Pub Date : 2026-02-07DOI: 10.1007/s11064-026-04688-9
Tianyi Dai, Qijun Dai, Yueqin Ding, Jianbin Su, Chao Huang, Rongrong Yang, Jie Peng, Zhuo Chen, Rongrong Song, Yunli Fang, Hanxiao Wang, Minxiu Ye, Jianwei Wang, Xu Lu
Conversion of microglia to a branching state is considered a potential strategy to ameliorate neuroinflammation. Inhibition of histone deacetylases (HDACs) may convert microglia to a branching state and thus prevent neuroinflammation. Drugs that inhibit HDACs could be used to alleviate neuroinflammation. Here, we hypothesize that 4-phenylbutyric acid (4-PBA), an HDAC inhibitor, could shift microglia to an anti-inflammatory phenotype by promoting microglial process elongation. As expected, our results showed that 4-PBA induced reversible elongation of branching processes in primary cultured mouse microglia and in microglia in the prefrontal cortex of mice. Pretreatment with 4-PBA also prevented lipopolysaccharide (LPS)-induced shortening of branching processes in microglia under both in vitro and ex vivo conditions, LPS-induced pro-inflammatory responses in cultured microglia and prefrontal cortex, and LPS-induced sickness behavior in mice. Short-term incubation with 4-PBA led to a significant increase in phosphorylation levels of protein kinase B (Akt) in cultured microglia. 4-PBA did not induce microglial process elongation in vitro or ex vivo when cultured microglia or mice were treated with the Akt signaling inhibitor LY294002, suggesting that the pro-elongation effect of 4-PBA on microglial processes require activation of Akt signaling. Moreover, 4-PBA did not prevent LPS-induced inflammatory responses in cultured microglia and prefrontal cortex or LPS-induced sickness behaviors when cultured microglia or mice were treated with LY294002. Altogether, these results indicate that 4-PBA induces microglial process elongation in an Akt-dependent manner, which may underlie the anti-neuroinflammatory properties of 4-PBA.
{"title":"4-Phenylbutyrate Induces Functional Elongation of the Microglial Process Through Activation of Akt.","authors":"Tianyi Dai, Qijun Dai, Yueqin Ding, Jianbin Su, Chao Huang, Rongrong Yang, Jie Peng, Zhuo Chen, Rongrong Song, Yunli Fang, Hanxiao Wang, Minxiu Ye, Jianwei Wang, Xu Lu","doi":"10.1007/s11064-026-04688-9","DOIUrl":"https://doi.org/10.1007/s11064-026-04688-9","url":null,"abstract":"<p><p>Conversion of microglia to a branching state is considered a potential strategy to ameliorate neuroinflammation. Inhibition of histone deacetylases (HDACs) may convert microglia to a branching state and thus prevent neuroinflammation. Drugs that inhibit HDACs could be used to alleviate neuroinflammation. Here, we hypothesize that 4-phenylbutyric acid (4-PBA), an HDAC inhibitor, could shift microglia to an anti-inflammatory phenotype by promoting microglial process elongation. As expected, our results showed that 4-PBA induced reversible elongation of branching processes in primary cultured mouse microglia and in microglia in the prefrontal cortex of mice. Pretreatment with 4-PBA also prevented lipopolysaccharide (LPS)-induced shortening of branching processes in microglia under both in vitro and ex vivo conditions, LPS-induced pro-inflammatory responses in cultured microglia and prefrontal cortex, and LPS-induced sickness behavior in mice. Short-term incubation with 4-PBA led to a significant increase in phosphorylation levels of protein kinase B (Akt) in cultured microglia. 4-PBA did not induce microglial process elongation in vitro or ex vivo when cultured microglia or mice were treated with the Akt signaling inhibitor LY294002, suggesting that the pro-elongation effect of 4-PBA on microglial processes require activation of Akt signaling. Moreover, 4-PBA did not prevent LPS-induced inflammatory responses in cultured microglia and prefrontal cortex or LPS-induced sickness behaviors when cultured microglia or mice were treated with LY294002. Altogether, these results indicate that 4-PBA induces microglial process elongation in an Akt-dependent manner, which may underlie the anti-neuroinflammatory properties of 4-PBA.</p>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 1","pages":"66"},"PeriodicalIF":3.8,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1007/s11418-026-02008-7
