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Antiviral Activity of Berbamine Against Influenza A Virus Infection.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-03-20 DOI: 10.3390/ijms26062819
Won-Kyung Cho, Hee-Jeong Choi, Jin Yeul Ma
{"title":"Antiviral Activity of Berbamine Against Influenza A Virus Infection.","authors":"Won-Kyung Cho, Hee-Jeong Choi, Jin Yeul Ma","doi":"10.3390/ijms26062819","DOIUrl":"10.3390/ijms26062819","url":null,"abstract":"<p><p>Berbamine (BBM) is a bibenzyl isoquinoline present in the traditional Chinese herbal medicine <i>Berberis amurensisis</i> Rupr. The present study demonstrates that BBM exerts strong antiviral efficacy against influenza A virus (IAV) infection. We examined the anti-IAV effect of BBM using green fluorescent protein (GFP)-expressing influenza A and H1N1 IAV. The fluorescence microscopy, fluorescence-activated cell sorting analysis, and plaque assay showed that BBM significantly hinders IAV infection. The immunofluorescence analysis confirmed the anti-influenza activity of BBM. From the time-of-addition and hemagglutination inhibition results, it is elucidated that the antiviral effect of BBM is closely related to its inhibitory effect against viral binding and entry at an early infection stage. Our findings imply that BBM has the potential to be developed as a potent antiviral drug against influenza viral infection.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An In-Depth Exploration of the Autoantibody Immune Profile in ME/CFS Using Novel Antigen Profiling Techniques.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-03-20 DOI: 10.3390/ijms26062799
Arnaud Germain, Jillian R Jaycox, Christopher J Emig, Aaron M Ring, Maureen R Hanson
{"title":"An In-Depth Exploration of the Autoantibody Immune Profile in ME/CFS Using Novel Antigen Profiling Techniques.","authors":"Arnaud Germain, Jillian R Jaycox, Christopher J Emig, Aaron M Ring, Maureen R Hanson","doi":"10.3390/ijms26062799","DOIUrl":"10.3390/ijms26062799","url":null,"abstract":"<p><p>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by serious physical and cognitive impairments. Recent research underscores the role of immune dysfunction, including the role of autoantibodies, in ME/CFS pathophysiology. Expanding on previous studies, we analyzed 7542 antibody-antigen interactions in ME/CFS patients using two advanced platforms: a 1134 autoantibody Luminex panel from Oncimmune and Augmenta Bioworks, along with Rapid Extracellular Antigen Profiling (REAP), a validated high-throughput method that measures autoantibody reactivity against 6183 extracellular human proteins and 225 human viral pathogen proteins. Unlike earlier reports, our analysis of 172 participants revealed no significant differences in autoantibody reactivities between ME/CFS patients and controls, including against GPCRs such as β-adrenergic receptors. However, subtle trends in autoantibody ratios between male and female ME/CFS subgroups, along with patterns of herpesvirus reactivation, suggest the need for broader and more detailed exploration.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Generation of New Knock-Out Mouse Strains of Lysophosphatidic Acid Receptor 1.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-03-20 DOI: 10.3390/ijms26062811
Georgia Antonopoulou, Christiana Magkrioti, Ismini Chatzidaki, Dimitris Nastos, Sofia Grammenoudi, Konstantinos Bozonelos, Vassilis Aidinis
{"title":"Generation of New Knock-Out Mouse Strains of <i>Lysophosphatidic Acid Receptor 1</i>.","authors":"Georgia Antonopoulou, Christiana Magkrioti, Ismini Chatzidaki, Dimitris Nastos, Sofia Grammenoudi, Konstantinos Bozonelos, Vassilis Aidinis","doi":"10.3390/ijms26062811","DOIUrl":"10.3390/ijms26062811","url":null,"abstract":"<p><p>The lysophosphatidic acid receptor 1 (LPAR1) is one of the six cognate G protein-coupled receptors of the bioactive, growth factor-like phospholipid lysophosphatidic acid (LPA). LPAR1 is widely expressed in different cell types and mediates many LPA effects. LPAR1 has been implicated in several chronic inflammatory diseases, and especially pulmonary fibrosis, where it has been established as a promising therapeutic target. Herein, we present the generation