Journal of Inorganic Biochemistry最新文献

{"title":"Nucleus-targeted ruthenium(II) complex triggers immunogenic cell death and sensitizes melanoma to anti-PD-1 therapy by activating cGAS–STING pathway","authors":"Bishu Wang ,&nbsp;Xingguo Tang ,&nbsp;Chuntao Xiao ,&nbsp;Zhijie Yu ,&nbsp;Huaben Bo ,&nbsp;Jie Wang ,&nbsp;Jinquan Wang","doi":"10.1016/j.jinorgbio.2025.112871","DOIUrl":"10.1016/j.jinorgbio.2025.112871","url":null,"abstract":"<div><div>A significant challenge in the treatment of melanoma with immune checkpoint blockades (ICBs) is the limited T cells response often observed in immunologically “cold” tumors. By leveraging the immunogenicity of immunogenic cell death (ICD), which increases the susceptibility of tumor cells to ICBs, this study investigated the potential of a nucleus-targeted ruthenium(II) complex (<strong>Ru1</strong>) as an inducer of ICD. Treatment with <strong>Ru1</strong> induced DNA damage in melanoma cells, activating the cyclic GMP–AMP synthase–stimulator of the interferon genes (cGAS–STING) pathway. This triggered endoplasmic reticulum (ER) stress, leading to ICD. <strong>Ru1</strong>-treated dying melanoma cells exhibited characteristics such as cell exposure of calreticulin (CRT) on the cell surface, release of adenosine triphosphate (ATP), and secretion of high-mobility group box 1 (HMGB1). Vaccination with <strong>Ru1</strong>-treated, dying melanoma cells elicited robust antitumor immune responses, as evidenced by CD8⁺ T cells activation, reduced Foxp3⁺ T cells count, and the development of a memory immune response that protected mice from subsequent melanoma challenges. Combining <strong>Ru1</strong> with anti-PD-1 therapy significantly promoted T cells infiltration, enhanced dendritic cell activation, and reduced tumor-associated immunosuppressive factors, indicating a reprogramming of the tumor microenvironment. These findings suggest that <strong>Ru1</strong> is a promising therapeutic agent for treating “cold” tumors in cancer chemoimmunotherapy.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"267 ","pages":"Article 112871"},"PeriodicalIF":3.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Zn(II)-Acetyl l-carnitine complex for simultaneous management of depression, chronic pain, and neuroprotection","authors":"Janetsi Y. Caro-Ramírez ,&nbsp;Leandro O. Bazán ,&nbsp;Oscar E. Piro ,&nbsp;Gustavo A. Echeverría ,&nbsp;Khalil Jori ,&nbsp;Martín Mizrahi ,&nbsp;Carlos A. Franca ,&nbsp;María Luz Lambrisca ,&nbsp;Joaquín A. Bustos ,&nbsp;Carlos H. Laino ,&nbsp;María Varcalcel ,&nbsp;Clarisa Salado ,&nbsp;Luciana G. Naso ,&nbsp;Patricia A.M. Williams ,&nbsp;Evelina G. Ferrer","doi":"10.1016/j.jinorgbio.2025.112857","DOIUrl":"10.1016/j.jinorgbio.2025.112857","url":null,"abstract":"<div><div>Acetyl-<span>l</span>-carnitine (ALC) is synthesized in the brain, liver, and kidneys and plays crucial roles in energy metabolism, acetylcholine production, protein synthesis, and neuronal protection, contributing to its antidepressant and neuroprotective properties. Zinc, a vital biometal, is essential for depression and neuroprotection, exhibiting antidepressive effects alone or combined with classical antidepressants. The pharmacological benefits of metal coordination complexes often result from synergistic or additive effects. In this study, we present a novel multifunctional zinc complex, Zn(<em>ALC</em>)Cl₂(H₂O), which crystallizes in the monoclinic chiral space group <em>P</em>2₁, featuring a distorted tetrahedral Zn(II) environment. This new compound demonstrates significantly higher antidepressant activity, reducing immobility in the forced swimming test by 54 % compared to commercial ALC. Additionally, it exhibits <em>in vivo</em> antinociceptive properties, increases latency time, and proves effective in a diabetic neuropathy model by preventing the glucose-induced decrease in intracellular GSH levels. <em>In vitro</em> studies indicate that the complex can cross the blood-brain barrier and offer neuroprotection against glutamate-induced excitotoxicity and oxygen-glucose deprivation, with a drug classification of 10 <em>versus</em> 5 for ALC. Furthermore, under astrocytosis conditions, the Zn complex neutralizes the toxic effects of TGFβ-treated astrocytes. These findings highlight Zn(<em>ALC</em>)Cl₂(H₂O) as a promising candidate for treating depression and neurodegenerative diseases.