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Insect Science · 2026 · IF 3.7

FoxO directly regulates the expression of odorant-binding protein genes to mediate olfactory plasticity in response to starvation in Apis cerana cerana

Longlong Chen,Jiahui Luo,Yu Gong,Weihua Ma,Jianhua Lv,Huiting Zhao

Internal energy fluctuations drive biological processes that influence behavior and enhance organismal efficiency and adaptability. This study investigated the effects of starvation and foraging-induced energy changes on olfactory sensitivity in Apis cerana cerana . Compared with the high-energy state, the low-energy state impaired antennal olfactory sensitivity and reduced the expression of olfactory-related genes. These deficits were rescued by supplemental feeding or insulin injection, demonstrating that insulin modulates olfactory perception under low-energy conditions. These findings suggest that the insulin/insulin-like signaling (IIS) pathway mediates the regulation of olfactory function in response to energy changes in A. cerana cerana . Further investigation of combined AccFoxO silencing (a key IIS component expressed in the antennae) and starvation revealed that AccFoxO regulates olfactory gene expression in response to energy fluctuations in A. cerana cerana . This study provides novel insights into the energy-dependent modulation of olfactory behavior.

✓ 已验证 DOI PubMed 高影响因子
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Molecular Medicine Reports · 2020 ·Vol. 22 ·期 6 ·5053-5068 · IF 2.1

Identifying the mechanisms underlying the protective effect of tetramethylpyrazine against cisplatin‑induced in vitro ototoxicity in HEI‑OC1 auditory cells using gene expression profiling

Guofang Guan,Xiao He,Jingjing Chen,Li Bin,Xuxia Tang

Sensorineural hearing loss is prevalent in patients receiving cisplatin therapy. Tetramethylpyrazine (Tet) and tanshinone IIA (Tan IIA) have protective roles against hearing impairment or ototoxicity. The present study aimed to investigate the molecular mechanisms underlying cisplatin‑induced ototoxicity and the protective effect of Tet and Tan IIA against it. House Ear Institute‑Organ of Corti 1 auditory cells were treated with titrating doses of Tan IIA, Tet, and cisplatin. In a cell viability assay, cisplatin, Tan IIA and Tet had IC50 values of 42.89 µM, 151.80 and 1.04x103 mg/l, respectively. Tan IIA augmented cisplatin‑induced cytotoxicity. However, Tet concentrations <75 mg/l attenuated cisplatin‑induced cytotoxicity and apoptosis. Moreover, RNA sequencing analysis was carried out on auditory cells treated for 30 h with 30 µM cisplatin alone for 48 h or combined with 37.5 mg/l Tet for 30 h. Differentially expressed genes (DEGs) induced in these conditions were identified and examined using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Cisplatin increased the expression of genes related to the p53 and FoxO pathways, such as Fas, p21/CDKN1A, and Bcl‑2 binding component 3, but decreased the expression of insulin‑like growth factor 1 (IGF1), as well as genes in the histone (Hist)1 and Hist2 clusters. Treatment with Tet downregulated FOXO3 and Bcl‑2 binding component 3, and increased the expression of IGF1. Moreover, Tet upregulated genes associated with Wnt signaling, but not p53‑related genes. Thus, the otoprotective properties of Tet might be mediated by activation of Wnt and IGF1 signaling, and inhibition of FoxO signaling.

CAS / MDL: 78-10-4
研究领域: 药理学 · 耳鼻喉科学 · 分子生物学 · 基因组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF APPLIED TOXICOLOGY · 2025 · IF 2.8

Potential Mechanisms Underlying Carbimazole-Induced Cardiotoxicity and Hepatotoxicity in Zebrafish

