261. Xihuang pill suppressed primary liver cancer growth by downregulation of AFP and YAP signaling.
作者: Sha Luo.;Zhen Huang.;Yuewen Dai.;Shuyang Wang.;Wantao Yu.;Zhihan Li.;Qing Pu.;Lihui Yang.;Tianyi Yang.;Yu Tang.;Zhang Wang.;Jiabo Wang.;Jingxiao Wang.
来源: J Ethnopharmacol. 2025年348卷119891页
Xihuang Pill (XHP) is a traditional Chinese medicine formula that was originally used to treat malignant ulcers. Recent studies revealed its therapeutic effects on various malignant tumors. However, its potential efficacy and mechanisms in primary liver cancer (PLC) were not thoroughly investigated.
262. Comparative in vitro study of chondrocyte viability and gene expression in wrought and additive manufactured CoCrMo sliding against articular cartilage.
作者: Rosa Maria Nothnagel.;Christoph Bauer.;Leonarda Vukonic.;Tímea Váradi.;Friedrich Franek.;Stefan Nehrer.;Manel Rodríguez Ripoll.
来源: J Mech Behav Biomed Mater. 2025年168卷107024页
Hemiarthroplasty consists of the replacement of local cartilage defects by a partial implant and provides a less aggressive alternative to total joint replacement. The material frequently selected nowadays for partial implants is CoCrMo alloy, which results in a sliding contact between articular cartilage and the alloy. Since the geometry of the implant needs to be tailored to the patient, partial implant technology would greatly profit from novel additive manufacturing techniques. This study examines the feasibility of using additive manufacturing techniques on partial implants made of CoCrMo alloys, with a particular focus on the impact of manufacturing technique on mechanical stimulation, cartilage analysis, and friction performance. To this end, in vitro biotribological experiments were performed between CoCrMo samples and bovine articular cartilage using PBS as simulated body fluid. Key findings reveal significant changes in microstructure between laser beam melted (LBM) and wrought CoCrMo alloys, despite having a comparable elemental composition. The coefficient of friction (CoF) measured between bovine articular cartilage and the CoCrMo specimens during biotribocorrosive testing revealed no significant differences resulting from the manufacturing techniques, even though wrought CoCrMo resulted in a higher reproducibility. Conventionally produced CoCrMo also exhibited a more anodic open circuit potential during the experiments, likely due to the significant differences in microstructure that affect corrosion resistance. The tested cartilage samples showed a slight increase in MMP13 (Matrix Metalloproteinases - degradative enzymes) in comparison to the controls, indicating potential remodeling effects, especially for the LBM CoCrMo alloy. Additionally, the metabolic activity in the cartilage specimens increased due to mechanical stimulation. No cracks or fissures were detected in histological imaging thus highlighting that the cartilage samples were not damaged during harvesting or testing. These findings indicate the possibility of an equivalent use of additive manufactured CoCrMo, enabling patient-specific surgeries and encourage further research to explore the long-term impact of corrosion stability on implant longevity and functionality.
263. Piperine derivative, (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-(2-hydroxyphenyl)penta-2,4-dienamide, exerted cytotoxic activity toward MCF-7 breast cancer cells via Apoptosis: Gene expression and biomolecular change study.
作者: Santi Phosri.;Alisa Naladta.;Nuttinee Teerakulkittipong.;La-Or Somsakeesit.;Sukanya Tastub.;Natsajee Nualkaew.;Anupong Joompang.
