it was shown that carnosine and carnosine DNICs effectively diminished the level of prooxidants formed by the interaction of heme groups with t-BOOH. In addition, carnosine and carnosine DNICs inhibited the formation of diene conjugates arising during the oxidation of arachidonic acid in the metMb–t-BOOH system. In the reaction systems used, the antioxidant effect of carnosine DNICs was higher than that of carnosine. The antioxidant effect of carnosine also depended on the presence of bivalent iron ions added at a concentration equivalent to their content in DNICs. These results show that the insertion of carnosine as a ligand to nitrosyl iron complexes enhances its antioxidant properties. [ABSTRACT FROM AUTHOR]

Hemin, a heme-like compound with significant biological activity, shows promise as an iron supplement for humans. Nonetheless, its poor solubility in water greatly impedes its absorption and utilization. To surmount this obstacle, researchers have chosen various cyclodextrins with distinct cavity sizes and derivative groups to act as hosts, forming inclusion complexes with hemin chloride. Among these, γ-cyclodextrin has been identified as the optimal carrier, based on a thorough evaluation of its encapsulation efficiency, solubility, and molecular docking. Multiple characterization techniques further confirmed the formation of these inclusion complexes. Results from IEC-6 cell experiments indicated that the cytotoxicity of the inclusion complexes was lower than that of FeSO4. Static and dynamic gastrointestinal simulation digestion systems were established, and the results showed that the bioavailability of the inclusion complex was significantly higher than that of raw hemin. Additionally, only about 0.29% of hemin chloride is digested by gastric enzymes, whereas 9.52% is digested by pancreatic enzymes in the static gastrointestinal simulation digestion system, with similar outcomes observed in the dynamic system. These findings suggest that targeted digestion in the intestine significantly enhances the bioavailability of hemin chloride by forming inclusion complexes in vitro. [ABSTRACT FROM AUTHOR]

Salt stress has become one of the most widespread abiotic stresses globally, negatively affecting crop growth, development, and yield. Rice is an important economic crop affected by salt stress. This study used Huanghuazhan ('HHZ') as the test material to investigate the mitigating effect of spraying Hemin (alone) or with Hb and ZnPP (in combination) on the oxidative damage induced by 100 mM NaCl solution. The results showed that Hemin treatment maintained the growth of rice seedlings under NaCl stress and improved shoot (plant height, stem base width, leaf area) and root (root length, root surface area, root volume, average root diameter and number of root tips) morphological parameters. In addition, exogenous Hemin increased root activity, raised the content of various photosynthetic pigments, improved leaf structure, and increased the area of vascular bundles, which sustained photosynthesis and promoted the accumulation of biomass. Furthermore, Hemin reduced the accumulation of malondialdehyde (MDA) and hydrogen peroxide (H2O2), by activating the activities of various antioxidant enzymes and increasing the content of non-enzymatic antioxidants. While ZnPP (a specific inhibitor of heme oxygenase-1 (HO-1)) and Hb (CO scavenger) reversed the positive regulation of Hemin, and the indexes (biomass of rice seedlings, root activity, and the activity of superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX)) somewhat decreased. In conclusion, this study demonstrated that Hemin reduced ROS accumulation, maintained leaf structure and photosynthetic pigment content, and mitigated the adverse effects of oxidative damage caused by NaCl stress in rice through improving the antioxidant capacity of leaves and roots. This research provides a theoretical basis for Hemin to regulate salt tolerance in other crops. However, the molecular mechanisms involved in Hemin regulation need to be further explored. [ABSTRACT FROM AUTHOR]

Hemozoin (Hz) is a heme crystal produced during malaria infection that stimulates immune cells, leading to the production of cytokines and chemokines. The immunostimulatory action of Hz has previously been applied in the development of alternative adjuvants. Crystallization of hemin is a chemical approach for producing Hz. Here, we focused on an enzymatic production method for Hz using the heme detoxification protein (HDP), which catalyzes heme dimer formation from hemin in Plasmodium. We examined the immunostimulatory effects of an enzymatically synthesized analog of Hz (esHz) produced by recombinant Plasmodium falciparum HDP. Enzymatically synthesized Hz stimulates a macrophage cell line and human peripheral mononuclear cells, leading to the production of interleukin (IL)-6 and IL-12p40. In mice, subcutaneous administration of esHz together with an antigen, ovalbumin (OVA), increased the OVA-specific immunoglobulin (Ig) G2c isotype level in the serum, whereas OVA-specific IgG1 was not induced. Our findings suggest that esHz is a useful Th-1 cell adjuvant. [ABSTRACT FROM AUTHOR]

Overexpression of recombinant Bacillus cereus TSPO (Bc TSPO) in E. coli bacteria leads to its recovery with a bound hemin both in bacterial membrane (MB) and inclusion bodies (IB). Unlike mouse TSPO, Bc TSPO purified in SDS detergent from IB is well structured and can bind various ligands such as high-affinity PK 11195, protoporphyrin IX (PPIX) and δ-aminolevulinic acid (ALA). For each of the three ligands, 1H–15N HSQC titration NMR experiments suggest that different amino acids of Bc TSPO binding cavity are involved in the interaction. PPIX, an intermediate of heme biosynthesis, binds to the cavity of Bc TSPO and its fluorescence can be significantly reduced in the presence of light and oxygen. The light irradiation leads to two products that have been isolated and characterized as photoporphyrins. They result from the addition of singlet oxygen to the two vinyl groups hence leading to the formation of hydroxyaldehydes. The involvement of water molecules, recently observed along with the binding of heme in Rhodobacter sphaeroides (Rs TSPO) is highly probable. Altogether, these results raise the question of the role of TSPO in heme biosynthesis regulation as a possible scavenger of reactive intermediates. [Display omitted] • Hemin is bound to Bc TSPO overexpressed in E. coli. • SDS-purified Bc TSPO is structured and binds ligands. • Purified Bc TSPO is functional and degrades PPIX upon UV light irradiation. • Oxygen-dependent PPIX degradation generates non-fluorescent products. • Products generated by ROS are hydroxyaldehydes. [ABSTRACT FROM AUTHOR]

We describe developments in understanding of the porphyrias associated with each step in the haem biosynthesis pathway and the role of individuals whose contributions led to major advances over the past 150 years. The first case of erythropoietic porphyria was reported in 1870, and the first with acute porphyria in 1889. Photosensitisation by porphyrin was confirmed by Meyer‐Betz, who self‐injected haematoporphyrin. Günther classified porphyrias into haematoporphyria acuta, acuta toxica, congenita and chronica. This was revised by Waldenström into porphyria congenita, acuta and cutanea tarda, with the latter describing those with late‐onset skin lesions. Waldenström was the first to recognise porphobilinogen's association with acute porphyria, although its structure was not solved until 1953. Hans Fischer was awarded the Nobel prize in 1930 for solving the structure of porphyrins and the synthesis of haemin. After 1945, research by several groups elucidated the pathway of haem biosynthesis and its negative feedback regulation by haem. By 1961, following the work of Watson, Schmid, Rimington, Goldberg, Dean, Magnus and others, aided by the availability of modern techniques of porphyrin separation, six of the porphyrias were identified and classified as erythropoietic or hepatic. The seventh, 5‐aminolaevulinate dehydratase deficiency porphyria, was described by Doss in 1979. The discovery of increased hepatic 5‐aminolaevulinate synthase activity in acute porphyria led to development of haematin as a treatment for acute attacks. By 2000, all the haem biosynthesis genes were cloned, sequenced and assigned to chromosomes and disease‐specific mutations identified in all inherited porphyrias. These advances have allowed definitive family studies and development of new treatments. [ABSTRACT FROM AUTHOR]