Koji Fujihara, Hiroaki Sasaki, Shin Koike, Yuki Ogasawara, Kaoru Kinoshita
Seven new saponins (1-7) isolated from Stenocereus eruca (Cactaceae) and four new saponins (8-11) isolated from Polaskia chichipe (Cactaceae) are described. Their structures were elucidated using high-resolution mass spectrometry and nuclear magnetic resonance analysis including 1H and 13C NMR, DEPT, HMQC, HMBC, H2BC, DQF-COSY, HSQC-TOCSY, phase sensitive TOCSY, 1D-TOCSY, phase sensitive NOESY, and ROESY experiments. One saponin required J-resolved spectroscopy experiments due to its complex 1H NMR spectrum. The inhibitory activity of Aβ aggregation, and protective effects on SH-SY5Y neuroblastoma cells against Aβ toxicity, were evaluated. Only 7 showed weak inhibitory activity of Aβ aggregation at 100 µM compared to the control group. No compounds showed obvious protective effects, but 8 possessed a very weak protective effect on SH-SY5Y cells. The acetylation of the C-16, C-22, and C-30 hydroxyl groups could be important for inhibitory activity of Aβ aggregation and protective effects on SH-SY5Y cells against Aβ toxicity.
{"title":"Saponins from cactus and their inhibitory effects on amyloid β aggregation.","authors":"Koji Fujihara, Hiroaki Sasaki, Shin Koike, Yuki Ogasawara, Kaoru Kinoshita","doi":"10.1007/s11418-026-02008-7","DOIUrl":"https://doi.org/10.1007/s11418-026-02008-7","url":null,"abstract":"<p><p>Seven new saponins (1-7) isolated from Stenocereus eruca (Cactaceae) and four new saponins (8-11) isolated from Polaskia chichipe (Cactaceae) are described. Their structures were elucidated using high-resolution mass spectrometry and nuclear magnetic resonance analysis including <sup>1</sup>H and <sup>13</sup>C NMR, DEPT, HMQC, HMBC, H2BC, DQF-COSY, HSQC-TOCSY, phase sensitive TOCSY, 1D-TOCSY, phase sensitive NOESY, and ROESY experiments. One saponin required J-resolved spectroscopy experiments due to its complex <sup>1</sup>H NMR spectrum. The inhibitory activity of Aβ aggregation, and protective effects on SH-SY5Y neuroblastoma cells against Aβ toxicity, were evaluated. Only 7 showed weak inhibitory activity of Aβ aggregation at 100 µM compared to the control group. No compounds showed obvious protective effects, but 8 possessed a very weak protective effect on SH-SY5Y cells. The acetylation of the C-16, C-22, and C-30 hydroxyl groups could be important for inhibitory activity of Aβ aggregation and protective effects on SH-SY5Y cells against Aβ toxicity.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1007/s11356-026-37480-x
Jan Klaus Hinrichs, Markus Herrmann, Aaron Bauer, Dieter Steffen
Ethylenediaminetetraacetic acid (EDTA), extensively used across multiple industries, has long been discussed for its potential to enhance heavy metal mobility in aquatic systems, with studies yielding contradictory results. This study examines the remobilization of particle-bound lead from suspended particulate matter (SPM) in the Innerste River (Lower Saxony, Germany), which is affected by historical mining and known for substantial Pb contamination. Using real river water containing its native SPM to preserve the chemical matrix of the system, we assessed Pb partitioning between total and dissolved phases to evaluate EDTA's remobilization potential. Baseline dissolved lead concentrations reached up to 1.8 µg L-1 (median 0.69 µg L-1). Across all batch experiments, a measurable increase in the dissolved Pb fraction occurred only at EDTA concentrations far exceeding those measured in the river (0.68-3.8 µg L-1). Bayesian concentration-response modelling yielded no-effect concentrations (NEC) between 210 and 530 µg L-1. Complementary speciation modelling showed that shifts in Pb speciation occur only at EDTA concentrations near the experimentally derived NEC values. These findings show that current EDTA concentrations in the Innerste are unlikely to remobilize Pb from SPM. The study also provides a statistically supported NEC estimate based on batch experiments using unaltered river water containing its naturally present SPM. To our knowledge, this is the first application of Bayesian NEC modelling to EDTA-induced Pb remobilization.