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"267 ","pages":"Article 112857"},"PeriodicalIF":3.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bio-inspired oxidation catalysis based on proton-coupled electron transfer: Toward efficient and selective oxidation of methane to methanol","authors":"Takahiko Kojima","doi":"10.1016/j.jinorgbio.2025.112856","DOIUrl":"10.1016/j.jinorgbio.2025.112856","url":null,"abstract":"<div><div>In this paper, a trail of my research is described starting from oxidation of alkanes by Fe^III-TPA (TPA = tris(2-pyridylmethyl)amine) complexes with alkyl hydroperoxides to Ru-pyridylamine complexes which can be converted to Ru^IV-oxo complexes in different spin states (<em>S</em> = 1 or 0) through proton-coupled electron-transfer oxidation of the corresponding Ru^II-aqua complexes, clarifying that those spin states do not affect the reactivity in water. The introduction of strongly donating N-heterocyclic carbene (NHC) moiety allows us to create a Ru^III-oxyl complex showing different reactivity from that of Ru^IV-oxo complexes. Manipulation of second coordination spheres (SCSs) of Ru-TPA complexes is also described, visualizing unique functionality. The introduction of hydrophobic SCS to a Fe^II-NHC complex enables to catalyze selective oxidation of methane to form methanol in high selectivity in aqueous media based on the “catch-and-release” strategy, which can also allow us to achieve highly selective two-electron oxidation of aromatic compounds.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"267 ","pages":"Article 112856"},"PeriodicalIF":3.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer organometallic half-sandwich complexes of estrone-derived (N,N) donor ligands with enhanced aqueous solubility","authors":"Tamás Pivarcsik ,&nbsp;Ferenc Kovács ,&nbsp;Gabriella Spengler ,&nbsp;Márta Nové ,&nbsp;Bernhard K. Keppler ,&nbsp;Wolfgang Kandioller ,&nbsp;Éva Frank ,&nbsp;Éva A. Enyedy","doi":"10.1016/j.jinorgbio.2025.112858","DOIUrl":"10.1016/j.jinorgbio.2025.112858","url":null,"abstract":"<div><div>Four steroidal derivatives (L^1-4) bearing an (N,N) metal-chelating subunit on the D-ring, in addition to the organometallic [M(arene)(N,N)Cl]Cl complexes of L^1,2 were synthesized and characterized, in which M(arene) is Rh(III)(η⁵-C₅Me₅) or Ir(III)(η⁵-C₅Me₅) or Ru(II)(η⁶-<em>p</em>-cymene). The solution chemical properties of both the estrone-based ligands and selected complexes were investigated by spectroscopic methods. At pH = 7.4, the ligands are predominantly positively charged, moderately lipophilic (log<em>D</em>_7.4 = +0.6 − +3.2), and exhibit low-to-medium micromolar solubility (<em>S</em>_7.4 = 9–543 μM) and are more hydrophilic than estrone; however, complexation improved the aqueous solubility of the obtained organometallics. The Rh(η⁵-C₅Me₅) and Ru(η⁶-<em>p</em>-cymene) complexes of L¹ demonstrated high stability in solution (&lt;1 % bidentate ligand dissociation at pH 7.4 for 48 h), forming a higher fraction of mixed hydroxido species [M(arene)(N,N)(OH)]⁺ in the case of the Ru complexes. Both coordination and intermolecular interactions of the organometallic complexes with human serum albumin were observed. The ligands and their complexes were tested in human cancer cell lines to investigate their <em>in vitro</em> anticancer activity. Studies in Colo-205 and MCF-7 cells revealed the moderate-to-strong cytotoxicity of the ligands (IC₅₀ = 5–50 μM) with limited selectivity toward cancer cells over the non-cancerous CCD-19Lu fibroblast cell line. Complexation increased the cytotoxicity, especially for Rh(III)(η⁵-C₅Me₅) and Ir(III)(η⁵-C₅Me₅) complexes in the MCF-7 cell line compared to the ligands.