[Display omitted] Dynamic self-assembly has significant implications in the regulation of the enzyme activities. In this study, we present a histidine-based enzyme-mimicking catalyst, formed by the self-assembly of carefully-engineered FH-based short peptides with hemin, showcasing switchable catalytic activity of hemin due to externally induced reversible inclusion of a cucurbit[7]uril-peptide hybrid. 1H NMR, ITC and theoretical simulation are employed to examine the binding affinity between the guest and host components, and UV–vis spectra are used to investigate changes in the hemin coordination environment. The histidine segment of the short peptide can be partially shielded by the cucurbituril and released following addition of the azo compound, leading to a decrease and subsequent restoration of the histidine-hemin coordination affinity and hemin activity. The photoisomeriziable nature of the azo compound enabled the activation of FHH/hemin activity to be switched on and off by exposure to different wavelengths of light. During the operation, the Phe residue remained within the cucurbituril, allowing reversible inclusion and exposure of the histidine residues. The hemin stayed connected to FHH/cucurbit[7]uril hybrid, preventing the severe aggregation of hemin and irreversible deactivation. This work may provide insights into engineering the dynamic behaviors of the cofactor-dependent catalytic assemblies. [ABSTRACT FROM AUTHOR]

Erythropoiesis is a multistep process of erythroid cell production that is controlled by multiple regulatory factors. Ribosome rescue factor PELO plays a crucial role in cell meiotic division and mice embryonic development. However, the function of PELO in erythroid differentiation remains unclear. Here, we showed that knockdown of PELO increased hemin‐induced erythroid differentiation of K562 and HEL cells, exhibiting a higher number of benzidine‐positive cells and increased mRNA levels of erythroid genes. PELO knockdown inhibited the proliferation and cell cycle progression and promoted apoptosis of K562 cells. Mechanistically, PELO could regulate the expression of KLF10 through interaction with MYC. Moreover, KLF10 knockdown also enhanced erythroid differentiation of K562 and HEL cells induced by hemin. Collectively, our results demonstrated that PELO regulates erythroid differentiation and increases KLF10 expression levels by interacting with MYC. [ABSTRACT FROM AUTHOR]

Nanomaterials excel in mimicking the structure and function of natural enzymes while being far more interesting in terms of structural stability, functional versatility, recyclability, and large‐scale preparation. Herein, the story assembles hemin, histidine analogs, and G‐quadruplex DNA in a catalytically competent supramolecular assembly referred to as assembly‐activated hemin enzyme (AA‐heminzyme). The catalytic properties of AA‐heminzyme are investigated both in silico (by molecular docking and quantum chemical calculations) and in vitro (notably through a systematic comparison with its natural counterpart horseradish peroxidase, HRP). It is found that this artificial system is not only as efficient as HRP to oxidize various substrates (with a turnover number kcat of 115 s−1) but also more practically convenient (displaying better thermal stability, recoverability, and editability) and more economically viable, with a catalytic cost amounting to <10% of that of HRP. The strategic interest of AA‐heminzyme is further demonstrated for both industrial wastewater remediation and biomarker detection (notably glutathione, for which the cost is decreased by 98% as compared to commercial kits). [ABSTRACT FROM AUTHOR]

Dragon fruits have abundant nutritional and antioxidant properties. High temperatures limit the growth and production of dragon fruits. Hemin can effectively alleviate abiotic stress in plants. However, the regulatory effect of Hemin on dragon fruit under heat stress remains unclear. In this study, we explored the impacts of foliar application of Hemin on dragon fruit size, yield and quality during the high temperatures of the summer season. In this experiment, dragon fruit variety 'Jindu No. 1' was used as material and treated with three Hemin concentrations, i.e., H1: 1 μmol.L−1, H2: 10 μmol.L−1, H3: 100 μmol.L−1, compared with CK: control. The results show that exogenous Hemin increased the single fruit weight, yield, fruit shape index and edible rate. It also improved pericarp L* value, a* value, C* and decreased ho, improving the peel colour; exogenous Hemin enhanced soluble solids content and phenolic compounds content and antioxidant enzyme activities in the pulp of dragon fruit. In addition, exogenous Hemin increased the content of chlorophyll content in dragon fruit stems. Differential metabolites determined by metabolomic assay also indicated that Hemin significantly increased the content of active substances such as selagin. Additionally, the Hemin treatment H2 also activated the activity of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), which helps to mitigate the effects of high temperatures on dragon fruit. The current findings strongly advocate that H2 treatment may effectively counteract the adverse effects of heat stress by regulating the morph-physiological and antioxidant traits. [ABSTRACT FROM AUTHOR]

Drug repurposing has gained significant interest in recent years due to the high costs associated with de novo drug development; however, comprehensive pharmacological information is needed for the translation of pre‐existing drugs across clinical applications. In the present study, we explore the current pharmacological understanding of the orphan drug, hemin, and identify remaining knowledge gaps with regard to hemin repurposing for the treatment of cardiovascular disease. Originally approved by the United States Food and Drug Administration in 1983 for the treatment of porphyria, hemin has attracted significant interest for therapeutic repurposing across a variety of pathophysiological conditions. Yet, the clinical translation of hemin remains limited to porphyria. Understanding hemin's pharmacological profile in health and disease strengthens our ability to treat patients effectively, identify therapeutic opportunities or limitations, and predict and prevent adverse side effects. However, requirements for the pre‐clinical and clinical characterization of biologics approved under the U.S. FDA's Orphan Drug Act in 1983 (such as hemin) differed significantly from current standards, presenting fundamental gaps in our collective understanding of hemin pharmacology as well as knowledge barriers to clinical translation for future applications. Using information extracted from the primary and regulatory literature (including documents submitted to Health Canada in support of hemin's approval for the Canadian market in 2018), we present a comprehensive case study of current knowledge related to hemin's biopharmaceutical properties, pre‐clinical/clinical pharmacokinetics, pharmacodynamics, dosing, and safety, focusing specifically on the drug's effects on heme regulation and in the context of acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Introduction: Porphyrias are enzymatic disorders of heme synthesis. Acute hepatic porphyrias (AHP) presents with acute neurovisceral symptoms such as abdominal pain, nausea, vomiting, constipation, muscle weakness, neuropathy, tachycardia, and hypertension. 5-aminolevulinic acid dehydratase (ALAD) deficiency is a rare autosomal recessive disorder that results in little or no elevation of porphobilinogen but elevates urinary 5-aminolevulinic acid and coproporphyrin III. There are no records of this type of porphyria in Colombia. Acute management requires comprehensive care, ranging from hemotherapy to liver transplantation. Case Presentation: A 24-year-old man with no prior medical history presented with a recurrent and acute episode of abdominal pain associated with changes in urine color, skin lesions, diarrhea, and dysregulation of body temperature. Initial paraclinical workup ruled out common causes of recurrent abdominal pain, with a negative porphobilinogen test, but further testing revealed elevated 5-aminolevulinic acid, confirming the diagnosis of ALAD porphyria. The patient showed improvement with hemotherapy and remission of acute kidney injury. A possible distractor associated with interstitial nephritis and skin manifestations related to nonsteroidal anti-inflammatory drug (NSAID) use was documented. Conclusions: ALAD porphyria and all acute hepatic porphyrias should be considered in any patient presenting with unexplained recurrent severe abdominal pain and neuropathy. Despite their relative rarity and complexity, most porphyrias can be easily defined and diagnosed. A common cause of diagnostic delay is the failure to consider porphyria in the differential diagnosis on time. There is still much to learn about ALAD porphyria. [ABSTRACT FROM AUTHOR]