Nian Liu,Shuchao Zhang,Yiliang Liu,Xing Lu,Xiaozhen He

Carbimazole, a first-line antithyroid agent, alleviates hyperthyroidism by inhibiting thyroid hormone synthesis. However, its clinical use is complicated by adverse effects such as cardiotoxicity and hepatotoxicity, underscoring the need to elucidate its mechanisms in model organisms. In this study, zebrafish embryos at 6-h postfertilization (hpf) were continuously exposed to increasing carbimazole concentrations, with systematic assessment of developmental and physiological parameters. Results demonstrated that concentrations above 3.5 μg/mL caused significant mortality and delayed hatching. Dose-dependent developmental abnormalities included shortened body length, reduced swim bladder area, and pericardial edema. Further analyses indicated carbimazole-induced cardiotoxicity characterized by impaired cardiac development, decreased heart rate, and dysregulation of apoptosis-related genes. A diminished fluorescence area suggested compromised cardiac tissue integrity. Concurrently, hepatotoxicity manifested as yolk sac enlargement and altered expression of liver-specific genes, indicating disrupted hepatic function. RNA sequencing (RNA-seq) analyses indicated that at 120 hpf, the 5-μg/mL carbimazole-treated group exhibited 158 upregulated genes and 562 downregulated genes compared with the wild-type (WT) group. GO and KEGG enrichment analyses revealed disruptions in several signaling pathways associated with liver metabolism and cardiac development, including metabolism, FoxO signaling, and the p53 signaling pathway. These findings demonstrate that carbimazole induces early embryonic developmental abnormalities, cardiotoxicity, and hepatotoxicity in zebrafish. This research provides new insights into carbimazole toxicity and valuable perspectives for optimizing its clinical dosing regimen.

CAS / MDL: 22232-54-8 67-68-5
研究领域: 药理学 · 毒理学 · 发育生物学 · 分子生物学 · 基因组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food & Function · 2021 ·Vol. 12 ·期 21 ·10538-10549 · IF 5.396

The dopaminergic neuroprotective effects of different phytosterols identified in rice bran and rice bran oil

Jiali Zhang,Lu Zhang,Zhengzhang Wu,Peng Zhang,Ruijie Liu,Ming Chang,Xingguo Wang

Phytosterols are important bioactive compounds in rice bran and rice bran oil, and the compositions of different phytosterols in rice bran and rice bran oil were investigated in our previous research. In this study, the dopaminergic neuroprotective effects and the underlying mechanisms of sitosterol, cycloartenyl ferulate, 24-methylenecycloartanyl ferulate and campesteryl ferulate identified in rice bran and rice bran oil were investigated in a rotenone-treated C. elegans model. The results indicated that the increased oxidative stress resistance induced by the activation of the DAF-16/FOXO pathway and the inhibition of the apoptotic protein CED-3 overexpression might play an important role in protecting the dopaminergic neurons. The results of this research reveal a new bioactivity of different phytosterols and are helpful for the further nutritional evaluation of rice bran and rice bran oil.

研究领域: 神经科学 · 营养学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2026 ·Vol. 27 ·期 5 · IF 5.6

Paederoside Promotes Longevity and Fitness in C. elegans Through Ubiquitination and Degradation of DAF-2/IGF1R, Activating DAF-16/FOXO and SKN-1/NRF2 Transcription Factors

Tong Chen,Jing Zhang,Shaoqin Jian,Bocen Chen,Yingjie Ma,Wenguang Wang,Tianpeng Ma,Jiran Shi,Jin Yang,Man Xiao

Paederia scandens(Lour.)Merris a substance exhibiting medicine–food homology (MFH), commonly used in China. However, the antioxidant and anti-aging effects ofpaederoside(PSG) have not been thoroughly investigated; therefore, in this study,Caenorhabditis elegans(C. elegans) was treated with PSG to investigate these effects. We found that 50, 80, and 100 μg/mL of PSG could prolong the lifespan ofC. elegans, and administration of 100 μg/mL PSG significantly reduced the accumulation of lipofuscin. Under conditions of oxidative stress, RT-qPCR analysis revealed that PSG treatment significantly up-regulated the expression of key antioxidant geneskn-1and longevity-associated genedaf-16. In addition, PSG increased the activity of the antioxidant enzymes SOD and CAT and reduced the level of MDA. When DAF-2 activity is reduced or inhibited inC. elegans, DAF-16 and SKN-1 are activated and translocate to the nucleus to promote stress resistance and prolong lifespan. Finally, by utilizing HeLa cell models, we demonstrated that the core component ofPaederia scandens, PSG, promotes targeted degradation of IGF1R through the ubiquitin–proteasome system. Our results suggest that feedingC. elegansPSG is effective in extending this organism’s lifespan by improving oxidative stress resistance; thus, PSG has significant potential for development as an anti-aging food product and drug.