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"267 ","pages":"Article 112858"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimics of [FeFe]‑hydrogenases: Diiron aza- versus oxadiphenylpropanedithiolate complexes with mono- versus diphosphines","authors":"Pei-Hua Zhao,&nbsp;Yan Gao,&nbsp;Yu-Long Sun,&nbsp;Xing-Bin Jing,&nbsp;Diao-Yu Zhou","doi":"10.1016/j.jinorgbio.2025.112859","DOIUrl":"10.1016/j.jinorgbio.2025.112859","url":null,"abstract":"<div><div>To extensively devolep the bioinspired chemistry of [FeFe]‑hydrogenases, this study performs an insigt into the selective substitution of all‑carbonyl diiron aza- versus oxadiphenylpropanedithiolate precursors Fe₂(<em>μ</em>-Ph₂xdt)(CO)₆ (Ph₂xdt = Ph₂odt = (SCHPh)₂O for <strong>1</strong> and Ph₂adt^NH = (SCHPh)₂NH for <strong>2</strong>) by mono- versus diphosphines P(C₆H₄R-<em>p</em>)₃ (R = Me and Cl) and (Ph₂P)₂R′ (R′ = <em>cis</em>-CH=CH- for dppv and -CH₂CH₂- for dppe). With monophosphines, their monosubstituted diiron Ph₂odt complexes Fe₂(<em>μ</em>-Ph₂odt)(CO)₅){<em>κ</em>¹-P(C₆H₄R-<em>p</em>)₃} (R = Me for <strong>1a</strong> and Cl for <strong>1b</strong>) were obtained through the oxidative decarbonylating of <strong>1</strong> at room temperature in MeCN with Me₃NO·2H₂O; in contrast, analogous diiron Ph₂adt^NH complexes Fe₂(<em>μ</em>-Ph₂adt^NH)(CO)₅){<em>κ</em>¹-P(C₆H₄R-<em>p</em>)₃} (R = Me for <strong>2a</strong> and Cl for <strong>2b</strong>) were afforded via the photolytic decarbonlating of <strong>2</strong> under UV irradiation (365 nm) in toluene. With diphosphines, the dppv-chelated diiron Ph₂xdt complexes Fe₂(<em>μ</em>-Ph₂xdt)(CO)₄(<em>κ</em>²-dppv) (Ph₂xdt = Ph₂odt for <strong>1c</strong> and Ph₂adt^NH for <strong>2c</strong>) were prepared from the UV-irradiated decarbonylation of <strong>1</strong> or <strong>2</strong> in toluene; by contrast, the dppe-chelated diiron similar complexes Fe₂(<em>μ</em>-Ph₂xdt)(CO)₄(<em>κ</em>²-dppe) (Ph₂xdt = Ph₂odt for <strong>1d</strong> and Ph₂adt^NH for <strong>2d</strong>) were synthesized from the Me₃NO-assisted decarbonylation of <strong>1</strong> in room-temperature MeCN and that of <strong>2</strong> at refluxing toluene, respectively. The elemental analysis, FT-IR and NMR (¹H, ³¹P) spectroscopy are used for the full elucidation of the molecular structures of these new diiron complexes and X-ray crystallography is applied for further confirmation of <strong>1</strong>, <strong>2</strong> and <strong>1a</strong>, <strong>2b</strong>. The electrochemical properties of representative complexes <strong>1</strong>, <strong>1a</strong>, <strong>1c</strong> and <strong>2</strong>, <strong>2a</strong>, <strong>2c</strong> have been explored and compared with and without acetic acid (AcOH).</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"267 ","pages":"Article 112859"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and characterization of porphyrin-based photosensitizing metalloproteins integrated with artificial metalloenzymes for photocatalytic hydrogen production","authors":"L.V. Opdam ,&nbsp;S.K. Goetzfried ,&nbsp;E. Polanco ,&nbsp;S. Bonnet ,&nbsp;A. Pandit","doi":"10.1016/j.jinorgbio.2025.112855","DOIUrl":"10.1016/j.jinorgbio.2025.112855","url":null,"abstract":"<div><div>Hydrogen is regarded as a promising alternative to fossil fuels. A desirable method of its generation is via photocatalysis, combining photosensitizers and hydrogen-evolution catalysts in the presence of an electron donor. Inspired by natural photosynthesis, we designed photosensitizing artificial metalloproteins (ArMs) and integrated them with ArM-based catalysts for photocatalytic hydrogen production from water. Metal porphyrins based on protoporphyrin IX (PPIX) were employed as they are naturally abundant and are effective both as photosensitizers and hydrogen-evolution catalysts. Photosensitizing proteins were created by binding zinc (Zn)PPIX or ruthenium (Ru)PPIX to the haem acquisition system A <em>from Pseudomonas aeruginosa</em> (HasAp). The photosensitizer ArMs were combined with cobalt (Co)PPIX-myoglobin (Mb) or free CoPPIX as hydrogen evolution catalysts. We found that free CoPPIX could replace ZnPPIX or RuPPIX in HasAp, forming CoPPIX-HasAp or RuPPIX-CoPPIX-HasAp complexes with enhanced stability compared to CoPPIX-Mb. Photocatalytic hydrogen production was achieved upon irradiation at 435 nm (ZnPPIX) or 385 nm (RuPPIX), using methyl viologen as an electron carrier and triethanolamine as an electron donor. The ZnPPIX-HasAp/CoPPIX-HasAp system remained intact and active for approximately 42 h, while Ru-based systems that were excited by UV light, exhibited signs of protein cleavage upon prolonged irradiation. These results demonstrate the potential of integrating porphyrin-based ArMs for photosensitization and hydrogen evolution, with HasAp providing a robust scaffold for sustained photocatalytic activity.