Due to the advantages of non-toxicity, high chemical stability, high activity and low cost, TiO2 is deemed as ideal material for photocatalytic degradation. However, due to its relatively high band-gap energy, anatase TiO2 can only absorb UV light and light with higher energy. In this work, the anatase TiO2 particles were decorated with two organic photosensitizers hemin and eosin Y. The morphology and chemical structure of the composites were verified by SEM, XRD patterns and Raman spectra, the light absorption ability and generation of free radicals were also investigated. The band-gap energy of TiO2, hemin/TiO2 and EY/TiO2 were found to be 2.82 eV, 0.72 eV and 0.95 eV, respectively. Additionally, absorption of more visible light and generation of more superoxide radicals were achieved after decoration of photosensitizers. Consequently, the photocatalytic degradation activity was largely improved, when the TiO2 particles was decorated with 3% of hemin, the degradation rate of methyl blue reached 76.89% and 63.82% in 120 min under UV light and visible light, respectively, which were 1.86 and 1.84 times that of neat TiO2. Comparatively, the ferric ions in hemin may capture the electrons generated by TiO2 and then deliver the electrons to oxygen to generate more superoxide radicals, thus hemin/TiO2 exhibits higher photocatalytic degradation activity than EY/TiO2. [ABSTRACT FROM AUTHOR]

The escalating environmental impact of pollution and the imperative to reduce carbon emissions have heightened the significance of developing biobased materials from natural biomass for electronic devices. This study investigates the utilization of biofermentation‐produced recombinant spider silk and animal‐derived hemin to create a novel biobased electret for field‐effect transistor memory. A critical challenge arises from the incompatibility between natural photoresponsive molecules and insulating biomaterials, resulting in severe phase separation that compromises film quality and morphology uniformity. This study systematically examines the effects of various film deposition and manufacturing techniques on the biobased electret's morphology, phase separation, and performance. Different methods demonstrate distinct advantages in terms of molecular aggregation/segregation, morphological homogeneity, and device performance. Phototransistor memory devices fabricated using spin coating and spray coating techniques exhibit robust aggregations and high memory windows of ≈30 V. Conversely, devices produced through solution shearing and electrospinning methods display enhanced smooth morphologies and high photoresponsivity. The phototransistor memory comprising electrospun fibers holds the potential to achieve the highest memory ratio, reaching ≈105. These findings not only highlight the applications of biobased materials through scalable film deposition processes but also underscore the importance of refining their morphology, phase separation, and performance in optoelectronic devices. [ABSTRACT FROM AUTHOR]

Enzymes have gained their unique efficiency and catalytic activity through billions of years of evolution, perfecting their active site to a desired reaction. Inspired by nature, a novel enzyme‐mimicking platform is designed based on stable protein 1 (SP1) to create a nano‐compartment that mimics peroxidase activity. The biohybrid reveals enhanced activity over the hemin cofactor alone and improved stability in organic solvents in comparison to native peroxidase. Furthermore, the utilization of the obtained biohybrid in an optical glucose biosensing platform is shown. The biohybrid crystallographic structure is solved, indicating that the SP1 structure is not affected by the hemin coordination. This work opens the path for developing new cofactor binding centers in engineered protein scaffolds for various artificial catalytic processes. [ABSTRACT FROM AUTHOR]

Anoctamin1 (ANO1), a calcium-activated chloride channel, is overexpressed in a variety of cancer cells, including prostate cancer, and is involved in cancer cell proliferation, migration, and invasion. Inhibition of ANO1 in these cancer cells exhibits anticancer effects. In this study, we conducted a screening to identify novel ANO1 inhibitors with anticancer effects using PC-3 human prostate carcinoma cells. Screening of 2978 approved and investigational drugs revealed that hemin is a novel ANO1 inhibitor with an IC50 value of 0.45 μM. Notably, hemin had no significant effect on intracellular calcium signaling and cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP (cAMP)-regulated chloride channel, and it showed a weak inhibitory effect on ANO2 at 3 μM, a concentration that completely inhibits ANO1. Interestingly, hemin also significantly decreased ANO1 protein levels and strongly inhibited the cell proliferation and migration of PC-3 cells in an ANO1-dependent manner. Furthermore, it strongly induced caspase-3 activation, PARP degradation, and apoptosis in PC-3 cells. These findings suggest that hemin possesses anticancer properties via ANO1 inhibition and could be considered for development as a novel treatment for prostate cancer. [ABSTRACT FROM AUTHOR]

A new sandwich-type electrochemical biosensing platform was developed by gold @polyphthalenediamine nanohybrids (AuNP@PoPD) as the sensing platform and phosphorus doped reduced graphene oxide-hemin-palladium nanoparticles (PrGO-Hemin-PdNP) as the signal amplifier for phosphatidylinositol proteoglycan 3 (GPC3). AuNP@PoPD, co-electrodeposited into the screen printed electrode with high conductivity and stability, is dedicated to assembling the primary GPC3 aptamer (GPC3Apt). The second GPC3Apt immobilized on the high conductivity and large surface area of PrGO-Hemin-PdNP was utilized as an electrochemical signal reporter by hemin oxidation (PrGO-Hemin-PdNP-GPC3Apt). In the range 0.001–10.0 ng/mL, the hemin oxidation current signal of the electrochemical aptasensor increased log-linearly with the concentration of GPC3, the lowest detection limit was 0.13 pg/mL, and the sensitivity was 2.073 μA/μM/cm2. The aptasensor exhibited good sensing performance in a human serum sample with the relative error of 4.31–8.07%. The sandwich sensor showed good selectivity and stability for detection GPC3 in human serum samples, providing a new efficient and sensitive method for detecting HCC markers. [ABSTRACT FROM AUTHOR]

Background: The potential toxicity of copper oxide nanoparticles (CuO NPs), which are frequently employed in a variety of commercial and industrial uses, remains unknown. Hemin is the inducer of heme oxygenase 1, which exerts cytoprotective actions.Objectives: We aimed to assess the potential protective impact of hemin on the sperm of adult rats treated with CuO NPs. Material and methods: 50 adult rats were split into five groups: Group I: control, group II: animals received 40 μmol/kg b.w./day of solvent, group III: rats received 40 μmol/kg b.w./day of hemin, group IV: animals received 250 mg/kg b.w./day of CuO NPs and group V: rats received 40 μmol/kg b.w./day of hemin followed by CuO NPs at a dose of 250 mg /kg b.w./day. Each rat was administered orally as a single dose day after day for 2 weeks. At the completion of the investigation, all rats were sacrificed. Serum sex hormones were quantified and testes homogenized for biochemical analysis. Sperm analysis was processed for light microscopic examination.Results: Nanocopper reduces fertility hormone levels leading to sperm toxicity. CuO NPs also significantly decreased the activities of antioxidant enzymes accompanied by significant elevation in the MDA levels in testes in contrast to the control group. Hemin treatment reduced the majority of the toxic impacts of CuO NPs via their antioxidative capacity. Conclusion: Administration of hemin ameliorated sex hormones, oxidative stress, lipid peroxidation and sperm characteristics in CuO NPs intoxicated rats. [ABSTRACT FROM AUTHOR]

