International Journal of Molecular Sciences最新文献

{"title":"Hypoxic Microenvironment Effects on Matrix Metalloproteinases' Expression and Enzymatic Activity, and HIFs' Expression in Non-Small Cell Lung Cancer Cells.","authors":"Georgina Gonzalez-Avila, Cuauhtemoc Sandoval, Bettina Sommer, A Armando Garcia-Hernandez, Jose S Lopez-Gonzalez, Arnoldo Aquino-Gálvez, Carina Becerril, Edgar Flores-Soto","doi":"10.3390/ijms27209314","DOIUrl":"10.3390/ijms27209314","url":null,"abstract":"<p><p>The hypoxic tumor microenvironment (TME) promotes metastasis, in which matrix metalloproteinases (MMPs) play a central role. The present work aimed to analyze the effects of hypoxia on MMP expression and enzymatic activity, as well as hypoxia-inducible factor (HIF) expression in different non-small cell lung cancer (NSCLC) cells. Cells were cultured in 1% O₂ for 6 and 12 h, and the effects of hypoxia on MMPs and HIFs were analyzed using Western blotting and zymography. The highest MMP-2 protein expression was detected in CALU-1 (<i>p</i> ≤ 0.003) and A549 cells (<i>p</i> ≤ 0.006) at 6 and 12 h, respectively. Higher levels of MMP-9 were detected in CALU-1 (<i>p</i> ≤ 0.003) at 6 h and in A549 cells (<i>p</i> ≤ 0.04) at 12 h. MMP-2 and MMP-9 had the highest enzymatic activity in SKMES-1 cells (<i>p</i> ≤ 0.003). Increased HIF-1α levels were detected in A427 (<i>p</i> ≤ 0.04) at 6 h and in SKLU-1 cells (<i>p</i> ≤ 0.01) at 12 h, while higher HIF-2α expression was found in SKMES-1 at 6 h and 12 h (<i>p</i> ≤ 0.04). In conclusion, although hypoxia induces changes in MMP-2 and MMP-9 expression in NSCLC cells through HIF-dependent or HIF-independent pathways, these effects are not necessarily similar to those observed in enzymatic activity and differ between cell lines.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267056","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}

{"title":"Hangeshashinto Induces Apoptosis and Suppresses Colorectal Cancer Growth In Vitro and In Vivo.","authors":"Yunhai Lin, Jingya Lu, Ailing Hu, Takuji Yamaguchi, Yasushi Ikarashi, Yoshinao Harada, Kaho Ohki, Takumi Iwasawa, Hiroyuki Kobayashi","doi":"10.3390/ijms27209310","DOIUrl":"10.3390/ijms27209310","url":null,"abstract":"<p><p>Hangeshashinto (HST) is a standardized seven-herb Kampo pharmaceutical used to manage gastrointestinal symptoms and chemotherapy-associated mucosal toxicity, but its direct antitumor activity remains insufficiently characterized. We examined the effects of HST in DLD-1 and SW480 colorectal cancer (CRC) cells and in non-malignant fibroblast and colonic epithelial cell models. Cell viability, colony formation, apoptosis-related endpoints, gene expression, responses to 5-fluorouracil (5-FU), and the activity of representative constituents were evaluated. Oral antitumor efficacy and tolerability were assessed in female BALB/c-nu mice bearing DLD-1 xenografts. HST preferentially reduced CRC cell viability and colony formation and increased annexin V positivity, caspase-3 activity, cleaved caspase-3 staining, and apoptotic nuclear changes. z-VAD-FMK showed a nonsignificant tendency toward partial recovery of cell viability. Reverse transcription-quantitative polymerase chain reaction findings were exploratory; statistical significance was not assessed. Co-treatment with HST (0.3 mg/mL) and 5-FU significantly reduced cell viability compared with 5-FU alone in both DLD-1 and SW480 cells; pharmacological synergy was not evaluated. Oral HST inhibited xenograft growth; tolerability assessment was limited to body weight and serum biochemistry, with reduced serum uric acid in the high-dose group after washout. These findings provide a preclinical basis for further investigation of standardized HST in CRC.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267222","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}