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"267 ","pages":"Article 112855"},"PeriodicalIF":3.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twenty years in metalloprotein bioinformatics: A short history of a long journey","authors":"Claudia Andreini","doi":"10.1016/j.jinorgbio.2025.112854","DOIUrl":"10.1016/j.jinorgbio.2025.112854","url":null,"abstract":"<div><div>The study of the structure and function of metalloproteins is a central subject of inorganic biochemistry. Starting from the 2000s, computational methods have flanked experimental research by exploiting the ever-increasing computing power and the huge amount of data produced by omics technologies. In this article, we retrace the major advancements that brought bioinformatics from being of minor relevance to being an essential tool for today's inorganic biochemists, focusing on the contributions coming from the Magnetic Resonance Center (CERM) of Florence, where we have been developing for twenty years methods and resources to investigate metalloproteins with computational approaches.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"266 ","pages":"Article 112854"},"PeriodicalIF":3.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antitumor activity of ruthenium(III) complexes with [N2O2]-tetradentate Schiff base ligands","authors":"Zdravka Petrova ,&nbsp;Teodora Mocanu ,&nbsp;Rossen Spasov ,&nbsp;Anamaria Hanganu ,&nbsp;Gabriela Marinescu ,&nbsp;Daniela C. Culita ,&nbsp;Radostina Alexandrova","doi":"10.1016/j.jinorgbio.2025.112853","DOIUrl":"10.1016/j.jinorgbio.2025.112853","url":null,"abstract":"<div><div>In this article, the antitumor and antiproliferative activity of three Ru(III) complexes, [Ru^III(Salen)(PPh₃)Cl] (<strong>RuSalen</strong>), [Ru^III(Salphen)(PPh₃)Cl] (<strong>RuSalphen</strong>), and [Ru^III(Salpn)(PPh₃)Cl] (<strong>RuSalpn</strong>) (H₂Salen, H₂Salphen and H₂Salpn are the Schiff bases obtained by the condensation between salicylaldehyde and ethylenediamine, 1,2-phenylenediamine, and 1,3-diaminopropanne, respectively) and their precursor, [Ru^II(PPh₃)₃Cl₂], were investigated against laboratory-cultured tumor cell lines: HT29 (human colorectal carcinoma), Saos-2 (human osteogenic sarcoma), HeLa (human cervical carcinoma), RST (rat transplantable sarcoma), and the non-tumor cell line Lep3 (embryonal human fibroblasts). It was found that all the cancer cell lines investigated were effectively dose-dependently inhibited in their growth by the Ru(III) complexes, while the non-tumor cell line Lep3 was the least affected by their cytotoxic effect. The Annexin V assay revealed that the Ru(III) complexes determined the occurrence of apoptosis in all cell lines tested, in a dose-dependent manner. <strong>RuSalpn</strong> exhibited the strongest ability to reduce tumor cell survival and proliferation, with efficacy that is either superior to or comparable to that of well-established clinical oncology agents such as cisplatin, oxaliplatin, epirubicin, and paclitaxel. The experiments revealed a cell-specific response, with varying degrees of sensitivity to the tested substances across different cell lines. <strong>RuSalpn</strong> demonstrated the strongest cytotoxic effect in the HT29 cell line, while <strong>RuSalen</strong>, <strong>RuSalphen</strong> showed the highest activity against RST cells. It was found that <strong>RuSalphen</strong> (≥7.0 μM) significantly inhibited cell migratory activity in the HT29 cell line, while in the RST cell line, <strong>RuSalen</strong> (≥37.6 μM), <strong>RuSalphen</strong> (≥14.0 μM), and <strong>RuSalpn</strong> (≥36.8 μM) demonstrated a strong inhibitory effect on cell migration.