{"title":"EDTA-induced remobilization of lead from suspended particulate matter in contaminated water samples from the Innerste River: a statistical evaluation.","authors":"Jan Klaus Hinrichs, Markus Herrmann, Aaron Bauer, Dieter Steffen","doi":"10.1007/s11356-026-37480-x","DOIUrl":"https://doi.org/10.1007/s11356-026-37480-x","url":null,"abstract":"<p><p>Ethylenediaminetetraacetic acid (EDTA), extensively used across multiple industries, has long been discussed for its potential to enhance heavy metal mobility in aquatic systems, with studies yielding contradictory results. This study examines the remobilization of particle-bound lead from suspended particulate matter (SPM) in the Innerste River (Lower Saxony, Germany), which is affected by historical mining and known for substantial Pb contamination. Using real river water containing its native SPM to preserve the chemical matrix of the system, we assessed Pb partitioning between total and dissolved phases to evaluate EDTA's remobilization potential. Baseline dissolved lead concentrations reached up to 1.8 µg L<sup>-1</sup> (median 0.69 µg L<sup>-1</sup>). Across all batch experiments, a measurable increase in the dissolved Pb fraction occurred only at EDTA concentrations far exceeding those measured in the river (0.68-3.8 µg L<sup>-1</sup>). Bayesian concentration-response modelling yielded no-effect concentrations (NEC) between 210 and 530 µg L<sup>-1</sup>. Complementary speciation modelling showed that shifts in Pb speciation occur only at EDTA concentrations near the experimentally derived NEC values. These findings show that current EDTA concentrations in the Innerste are unlikely to remobilize Pb from SPM. The study also provides a statistically supported NEC estimate based on batch experiments using unaltered river water containing its naturally present SPM. To our knowledge, this is the first application of Bayesian NEC modelling to EDTA-induced Pb remobilization.</p>","PeriodicalId":545,"journal":{"name":"Environmental Science and Pollution Research","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1007/s11064-025-04659-6
Bruna Mafra de Faria, Fernanda Leme da Silva Pinheiro, Isabelle Medeiros, Jonathas F R Lobo, Andrew Magno Teixeira, Leandro Machado Rocha, Ricardo M Borges, Maria Isabel Doria Rossi, Loraine Campanati de Andrade, Bruno Pontes, Luiz Gustavo Dubois, Luciana Ferreira Romão
Glioblastoma (GB) is the most aggressive and lethal primary brain tumor, characterized by high proliferative, migratory, and invasive capacities, as well as marked resistance to apoptosis. Despite standard therapy with temozolomide (TMZ), prognosis remains poor, underscoring the need for novel therapeutic strategies. In this study, we investigated the antitumor potential of centratherin, a sesquiterpene lactone, in established GB cell lines and patient-derived GB cells (GBM02, GBM95). Centratherin significantly reduced cell viability in a dose-dependent manner, with IC50 values varying across GB cells, while exhibiting no cytotoxicity to healthy human astrocytes. Functional assays revealed that centratherin impairs cell proliferation, migration, and invasion, and alters cytoskeletal architecture, as evidenced by morphological changes, reduced actin and tubulin organization. Additionally, centratherin induced double-strand DNA breaks, increased γH2AX levels, and triggered cell death predominantly via necrosis, as demonstrated by LIVE/DEAD staining, Annexin V/PI flow cytometry, and ultrastructural analysis. Notably, this cytotoxic effect did not involve necroptosis, as RIP1 expression and Nec-1 sensitivity were unchanged. Furthermore, centratherin failed to sensitize GB cells to TMZ, suggesting distinct mechanisms of action, in spite of its remarked effect on inducing cell death in GB cancer stem-like cells. Overall, our findings highlight centratherin as a promising selective cytotoxic agent against GB, capable of inducing cell death and disrupting key malignant phenotypes, which may be advantageous for GB treatment.