Acute hepatic porphyrias (AHP) are rare genetic disorders associated with acute neurovisceral attacks and chronic symptoms. This analysis was conducted to examine the long-term efficacy and safety of givosiran in Taiwanese participants in the ENVISION study (NCT03338816). Patients (age ≥12 years) with AHP and recurrent attacks were randomized to receive givosiran 2.5 mg/kg or placebo for 6 months during the double-blind period. Patients then switched from placebo to givosiran (placebo crossover group) or continued taking givosiran (continuous givosiran group) during a 30-month open-label extension period. The total study duration was 36 months. An analysis was conducted that included patients enrolled in Taiwan (N = 7). During the double-blind period and open-label extension period, the median annualized attack rates were 0.0 and 0.0, respectively, in the continuous givosiran group (n = 5) and 15.1 and 4.6, respectively, in the placebo crossover group (n = 2; 70 % decrease). Median annualized days of hemin use in the double-blind period and open-label extension period were 0.0 and 0.0, respectively, in the continuous givosiran group, and 23.8 and 5.0, respectively, in the placebo crossover group (79 % decrease). EQ-5D VAS scores remained relatively stable in both groups, and PPEQ responses indicated improved functioning and satisfaction in both groups. Delta-aminolevulinic acid and porphobilinogen levels remained low with long-term givosiran treatment. Serious adverse events were reported by 3 patients (43 %). Long-term efficacy and safety results in the Taiwan cohort are consistent with those in the global cohort. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus), as a Gram-positive bacterium, is commonly encountered in various infectious diseases, such as acute skin and soft tissue infections. Despite that many efforts have been made, sensitive and reliable quantitative determination of S. aureus remains a huge challenge. Here, we depict a novel colorimetric approach for sensitive and accurate detection by combining allosteric probe-based target recognition and chain extension-based dual signal recycling. The single-strand DNA (ssDNA) products generated by the chain extension process lead to the liberation of G-quadruplex sequences, which can fold into active DNAzyme under the assistance of hemin. The active DNAzyme can work as peroxidase mimics to catalyze the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS2−)-H2O2 system, causing the color change of the system. Eventually, the method exhibits a wide detection range from 103 cfu/mL to 106 cfu/mL. The limit of detection of the approach was determined 232 cfu/mL. Considering the robust capability of the approach in S. aureus detection, we believe that it will be a potential alternative tool for biomedical research and clinical molecular diagnostics. [ABSTRACT FROM AUTHOR]

The current investigation assessed the impact of external hemin on cadmium (Cd)-induced toxicity regarding metal accumulation and stress tolerance in Sorghum bicolor. Two-week-old S. bicolor seedlings were treated at concentrations of 10 µM Cd, 75 µM Cd, 150 µM Cd, and 1 µM hemin individually as well as in collection with hemin within a Hoagland medium. After 120 h, the subjected plants were collected for the study of cellular homeostasis and metal tolerance mechanisms, involving the examination of growth and stress parameters as well as non-enzymatic and enzymatic antioxidants. However, augmentation of hemin under Cd-induced stress environments ameliorated plant development by augmenting biomass and chlorophyll pigments. This augmentation also encouraged antioxidant activities, including ascorbate peroxidase and guaiacol peroxidase levels, while simultaneously mitigating oxidative impairment and enhancing Cd tolerance in plants. Moreover, the utilization of hemin improves the efficacy of S. bicolor in Cd removal by enhancing the uptake of Cd. Hence, the investigation proposes that hemin holds promise for improving the Cd tolerance and accumulation capabilities of Cd-tolerant plants. [ABSTRACT FROM AUTHOR]

Introduction: Acute hepatic porphyrias (AHP) are a rare group of inherited disorders caused by abnormal functioning of the heme synthesis pathway. Patients often present with diffuse abdominal pain, neurologic dysfunction, and hyponatremia. Case Report: We present a case of a 25-year-old female who presented with AHP after implantation of progestin birth control. The patient was confused, markedly tachycardic and hypertensive, and complained of severe abdominal pain. Spot urine ordered during the emergency department workup was later found positive for porphyrins and porphobilinogen (PBG).Conclusion: Acute hepatic porphyrias typically present with nonspecific symptoms in young women and are often overlooked in the acute care setting. Spot urine testing for PBG and urine porphyrins should be initiated early in patients with clinical suspicion of AHP.

DescriptionThe acute hepatic porphyrias (AHP) are rare, inborn errors of heme-metabolism and include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase. Acute intermittent porphyria is the most common type of AHP, with an estimated prevalence of patients with symptoms of approximately 1 in 100,000. The major clinical presentation involves attacks of severe pain, usually abdominal and generalized, without peritoneal signs or abnormalities on cross-sectional imaging. Acute attacks occur mainly in women in their childbearing years. AHP should be considered in the evaluation of all patients, and especially women aged 15-50 years with recurrent severe abdominal pain not ascribable to common causes. The screening tests of choice include random urine porphobilinogen and δ-aminolevulinic acid corrected to creatinine. All patients with elevations in urinary porphobilinogen and/or δ-aminolevulinic acid should initially be presumed to have AHP. The cornerstones of management include discontinuation of porphyrinogenic drugs and chemicals, administration of oral or intravenous dextrose and intravenous hemin, and use of analgesics and antiemetics. Diagnosis of AHP type can be confirmed after initial treatment by genetic testing for pathogenic variants in HMBS, CPOX, PPOX, and ALAD genes. AHP is also associated with chronic symptoms and long-term risk of systemic arterial hypertension, chronic renal and liver disease, and hepatocellular carcinoma. Patients who have recurrent acute attacks (4 or more per year) should be considered for prophylactic therapy with intravenous hemin or subcutaneous givosiran. Liver transplantation is curative and reserved for patients with intractable symptoms who have failed other treatment options.MethodsThis expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Women aged 15-50 years with unexplained, recurrent severe abdominal pain without a clear etiology after an initial workup should be considered for screening for an AHP. BEST PRACTICE ADVICE 2: Initial diagnosis of AHP should be made by biochemical testing measuring δ-aminolevulinic acid, porphobilinogen, and creatinine on a random urine sample. BEST PRACTICE ADVICE 3: Genetic testing should be used to confirm the diagnosis of AHP in patients with positive biochemical testing. BEST PRACTICE ADVICE 4: Acute attacks of AHP that are severe enough to require hospital admission should be treated with intravenous hemin, given daily, preferably into a high-flow central vein. BEST PRACTICE ADVICE 5: In addition to intravenous hemin, management of acute attacks of AHP should include pain control, antiemetics, management of systemic arterial hypertension, tachycardia, and hyponatremia, and hypomagnesemia, if present. BEST PRACTICE ADVICE 6: Patients should be counseled to avoid identifiable triggers that may precipitate acute attacks, such as alcohol and porphyrinogenic medications. BEST PRACTICE ADVICE 7: Prophylactic heme therapy or givosiran, administered in an outpatient setting, should be considered in patients with recurrent attacks (4 or more per year). BEST PRACTICE ADVICE 8: Liver transplantation for AHP should be limited to patients with intractable symptoms and significantly decreased quality of life who are refractory to pharmacotherapy. BEST PRACTICE ADVICE 9: Patients with AHP should be monitored annually for liver disease. BEST PRACTICE ADVICE 10: Patients with AHP, regardless of the severity of symptoms, should undergo surveillance for hepatocellular carcinoma, beginning at age 50 years, with liver ultrasound every 6 months. BEST PRACTICE ADVICE 11: Patients with AHP on treatment should undergo surveillance for chronic kidney disease annually with serum creatinine and estimated glomerular filtration rate. BEST PRACTICE ADVICE 12: Patients should be counseled on the chronic and long-term complications of AHP, including neuropathy, chronic kidney disease, hypertension, and hepatocellular carcinoma, and need for long-term monitoring.