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"266 ","pages":"Article 112853"},"PeriodicalIF":3.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclometalated iridium(III)-lonidamine conjugates: Mitochondrial targeting and pyroptosis induction","authors":"Xing-Yun Lu ,&nbsp;Lin-Yuan Zhu ,&nbsp;Hou Zhu,&nbsp;Shao-Jun Huang,&nbsp;Yong-Sheng Yang,&nbsp;Chun-Rong Jiang,&nbsp;Rui-Rong Ye","doi":"10.1016/j.jinorgbio.2025.112852","DOIUrl":"10.1016/j.jinorgbio.2025.112852","url":null,"abstract":"<div><div>A series of cyclometalated Ir(III)-lonidamine (LND) complexes (<strong>Ir-LND-1–6</strong>) with the formula [Ir(C^N)₂bpy(4-CH₃–4’-CH₂OLND)](PF₆) (<strong>Ir-LND-1–3</strong>) and [Ir(C^N)₂bpy(4-CH₂OLND-4’-CH₂OLND)](PF₆) (<strong>Ir-LND-4–6</strong>) (C^<em>N</em> = 2-phenylpyridine (ppy, in <strong>Ir-LND-1</strong> and <strong>Ir-LND-4</strong>), 2-(2-thienyl) pyridine (thpy, in <strong>Ir-LND-2</strong> and <strong>Ir-LND-5</strong>) and 2-(2,4-difluorophenyl) pyridine (dfppy, in <strong>Ir-LND-3</strong> and <strong>Ir-LND-6</strong>)), were designed and synthesized. 3-(4,5-dimethylthiazol-2-yl)-2,5-biphenyltetrazolium bromide (MTT) assay data showed that the cytotoxicity of <strong>Ir-LND-1–3</strong> carry one LND moiety was superior to that of <strong>Ir-LND-4</strong>–<strong>6</strong> with two LND moieties. Therefore, we selected <strong>Ir-LND-1–3</strong> as model compounds to investigate the anti-tumor mechanism of the Ir(III)-LND system. The results showed that <strong>Ir-LND-1–3</strong> could inhibit cancer cell migration and colony formation. In addition, <strong>Ir-LND-1–3</strong> could penetrate into HeLa cells and localized to mitochondria, further disrupting mitochondrial membrane potential (MMP), increasing intracellular reactive oxygen species (ROS), and reducing intracellular adenosine triphosphate (ATP). Further exploration of anti-tumor mechanisms showed that pyroptosis was the main mode of <strong>Ir-LND-1–3</strong> induced cell death, manifested as membrane perforation and swelling, activation of caspase-3 and cleavage of Gasdermin E (GSDME), as well as release of lactic dehydrogenase (LDH) and ATP. The pyroptosis induced by <strong>Ir-LND-1–3</strong> also initiated immunogenic cell death (ICD) by triggering the release of calreticulin (CRT) and high mobility group protein b1 (HMGB1) on the cell surface.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"266 ","pages":"Article 112852"},"PeriodicalIF":3.8,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heme and immunity: The heme oxygenase dichotomy","authors":"Melissa Perry ,&nbsp;Iqbal Hamza","doi":"10.1016/j.jinorgbio.2025.112844","DOIUrl":"10.1016/j.jinorgbio.2025.112844","url":null,"abstract":"<div><div>Heme, an iron containing organic ring, is required for a diverse range of biological processes across all forms of life. Although this nutrient is essential, its pro-inflammatory and cytotoxic properties can lead to cellular damage. Heme oxygenase 1 (HO-1) is an endoplasmic reticulum (ER)-anchored enzyme that degrades heme, releasing equimolar amounts of carbon monoxide (CO), biliverdin (BV), and iron. The induction of HO-1 by heme presents an interesting dichotomy in the cell: CO and BV possess anti-inflammatory and antioxidant properties while free iron can be detrimental as it can generate hydroxyl radicals through the Fenton reaction. The heme/HO-1 axis is tightly regulated, and can influence cell fate, local tissue environments, and disease outcomes during pathogen infection. In this review we explore the role of heme during macrophage polarization and its ability to act as an immune activator while also examining the contribution of HO-1 and heme during infections with intracellular and extracellular pathogens. We highlight work from the emerging field of nutritional immunity of heme and iron, and how the substrates and byproducts of heme metabolism via HO-1 can be beneficial to the host or the pathogen depending on the context.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"267 ","pages":"Article 112844"},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}