{"title":"Centratherin Exhibits Antitumor Activity Against Glioblastoma Cells.","authors":"Bruna Mafra de Faria, Fernanda Leme da Silva Pinheiro, Isabelle Medeiros, Jonathas F R Lobo, Andrew Magno Teixeira, Leandro Machado Rocha, Ricardo M Borges, Maria Isabel Doria Rossi, Loraine Campanati de Andrade, Bruno Pontes, Luiz Gustavo Dubois, Luciana Ferreira Romão","doi":"10.1007/s11064-025-04659-6","DOIUrl":"https://doi.org/10.1007/s11064-025-04659-6","url":null,"abstract":"<p><p>Glioblastoma (GB) is the most aggressive and lethal primary brain tumor, characterized by high proliferative, migratory, and invasive capacities, as well as marked resistance to apoptosis. Despite standard therapy with temozolomide (TMZ), prognosis remains poor, underscoring the need for novel therapeutic strategies. In this study, we investigated the antitumor potential of centratherin, a sesquiterpene lactone, in established GB cell lines and patient-derived GB cells (GBM02, GBM95). Centratherin significantly reduced cell viability in a dose-dependent manner, with IC50 values varying across GB cells, while exhibiting no cytotoxicity to healthy human astrocytes. Functional assays revealed that centratherin impairs cell proliferation, migration, and invasion, and alters cytoskeletal architecture, as evidenced by morphological changes, reduced actin and tubulin organization. Additionally, centratherin induced double-strand DNA breaks, increased γH2AX levels, and triggered cell death predominantly via necrosis, as demonstrated by LIVE/DEAD staining, Annexin V/PI flow cytometry, and ultrastructural analysis. Notably, this cytotoxic effect did not involve necroptosis, as RIP1 expression and Nec-1 sensitivity were unchanged. Furthermore, centratherin failed to sensitize GB cells to TMZ, suggesting distinct mechanisms of action, in spite of its remarked effect on inducing cell death in GB cancer stem-like cells. Overall, our findings highlight centratherin as a promising selective cytotoxic agent against GB, capable of inducing cell death and disrupting key malignant phenotypes, which may be advantageous for GB treatment.</p>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 1","pages":"67"},"PeriodicalIF":3.8,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The genetic basis of agronomic traits is critical for enhancing yield, quality, and disease resistance in tomato. In this study, genome-wide association study (GWAS) was performed on a diverse panel of 72 tomato accessions to identify genomic regions linked to 18 agronomic, processing, and disease resistance traits. Phenotypic data were collected over two growing seasons, and genotyping was conducted using genotyping-by-sequencing (GBS) on the Illumina platform. A total of 78,828 high-quality single nucleotide polymorphisms (SNPs) were identified, primarily located in intergenic (54.66%), upstream (15.46%), downstream (14.35%), intronic (10.73%), and exonic (2.90%) regions. After stringent filtering, 7751 SNPs were retained for GWAS, leading to the identification of 47 significant quantitative trait loci (QTLs) associated with 13 traits. Fruit length exhibited the highest number of QTLs (23), while chromosomes 1 and 4 contained the most QTLs (9 each). Several candidate genes were identified for key traits, including F-box protein CPR1-like and transcription factor bHLH162-like for fruit weight, F-box protein At5g49610 for fruit length, transcription factor TGA9 for fruit diameter, F-box protein CPR1-like and Beta-D-xylosidase 2 for fruit yield, Cinnamoyl-CoA reductase-like SNL6 and UDP-glucosyltransferase, as well as stress-induced protein KIN2-like and serine/threonine-protein kinase BLUS1 for ToLCV resistance. Population structure and phylogenetic analyses indicated variation among ancestral populations (K = 3). These findings provide valuable genomic resources and identify candidate genes for key traits, supporting genomics-driven breeding in tomato.