{"title":"Procaine at Low Concentration Modulates Mitochondrial Features in Cultured Fibroblasts and Myoblasts: A Clue to the Cellular Mechanisms Underlying Neural Therapy.","authors":"Chiara Rita Inguscio, Giada Remoli, Ilaria Scambi, Franco Donati, Manuela Malatesta","doi":"10.3390/ijms27209327","DOIUrl":"10.3390/ijms27209327","url":null,"abstract":"<p><p>Procaine is a local anesthetic used at low concentrations in a complementary medical approach, neural therapy, due to its ability to promote antioxidant and anti-inflammatory response. Previous biochemical studies showed that low concentrations of procaine may also stimulate mitochondrial function. In the present study, low procaine concentrations were used to investigate in vitro the effects on mitochondria of human fibroblasts and mouse myoblasts. Histochemical, ultrastructural, and biomolecular techniques were employed. After 24 h from procaine treatment, mitochondrial membrane potential was unaltered in both cell types, but some mitochondrial features showed cell-specific modifications. In detail, in fibroblasts, procaine induced decreased mitochondrial cristae length and cellular adenosine triphosphate (ATP) levels. In myoblasts, procaine induced modifications of mitochondrial shape and oxidative phosphorylation subunit amount, together with increased cellular ATP levels. Most modifications were restored at 48 h. To explain the differential response of the two cell lines, we hypothesize a species-specific sensitivity to procaine or a cell-specific sensitivity related to the different extent of the endoplasmic reticulum, which is especially susceptible to procaine. Taken together, the results of this pilot study show that procaine at low concentration exerts a modulatory effect on mitochondrial features, opening the way to further studies aimed at elucidating the cellular pathways involved in the beneficial effects observed in procaine-based neural therapy.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13704911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267017","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}

{"title":"Multimodal Evaluation of [²²⁵Ac]Ac-PSMA-617 Therapy in mCRPC: PET Based Total Tumor Volume, PSA Kinetics, and Blood Biomarkers.","authors":"Ali Ebrahimifard, Shamim Bagheri, Qi Wang, Azimeh Hojjat Shamami, Pietro Di Fazio, Friederike Eilsberger, Laura Müller, Markus Luster, Damiano Librizzi, Behrooz Hooshyar Yousefi","doi":"10.3390/ijms27209330","DOIUrl":"10.3390/ijms27209330","url":null,"abstract":"<p><p>This retrospective analysis interrogates the value of a multimodal biomarker paradigm to characterize molecular and clinical responses to [²²⁵Ac]Ac-PSMA-617-targeted α-therapy (TAT) in cohorts of heavily pretreated metastatic castration-resistant prostate cancer patients who had shown limited benefit from prior [¹⁷⁷Lu]Lu-PSMA-617. By integrating quantitative PSMA-PET/CT metrics-notably total tumor volume (TTV) and lesion SUV indices-with longitudinal PSA kinetics, routine hematologic and biochemical markers, and semiquantitative assessment of salivary gland uptake, we sought to delineate treatment effect, organ-specific off-target impact, and prognostic biomarker signatures. In twelve patients receiving 2-6 cycles of therapy (median activity 8 MBq), biochemical responses were frequent: 8/12 experienced PSA declines and 5/12 achieved ≥50% reduction. Concordant molecular responses were observed on PSMA-PET, with SUV_peak-based partial response in 7/12, stable disease in 3/12, and progressive disease in 2/12 of the target lesions. Qualitative concordance between TTV and PSA response was observed in four illustrative patients; no formal cohort-level concordance analysis was performed. Notably, salivary gland tracer uptake on [⁶⁸Ga]Ga-PSMA-11 PET/CT decreased after two cycles of [²²⁵Ac]Ac-PSMA-617 compared with baseline (SUV_max -63.7%; SUV_mean -45.5%). In this exploratory cohort, elevations in PSA, alkaline phosphatase, and LDH measured after two cycles of therapy, along with low hemoglobin, platelet count, and creatinine, were associated with shorter overall survival. Median progression-free survival and overall survival were 27 and 53 weeks, respectively. Collectively, these findings suggest that a combined PSMA-PET TTV-PSA-blood biomarker framework may offer complementary insight alongside PSA alone for characterizing therapeutic response, although its incremental value over PSA was not formally tested in this exploratory cohort; blood-based biomarkers (PSA, ALP) showed the most consistent prognostic association with survival, providing objective measures of both tumor response and collateral tissue impact. Prospective validation in larger, controlled cohorts is warranted to refine biomarker thresholds and guide personalized TAT strategies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267177","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}