of several <i>Lpar1</i> mouse strains through genetic recombination. These strains include an initial versatile <i>Lpar1</i> strain (tm1a) from which three other strains derive: an <i>Lpar1</i> reporter knockout strain (tm1b) where LacZ has replaced exon 3 of <i>Lpar1</i>; a \"floxed\" <i>Lpar1</i> strain (tm1c), where exon 3 is flanked by two loxP sites allowing conditional, cell-specific <i>Lpar1</i> inactivation; and a complete KO strain of <i>Lpar1</i> (tm1d), where exon 3 has been deleted. The generated strains are novel genetic tools, that can have various applications in studying LPA-LPAR1 signaling and its role in normal physiology and disease.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Harnessing Plasma Biomarkers to Predict Immunotherapy Outcomes in Hepatocellular Carcinoma: The Role of cfDNA, ctDNA, and Cytokines.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-03-20 DOI: 10.3390/ijms26062794
Elena Vargas-Accarino, Mónica Higuera, María Bermúdez-Ramos, Agnès Soriano-Varela, María Torrens, Mònica Pons, Ana María Aransay, José Ezequiel Martín, Francisco Rodríguez-Frías, Xavier Merino, Beatriz Mínguez
{"title":"Harnessing Plasma Biomarkers to Predict Immunotherapy Outcomes in Hepatocellular Carcinoma: The Role of cfDNA, ctDNA, and Cytokines.","authors":"Elena Vargas-Accarino, Mónica Higuera, María Bermúdez-Ramos, Agnès Soriano-Varela, María Torrens, Mònica Pons, Ana María Aransay, José Ezequiel Martín, Francisco Rodríguez-Frías, Xavier Merino, Beatriz Mínguez","doi":"10.3390/ijms26062794","DOIUrl":"10.3390/ijms26062794","url":null,"abstract":"<p><p>Immunotherapy has improved survival in patients with advanced hepatocellular carcinoma (HCC); yet, objective radiological responses occur in only about 20% of cases, suggesting variable benefits. This study aimed to identify serologic markers predictive of response to immune checkpoint inhibitors (ICIs). A cohort of 38 advanced HCC patients receiving immunotherapy was prospectively analyzed. Levels of cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and cytokines were measured pre-treatment and three months post-treatment initiation. Genomic profiling of ctDNA was also conducted. Baseline levels of cfDNA and ctDNA effectively discriminated HCC patients based on their radiological response to ICIs. Additionally, individuals with pathologic mutations in the <i>CDKN2A</i> gene exhibited significantly reduced survival. Patients with progressive disease (PD) as their best radiological response had significantly fewer copy number variations (CNVs) than those with a radiological response. Furthermore, levels of IL10, PD1, and TGFβ assessed after three months of treatment showed significant variations correlating with survival status. In conclusion, the analysis of cfDNA, ctDNA, and cytokines may improve treatment selection for HCC patients by predicting their expected response to immunotherapies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanotransduction and Skeletal Muscle Atrophy: The Interplay Between Focal Adhesions and Oxidative Stress.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-03-20 DOI: 10.3390/ijms26062802
Khaled Y Kamal, Marina Trombetta-Lima
{"title":"Mechanotransduction and Skeletal Muscle Atrophy: The Interplay Between Focal Adhesions and Oxidative Stress.","authors":"Khaled Y Kamal, Marina Trombetta-Lima","doi":"10.3390/ijms26062802","DOIUrl":"10.3390/ijms26062802","url":null,"abstract":"<p><p>Mechanical unloading leads to profound musculoskeletal degeneration, muscle wasting, and weakness. Understanding the specific signaling pathways involved is essential for uncovering effective interventions. This review provides new perspectives on mechanotransduction pathways, focusing on the critical roles of focal adhesions (FAs) and oxidative stress in skeletal muscle atrophy under mechanical unloading. As pivotal mechanosensors, FAs integrate mechanical and biochemical signals to sustain muscle structural integrity. When disrupted, these complexes impair force transmission, activating proteolytic pathways (e.g., ubiquitin-proteasome system) that accelerate atrophy. Oxidative stress, driven by mitochondrial dysfunction and NADPH oxidase-2 (NOX2) hyperactivation, exacerbates muscle