来源: Biochem Biophys Res Commun. 2025年766卷151895页
Breast cancer is one of the leading causes of mortality in women worldwide. Adverse side effects have been reported from chemotherapeutic agents of systematic therapies. Therefore, new agents are still needed for breast cancer treatment. This research aimed to investigate anticancer activity and mechanisms of a piperine derivative, named (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-(2-hydroxyphenyl)penta-2,4-dienamide (1f), against MCF-7 breast cancer cell. The results show that 1f ranging from 7.5 to 60 μg/mL inhibited MCF-7 cells in dose-dependent manner with IC50 values of 17.02 ± 1.74 μg/mL. It inhibited cell migration in dose and time dependent manners. In addition, it induced morphological characteristics of apoptosis and increased the level of intracellular reactive oxygen species (ROS). Phosphatidylserine (PS) exposure staining and DNA fragmentation confirmed the induction of apoptosis. 1f induced the gene expression of TP53, PTEN, and CASP9, while ESR1, BRCA1, BRCA2, PIK3CA, AKT1 CHEK2, BRIP1 and KRAS expression were decreased. STRING protein-protein interaction network and KEGG pathway analysis predicted the induction of apoptosis linked with DNA repair, estrogen receptor-α (ER-α), and PI3K/AKT signaling pathways. Moreover, Fourier transform infrared spectroscopy (FTIR) results shows that 1f reduced the lipid utilization rate and inhibited protein synthesis, resulting in the induction of apoptosis. Overall, 1f is an interesting candidate for development as an anticancer agent for breast cancer.
264. FAT1 Enhances the Sensitivity of Non-Small Cell Lung Cancer to VCP Inhibitors by Regulating the Activation of the Endoplasmic Reticulum Stress Pathway.
作者: Xiangning Liu.;Peiying Zhang.;Fujing Ge.;Tao Yuan.;Runqiu Guo.;Shuyu Yang.;Bo Yang.;Hong Zhu.;Fangjie Yan.;Qiaojun He.
来源: FASEB J. 2025年39卷9期e70585页
FAT atypical cadherin 1 (FAT1) is prevalently expressed in non-small cell lung cancer (NSCLC) tissues and is associated with poor prognosis in patients. Using data from the PRISM Repurposing drug sensitivity database, we observed that among compounds related to protein homeostasis, the valosin-containing protein (VCP) inhibitor CB-5083 demonstrated the most significant variation in sensitivity among NSCLC cells, categorized according to FAT1 expression levels. Notably, CB-5083 markedly inhibits cell proliferation and induces apoptosis in NSCLC cells with high expression of FAT1. Targeting VCP may trigger strong endoplasmic reticulum stress (ER stress) in NSCLC cells, leading to inhibition of cell proliferation in tumor cells. Mechanically, knockdown of FAT1 stimulates YAP signaling and target gene transcription, thereby attenuating the UPR pathway signal induced by CB-5083 stimulation in NSCLC cells. Our results suggest that FAT1 regulates the activation of the ER stress pathway through YAP signaling, influencing the susceptibility of NSCLC cells to VCP inhibitors. These insights provide novel perspectives for NSCLC treatment and extend the therapeutic applications of VCP inhibitors in clinical settings.
265. Transcriptional mechanisms underlying thiazolidine-4-carboxylic acid (T4C)-primed salt tolerance in Arabidopsis.
作者: Wei-Yung Hsu.;Yi-Zhen Wu.;Yu-Min Lin.;Mei-Juan Zheng.;Liang-Jwu Chen.;Chuan-Ming Yeh.
来源: Plant Cell Rep. 2025年44卷5期104页
T4C enhances salt stress tolerance in Arabidopsis by regulating osmotic and oxidative stress responses, activating ABA-related pathways, and inducing stress-responsive genes, including LEA proteins. High soil salinity is a major environmental stress that restricts crop productivity worldwide, necessitating strategies to enhance plant salt tolerance. Thiazolidine-4-carboxylic acid (T4C) has been reported to regulate proline biosynthesis, which is essential for abiotic stress responses, yet its role in stress tolerance remains unclear. This study investigates the physiological and molecular effects of T4C on Arabidopsis thaliana under salt stress conditions. T4C treatment alleviated salt-induced growth inhibition, improving biomass, relative water content, and chlorophyll retention while reducing oxidative stress markers such as malondialdehyde and anthocyanin accumulation. Transcriptomic and quantitative PCR analyses revealed that T4C upregulated proline biosynthesis genes, ABA-dependent signaling (RD29b, ABI3), and Late Embryogenesis Abundant (LEA) genes. Gene Ontology (GO) enrichment analysis identified biological processes related to water deprivation, ABA signaling, and salt stress, while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated the involvement of phenylpropanoid biosynthesis, plant hormone signal transduction, and MAPK signaling in T4C-mediated responses. Notably, several transcription factors, including NAC, MYB, and WRKY family members, were identified as candidates involved in T4C-mediated stress priming. Collectively, these findings suggest that T4C may enhance salt tolerance by modulating osmotic balance, reducing oxidative stress, and activating stress-responsive genes and transcriptional regulators. Our results provide novel insights into the molecular mechanisms underlying T4C-mediated stress responses, highlighting its potential as a chemical priming agent to improve plant resilience under saline conditions.