农艺性状的遗传基础是提高番茄产量、品质和抗病性的关键。在这项研究中,对72个番茄材料进行了全基因组关联研究(GWAS),以确定与18个农艺、加工和抗病性状相关的基因组区域。在两个生长季节收集表型数据,并在Illumina平台上使用基因分型测序(GBS)进行基因分型。共鉴定出78,828个高质量单核苷酸多态性(snp),主要分布在基因间区(54.66%)、上游区(15.46%)、下游区(14.35%)、内含子区(10.73%)和外显子区(2.90%)。经过严格筛选,GWAS保留了7751个snp,鉴定出了与13个性状相关的47个显著数量性状位点(qtl)。果实长度的qtl数量最多(23个),染色体1和4的qtl数量最多(9个)。鉴定出几个关键性状的候选基因,包括决定果实重量的F-box蛋白cpr1样和转录因子bhlh162样,决定果实长度的F-box蛋白At5g49610,决定果实直径的转录因子TGA9,决定果实产量的F-box蛋白cpr1样和β - d -木糖苷酶2,肉桂酰辅酶a还原酶样SNL6和udp -葡萄糖基转移酶,以及决定ToLCV抗性的胁迫诱导蛋白kin2样和丝氨酸/苏氨酸蛋白激酶腼腆1。种群结构和系统发育分析表明祖先种群之间存在差异(K = 3)。这些发现提供了宝贵的基因组资源,并确定了关键性状的候选基因,为基因组驱动的番茄育种提供了支持。
{"title":"Genome Wide Association Study Reveals Novel Loci Controlling Agronomic Traits in Tomato (Solanum lycopersicum L.).","authors":"Jagesh Kumar Tiwari, Nagendra Rai, Manish Kumar Singh, Rajat Singh, Tushar Kant, Suresh Reddy Yerasu, Achuit Kumar Singh, Rajesh Kumar","doi":"10.1007/s10528-026-11329-x","DOIUrl":"https://doi.org/10.1007/s10528-026-11329-x","url":null,"abstract":"<p><p>The genetic basis of agronomic traits is critical for enhancing yield, quality, and disease resistance in tomato. In this study, genome-wide association study (GWAS) was performed on a diverse panel of 72 tomato accessions to identify genomic regions linked to 18 agronomic, processing, and disease resistance traits. Phenotypic data were collected over two growing seasons, and genotyping was conducted using genotyping-by-sequencing (GBS) on the Illumina platform. A total of 78,828 high-quality single nucleotide polymorphisms (SNPs) were identified, primarily located in intergenic (54.66%), upstream (15.46%), downstream (14.35%), intronic (10.73%), and exonic (2.90%) regions. After stringent filtering, 7751 SNPs were retained for GWAS, leading to the identification of 47 significant quantitative trait loci (QTLs) associated with 13 traits. Fruit length exhibited the highest number of QTLs (23), while chromosomes 1 and 4 contained the most QTLs (9 each). Several candidate genes were identified for key traits, including F-box protein CPR1-like and transcription factor bHLH162-like for fruit weight, F-box protein At5g49610 for fruit length, transcription factor TGA9 for fruit diameter, F-box protein CPR1-like and Beta-D-xylosidase 2 for fruit yield, Cinnamoyl-CoA reductase-like SNL6 and UDP-glucosyltransferase, as well as stress-induced protein KIN2-like and serine/threonine-protein kinase BLUS1 for ToLCV resistance. Population structure and phylogenetic analyses indicated variation among ancestral populations (K = 3). These findings provide valuable genomic resources and identify candidate genes for key traits, supporting genomics-driven breeding in tomato.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1007/s11064-026-04678-x
Pingting Chen, Genru Li, Lingyan Cheng, Yumei Liu, Yan Liu
Alzheimer's disease (AD), a major neurodegenerative disorder, lacks effective early diagnostic and therapeutic strategies. This study aimed to investigate the diagnostic utility of Long non-coding RNAs HLA Complex Group 18 ( HCG18) in AD and elucidate its molecular mechanisms in neuronal injury. Eighty-three AD patients and 83 healthy controls (HC) were enrolled. Serum samples were analyzed for HCG18 expression using qRT-PCR and cerebrospinal fluid (CSF) samples were analyzed for AD biomarkers by ELISA. Diagnostic performance was assessed using ROC analysis. Aβ1-42-treated HT22 cells (Immortalized murine hippocampal neuronal-like cell line) were employed to model neuronal injury, with HCG18 knockdown and miR-425-3p inhibition experiments conducted to validate functional interactions. HT22 cell apoptosis, oxidative stress markers (SOD, GSH-Px, MDA, ROS), and HCG18/miR-425-3p interactions were evaluated through flow cytometry, biochemical assays, and dual-luciferase reporter systems. Serum HCG18 levels were significantly elevated in AD patients compared to HC (P < 0.001), exhibiting strong diagnostic accuracy (AUC = 0.889). HCG18 expression correlated negatively with CSF Aβ1-42 (r=-0.709) and MMSE scores (r=-0.657), but positively with t-tau (r = 0.591) and p-tau181 (r = 0.582). In Aβ1-42-treated HT22 cells, HCG18 knockdown reduced apoptosis, suppressed ROS, and normalized oxidative stress markers. Mechanistically, HCG18 directly bound to and acted as a molecular sponge for miR-425-3p, sequestering its function; the downregulation of miR-425-3p mediated by a synthetic inhibitor reversed the protective effects of HCG18 silencing. HCG18 serves as a potential non-invasive biomarker for AD, exacerbating neuronal injury via sponging miR-425-3p to disrupt redox balance. Targeting the HCG18/miR-425-3p axis may offer new therapeutic strategies for AD.