Colorectal cancer (CRC) risk, associated with a high intake of red/processed meat, may be related to hemin. A potential chemopreventive agent, Arthrospira (Spirulina platensis) spp. (AP) is a cyanobacteria employed as a functional food with the potential to reduce malnutrition in developing countries. Thus, we assessed the effects of dietary AP against hemin-promoting effects in a dimethylhydrazine (DMH)-induced colorectal carcinogenesis model. Male Sprague-Dawley rats were allocated into five groups. G1–G4 received four subcutaneous DMH injections (40 mg/kg body weight, twice a week for 2 weeks) and G5 received DMH vehicle. At weeks 4 to 16, groups were fed a balanced diet (BD, G1 and G5), BD containing 2 % AP (20 g powder/kg chow, G2), BD containing hemin (0.32 g/kg chow, G3) or BD containing hemin+2 % AP (G4), respectively. Hemin group (G3) increased aberrant crypt foci (ACF) development, malondialdehyde (MDA), and Nox-1 levels and reduced glutathione (GSH) and GSH-Px levels in colonic mucosa when compared to DMH group (G1). In contrast, the dietary hemin+2 % AP regimen (G4), reduced both preneoplastic lesion development and MDA levels while increased GSH levels, compared to the DMH+hemin group (G3). Dietary AP may reduce hemin-promoting effects by modulating oxidative stress and ACF lesions.

Hemolysis is associated with thrombosis and vascular dysfunction, which are the pathological components of many diseases. Hemolytic products, including hemoglobin and hemin, activate platelets (PLT). Despite its activation, the effect of hemolysis on platelet clearance remains unclear, It is critical to maintain a normal platelet count and ensure that circulating platelets are functionally viable. In this study, we used hemin, a degradation product of hemoglobin, as a potent agonist to treat platelets and simulate changes in vivo in mice. Hemin treatment induced activation and morphological changes in platelets, including an increase in intracellular Ca2+ levels, phosphatidylserine (PS) exposure, and cytoskeletal rearrangement. Fewer hemin-treated platelets were cleared by macrophages in the liver after transfusion than untreated platelets. Hemin bound to glycoprotein Ibα (GPIbα), the surface receptor in hemin-induced platelet activation and aggregation. Furthermore, hemin decreased GPIbα desialylation, as evidenced by reduced Ricinus communis agglutinin I (RCA- I) binding, which likely extended the lifetime of such platelets in vivo. These data provided new insight into the mechanisms of GPIbα-mediated platelet activation and clearance in hemolytic disease.

Candida albicans is a prominent fungal pathogen that can infect the bloodstream and deep tissues. One key pathogenicity trait is the ability to transition between yeast and hyphal growth. Hyphae are critical for the formation of biofilms, which in turn enable device-associated infection. Among signals that drive hypha formation is the presence of hemin, an oxidized Fe(III)-containing heme derivative found in blood. In this study, we asked 4 questions. First, how uniform is the filamentation response to hemin among C. albicans strains? We tested 26 diverse isolates and found that the strength of a strain's filamentation response to hemin reflected its filamentation level in the absence of hemin. Second, does hemin induce biofilm formation? Hemin biofilm induction was evident in 5 out of 10 isolates tested, including most of the weaker biofilm formers tested. Third, what is the gene expression response to hemin? We compared RNA-seq data for type strain SC5314 grown in pH 5.5 minimal media with or without hemin. We also compared that response to SC5314 grown in pH 7.0 minimal media, where it undergoes well-studied pH-dependent filamentation. We found a common set of 72 genes with upregulated RNA levels in response to both signals, including many known hypha-associated genes. Surprisingly, overlap among those 72 genes with 2 recent consensus definitions of hypha-associated genes was limited to only 16 genes. Fourth, which regulators govern hemin-induced filamentation? A mutant survey indicated that the response depends upon filamentation regulators Efg1, Brg1, and Rim101, but not upon heme acquisition regulator Hap1 or its target genes HMX1 , RBT5 , PGA10 , PGA7 , and CSA2. These findings argue that hemin induces hypha formation independently of its utilization. [ABSTRACT FROM AUTHOR]

The immune checkpoint TIGIT/PVR blockade exhibits significant antitumor effects through activation of NK and CD8+ T cell-mediated cytotoxicity. Immune checkpoint blockade (ICB) could induce tumor ferroptosis through IFN-γ released by immune cells, indicating the synergetic effects of ICB with ferroptosis in inhibiting tumor growth. However, the development of TIGIT/PVR inhibitors with ferroptosis-inducing effects has not been explored yet. In this study, the small molecule Hemin that could bind with TIGIT to block TIGIT/PVR interaction was screened by virtual molecular docking and cell-based blocking assay. Hemin could effectively restore the IL-2 secretion from Jurkat-hTIGIT cells. Hemin reinvigorated the function of CD8+ T cells to secrete IFN-γ and the elevated IFN-γ could synergize with Hemin to induce ferroptosis in tumor cells. Hemin inhibited tumor growth by boosting CD8+ T cell immune response and inducing ferroptosis in CT26 tumor model. More importantly, Hemin in combination with PD-1/PD-L1 blockade exhibited more effective antitumor efficacy in anti-PD-1 resistant B16 tumor model. In summary, our finding indicated that Hemin blocked TIGIT/PVR interaction and induced tumor cell ferroptosis, which provided a new therapeutic strategy to combine immunotherapy and ferroptosis for cancer treatment. [ABSTRACT FROM AUTHOR]

Hemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk. In this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay. A total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups. We failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo. ClinicalTrials.gov number, NCT01855841). [ABSTRACT FROM AUTHOR]

The results reported herein demonstrate for the first time that typical reducing agents in an alkaline medium initiate chemiluminescence of luminol in the presence of hemin, and the efficiency of their action is comparable to that of hydrogen peroxide and exceeds it in the case of the superoxide anion. The pertinent implications of these findings refer to new possibilities for developing chemiluminescence assays and biosensors and to precautions for determining hydrogen peroxide using luminol and hemin in samples of unknown composition, most prominently, of biological origin. [ABSTRACT FROM AUTHOR]