266. Ursodeoxycholic Acid Exhibits Greater Inhibitory Effects on Cancerous HCT116 Colon Cells than on Noncancerous NCM460 Colon Cells.
作者: Huawei Zeng.;Bryan D Safratowich.;Wen-Hsing Cheng.;Mary Briske-Anderson.
来源: Nutrients. 2025年17卷6期
Background/Objectives: Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, exhibits anti-inflammatory effects and attenuates the process of colon carcinogenesis. Certain healthy diets increase colonic UDCA concentrations, but its anticancer mechanistic actions remain largely unknown. We hypothesize that UDCA preferentially inhibits cancerous colon cell proliferation with a minimal effect on noncancerous colon cells. Methods: With human noncancerous NCM460 colon cell and cancerous HCT116 colon cell culture models, we performed biochemical, western blotting, PCR array, cell cycle, apoptosis, and immunofluorescent assays to determine the effects of UDCA treatment on colon cell proliferation and the underlying molecular mechanisms. Results: The inhibitory potential of UDCA against cell proliferation (via cell cycle arrest and apoptosis) was 90% greater in cancerous HCT116 cells than noncancerous NCM460 cells when treated with UDCA (0 to 0.4 mM) for 48 h. In UDCA-treated HCT116 cells, we identified 18 genes with ≥80% change (compared to untreated cells) in mRNA levels out of 93 apoptotic genes which were involved in caspase, death receptor, and NFκB pathways. At the molecular level, 0.4 mM UDCA reduced the protein level of the proto-oncogenic c-Myc gene but increased the putative tumor suppressor p21 gene (≥100%) via the ERK1/2/c-Myc/p21 pathway, which regulates cell cycle and apoptosis. These data are consistent with lower c-Myc but higher p21 expression in normal colon tissues compared to cancerous colon tissues. Conclusions: Collectively, UDCA inhibits cancerous HCT116 colon cells to a higher degree than in noncancerous NCM460 colon cells through cell cycle and apoptosis involving ERK1/2/c-Myc/p21 signaling.
267. Genome-Wide Impact of Folic Acid on DNA Methylation and Gene Expression in Lupus Adipocytes: An In Vitro Study on Obesity.
作者: Leticia L Souza.;Jhulia C N L da Mota.;Lucas M Carvalho.;Amanda A Ribeiro.;Cesar A Caponi.;Marcela A S Pinhel.;Nicolas Costa-Fraga.;Angel Diaz-Lagares.;Andrea G Izquierdo.;Carla B Nonino.;Ana B Crujeiras.;Carolina F Nicoletti.
来源: Nutrients. 2025年17卷6期
This in vitro study aimed to investigate the impact of folic acid on DNA methylation and gene expression in adipocytes from subcutaneous adipose tissue of patients with systemic lupus erythematosus (SLE), with a focus on the influence of obesity on these epigenetic changes.
268. Zinc sulfate acts as an efflux pump inhibitor on Pseudomonas aeruginosa clinical isolates.
作者: Wedad M Abdelraheem.;Hadeer Ibrahim Yassin.;Shaimaa Zaki.;Mona Abdel Monem Esmail.