degeneration through excessive reactive oxygen species (ROS) production, impaired repair mechanisms, and dysregulated redox signaling. The interplay between FA dysfunction and oxidative stress underscores the complexity of muscle atrophy pathogenesis: FA destabilization heightens oxidative damage, while ROS overproduction further disrupts FA integrity, creating a self-amplifying vicious cycle. Therapeutic strategies, such as NOX2 inhibitors, mitochondrial-targeted antioxidants, and FAK-activating compounds, promise to mitigate muscle atrophy by preserving mechanotransduction signaling and restoring redox balance. By elucidating these pathways, this review advances the understanding of muscle degeneration during unloading and identifies promising synergistic therapeutic targets, emphasizing the need for combinatorial approaches to disrupt the FA-ROS feedback loop.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Crosstalk Between NETs and the Complement Cascade: An Overview in Nephrological Autoimmune Disease.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-03-20 DOI: 10.3390/ijms26062789
Xhuliana Kajana, Gianluca Caridi, Maurizio Bruschi, Sonia Spinelli, Francesca Lugani, Gian Marco Ghiggeri, Edoardo La Porta, Gabriele Mortari, Enrico E Verrina, Andrea Angeletti, Carolina Bigatti
{"title":"The Crosstalk Between NETs and the Complement Cascade: An Overview in Nephrological Autoimmune Disease.","authors":"Xhuliana Kajana, Gianluca Caridi, Maurizio Bruschi, Sonia Spinelli, Francesca Lugani, Gian Marco Ghiggeri, Edoardo La Porta, Gabriele Mortari, Enrico E Verrina, Andrea Angeletti, Carolina Bigatti","doi":"10.3390/ijms26062789","DOIUrl":"10.3390/ijms26062789","url":null,"abstract":"<p><p>The complement cascade and Neutrophil Extracellular Traps (NETs) represent fundamental tools in protecting the host from foreign pathogens. Complement components and relative fragments, classically assigned to the innate immunity, represent a key link with the humoral immune response. NETs are a crucial component of the innate immune response, consisting of chromatin release from activated neutrophils. These web-like structures facilitate pathogen entrapment and elimination through proteolytic degradation and antimicrobial effectors. Previous findings suggested complement components and NETs have a significant role in the pathogenesis of several diseases characterized by inflammation, such as autoimmune and infectious diseases. However, the crosstalk between NETs and the complement cascade has only recently been investigated, and several aspects still need to be fully clarified. Recent evidence seems to suggest a bidirectional link between the complement cascade and NETosis. We here present the interaction between complement components and NETs in specific autoimmune diseases that mostly affect the kidney, such as systemic lupus erythematosus, Antineutrophilic Cytoplasmic Antibody (ANCA)-associated vasculitis and antiphospholipid syndrome. The mechanisms reported here may represent specific targets for the development of possible therapeutic strategies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A TMT-Based Proteomic Analysis of Osmoregulation in the Gills of Oreochromis mossambicus Exposed to Three Osmotic Stresses.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-03-20 DOI: 10.3390/ijms26062791
Huanhuan Su, Dongmei Ma, Jiajia Fan, Zaixuan Zhong, Yuanyuan Tian, Huaping Zhu
{"title":"A TMT-Based Proteomic Analysis of Osmoregulation in the Gills of <i>Oreochromis mossambicus</i> Exposed to Three Osmotic Stresses.","authors":"Huanhuan Su, Dongmei Ma, Jiajia Fan, Zaixuan Zhong, Yuanyuan Tian, Huaping Zhu","doi":"10.3390/ijms26062791","DOIUrl":"10.3390/ijms26062791","url":null,"abstract":"<p><p>Salinity and alkalinity are critical environmental factors that affect fish physiology and ability to survive. <i>Oreochromis mossambicus</i> is a euryhaline species that can endure a wide range of salinities and has the potential to serve as a valuable model animal for environmental science. In order to detect the histomorphological changes, antioxidant enzymes, and proteomic responses of <i>O. mossambicus</i> to different osmotic stresses, <i>O. mossambicus</i> was subjected to salinity