CAS / MDL: 14769-73-4
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Anti-inflammasome bio-heterojunction (AI-bioHJ): Revolutionizing diabetic wound healing with in situ self-transformation and programmed gas therapy

Fan Yang,Rui Shu,Bin Li,Wenyu Dai,Wanxi Chen,Jiamin Sun,Ding Bai,Weizhong Yang,Yi Deng

Persistent activation of NLRP3 inflammasomes in infectious diabetic wounds lead to uncontrolled inflammation. Hydrogen sulfide (H 2 S) gas therapy shows promise in inhibiting inflammasomes. However, on-demand delivery of H 2 S is challenging, as its biological characteristics are Janus-faced. Herein, we present the anti-inflammasome bio-heterojunction (AI-bioHJ), comprising FeS, Cu 2 O, and glucose oxidase (GOx), capable of H 2 S gas evolution and in situ self-transformation to accelerate diabetic wound healing. In this system, AI-bioHJ release H 2 S to inhibit NLRP3 inflammasomes and recycle excess H 2 S through a reaction between Cu 2 O and H 2 S, maintaining a low H 2 S concentration while upgrading type I FeS/Cu 2 O to Z-scheme FeS/CuS bioHJ, and markedly enhancing phototherapy. Additionally, GOx depletes local glucose to generate H 2 O 2 , promoting Fenton-like reactions and rapid pathogenic elimination. In vivo and in vitro assessments confirm AI-bioHJ effectively eliminate pathogen, inhibit inflammasomes and facilitate diabetic wound healing. Transcriptome analysis indicates that the FoxO–autophagy axis may mediate the anti-inflammasome effects. Altogether, our work provides enlightenments into programmed H 2 S-releasing bioHJ for remedying diabetic wounds.

研究领域: 生物材料 · 伤口愈合 · 炎症 · 气体疗法 · 纳米技术 · 生物医学工程
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Food & Function · 2024 · IF 5.1

Novel approach for ameliorating high-fat diet-induced syndromes via probiotic-fermented oyster mushroom: from metabolites and microbiota to regulation mechanisms

Zhen Dai,Yanhong Lin,Guandi Chen,Peng Yu,Haotian Wu,Ming Ning,Chris Blanchard,Zhongkai Zhou

The potential effects of probiotics on lowering lipid accumulation and alleviating gut microbiota perturbation have been extensively substantiated, but whether Lactobacillus rhamnoses-fermented oyster mushroom (FOM) could more pronouncedly attenuate obesity remains unclear. In this study, the anti-obesity effect of FOM was estimated based on the gut microbiota profile and analysis of hepatic lipid metabolic characteristics. The results revealed that FOM intervention dramatically improved hepatic lipid accumulation, characterized by reduction in fat-related factor metabolism levels and liver lesion enzymatic activities and down-regulation of the expression of genes associated with glycolipid metabolism (Foxo1, Gck, G6pd, Il6r and IL-β). Metabolomics analysis indicated HFD-induced dysglycaemia and disturbed amino acid metabolism, characterized by significant enrichment of pathways (butanoate metabolism, arginine biosynthesis, etc.) and elevated levels of D-mannose, succinate and β-D-fructose, followed by a decreased galactitol content. Furthermore, FOM intervention showed significant enrichment of specific pathways, particularly transcriptional misregulation in cancer and FoxO signaling pathways, while the MAPK signaling pathway demonstrated consistent enrichment across all experimental groups. FOM intervention reshaped the gut microbiota structure by facilitating the proliferation of SCFA producers (Romboutsia, Ruminococcaceae and Allobaculum), together with the depletion of Lachnospiraceae population. The current study strengthened our understanding of FOM prebiotic activities and obesity alleviation mechanisms.

研究领域: 营养学 · 微生物学 · 代谢组学 · 分子生物学 · 胃肠病学
✓ 已验证 DOI PubMed 高影响因子
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Antioxidants · 2021 ·Vol. 10 ·期 11 ·1697 · IF 6.313

Oleuropein Enhances Stress Resistance and Extends Lifespan via Insulin/IGF-1 and SKN-1/Nrf2 Signaling Pathway in Caenorhabditis elegans

Shiling Feng,Chunyan Zhang,Tao Chen,Lijun Zhou,Yan Huang,Ming Yuan,Tian Li,Chunbang Ding