来源: World J Microbiol Biotechnol. 2025年41卷5期139页
Efflux pumps in Pseudomonas aeruginosa play an important role in decreasing the bacterium's antibiotic susceptibility. This study aimed to identify P. aeruginosa efflux pumps and examine the effect of Zinc sulfate on these pumps. This study was conducted on 104 P. aeruginosa clinical isolates collected from different types of specimens. The antimicrobial susceptibility pattern of all isolates was examined by disc diffusion and microdilution methods. A Cartwheel test was done for phenotypic detection of P. aeruginosa efflux pumps in the presence and absence of zinc sulfate. The expression of efflux pumps encoding genes and their regulators in the presence and absence of zinc sulfate was measured using real-time reverse transcriptase PCR. A high rate of multidrug-resistant (MDR) pattern was observed among the tested isolates (55.7%). Combining different antibiotics with Zinc sulfate exhibited synergistic effects against most of the studied isolates. The addition of sub-inhibitory concentrations of Zinc sulfate to the cartwheel test was found to inhibit efflux pump activity in all tested isolates. The expression of the positive regulator gene, mexT, was significantly decreased. Additionally, Zinc sulfate significantly upregulated the expression of the mexR gene (P-value < 0.05), a negative regulator of the MexAB-OprM efflux pump. Zinc sulfate demonstrated a strong antimicrobial effect against P. aeruginosa clinical isolates. We recommend the use of Zinc sulfate as an antibiotic adjuvant and efflux pump inhibitor in the treatment of P. aeruginosa infections to enhance the bacterium's susceptibility to antimicrobial agents.
269. FBL promotes hepatocellular carcinoma tumorigenesis and progression by recruiting YY1 to enhance CAD gene expression.
作者: Yafei Zhi.;Yan Guo.;Shiliang Li.;Xinyu He.;Huifang Wei.;Kyle Laster.;Qiong Wu.;Dengyun Zhao.;Jinxin Xie.;Shanshan Ruan.;Nicholas R Lemoine.;Honglin Li.;Zigang Dong.;Kangdong Liu.
来源: Cell Death Dis. 2025年16卷1期348页
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Accumulating evidence suggests that epigenetic dysregulation contributes to the initiation and progression of HCC. We aimed to investigate key epigenetic regulators that contribute to tumorigenesis and progression, providing a theoretical basis for targeted therapy for HCC. We performed a comprehensive epigenetic analysis of differentially expressed genes in LIHC from the TCGA database. We identified fibrillarin (FBL), an rRNA 2'-O-methyltransferase, as an essential contributor to HCC. A series of in vitro and in vivo biological experiments were performed to investigate the potential mechanisms of FBL. FBL knockdown suppressed the proliferation of HCC cells. In vivo studies using cell-derived xenograft (CDX), patient-derived xenograft (PDX), and diethylnitrosamine (DEN)-induced HCC models in Fbl liver-specific knockout mice demonstrated the critical role of FBL in HCC carcinogenesis and progression. Mechanistically, FBL regulates the expression of CAD in HCC cells by recruiting YY1 to the CAD promoter region. We also revealed that fludarabine phosphate is a novel inhibitor of FBL and can inhibit HCC growth in vitro and in vivo. The antitumor activity of lenvatinib has been shown to be synergistically enhanced by fludarabine phosphate. Our study highlights the cancer-promoting role of the FBL-YY1-CAD axis in HCC and identifies fludarabine phosphate as a novel inhibitor of FBL. A schematic diagram depicting the FBL-YY1-CAD signaling pathway and its regulatory role in HCC progression.
270. An anti-androgen resistance-related gene signature acts as a prognostic marker and increases enzalutamide efficacy via PLK1 inhibition in prostate cancer.
作者: Ruilin Zhuang.;Ruihui Xie.;Shirong Peng.;Qianghua Zhou.;Weilong Lin.;Yuan Ou.;Bingliang Chen.;Tong Su.;Zean Li.;Hai Huang.;Kaiwen Li.;Yu Duan.