阿尔茨海默病(AD)是一种主要的神经退行性疾病,缺乏有效的早期诊断和治疗策略。本研究旨在探讨长链非编码rna HLA Complex Group 18 (HCG18)在AD中的诊断价值,并阐明其在神经元损伤中的分子机制。83例AD患者和83例健康对照(HC)被纳入研究。采用qRT-PCR检测血清中HCG18的表达,ELISA检测脑脊液中AD生物标志物的表达。采用ROC分析评估诊断表现。采用a β1-42处理的HT22细胞(永生化小鼠海马神经元样细胞系)来模拟神经元损伤,通过HCG18敲除和miR-425-3p抑制实验来验证功能相互作用。通过流式细胞术、生化试验和双荧光素酶报告系统评估HT22细胞凋亡、氧化应激标志物(SOD、GSH-Px、MDA、ROS)和HCG18/miR-425-3p相互作用。与HC相比,AD患者血清HCG18水平显著升高(P
{"title":"HCG18 is a Potential Pathogenic Factor and Diagnostic Biomarker Alzheimer's Disease.","authors":"Pingting Chen, Genru Li, Lingyan Cheng, Yumei Liu, Yan Liu","doi":"10.1007/s11064-026-04678-x","DOIUrl":"https://doi.org/10.1007/s11064-026-04678-x","url":null,"abstract":"<p><p>Alzheimer's disease (AD), a major neurodegenerative disorder, lacks effective early diagnostic and therapeutic strategies. This study aimed to investigate the diagnostic utility of Long non-coding RNAs HLA Complex Group 18 ( HCG18) in AD and elucidate its molecular mechanisms in neuronal injury. Eighty-three AD patients and 83 healthy controls (HC) were enrolled. Serum samples were analyzed for HCG18 expression using qRT-PCR and cerebrospinal fluid (CSF) samples were analyzed for AD biomarkers by ELISA. Diagnostic performance was assessed using ROC analysis. Aβ1-42-treated HT22 cells (Immortalized murine hippocampal neuronal-like cell line) were employed to model neuronal injury, with HCG18 knockdown and miR-425-3p inhibition experiments conducted to validate functional interactions. HT22 cell apoptosis, oxidative stress markers (SOD, GSH-Px, MDA, ROS), and HCG18/miR-425-3p interactions were evaluated through flow cytometry, biochemical assays, and dual-luciferase reporter systems. Serum HCG18 levels were significantly elevated in AD patients compared to HC (P < 0.001), exhibiting strong diagnostic accuracy (AUC = 0.889). HCG18 expression correlated negatively with CSF Aβ1-42 (r=-0.709) and MMSE scores (r=-0.657), but positively with t-tau (r = 0.591) and p-tau181 (r = 0.582). In Aβ1-42-treated HT22 cells, HCG18 knockdown reduced apoptosis, suppressed ROS, and normalized oxidative stress markers. Mechanistically, HCG18 directly bound to and acted as a molecular sponge for miR-425-3p, sequestering its function; the downregulation of miR-425-3p mediated by a synthetic inhibitor reversed the protective effects of HCG18 silencing. HCG18 serves as a potential non-invasive biomarker for AD, exacerbating neuronal injury via sponging miR-425-3p to disrupt redox balance. Targeting the HCG18/miR-425-3p axis may offer new therapeutic strategies for AD.</p>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 1","pages":"64"},"PeriodicalIF":3.8,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1007/s11418-025-01997-1
Eun Hye Park, Hyungkuen Kim, Sung-Jo Kim
{"title":"In silico pharmacology and 3D-bioprinting reveal Dicranum scoparium as an inhibitor of NF-κB-induced inflammation in the 3D4/31 alveolar macrophage cell line.","authors":"Eun Hye Park, Hyungkuen Kim, Sung-Jo Kim","doi":"10.1007/s11418-025-01997-1","DOIUrl":"https://doi.org/10.1007/s11418-025-01997-1","url":null,"abstract":"","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the context of the circular economy, managing sewage sludge (SS) is vital for resource valorization and sustainability. This study aims to compare the impact of different application methods (two phase mulch, single phase mulch, incorporation) and doses (10, 25, 40 and 50 t/ha) of residual sewage sludge on the quality of sandy-silty soils and the morpho-physiological characteristics of durum wheat (Triticum durum) plants, specifically the Oued El Bared G4 variety. The field experiment was conducted in a hot arid region in northeastern Algeria. Results demonstrated that