Oleuropein (OLE) is a secoiridoid glycoside that mainly exists in olives with multifaceted health benefits. The present study aimed to investigate the stress resistance and lifespan extension effects of OLE inCaenorhabditis elegans. The results showed that OLE could significantly prolong the lifespan ofC. elegansby 22.29%. Treatment with OLE also significantly increased the survival rates of worms against lethal heat shock and oxidative stress. Meanwhile, OLE supplementation increased the expression and activity of antioxidant enzymes and suppressed the generation of malondialdehyde in nematodes. In addition, the results from mutants implied that OLE might mediate longevity and stress resistance via DAF-16/FoxO, which played a vital role in the insulin/IGF-1 signaling (IIS) pathway. To further identify the molecular targets of OLE, mRNA level and loss-of-function mutants of IIS-associated genes were investigated. The data revealed that OLE activated IIS by down-regulating the upstream components,daf-2andage-1. Furthermore, another stress response and longevity pathway in parallel to DAF-16, SKN-1/Nrf2, was also shown to involve in OLE-induced beneficial effects. Collectively, these results provide the theoretical basis that OLE could enhance the stress resistance and increase the lifespan ofC. elegansthrough the IIS and SKN-1/Nrf2 signaling pathways.Keywords:oleuropein;Caenorhabditis elegans;longevity;stress resistance

研究领域: 分子生物学 · 老年学 · 药理学 · 遗传学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2024 · IF 3.1

Exploring the gut microbiota mediated biotransformation of Senecio scandens Buch.-Ham.: Insights from metabolite spectrum with UHPLC-Q-Orbitrap HRMS and bioinformatics analysis of gut microbiota metabolites

Jiayue Wang,Feixu Qin,Hongjin Wang,Lu Wang,Caihong Li,Lixin Sun

Senecio scandens Buch.-Ham., a traditional Chinese medicine commonly used clinically, exhibits various pharmacological properties, including anti-inflammatory, anti-tumor, antiviral, and antibacterial activities. However, its water extracts' chemical components and metabolites are inadequately understood, limiting further research. In this study, the chemical components and metabolism processes of Senecio scandens, both in vivo (plasma, feces, urine, and bile) and in vitro (gut microbiota and liver microsomes), were characterized based on ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry. Additionally, metabolites detectable in fecal samples and intestinal microbiota incubated but absent in liver microsomes were identified as characteristic metabolites of intestinal microbiota. The targets of the characteristic metabolites of intestinal microbiota were collected, followed by exploration of potential pathways through KEGG enrichment analysis. As a result, a total of 133 chemical components were preliminarily identified, including 35 organic acids, 21 alkaloids, 19 flavonoids and their glycosides, 17 phenylpropanoids, 10 jacaranda ketones, and 31 other compounds. Notably, 12 of these were potentially novel compounds. In addition, 39 prototype components in rats and 109 metabolites were identified and characterized, including 102 in vivo and 52 metabolites in vitro (51 in rat gut microbiota and 24 in rat liver microsomes). The main metabolic pathways include oxidation, reduction, hydrolysis, methylation, glucuronidation, sulfonation, and acetylation reactions. Furthermore, KEGG enrichment analysis revealed that the characteristic metabolites of intestinal microbiota may be related to the ErbB, FoxO, mTOR, and MAPK signaling pathways, exhibiting anti-inflammatory and anti-tumor effects. In summary, the chemical components and metabolites of Senecio scandens were comprehensively identified using a rapid and accurate method, providing a scientific basis for the in-depth study of the material basis and its clinical application of Senecio scandens .

CAS / MDL: 64-18-6
研究领域: 药理学 · 代谢组学 · 生物信息学 · 中药学 · 化学生物学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Foods · 2024 ·Vol. 13 ·期 22 ·3543 · IF 4.7

Non-Covalent Interactions of Lotus Root Polysaccharides and Polyphenols and their Regulatory Mechanism on Macrophage Functions

Yajie Li,Nan Huang,Qiulan Liu,Ying Sun,Kaidi Peng,Xueyu Jiang,Yang Yi

Despite the interaction between polyphenols and polysaccharides in food products, their specific non-covalent interactions and effects on macrophage functions are not well understood. Therefore, the interaction and mechanism of purified lotus root polysaccharide (PLRP) with polyphenols, and the regulatory mechanisms of the PLRP-polyphenol complex on the macrophage functionals were studied. By combining ferulic acid (FA) and chlorogenic acid (CHA) with PLRP, the complexes PLRP-FA, PLRP-CHA and the physical mixtures PLRP&FA and PLRP&CHA were prepared, where their mass ratios of polyphenols to PLRP were 143.97 and 601.67 mg g−1. Nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), Ultraviolet (UV), and Transmission electron microscopy (TEM) analyses confirmed that PLRP and polyphenols may engage in non-covalent interactions via hydrogen bonds and hydrophobic interactions. We confirmed that non-covalent interactions led to high molecular weight, dense complexes. Both PLRP and its polyphenol complexes stimulated NO production by macrophages to varying degrees without exacerbating lipopolysaccharide-induced inflammatory responses. PLRP and PLRP-polyphenol complexes repaired cells with impaired antioxidant capacity, depending on doses. Those results indicated that after the combination of lotus root polysaccharide and polyphenol, the molecular weight and conformation changed significantly, which influenced the biological activity. RNA-seq analysis suggested that the regulatory mechanism of PLRP-polyphenol complex in macrophages may mainly involve oxidative phosphorylation, FoxO, TNF, IL-17, MAPK, NF-kappa B, and other signaling pathways. This study investigated the effects of polyphenol binding on the physicochemical characteristics and functional activities of polysaccharides, which provided references for the development of polysaccharide functional products and the control of nutritional quality.