来源: J Transl Med. 2025年23卷1期480页
Anti-androgen resistance remains a major clinical challenge in the treatment of prostate cancer (PCa), leading to disease progression and treatment failure. Despite extensive research on resistance mechanisms, a reliable prognostic model for predicting patient outcomes and guiding therapeutic strategies is still lacking. This study aimed to develop a novel gene signature related to anti-androgen resistance and evaluate its prognostic and therapeutic implications.
271. Bexarotene regulates zebrafish embryonic development by activating Wnt signaling pathway.
作者: Wenwen Zha.;Ziang Wang.;Weitao Hu.;Chenkai Ge.;Wenbin Yuan.;Qinyuan Shen.;Weirong Li.;Wanqing Chen.;Jingrong Tang.;Zhonghao Xiao.;Yunlong Meng.;Lirong Huang.;Zilin Zhong.;Tao-Sheng Li.;Jianjun Chen.;Zigang Cao.
来源: Life Sci. 2025年373卷123664页
Bexarotene (Bex) is a selective retinoid X receptor (RXR) agonist and is commonly used as an anti-tumor drug in the clinic to treat patients with cutaneous T-cell lymphoma (CTCL). With the widespread use of this drug, people are increasingly concerned about its side effects and safety of use. At present, the effects of bexarotene drugs on the health of organisms remain uncertain, but retinoid drugs are generally biologically active and may pose potential risks to them. Therefore, in this study, we used a zebrafish model to evaluate the effects of Bex on embryonic development. Six hours after fertilization, we exposed zebrafish embryos to 3 μg/L, 6 μg/L, and 9 μg/L bexarotene. At 96 hpf, compared with the control group, zebrafish embryos exposed to bexarotene showed obvious heart and liver development defects, including reduced hatching rate, pericardial enlargement, heart rate disorder, yolk sac edema, small liver area and abnormal photo-optical motor responses. Transcriptome and qPCR results showed abnormal expression of genes related to heart and liver development was induced by Bexarotene. Mechanistically, bexarotene induced a significant upregulation of the transcriptional expression levels of genes related to the Wnt signaling pathway, and IWR-1 was able to effectively rescue the heart and liver developmental defects of zebrafish caused by bexarotene. Therefore, our study showed that bexarotene may cause zebrafish embryonic developmental defects by upregulating the Wnt signaling pathway, revealing the side effects and associated novel mechanisms of bexarotene, and providing a theoretical basis for its safe and effective use in the treatment of clinically related diseases.
272. Single-Cell Transcriptome Reveals the Cellular Response to PEG-Induced Stress in Wheat Leaves.
作者: Xiaorui Guo.;Aiju Zhao.;Jiangwei Han.;Liu Yuping.;Xiyong Chen.;Ziyi Cheng.;Liang Hou.;Liangjie Lv.
来源: J Agric Food Chem. 2025年73卷18期10764-10777页
Drought is a major factor limiting the production and yield of wheat bread (Triticum aestivum). Therefore, investigating the wheat drought-related response mechanism is an urgent priority. Here, the single-cell transcriptome of drought-nonsusceptible and susceptible wheat seedlings subjected to PEG-induced stress was systematically analyzed to study the drought-related response at the cellular level. We identified five major cell types using known marker genes and constructed a wheat leaf cell atlas. On this foundation, several potential specific marker genes for each cell type were identified, which provide a reference for further cell type annotation. Moreover, we identified cellular heterogeneity in the drought-related response mechanisms and regulatory networks among cell types. Specifically, the drought response of mesophyll cells was correlated with the photosynthetic pathway. Pseudotime trajectory analysis revealed the transition of epidermal cells from their normal function to a defense response under stress. Moreover, we also characterized the genes associated with the drought response. Notably, we identified two transcription factors (TraesCS1D02G223600 and TraesCS1D02G072900) as master regulators in most cell types. Our study provides detailed insights into the response heterogeneity of cells under PEG-induced stress. The gene resources obtained in our study could be applied to breed better crop plants with improved drought tolerance.
273. Identification and validation of reference genes with stable expression under elicitor treatments of the medicinal plant Arnica montana L.
作者: Magdalena Sozoniuk.;Maria Petrova.;Kiril Mishev.;Kamelia Miladinova-Georgieva.;Maria Geneva.