{"title":"Plant-Derived Functional Molecules for Photoelectrochemical Water Splitting: From Molecular Design to Hybrid Materials Engineering.","authors":"Sangmin Kim, Inseo Hwang, Gihoon Kim, Hyeonseok Yoon","doi":"10.3390/ijms27209326","DOIUrl":"10.3390/ijms27209326","url":null,"abstract":"<p><p>Plant-derived molecules offer tunable coordination and surface chemistry for photoelectrochemical (PEC) water splitting. A Scopus survey retrieved 45 documents linking both topics in 2005-2025, equivalent to 0.34% of the PEC literature. A supplementary search added 15 records, and screening retained 26 research articles. The review organizes molecular functions into light harvesting, charge-transfer mediation, coordination of catalytic overlayers, and passivation. A molecular readiness scale and a validation protocol connect molecular identity to verified device performance. Hybrid layers combining plant ligands with Co, Ni, or Fe raised BiVO₄ photocurrents to approximately 3-6 mA cm^-2 at 1.23 V vs. the reversible hydrogen electrode (RHE). Comparable inorganic overlayers preclude a general claim of superior activity. Ambient solution processing and control of interfacial coordination provide the principal design opportunities. Two-electron phenol/quinone potentials do not establish the feasibility of one-electron hole relay, which requires independent kinetic and redox evidence. At a coverage of 0.1 nmol cm^-2, a chlorophyll layer has a calculated photocurrent upper bound of approximately 0.05 mA cm^-2 within 640-680 nm alone. Broadband enhancement requires wavelength-resolved attribution. Operation for 1000 h at 1 mA cm^-2 and a loading of 1 nmol cm^-2 corresponds to approximately 3.7 × 10⁷ electrons per initially loaded molecule. The proposed framework links molecular structure, interfacial function, and product verification to guide durable molecular photoelectrodes.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267298","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}

{"title":"Beyond Classical Reward Circuits: Dorsal Striatum Proteomic Alterations in an Adolescent Phencyclidine-Induced Mouse Model of Schizophrenia and Nicotine Use.","authors":"Thainá Pereira Souza, Andrés Rodríguez-Vega, Ana Carolina Dutra-Tavares, Keila Alves Semeão, Claudio Carneiro Filgueiras, Anderson Ribeiro-Carvalho, Alex Christian Manhães, Yael Abreu-Villaça","doi":"10.3390/ijms27209328","DOIUrl":"10.3390/ijms27209328","url":null,"abstract":"<p><p>Schizophrenia and nicotine misuse comorbidity frequently emerges during adolescence. Although the dorsal striatum has received less attention than mesolimbic regions in this context, growing evidence supports its involvement in both schizophrenia-related dysfunction and the transition to compulsive drug-seeking. Here, we investigated dorsal striatal proteomic alterations in adolescent male and female C57BL/6 mice modeled to schizophrenia (phencyclidine: 2.5 mg/kg, s.c., 15 days) with a history of nicotine exposure (nicotine: 24 mg/kg/day, minipump infusions, 7 days). Dorsal striatum samples were analyzed by label-free quantitative proteomics, followed by Reactome pathway enrichment and interactome map analyses. Co-exposure induced sex-dependent alterations. Females exhibited greater proteomic disruption, whereas in males, co-exposure amplified phencyclidine-associated alterations while attenuating nicotine-driven effects. Across sexes, convergent enrichment was observed in pathways related to immune signaling, metabolic regulation and signal transduction. Female interactome analysis identified glyceraldehyde-3-phosphate dehydrogenase (Gapdh) as the most highly connected node linked to proteins involved in bioenergetics, RNA processing, and apoptosis, while the male network was centered on peptidyl-prolyl cis-trans isomerase (Fkbp1a) and associated with proteostasis-related processes. Our results identify the dorsal striatum as an emerging molecular target in an animal model combining schizophrenia-related and nicotine exposure-related insults and highlight pathways and candidate molecular markers to be further investigated and validated.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267012","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}