stress (25 g/L, S_S), alkalinity stress (4 g/L, A_S), saline-alkalinity stress (salinity: 25 g/L, alkalinity: 4 g/L, SA_S), and freshwater (the control group; C_S). The histomorphological and antioxidant enzyme results indicated that salinity, alkalinity, and saline-alkalinity stresses have different degrees of damage and effects on the gills and liver of <i>O. mossambicus</i>. Compared with the control, 83, 187, and 177 differentially expressed proteins (DEPs) were identified in the salinity, alkalinity, and saline-alkalinity stresses, respectively. The obtained DEPs can be summarized into four categories: ion transport channels or proteins, energy synthesis and metabolism, immunity, and apoptosis. The KEGG enrichment results indicated that DNA replication and repair were significantly enriched in the salinity stress group. Lysosomes and oxidative phosphorylation were considerably enriched in the alkalinity stress group. Comparatively, the three most important enriched pathways in the saline-alkalinity stress group were Parkinson's disease, Alzheimer's disease, and Huntington's disease. The findings of this investigation yield robust empirical evidence elucidating osmoregulatory mechanisms and adaptive biological responses in euryhaline teleost, thereby establishing a scientific foundation for the cultivation and genomic exploration of high-salinity-tolerant teleost species. This advancement facilitates the sustainable exploitation of saline-alkaline aquatic ecosystems while contributing to the optimization of piscicultural practices in hypersaline environments.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rare Case with Pathogenic Variant in DHX16 Gene Causing Neuromuscular Disease and Oculomotor Anomalies.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-03-20 DOI: 10.3390/ijms26062812
Stefania Kalampokini, Dimitrios G Goulis, Georgia Pepe, Stavrenia Koukoula, Antonis Frontistis, Maria Moschou, Marianthi Arnaoutoglou, Vasileios Papaliagkas, Vasilios K Kimiskidis
{"title":"Rare Case with Pathogenic Variant in DHX16 Gene Causing Neuromuscular Disease and Oculomotor Anomalies.","authors":"Stefania Kalampokini, Dimitrios G Goulis, Georgia Pepe, Stavrenia Koukoula, Antonis Frontistis, Maria Moschou, Marianthi Arnaoutoglou, Vasileios Papaliagkas, Vasilios K Kimiskidis","doi":"10.3390/ijms26062812","DOIUrl":"10.3390/ijms26062812","url":null,"abstract":"<p><p>The DEAD/DExD/H-box RNA helicases are a group of RNA-binding proteins involved in the metabolism of mRNAs. They coordinate gene expression programs and play a role in cellular signaling, fate, and survival. We describe a case of a 36-year-old female with neuromuscular disease, sensorineural hearing loss, retinitis pigmentosa, and primary ovarian insufficiency harboring a heterozygous de novo missense pathogenic variant in the DEAH-box helicase 16 (<i>DHX16</i>) gene. This is the first case exhibiting a high intellectual level and the highest survival outcome so far. Eight previous cases of <i>DHX16</i> disease-causing variant carriers have been described with common features, including muscle weakness with hypotonia, myopathy or peripheral neuropathy, sensorineural hearing loss, abnormal retinal findings, and infantile spasms or epilepsy. Increasing evidence associates RNA-binding proteins, including the DEAD/DExD/H-box helicase family genes, with neuropsychiatric or neurodevelopmental disorders. <i>DHX16</i> genetic analysis should be considered early when diagnosing a child or young adult with muscular disease, severe hearing loss, and ocular anomalies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prediction of 57Fe Mössbauer Nuclear Quadrupole Splittings with Hybrid and Double-Hybrid Density Functionals.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-03-20 DOI: 10.3390/ijms26062821
Yihao Zhang, Haonan Tang, Wenli Zou