来源: BMC Plant Biol. 2025年25卷1期546页
In view of enhancing secondary metabolites biosynthesis in Arnica montana through elicitation, comprehensive studies are needed to fully understand the molecular background of biosynthetic pathways in this species. Analysis of transcriptional changes via RT-qPCR technique might shed light on the molecular mechanisms underlying plant reaction to elicitors. This study aimed to identify reference genes which are stably expressed in Arnica under methyl jasmonate, salicylic acid, and yeast extract treatment to provide the basis for current and future gene expression studies in this important medicinal plant.
274. Physiological and molecular mechanisms of nitrogen in alleviating drought stress in Phoebe bournei.
作者: Jing An.;Honghao Huo.;Qiyuan Liu.;Yunli Jiang.;Hong Luo.;Yupei Hao.
来源: Sci Rep. 2025年15卷1期14684页
To explore the mechanisms by which nitrogen alleviates drought stress in Phoebe bournei, this study integrated drought treatment with exogenous nitrogen application to assess physiological characteristics and employed transcriptome sequencing to decipher transcriptional responses. The results indicated that nitrogen fertilizer mitigated leaf wilting in P. bournei under drought stress and significantly enhanced leaf dry weight, fresh weight, thickness, and chlorophyll content. Furthermore, nitrogen improved photosynthesis by inhibiting stomatal closure, enhancing light energy absorption, and accelerating electron transport in PSII. 11 photosynthesis-related genes, including PFP, TRY, LQY, FTSH, FRO, CURT, PETF, ATPF, PETA, CRRSP, and MEN and 17 carbohydrate metabolism-associated genes, such as PWD, GBE1, GAPA, PFKA, RFS, ISA, GLGC, PGK, ALDO, GUX, RX9, MIOX, HCT, BAM, MPFP, and ERNI exhibited differential expression in response to nitrogen. Moreover, nitrogen treatment significantly modulated plant hormone metabolism, with 44 upregulated and 14 downregulated differentially expressed genes (DEGs) primarily associated with jasmonic acid (JA) synthesis and signaling. These findings provide new insights into enhancing the drought tolerance of P. bournei in the context of global climate change.
275. A feasibility of computational drug screening for Fuchs endothelial corneal dystrophy.
作者: Itsuki Oka.;Yoshiaki Toyokawa.;Kouta Imai.;Tatsuya Nakagawa.;Theofilos Tourtas.;Ursula Schlötzer-Schrehardt.;Friedrich Kruse.;Noriko Koizumi.;Naoki Okumura.
来源: Sci Rep. 2025年15卷1期14665页
Fuchs endothelial corneal dystrophy (FECD) remains a leading cause of corneal blindness globally, with corneal transplantation being the primary treatment. FECD is characterized by the formation of guttae, extracellular matrix (ECM) deposits beneath the corneal endothelium, and progressive endothelial cell loss. These pathological changes cause visual deterioration through light scattering by guttae and corneal edema due to endothelial cell loss. However, limitations such as donor shortage and graft failure necessitate alternative therapeutic approaches. We employed computational drug screening using three platforms (L1000FWD, L1000CDS2, and SigCom LINCS) to identify compounds capable of normalizing FECD-associated differentially expressed genes (DEGs). Analysis of transcriptome data from FECD patients with TCF4trinucleotide repeat expansion identified 706 upregulated and 962 downregulated genes. The screening platforms identified 200, 35, and 76 compounds through L1000FWD, L1000CDS2, and SigCom LINCS, respectively, with five compounds commonly predicted across all platforms. Among these, LDN193189 and cercosporin were selected for further evaluation based on availability and lack of cytotoxicity. Both compounds significantly decreased the expression of ECM-related genes (FN1, MATN3, BGN, and LTBP2) in FECD cell models and suppressed TGF-β-induced fibronectin expression. Additionally, both compounds reduced aggresome formation to normal control levels, suggesting protection against endoplasmic reticulum stress-induced cell death. This study demonstrates the feasibility of computational drug screening for identifying therapeutic candidates for FECD, with LDN193189 and cercosporin showing promise in normalizing FECD-associated pathological changes.