Introduction: The hemin acquisition system is composed of an outer membrane TonB-dependent transporter that internalizes hemin into the periplasm, periplasmic hemin-binding proteins to shuttle hemin, an inner membrane transporter that transports hemin into the cytoplasm, and cytoplasmic heme oxygenase to release iron. Fur and HemP are two known regulators involved in the regulation of hemin acquisition. The hemin acquisition system of Stenotrophomonas maltophilia is poorly understood, with the exception of HemA as a TonB-dependent transporter for hemin uptake. Methods: Putative candidates responsible for hemin acquisition were selected via a homolog search and a whole-genome survey of S. maltophilia. Operon verification was performed by reverse transcription-polymerase chain reaction. The involvement of candidate genes in hemin acquisition was assessed using an in-frame deletion mutant construct and iron utilization assays. The transcript levels of candidate genes were determined using quantitative polymerase chain reaction. Results: Smlt3896-hemU-exbB2-exbD2-tonB2 and tonB1-exbB1-exbD1aexbD1b operons were selected as candidates for hemin acquisition. Compared with the parental strain, hemU and tonB1 mutants displayed a defect in their ability to use hemin as the sole iron source for growth. However, hemin utilization by the Smlt3896 and tonB2 mutants was comparable to that of the parental strain. HemA expression was repressed by Fur in iron-replete conditions and derepressed in iron-depleted conditions. HemP negatively regulated hemA expression. Like hemA, hemU was repressed by Fur in iron-replete conditions; however, hemU was moderately derepressed in response to iron-depleted stress and fully derepressed when hemin was present. Unlike hemA and hemU, the TonB1-exbB1-exbD1a-exbD1b operon was constitutively expressed, regardless of the iron level or the presence of hemin, and Fur and HemP had no influence on its expression. Conclusion: HemA, HemU, and TonB1 contribute to hemin acquisition in S. maltophilia. Fur represses the expression of hemA and hemU in iron-replete conditions. HemA expression is regulated by low iron levels, and HemP acts as a negative regulator of this regulatory circuit. HemU expression is regulated by low iron and hemin levels in a hemP-dependent manner. [ABSTRACT FROM AUTHOR]

As a H 2 O 2 electrochemical biomimetic enzyme sensor, the stability, repeatability and sensitivity of hemin-based composites are closely connected with the loading of hemin on high-performance matrix. Herein, polypyrrole/paper-derived carbon (PPy/PC) nanocomposite was used for the construction of a hemin-based non-enzymatic sensor to detect H 2 O 2. Where the poplar wood is used to obtain crude cellulose through a straightforward paper-making process. This crude cellulose is then subjected to pyrolysis to yield the desired paper-based carbon material. The hemin-decorated PPy/PC was demonstrated possessing remarkable electrocatalytic activity for H 2 O 2 reduction, and the possible mechanism of the reactions was discussed. The electrochemical sensor, utilizing the H-PPy/PC composite, achieved a low detection limit of 30 ​nM, along with enhanced selectivity and stability under optimized conditions. The favorable results observed can primarily be attributed to the superior electrochemical performance of PPy/PC, as well as its unique 3D interconnected structure. This structure effectively impedes the self-dimerization of hemin, thereby ensuring the generation of active catalytic species. [ABSTRACT FROM AUTHOR]

Objective: Neuronal precursor cells expressed developmentally down‐regulated 4 (Nedd4) are believed to play a critical role in promoting the degradation of substrate proteins and are involved in numerous biological processes. However, the role of Nedd4 in intracerebral hemorrhage (ICH) remains unknown. This study aims to investigate the regulatory role of Nedd4 in the ICH model. Methods: Male C57BL/6J mice were induced with ICH. Subsequently, the levels of glutathione peroxidase 4 (GPX4), malondialdehyde (MDA) concentration, iron content, mitochondrial morphology, as well as the expression of divalent metal transporter 1 (DMT1) and Nedd4 were assessed after ICH. Furthermore, the impact of Nedd4 overexpression was evaluated through analyses of hematoma area, ferroptosis, and neurobehavioral function. The mechanism underlying Nedd4‐mediated degradation of DMT1 was elecidated using immunoprecipitation (IP) after ICH. Results: Upon ICH, the level of DMT1 in the brain increased, but decreased when Nedd4 was overexpressed using Lentivirus, suggesting a negative correlation between Nedd4 and DMT1. Additionally, the degradation of DMT1 was inhibited after ICH. Furthermore, it was found that Nedd4 can interact with and ubiquitinate DMT1 at lysine residues 6, 69, and 277, facilitating the degradation of DMT1. Functional analysis indicated that overexpression of Nedd4 can alleviate ferroptosis and promote recovery following ICH. Conclusion: The results demonstrated that ferroptosis occurs via the Nedd4/DMT1 pathway during ICH, suggesting it potential as a valuable target to inhibit ferroptosis for the treatment of ICH. [ABSTRACT FROM AUTHOR]

Background: Hemin is clinically used in acute attacks of porphyria; however, recent evidence has also highlighted its capability to stimulate the heme oxygenase enzyme, being associated with cytoprotective, antioxidant, and anti-inflammatory effects. Indeed, current preclinical evidence emphasizes the potential anti-inflammatory role of hemin through its use in animal models of disease. Nevertheless, there is no consensus about the underlying mechanism(s) and the most optimal therapeutic regimens. Therefore, this review aims to summarize, analyze, and discuss the current preclinical evidence concerning the pharmacological effect of hemin. Methods: Following the application of the search expression and the retrieval of the articles, only nonclinical studies in vivo written in English were considered, where the potential anti-inflammatory effect of hemin was evaluated. Results: Forty-nine articles were included according to the eligibility criteria established. The results obtained show the preference of using 30 to 50 mg/kg of hemin, administered intraperitoneally, in both acute and chronic contexts. This drug demonstrates significant anti-inflammatory and antioxidant activities considering its capacity for reducing the expression of proinflammatory and oxidative markers. Conclusions: This review highlighted the significant anti-inflammatory and antioxidant effects of hemin, providing a clearer vision for the medical community about the use of this drug in several human diseases. [ABSTRACT FROM AUTHOR]

Abiotic stress caused by soil salinization remains a major global challenge that threatens and severely impacts crop growth, causing yield reduction worldwide. In this study, we aim to investigate the damage of salt stress on the leaf physiology of two varieties of rice (Huanghuazhan, HHZ, and Xiangliangyou900, XLY900) and the regulatory mechanism of Hemin to maintain seedling growth under the imposed stress. Rice leaves were sprayed with 5.0 mmol•L-1 Hemin or 25.0 mmol•L-1 ZnPP (Zinc protoporphyrin IX) at the three leaf and one heart stage, followed by an imposed salt stress treatment regime (50.0 mmol•L-1 sodium chloride (NaCl)). The findings revealed that NaCl stress increased antioxidant enzymes activities and decreased the content of nonenzymatic antioxidants such as ascorbate (AsA) and glutathione (GSH). Furthermore, the content of osmoregulatory substances like soluble proteins and proline was raised. Moreover, salt stress increased reactive oxygen species (ROS) content in the leaves of the two varieties. However, spraying with Hemin increased the activities of antioxidants such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) and accelerated AsA-GSH cycling to remove excess ROS. In summary, Hemin reduced the effect of salt stress on the physiological characteristics of rice leaves due to improved antioxidant defense mechanisms that impeded lipid peroxidation. Thus, Hemin was demonstrated to lessen the damage caused by salt stress. [ABSTRACT FROM AUTHOR]