{"title":"Prediction of <sup>57</sup>Fe Mössbauer Nuclear Quadrupole Splittings with Hybrid and Double-Hybrid Density Functionals.","authors":"Yihao Zhang, Haonan Tang, Wenli Zou","doi":"10.3390/ijms26062821","DOIUrl":"10.3390/ijms26062821","url":null,"abstract":"<p><p>As a crucial parameter in Mössbauer spectroscopy, nuclear quadrupole splitting (NQS) exhibits a strong dependence on quantum chemistry methods, which makes accurate theoretical predictions challenging. Meanwhile, the continuous emergence of new density functionals presents opportunities to advance current NQS research. In this study, we evaluate the performance of eleven hybrid density functionals and twelve double-hybrid density functionals, selected from widely used functionals and newly developed functionals, in predicting the NQS values of the <sup>57</sup>Fe nuclide for 32 iron-containing molecules within about 70 atoms. The calculations have incorporated scalar relativistic effects using the exact two-component (X2C) Hamiltonian. In general, the double-hybrid functional PBE-0DH demonstrates superior performance compared to the experimental values, achieving a mean absolute error (MAE) of 0.20 mm/s. Meanwhile, <i>r</i>SCAN38 is the best hybrid functional for our database with an MAE = 0.25 mm/s, and it offers a significant advantage in computational efficiency over PBE-0DH. The +/- sign of NQS has also been considered in our error statistics when it has a clear physical meaning; if neglected, the errors of many functionals decrease, but PBE-0DH and <i>r</i>SCAN38 remain unaffected. Notably, when calculating ferrocene [Fe(C<sub>5</sub>H<sub>5</sub>)<sub>2</sub>], which involves strong static correlations, all hybrid functionals that incorporate more than 10% exact exchange fail, while several double-hybrid functionals continue to deliver reliable results. In addition, we encountered two particularly challenging species characterized by strong static correlations: [Fe(H<sub>2</sub>O)<sub>5</sub>NO]<sup>2</sup>+ and FeO<sub>2</sub><sup>-</sup>-porphyrin. Unfortunately, none of the density functionals tested in our study yielded satisfactory results for the two cases since the density functional theory (DFT) is a single-determinant approach, and it is imperative to explore large-scale multi-configurational methods for these species. This research offers valuable guidance for selecting density functionals in Mössbauer NQS calculations and serves as a reference point for the future development of new density functionals.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gemcitabine-Doxorubicin Combination Polymer-Drug Conjugate Prepared by SPAAC Click Chemistry: In Vitro Characterization.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-03-20 DOI: 10.3390/ijms26062798
Omotola D Gbadegesin, Simeon K Adesina
{"title":"Gemcitabine-Doxorubicin Combination Polymer-Drug Conjugate Prepared by SPAAC Click Chemistry: In Vitro Characterization.","authors":"Omotola D Gbadegesin, Simeon K Adesina","doi":"10.3390/ijms26062798","DOIUrl":"10.3390/ijms26062798","url":null,"abstract":"<p><p>Combination chemotherapy is preferred for the treatment of ovarian cancer (OC). Systemic toxicity, however, frequently limits the effectiveness of treatment. Polymer-drug conjugates (PDCs) containing synergistic combinations of chemotherapeutic drugs can be used to enhance therapeutic efficacy. We earlier reported the use of a strain-promoted [3 + 2] azide-alkyne cycloaddition (SPAAC)-mediated polymerization method for the preparation of single-drug PDCs. In this report, the polymerization method was used to prepare gemcitabine-doxorubicin combination PDC. The PDC had a high molecular weight (M<sub>w</sub> 1360 kDa) and high drug loading (36.6% weight gemcitabine; 7.0% weight doxorubicin). It demonstrated cathepsin B-catalyzed drug release at pH 5.0 and good hydrolytic stability at pH 7.4. The combination index analysis of free gemcitabine and free doxorubicin showed a concentration-dependent synergism (combination index < 1) in OVCAR-3 OC cells. Compared to individual gemcitabine PDC (the concentration that inhibited 50% growth (IC<sub>50</sub>) > 50 µg/mL) and doxorubicin PDC (IC<sub>50</sub> = 1.79 µg/mL), the combination PDC (IC<sub>50</sub> = 0.99 µg/mL) showed greater cytotoxicity against OVCAR-3 cells and was less cytotoxic than the equivalent free drug combination (IC<sub>50</sub> = 0.11 µg/mL). The gemcitabine-doxorubicin combination PDC is promising for targeted combination chemotherapy of OC.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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