276. Therapeutic effects and potential mechanisms of caffeine on obese polycystic ovary syndrome: bioinformatic analysis and experimental validation.
The risk of PCOS is significantly increased in obese women, and studies have shown that weight loss can improve symptoms of PCOS. Coffee has been shown to be effective in reducing body weight. In this study, we focused on the SLC16A6 gene using bioinformatics and searched for coffee and its monomers using reverse network pharmacology. The gene expression omnibus (GEO) database was searched to screen for differentially expressed genes (DEGs) in PCOS patients. Gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were then performed. The effects of caffeine on body weight, estrous cycle, ovarian pathology, serum insulin concentration and insulin resistance index, and SLC16A6 transporter gene expression in ovarian tissue of obese PCOS rats were monitored. The common differentially expressed gene SLC16A6 was identified in this study, and animal experiments confirmed the efficacy of caffeine in the treatment of obese PCOS rats. Caffeine can effectively improve the symptoms of obese PCOS rats. The mechanism by which caffeine can treat obese patients with PCOS is related to increasing the expression of the SLC16A6 gene.
277. MMP1-induced NF-κB activation promotes epithelial-mesenchymal transition and sacituzumab govitecan resistance in hormone receptor-positive breast cancer.
作者: Letian Chen.;Yinghuan Cen.;Keyang Qian.;Wang Yang.;Wenbin Zhou.;Yaping Yang.
来源: Cell Death Dis. 2025年16卷1期346页
Sacituzumab govitecan (SG), a novel antibody-drug conjugate (ADC), shows promise in the treatment of breast cancer (BC); however, drug resistance limits its clinical application. Matrix metalloproteinase 1 (MMP1), which is overexpressed in many tumor types, plays a key role in tumor metastasis and drug resistance. The involvement of MMP1 in SG resistance in metastatic hormone receptor-positive (HR + ) BC has not been previously reported. In this study, we employed various in vitro and in vivo approaches to investigate the role of MMP1 in SG resistance in BC. MMP1 expression was manipulated in different BC cell lines through lentiviral transfection and small interfering RNA techniques. Key methodologies included Western blot, quantitative reverse transcription PCR, and RNA sequencing to assess marker expression and identify differentially expressed genes. Functional assays were conducted to evaluate cell viability, proliferation, invasion, and migration. In vivo, a cell-derived xenograft model in nude mice was utilized to assess tumor growth and drug response. Bioinformatics analyses further explored MMP1 expression and its clinical relevance across different cancer types. Our findings indicate that MMP1 is overexpressed by approximately 30-fold in HR + BC tissues and is associated with poorer prognosis among HR + BC patients. Furthermore, our analysis reveals that HR + BC with high MMP1 expression displays resistance to SG, supporting the hypothesis that MMP1 plays a key role in regulating ADC resistance. Mechanistic studies demonstrate that MMP1 can activate the NF-κB pathway, which subsequently influences the epithelial-mesenchymal transition, thereby contributing to SG resistance. Ultimately, our research underscores the potential of MMP1 as a therapeutic target and biomarker, facilitating personalized treatment strategies that could enhance patient outcomes in BC therapy.
278. Unveiling the regulatory role of GRP7 in ABA signal-mediated mRNA translation efficiency regulation.
作者: Jing Zhang.;Wenna Shao.;Yongxin Xu.;Fa'an Tian.;Jinchao Chen.;Dongzhi Wang.;Xuelei Lin.;Chongsheng He.;Xiaofei Yang.;Dorothee Staiger.;Yiliang Ding.;Xiang Yu.;Jun Xiao.