CAS / MDL: 327-97-9 1135-24-6
研究领域: 食品科学 · 免疫学 · 分子生物学 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Nano · 2023 · IF 17.1

Near-Infrared Phototheranostic Iron Pyrite Nanocrystals Simultaneously Induce Dual Cell Death Pathways via Enhanced Fenton Reactions in Triple-Negative Breast Cancer

Chunhua Zhao,Zekun Liu,Chia-Che Chang,Yi-Chia Chen,Qize Zhang,Xiao-Dong Zhang,Chrysafis Andreou,Jiadong Pang,Ze-Xian Liu,Di-Yan Wang,Moritz F. Kircher,Jiang Yang

Triple-negative breast cancer (TNBC) is considered more aggressive with a poorer prognosis than other breast cancer subtypes. Through systemic bioinformatic analyses, we established the ferroptosis potential index (FPI) based on the expression profile of ferroptosis regulatory genes and found that TNBC has a higher FPI than non-TNBC in human BC cell lines and tumor tissues. To exploit this finding for potential patient stratification, we developed biologically amenable phototheranostic iron pyrite FeS2 nanocrystals (NCs) that efficiently harness near-infrared (NIR) light, as in photovoltaics, for multispectral optoacoustic tomography (MSOT) and photothermal ablation with a high photothermal conversion efficiency (PCE) of 63.1%. Upon NIR irradiation that thermodynamically enhances Fenton reactions, dual death pathways of apoptosis and ferroptosis are simultaneously triggered in TNBC cells, comprehensively limiting primary and metastatic TNBC by regulating p53, FoxO, and HIF-1 signaling pathways and attenuating a series of metabolic processes, including glutathione and amino acids. As a unitary phototheranostic agent with a safe toxicological profile, the nanocrystal represents an effective way to circumvent the lack of therapeutic targets and the propensity of multisite metastatic progression in TNBC in a streamlined workflow of cancer management with an integrated image-guided intervention.

研究领域: 癌症生物学 · 纳米技术 · 光疗 · 分子生物学 · 医学成像
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Materials Today Bio · 2023 · IF 8.2

Lineage-specific multifunctional double-layer scaffold accelerates the integrated regeneration of cartilage and subchondral bone

Chunhui Ma,Tao Wang,Xinmeng Jin,Wanglin Zhang,Qi Lv

Repairing cartilage/subchondral bone defects that involve subchondral bone is a major challenge in clinical practice. Overall, the integrated repair of the structure and function of the osteochondral (OC) unit is very important. Some studies have demonstrated that the differentiation of cartilage is significantly enhanced by reducing the intake of nutrients such as lipids. This study demonstrates that using starvation can effectively optimize the therapeutic effect of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs). A hyaluronic acid (HA)-based hydrogel containing starved BMSCs-EVs displayed continuous release for more than 3 weeks and significantly promoted the proliferation and biosynthesis of chondrocytes around the defect regulated by the forkhead-box class O (FOXO) pathway. When combined with vascular inhibitors, the hydrogel inhibited cartilage hypertrophy and facilitated the regeneration of hyaline cartilage. A porous methacrylate gelatine (GelMA)-based hydrogel containing calcium salt loaded with thrombin rapidly promoted haematoma formation upon contact with the bone marrow cavity to quickly block the pores and prevent the blood vessels in the bone marrow cavity from invading the cartilage layer. Furthermore, the haematoma could be used as nutrients to accelerate bone survival. The in vivo experiments demonstrated that the multifunctional lineage-specific hydrogel promoted the integrated regeneration of cartilage/subchondral bone. Thus, this hydrogel may represent a new strategy for osteochondral regeneration and repair.

CAS / MDL: 10043-52-4
研究领域: 组织工程 · 再生医学 · 骨科 · 干细胞生物学 · 生物材料
✓ 已验证 产品关联 DOI PubMed 高影响因子
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