{"title":"Release Is Not Dose: Speciation, Bioavailability and Cellular Signalling of Metal Ions from Orthodontic and Prosthetic Alloys in the Oral Environment.","authors":"Marcin Mikulewicz","doi":"10.3390/ijms27209318","DOIUrl":"10.3390/ijms27209318","url":null,"abstract":"<p><p>Metal release from orthodontic and prosthetic alloys is measured almost universally as total elemental concentration in artificial or whole saliva and declared safe by comparison with dietary intake, drinking-water limits or toxic thresholds. This critical review argues that the comparison, a legitimate screen for systemic exposure, becomes a category error when used to exclude local mucosal effects. It traces the release literature's reasoning since 1986 and shows that the extraction medium, not the alloy, determines the quantity and chemical form of what is measured. It then maps oral species onto cellular uptake routes and signalling pathways. Biological effect depends on species (aquo-ion, low-molecular-mass complex, protein adduct, oxyanion or particle); species dictate entry via divalent metal transporter 1, anion transporters, receptor-mediated endocytosis, membrane interaction or phagocytosis, thereby selecting between Toll-like receptor 4, NOD-like receptor family pyrin domain-containing 3, caspase-8, hypoxia-inducible factor 1α and non-apoptotic death programmes; and whole-saliva totals do not describe biofilm, crevicular or intracellular exposure. Oral speciation evidence rests on two nuclear magnetic resonance titrations and one chromium(VI) separation, and most mechanisms are borrowed from other tissues. A speciation-aware exposure model, presented as a hypothesis-generating framework, a minimum reporting set and prioritised experiments are proposed.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267369","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}

{"title":"HDL Remodeling in Severe Bacterial Infection in Children: A Potential Biomarker for Diagnosis and Therapeutic Monitoring.","authors":"Arianna Finizio, Marco Sarno, Chiara Botti, Alice Castaldo, Andrea Catzola, Gustavo Cernera, Gilda Crispino, Giovanna Di Nardo, Monica Gelzo, Lorenza Lepore, Claudia Mandato, Virginia Mirra, Silvia Moggia, Francesco Nunziata, Francesca Orlando, Antonia Pascarella, Luca Pierri, Margherita Rosa, Fabio Savoia, Paolo Siani, Giuseppe Castaldo","doi":"10.3390/ijms27209300","DOIUrl":"10.3390/ijms27209300","url":null,"abstract":"<p><p>Many pediatric patients with severe bacterial infection (SBI) present with a compromised general clinical picture. Early identification of the infectious and inflammatory state can improve clinical outcomes. Although microbiological culture remains the gold standard for diagnosis, its delayed results highlight the need for early biomarkers to improve clinical decision-making and patient outcomes. During infection, the acute phase response alters lipid metabolism, compromising cholesterol efflux. In this study, we characterized the serum lipid profile and HDL subclasses in 63 children with SBI at hospital admission (T0) and discharge (T1), comparing them with 63 age- and sex-matched healthy subjects. At T0, we found a significant reduction in serum total cholesterol, LDL cholesterol, and HDL cholesterol in subjects with SBI compared to controls. Interestingly, at a cut-off value of 41.5 mg/dL, HDL cholesterol discriminated the two groups with a sensitivity of 76% and a specificity of 86% for SBI. At T1, total and LDL cholesterol increased, while HDL cholesterol remained unchanged. Moreover, we observed at T1 a clear remodeling of HDL classes, with a significant decrease in large HDL with pro-inflammatory activity and an increase in the intermediate and small HDL with anti-inflammatory activity, compared to time T0. This study proposes serum HDL cholesterol as a candidate biomarker and highlights the role of HDL cholesterol and its classes in inflammatory and immune regulation in systemic bacterial infection, potentially identifying patients who could benefit from HDL-based therapies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13704984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267299","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}