Pathologies such as malaria, hemorrhagic stroke, sickle cell disease, and thalassemia are characterized by the release of hemoglobin degradation products from damaged RBCs. Hematin (liganded with OH−) and hemin (liganded with Cl−)—are the oxidized forms of heme with toxic properties due to their hydrophobicity and the presence of redox-active Fe3. In the present study, using the original LaSca-TM laser particle analyzer, flow cytometry, and confocal microscopy, we showed that both hematin and hemin induce dose-dependent RBC spherization and hemolysis with ghost formation. Hematin and hemin at nanomolar concentrations increased [Ca2+]i in RBC; however, spherization and hemolysis occurred in the presence and absence of calcium, indicating that both processes are independent of [Ca2+]i. Both compounds triggered acute phosphatidylserine exposure on the membrane surface, reversible after 60 min of incubation. A comparison of hematin and hemin effects on RBCs revealed that hematin is a more reactive toxic metabolite than hemin towards human RBCs. The toxic effects of heme derivatives were reduced and even reversed in the presence of albumin, indicating the presence in RBCs of the own recovery system against the toxic effects of heme derivatives. [ABSTRACT FROM AUTHOR]

A general egg white gel-sol strategy for fabrication of highly fluorescent Au, Ag, Cu, and Pt nanoclusters (NCs) and the first example of using Au NCs for assay of nuclease activity and inhibition were described. The Au NCs enabled bright red fluorescence, and the other Ag, Cu, and Pt NCs have highly blue emission. The red-emitting Au NCs were further applied in assay of S1 nuclease activity and inhibition. Free hemin efficiently quenches the emission of Au NCs by photoinduced electron transfer due to the formation of Au NCs-hemin conjugates. However, G-quadruplex/hemin exerts negligible effect on its fluorescence due to no Au NCs-hemin conjugate formed. There are stronger electrostatic repulsion effects between both negatively charged G-quadruplex and Au NCs. Therefore, a novel G-quadruplex/hemin-based Au NCs fluorescent sensor for S1 nuclease was designed. A known G-rich oligonucleotide (ODN) serves as not only substrate for S1 nuclease but also for the construction of G-quadruplex/hemin. The G-rich ODN is hydrolyzed into fragments by S1 nuclease resulting in no G-quadruplex/hemin formation. Therefore, the free hemin quenches Au NCs fluorescence remarkably and the assay of S1 nuclease activity and inhibition has accomplished. Both the fluorescent NCs syntheses and the detection of S1 nuclease are facile and efficient. [ABSTRACT FROM AUTHOR]

The existence of a delicate redox balance in tumors usually leads to cancer treatment failure. Breaking redox homeostasis by amplifying oxidative stress and reducing glutathione (GSH) can accelerate cancer cell death. Herein, we construct a ferroptosis-reinforced nanocatalyst (denoted as HBGL) to amplify intracellular oxidative stress via dual H 2 O 2 production-assisted chemodynamic therapy (CDT). Specifically, a long-circulating liposome is employed to deliver hemin (a natural iron-containing substrate for Fenton reaction and ferroptosis), β -lapachone (a DNA topoisomerase inhibitor with H 2 O 2 generation capacity for chemotherapy), and glucose oxidase (which can consume glucose for starvation therapy and generate H 2 O 2). HBGL can achieve rapid, continuous, and massive H 2 O 2 and •OH production and GSH depletion in cancer cells, resulting in increased intracellular oxidative stress. Additionally, hemin can reinforce the ferroptosis-inducing ability of HBGL, which is reflected in the downregulation of glutathione peroxidase-4 and the accumulation of lipid peroxide. Notably, HBGL can disrupt endo/lysosomes and impair mitochondrial function in cancer cells. HBGL exhibits effective tumor-killing ability without eliciting obvious side effects, indicating its clinical translation potential for synergistic starvation therapy, chemotherapy, ferroptosis therapy, and CDT. Overall, this nanocatalytic liposome may be a promising candidate for achieving potentiated cancer treatment. [Display omitted] • A strategy of breaking cell redox homeostasis is employed. • A dual energy-depletion strategy is introduced. • A nanocatalyst with dual H 2 O 2 self-production ability is constructed. • The strong ferroptosis-inducing capacity and lysosome-disrupting effect are verified. • Combined CDT, ferroptosis, chemotherapy, and starvation therapy are achieved. [ABSTRACT FROM AUTHOR]

Enzymatic cascades are routinely used for electroanalysis of redox inactive species that can be enzymatically converted into species electroactive at moderate potentials, such as H2O2 produced by FAD‐dependent oxidases oxidising their substrates by O2. However, such cascades adaptation to micro‐biosensors is limited by enhanced mass‐transfer of produced H2O2 into solution, not to the sensing layer. Here, bi‐enzyme sensors for glucose or glutamate, produced by cross‐linking peroxidase and oxidases on carbon‐nanotube‐modified graphite macro‐electrodes (Gr), showed the from 0.1 to 10 mM glucose/glutamate linear response, while bio‐modified 5 μm carbon fibre electrodes (CFE) were mute due to fast transfer of enzymatically produced H2O2 into solution. By replacing peroxidase with peroxidase‐mimicking hemin in polyethyleneimine, the sensitivity of detection at Gr improved 3‐fold, enabling 2.8 μM glucose and 4.5 μM glutamate limits of detection, but not at CFE. Fast mass‐transfer of H2O2 from CFE to solution was restricted by the Nafion membrane facilitating glucose detection at CFE with a sensitivity of 1.67 A cm−2 M−1, at −0.6 V, escaping interference from other brain‐fluid components, redox‐inactive at this potential. Such membrane‐restricted cascade system provides the analytical access to a large group of enzymes that can be integrated in multiple enzymatic cascades for biosensing at microelectrodes. [ABSTRACT FROM AUTHOR]

Previous research has found that an adaptive response to ferroptosis involving glutathione peroxidase 4 (GPX4) is triggered after intracerebral hemorrhage. However, little is known about the mechanisms underlying adaptive responses to ferroptosis. To explore the mechanisms underlying adaptive responses to ferroptosis after intracerebral hemorrhage, we used hemin-treated HT22 cells to mimic brain injury after hemorrhagic stroke in vitro to evaluate the antioxidant enzymes and performed bioinformatics analysis based on the mRNA sequencing data. Further, we determined the expression of GSTO2 in hemin-treated hippocampal neurons and in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH) by using Western blot. After hemin treatment, the antioxidant enzymes GPX4, Nrf2, and glutathione (GSH) were upregulated, suggesting that an adaptive response to ferroptosis was triggered. Furthermore, we performed mRNA sequencing to explore the underlying mechanism, and the results showed that 2234 genes were differentially expressed. Among these, ten genes related to ferroptosis (Acsl1, Ftl1, Gclc, Gclm, Hmox1, Map1lc3b, Slc7a11, Slc40a1, Tfrc, and Slc39a14) were altered after hemin treatment. In addition, analysis of the data retrieved from the GO database for the ten targeted genes showed that 20 items on biological processes, 17 items on cellular components, and 19 items on molecular functions were significantly enriched. Based on the GO data, we performed GSEA and found that the glutathione metabolic process was significantly enriched in the hemin phenotype. Notably, the expression of glutathione S-transferase omega (GSTO2), which is involved in glutathione metabolism, was decreased after hemin treatment, and overexpression of Gsto2 decreased lipid reactive oxygen species level in hemin-exposed HT22 cells. In addition, the expression of GSTO2 was also decreased in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH). The decreased expression of GSTO2 in the glutathione metabolic process may be involved in ferroptotic neuronal injury following hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