来源: Nat Commun. 2025年16卷1期3947页
Abscisic acid (ABA) is a crucial phytohormone involved in plant growth and stress responses. While the transcriptional regulation triggered by ABA is well-documented, its effects on translational regulation have been less studied. Through Ribo-seq and RNA-seq analyses, we find that ABA treatment not only influences gene expression at the mRNA level but also significantly impacts mRNA translation efficiency (TE) in Arabidopsis thaliana. ABA inhibits global mRNA translation via its core signaling pathway, which includes ABA receptors, protein phosphatase 2Cs (PP2Cs), and SNF1-related protein kinase 2 s (SnRK2s). Upon ABA treatment, Glycine-rich RNA-binding proteins 7 and 8 (GRP7&8) protein levels decrease due to both reduced mRNA level and decreased TE, which diminishes their association with polysomes and leads to a global decline in mRNA TE. The absence of GRP7&8 results in a global impairment of ABA-regulated translational changes, linking ABA signaling to GRP7-dependent modulation of mRNA translation. The regulation of GRP7 on TE relies significantly on its direct binding to target mRNAs. Moreover, mRNA translation efficiency under drought stress is partially dependent on the ABA-GRP7&8 pathways. Collectively, our study reveals GRP7's role downstream of SnRK2s in mediating translation regulation in ABA signaling, offering a model for ABA-triggered multi-route regulation of environmental adaptation.
279. Eicosapentaenoic acid (EPA) reduced lipopolysaccharide-stimulated inflammatory response of RAW264.7 cells via the miR-125b-5p/CREB axis.
作者: Liyuan Zhang.;Lingli Lin.;Baoping Xiao.;Kaiyan Huang.;Jingwen Liu.;Yu-Lei Chen.;Liming Lu.;Zhengxiao Zhang.;Lingyu Zhang.;Jian Li.;Kuo-Ting Ho.;Lianzhong Luo.;Shi-Ying Huang.;Guiling Li.
来源: Int J Biol Macromol. 2025年310卷Pt 4期143511页
Inflammation represents an adaptive physiological response of body immune system to infection or tissue damage, which may be regulated by food supplementation. Eicosapentaenoic acid (EPA) has multi-functions and its anti-inflammatory effect has gained great attention. This study aimed to address the exact molecular mechanism underlying its inflammatory control. The results showed that EPA decreased lipopolysaccharide-induced inflammatory response in RAW264.7 cells by modulating the production of cellular cytokines. In addition, EPA downregulated miR-125b-5p, which showed pro-inflammatory effect and its forced expression attenuated EPA's anti-inflammatory activity. Moreover, the cAMP-responsive element-binding protein (CREB) is targeted by miR-125b-5p. CREB overexpression reduced inflammation probably via modulating the PGC-1α/NF-κB pathway, which resembled the effect of EPA pre-treatment. Therefore, EPA exhibited anti-inflammatory activity by targeting the miR-125b-5p/CREB axis, which modulated the production of inflammatory mediators probably via transcription control. This study provides insights into microRNA-mediated action mechanism and facilitates the relief of inflammation-associated diseases by food ingredients.
280. Emerging roles of histone modifications in environmental toxicants-induced neurotoxicity.
作者: Ishita Mehta.;Manika Verma.;Mohammed Nazish Quasmi.;Dinesh Kumar.;Ashok Jangra.
来源: Toxicology. 2025年515卷154164页
Epigenetics describes itself as heritable modifications in gene function that eventually alter gene and protein expression levels without any alterations in the genome sequence. Epigenetic alterations are closely association with several neurological diseases and neurodevelopmental disorders. In recent years, growing shreds of evidences suggested the crucial role of epigenetic modifications especially histone modifications in environmental toxicants-induced neurotoxicity. This review will give an overview of the state of knowledge on histone alterations and the ways in which environmental pollutants bisphenol-A, heavy metals, pesticides, and phthalates affects post-translational modifications to alter gene transcription and cause neurological abnormalities. We provide a brief summary of the results of recent research on the effects of environmental toxins on each of the prior identified processes of histone modifications, including the neurological consequences and changes in histones. There is also discussion of the limitations of current research findings. Furthermore, this review aims to provide viewers a comprehensive knowledge regarding the role of histone modifications in various environmental toxicants-induced neurological diseases and offers insights for future research.
|