SS significantly improved soil fertility and wheat performance (p < 0.001). Soil organic matter (OM) and Phosphorus peaked at 1.92% (T2D3) and 258.46 ppm (T1D4) respectively, representing a substantial enrichment compared to lower doses. Regarding crop yield, the 1000 grain weight (WTG) reached a maximum of 54.88 g with single phase mulch (T2D1), which is 33.8% higher than the two phase application method. Similarly, plant height and leaf surface area (LSA) were maximized under the T2 method (91 cm and 37.41 cm2, respectively). While soil pH remained stable, electrical conductivity (EC) increased with dosage, peaking at 1.87 µS/cm (T2D4). This finding suggest that sludge biorecycling in single phase mulch application (T2) at moderate doses optimizes both soil quality and durum wheat yield component in arid region. Future research should focus on the long term cumulative effects of repeated sludge application on soil heavy metal dynamics and groundwater quality in arid environment.
在循环经济的背景下,管理污水污泥(SS)对资源增值和可持续性至关重要。本研究旨在比较不同施用方式(两期覆盖、单相覆盖、掺入)和污泥残留量(10、25、40和50 t/ha)对砂质粉质土壤质量和硬粒小麦(Triticum durum)植物形态生理特性的影响,特别是Oued El Bared G4品种。田间试验在阿尔及利亚东北部炎热干旱地区进行。结果表明,SS显著提高了土壤肥力和小麦生产性能(p < 2)。在土壤pH保持稳定的情况下,土壤电导率(EC)随添加量的增加而增加,最高为1.87µS/cm (T2D4)。这一发现表明,在干旱地区,中等剂量的单相覆盖(T2)下污泥生物循环可以优化土壤质量和硬粒小麦产量成分。今后的研究重点应放在反复施用污泥对干旱环境下土壤重金属动态和地下水质量的长期累积效应上。
{"title":"Field applications of sewage sludge improved soil properties and increased wheat yield in sand-textured soils of hot drylands.","authors":"Nawal Ababsa, Sihem Fellah, Sonia Boudjabi, Rania Lallaouna, Mounir Sifi, Mourad Bessaih, Haroun Chenchouni","doi":"10.1007/s10532-026-10251-8","DOIUrl":"https://doi.org/10.1007/s10532-026-10251-8","url":null,"abstract":"<p><p>In the context of the circular economy, managing sewage sludge (SS) is vital for resource valorization and sustainability. This study aims to compare the impact of different application methods (two phase mulch, single phase mulch, incorporation) and doses (10, 25, 40 and 50 t/ha) of residual sewage sludge on the quality of sandy-silty soils and the morpho-physiological characteristics of durum wheat (Triticum durum) plants, specifically the Oued El Bared G4 variety. The field experiment was conducted in a hot arid region in northeastern Algeria. Results demonstrated that SS significantly improved soil fertility and wheat performance (p < 0.001). Soil organic matter (OM) and Phosphorus peaked at 1.92% (T2D3) and 258.46 ppm (T1D4) respectively, representing a substantial enrichment compared to lower doses. Regarding crop yield, the 1000 grain weight (WTG) reached a maximum of 54.88 g with single phase mulch (T2D1), which is 33.8% higher than the two phase application method. Similarly, plant height and leaf surface area (LSA) were maximized under the T2 method (91 cm and 37.41 cm<sup>2</sup>, respectively). While soil pH remained stable, electrical conductivity (EC) increased with dosage, peaking at 1.87 µS/cm (T2D4). This finding suggest that sludge biorecycling in single phase mulch application (T2) at moderate doses optimizes both soil quality and durum wheat yield component in arid region. Future research should focus on the long term cumulative effects of repeated sludge application on soil heavy metal dynamics and groundwater quality in arid environment.</p>","PeriodicalId":486,"journal":{"name":"Biodegradation","volume":"37 2","pages":"29"},"PeriodicalIF":3.2,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1007/s12010-025-05491-y
Xiaojuan Zhang, Xiaoting Zhang
Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by memory deficits, oxidative stress, and neuroinflammation. Plumbagin (PB), a bioactive naphthoquinone derived from Nepenthes khasiana, possesses therapeutic potential but is limited by poor solubility and bioavailability. To overcome these challenges, PB was encapsulated into hyaluronic acid nanogels (PB-NGs) and systematically evaluated for anti-Alzheimer's efficacy. The study aimed to evaluate the neuroprotective and anti-inflammatory properties of PB-NGs by in vitro and in vivo analyses. PB-NGs were synthesized and characterized using FT-IR, NMR, and TEM, confirming successful encapsulation. In silico docking demonstrated strong binding affinities of PB to β-amyloid and tau proteins, suggesting potential inhibition of AD-related pathological processes. In vitro, PB-NGs significantly decreased ROS production, mitigated pro-inflammatory cytokines (IL-1β, TNF-α), and improved cell viability in LPS-stimulated SH-SY5Y cells relative to free PB. In vivo, administration of PB-NGs to AD-induced mice significantly improved behavioral outcomes, including enhanced spatial memory and exploratory activity in Y-maze, open field, and Morris's water maze tests. Biochemical assays further revealed reduced oxidative stress (decreased MDA, increased SOD, CAT, GST) and modulation of cholinergic dysfunction (reduced AChE, increased ChAT). Histopathological analysis supported neuronal protection with diminished amyloid burden. Collectively, these findings demonstrate that PB-NGs effectively enhance bioavailability and exert significant neuroprotective and anti-inflammatory effects, supporting their potential as a promising nanotherapeutic approach for mitigating cognitive deficits in AD.
{"title":"Nanogel Delivery of Plumbagin from Nepenthes Khasiana Attenuates Neuroinflammation and Cognitive Decline in Alzheimer's Mice Models.","authors":"Xiaojuan Zhang, Xiaoting Zhang","doi":"10.1007/s12010-025-05491-y","DOIUrl":"https://doi.org/10.1007/s12010-025-05491-y","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by memory deficits, oxidative stress, and neuroinflammation. Plumbagin (PB), a bioactive naphthoquinone derived from Nepenthes khasiana, possesses therapeutic potential but is limited by poor solubility and bioavailability. To overcome these challenges, PB was encapsulated into hyaluronic acid nanogels (PB-NGs) and systematically evaluated for anti-Alzheimer's efficacy. The study aimed to evaluate the neuroprotective and anti-inflammatory properties of PB-NGs by in vitro and in vivo analyses. PB-NGs were synthesized and characterized using FT-IR, NMR, and TEM, confirming successful encapsulation. In silico docking demonstrated strong binding affinities of PB to β-amyloid and tau proteins, suggesting potential inhibition of AD-related pathological processes. In vitro, PB-NGs significantly decreased ROS production, mitigated pro-inflammatory cytokines (IL-1β, TNF-α), and improved cell viability in LPS-stimulated SH-SY5Y cells relative to free PB. In vivo, administration of PB-NGs to AD-induced mice significantly improved behavioral outcomes, including enhanced spatial memory and exploratory activity in Y-maze, open field, and Morris's water maze tests. Biochemical assays further revealed reduced oxidative stress (decreased MDA, increased SOD, CAT, GST) and modulation of cholinergic dysfunction (reduced AChE, increased ChAT). Histopathological analysis supported neuronal protection with diminished amyloid burden. Collectively, these findings demonstrate that PB-NGs effectively enhance bioavailability and exert significant neuroprotective and anti-inflammatory effects, supporting their potential as a promising nanotherapeutic approach for mitigating cognitive deficits in AD.</p>","PeriodicalId":465,"journal":{"name":"Applied Biochemistry and Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}