Abstract Nanomaterials excel in mimicking the structure and function of natural enzymes while being far more interesting in terms of structural stability, functional versatility, recyclability, and large‐scale preparation. Herein, the story assembles hemin, histidine analogs, and G‐quadruplex DNA in a catalytically competent supramolecular assembly referred to as assembly‐activated hemin enzyme (AA‐heminzyme). The catalytic properties of AA‐heminzyme are investigated both in silico (by molecular docking and quantum chemical calculations) and in vitro (notably through a systematic comparison with its natural counterpart horseradish peroxidase, HRP). It is found that this artificial system is not only as efficient as HRP to oxidize various substrates (with a turnover number kcat of 115 s−1) but also more practically convenient (displaying better thermal stability, recoverability, and editability) and more economically viable, with a catalytic cost amounting to

Background: Photodynamic therapy (PDT) has been utilized as a promising alternative cancer treatment due to its minimum invasiveness over the years. Exogenous 5-aminolevulinic acid (ALA) triggers protoporphyrin IX (PpIX) accumulation, which happens in cancer cells. However, certain types of cancer exhibit reduced effectiveness in the PpIX accumulation mechanism. This study aimed to determine the effect of ALA-PDT combination with hemin on gastric carcinoma TMK-1 cells. Methods: This study utilized TMK-1 gastric cancer cell line to evaluate PpIX, ROS, and Fe2+ accumulation following the administration of ALA, hemin, and a combination of ALA and hemin PDT. We also evaluate the mRNA expressions related to iron homeostasis and treatment impacts on cell viability. Results: The co-addition of ALA and hemin PDT for 4 h of treatment resulted in a significant decrease in cell viability by up to 18 %. While ALA-PDT enhanced PpIX metabolism, the addition of hemin influenced both the production of reactive oxygen species (ROS) and cellular iron homeostasis by inducing Fe2+ accumulation and affecting mRNA levels of IRP, Tfr1, Ferritin, NFS1, and SDHB. Conclusion: These findings suggest that the addition of ALA and hemin enhances phototoxicity in TMK-1 cells. The combination of ALA and hemin with PDT induces cell death, evidenced by increased cytotoxicity properties such as PpIX and ROS, along with significant changes in TMK-1 gastric cancer iron homeostasis. Therefore, the combination of ALA and hemin could be one of the alternatives in photodynamic therapy for cancer in the future.

Introduction: Gestation under chronic hypoxia causes pulmonary hypertension, cardiovascular remodeling, and increased aortic stiffness in the offspring. To mitigate the neonatal cardiovascular risk, pharmacological treatments (such as hemin and sildenafil) have been proposed to improve pulmonary vasodilation. However, little is known about the effects of these treatments on the aorta. Therefore, we studied the effect of hemin and sildenafil treatments in the aorta of lambs gestated and raised at highlands, thereby subjected to chronic hypoxia.Methods: Several biomechanical tests were conducted in the descending thoracic aorta (DTA) and the distal abdominal aorta (DAA), assessing 3 groups of study of hypoxic animals: non-treated (Control) and treated either with hemin or sildenafil. Based on them, the stiffness level has been quantified in both zones, along with the physiological strain in the unloaded aortic duct. Furthermore, a morphological study by histology was conducted in the DTA.Results: Biomechanical results indicate that treatments trigger an increment of axial pre-stress and circumferential residual stress levels in DTA and DAA of lambs exposed to high-altitude chronic hypoxia, which reveals a vasodilatation improvement along with an anti-hypertensive response under this characteristic environmental condition. In addition, histological findings do not reveal significant differences in either structure or microstructural content.Discussion: The biomechanics approach emerges as a valuable study perspective, providing insights to explain the physiological mechanisms of vascular function. According to established results, alterations in the function of the aortic wall may not necessarily be explained by morphostructural changes, but rather by the characteristic mechanical state of the microstructural components that are part of the studied tissue. In this sense, the reported biomechanical changes are beneficial in mitigating the adverse effects of hypobaric hypoxia exposure during gestation and early postnatal life.

Sensitization of wide-gap metal oxides by the porphyrins has been promising to utilize the major fraction of solar light for photocatalytic reactions. In this context, rutile-SnO2 was anchored with hemin complex and their performance was evaluated for the 4-nitro phenol (4-NP) degradation under UV/visible light. Driven by the significant interactions between -COOH and surface -OH functional groups of hemin and SnO2 respectively, a new linkage O=CO-Sn was formed at the interface, which was vital for charge carrier transfer between them. Both X-ray diffraction studies and scanning electron microscope analysis confirmed that the surface hemin adsorption did not alter the crystal structure and the morphology of pristine SnO2. The light absorption properties revealed a red shift in the optical response of the composite, which facilitated the photocatalytic reactions to operate under visible light. The electrochemical and photoluminescence measurements collectively attested to the enhanced charge carrier separation in the composite compared to pure SnO2. The synergism arising from the photo-Fenton and photocatalytic reactions was derived from the cyclic reactions of Fe(II)/Fe(III) and oxidation of hydroxyl radicals by the valence band holes of SnO2 with H2O2 under UV light. In contrast, the sensitization process resulted in electron transfer from the excited state of hemin to the conduction band (CB) of SnO2 under visible light. Such distinct mechanistic pathways by the metal oxide-porphyrin composite would be promising for wastewater purification under UV–visible light region in near future.

Hemin, a heme-like compound with significant biological activity, shows promise as an iron supplement for humans. Nonetheless, its poor solubility in water greatly impedes its absorption and utilization. To surmount this obstacle, researchers have chosen various cyclodextrins with distinct cavity sizes and derivative groups to act as hosts, forming inclusion complexes with hemin chloride. Among these, γ-cyclodextrin has been identified as the optimal carrier, based on a thorough evaluation of its encapsulation efficiency, solubility, and molecular docking. Multiple characterization techniques further confirmed the formation of these inclusion complexes. Results from IEC-6 cell experiments indicated that the cytotoxicity of the inclusion complexes was lower than that of FeSO4. Static and dynamic gastrointestinal simulation digestion systems were established, and the results showed that the bioavailability of the inclusion complex was significantly higher than that of raw hemin. Additionally, only about 0.29% of hemin chloride is digested by gastric enzymes, whereas 9.52% is digested by pancreatic enzymes in the static gastrointestinal simulation digestion system, with similar outcomes observed in the dynamic system. These findings suggest that targeted digestion in the intestine significantly enhances the bioavailability of hemin chloride by forming inclusion complexes in vitro.