{"title":"Effects of Zinc Deficiency and Supplementation on Hippocampal ZnT3, NOGO-A, IL-6, and SESN2 Expression and Oxidative Stress Markers in a Cuprizone-Induced Toxic Demyelination Model.","authors":"Adem Atacak, Elif Gulbahce-Mutlu, Gozde Acar, Saltuk Bugra Baltaci, Rasim Mogulkoc, Abdulkerim Kasim Baltaci","doi":"10.3390/ijms27209329","DOIUrl":"10.3390/ijms27209329","url":null,"abstract":"<p><p>This study investigated the effects of zinc deficiency and supplementation on oxidative stress markers and the expression of ZnT3, NOGO-A, IL-6, and SESN2 in hippocampal tissue within a cuprizone (CPZ)-induced toxic demyelination model. Methods: Forty-six adult male Wistar rats were divided into five groups: Control (<i>n</i> = 6), Sham (<i>n</i> = 10), CPZ (<i>n</i> = 10), CPZ + zinc-deficient diet (<i>n</i> = 10), and CPZ + zinc supplementation (5 mg/kg/day, i.p., <i>n</i> = 10). Toxic demyelination was induced by continuous cuprizone administration for eight weeks. At the end of the experimental period, hippocampal malondialdehyde (MDA) and glutathione (GSH) levels were measured; additionally, hippocampal ZnT3, NOGO-A, IL-6, and SESN2 mRNA expression levels were analyzed using quantitative real-time PCR. Cuprizone administration led to significant hippocampal oxidative stress, characterized by increased MDA levels and decreased GSH concentrations (<i>p</i> < 0.05); these oxidative changes were further exacerbated in CPZ-treated animals fed a zinc-deficient diet (<i>p</i> < 0.05). Furthermore, CPZ-induced demyelination suppressed ZnT3 expression in hippocampal tissue while significantly increasing NOGO-A, IL-6, and SESN2 mRNA expression (<i>p</i> < 0.05). These molecular alterations were more pronounced in the zinc-deficient CPZ group (<i>p</i> < 0.05). Intraperitoneal zinc supplementation effectively mitigated these changes by suppressing oxidative stress, attenuating the upregulation of NOGO-A, IL-6, and SESN2 transcripts, and restoring ZnT3 expression to levels comparable to controls (<i>p</i> < 0.05). While dietary zinc deficiency exacerbated hippocampal oxidative stress, neuroinflammatory transcripts, and molecular markers associated with neurodegeneration in the cuprizone model, zinc supplementation restored oxidative balance; increased ZnT3 expression; and suppressed the upregulation of NOGO-A, IL-6, and SESN2. These findings suggest that zinc homeostasis significantly modulates cuprizone-induced hippocampal damage and that zinc supplementation may exert protective transcriptional and antioxidant effects during toxic demyelination.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13704965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267053","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}

{"title":"Condition-Controlled Divergent Reactivity of Nitroaldol Isatin Adducts with Phenols: Friedel-Crafts Alkylation, Skeletal Rearrangement, and Spirocyclic Oxime Formation.","authors":"Nikolai A Arutiunov, Daria A Shtal, Kirill V Tolstov, Anastasia A Korneeva, Olga V Petrova, Anna M Zatsepilina, Nicolai A Aksenov, Sergei N Ovcharov, Alexander V Aksenov","doi":"10.3390/ijms27209320","DOIUrl":"10.3390/ijms27209320","url":null,"abstract":"<p><p>We describe the condition-controlled divergent reactivity of nitroaldol isatin adducts with phenols. Under methanesulfonic acid, nitroalcohols undergo Friedel-Crafts alkylation to afford 3-aryl-3-(nitromethyl)indolin-2-ones in yields of up to 99%. Prolonged acidic treatment of selected Friedel-Crafts adducts leads to an unusual C3-to-C2 skeletal rearrangement, providing tetracyclic chromenoindolones in moderate yields. In contrast, treatment of the alkylation products with KOH in aqueous ethanol promotes intramolecular cyclization to spirocyclic hydroxyimino derivatives. This transformation afforded 16 compounds in 80-96% yields, whereas five new chromenoindolones were obtained in 40-56% yields. In total, 51 new compounds were synthesized, comprising 30 Friedel-Crafts alkylation products, 16 spirocyclic oxime derivatives, and five new chromenoindolones. The structures of representative products <b>8aa</b> and <b>13ab</b> were established by X-ray crystallography. The Friedel-Crafts reaction tolerates a range of alkyl, halogen, hydroxy, alkoxy, and N-substituted substrates, although several strongly electron-withdrawing substituents and α-naphthol were not compatible with the reaction conditions. Scalability was demonstrated on a 10 mmol scale for the synthesis of <b>7ae</b> and its subsequent conversion to <b>13ae</b>. The results demonstrate that nitroaldol isatin adducts can undergo markedly different reaction pathways depending on the reaction conditions, providing access to structurally distinct indole-containing frameworks.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13704967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267084","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}