TOXICOLOGY LETTERS
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2025
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IF 2.9
Chenyu Xiao,Qianru Li,Meiqi Li,Yongshu Han,Hubin Xu,Haimin Jiang,Suer Zhang,Zhen Jin,Leilei Gao
Iodoacetamide (IAcAm) is a harmful disinfection by-product. Studies have demonstrated that IAcAm can produce toxic effects in various tissues; however, its effect on female reproductive function remains unclear. To explore the effects of IAcAm on ovaries, we constructed a female mouse IAcAm toxicity model of free drinking model. The findings indicated that IAcAm exposure for five weeks did not affect the body growth of mice but increased the ovary/body weight ratio. At the tissue level, the numbers of atretic follicles increased. After the exposure, ovarian and blood samples were collected for analysis. IAcAm exposure caused changes in serum sex hormone levels, with an increase in follicle-stimulating hormone concentration(follicle-stimulating hormone) and a decrease in anti-Müllerian hormone concentration (anti-Müllerian hormone). Subsequent investigations revealed that IAcAm activated the transforming growth factor-β (TGF-β) signaling pathway and promoted ovarian fibrosis in mice. Simultaneously, IAcAm stimulated the granulosa cell apoptosis pathway and promoted granulosa cell apoptosis. Moreover, IAcAm interfered with mitochondrial function and increased reactive oxygen species, leading to a decrease in oocyte developmental potential. In conclusion, IAcAm exposure causes ovarian inflammation and leads to mitochondrial dysfunction in oocytes, affecting follicle maturation and reducing oocyte quality.
研究领域:
生殖生物学
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毒理学
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分子生物学
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PHARMACEUTICAL RESEARCH
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2020
·Vol. 37
·期 11
·1-12
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IF 3.242
Shen Bin-Bin,Zhang Zhongwei,Yuan Jun-Jie,Zheng Aiping,Zeng Su,Gao Jian-Qing,Bao Wenhan,Barnard James,Wang Haibin,Fang Wei-Jie
Purposes The main purposes of this article are to describe an unprecedented phenomenon in which significant amount of a shoulder peak impurity was observed during normal non-reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) analysis of a recombinant fusion protein X, and to evaluate the root cause for this phenomenon. Methods A series of experiments were conducted to study the nature of this degradation. Effects of iodoacetamide (IAM), heating temperature, duration, and SDS on the formation of this specific impurity were evaluated using a variety of characterization techniques. Results The formation of the impurity as observed in CE-SDS was actually due to alkylation of lysine and serine residues with IAM, as confirmed by peptide mapping and LC-MS/MS, which increased the molecular weight and therefore decreased the electrophoretic mobility. The amount of impurity was also strongly dependent on sample preparation conditions including the presence or absence of SDS. Conclusions Our study clearly suggested that even though IAM has been used extensively as an alkylation reagent in the traditional non-reducing CE-SDS analysis of monoclonal antibodies and other proteins, alkylation with IAM could potentially lead to additional impurity peak, and therefore complicating analysis. Therefore, before performing CE-SDS and other analyses, the effects of sample preparation procedures on analytical results must be evaluated. For protein X, IAM should be excluded for CE-SDS analysis.
研究领域:
生物化学
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蛋白质分析
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药物开发
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Tianxu Liu,Ismail Muhammad Asif,Lichong Liu,Minghui Zhang,Bin Li,Ling Wang
Visceral and somatic hypersensitivity is a common cause of functional dyspepsia. Marine bioactive components have been revealed to possess numerous valuable abilities. However, as a kind of polysaccharide extracted from brown algae, the study focused on the biological properties of laminarin is still limited, especially in gastrointestinal disorders. In our study, indicators associated with visceral sensational function and gastrointestinal microecology were determined to investigate the modulatory effects of laminarin on functional dyspepsia induced by iodoacetamide. Mice with visceral hypersensitivity were orally administrated with laminarin (50 and 100 mg per kg bw) for fourteen days. The results indicated that laminarin partly alleviated the dysfunction by regulating corticosterone secretion, the expression of 5HT 3 receptors at both protein and mRNA levels, and mechanical transduction through the PIEZO2-EPAC1 axis. Furthermore, laminarin administration moderated the imbalanced gut microbial profile, including modulating the abundance of Bacteroidetes and Firmicutes. Our findings revealed that laminarin may restore the overexpression of 5HT 3 receptors, the abnormal mechanical transduction, and impaired gut microecology. In conclusion, we provide evidence to support the utilization of laminarin as the ingredient of complementary and alternative medicine of regulating visceral and somatic hypersensitivity.
研究领域:
胃肠病学
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药理学
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微生物学
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神经科学
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ANALYTICAL CHEMISTRY
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2025
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IF 6.7
Jiahua Zhou,Kailu Tian,Yanan Li,Jiaying Li,Xiangxin Zhang,Chengfei Ruan,Yan Wang,Hongqiang Qin,Mingliang Ye
Iodoacetamide (IAM)-based probes have established the activity-based protein profiling (ABPP) paradigm; however, their reliance on the SN2 mechanism limits the labeling of all cysteine residues, highlighting the need for complementary probes based on alternative reactions. Additionally, probe design must balance between minimizing probe size and simplifying workflow complexity. As a solution to the above issues, we propose acrolein (ACR), a simple α, β-unsaturated carbonyl compound, as an alternative broadly reactive ABPP probe. ACR possesses sp2-hybridized electrophilic groups that react with nucleophilic amino acids via Michael addition, and its aldehyde group facilitates efficient enrichment. We developed a user-friendly chemoproteomic platform for ACR, enabling the identification of over 28,000 nucleophilic residues across three cell lines. ACR demonstrated its ability to detect reactivity changes in nucleophilic residues under native and denatured conditions and to identify known targets of entacapone. Overall, ACR represents a versatile and efficient tool for studying functional nucleophilic sites, with potential applications in drug discovery.
研究领域:
化学生物学
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蛋白质组学
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生物有机化学
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药物发现
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分子生物学
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Yemian Zhou,Yun Liu,Tong Wang,Han Li,Jing He,An Xu
Disinfection by-products (DBPs) generated from water treatment have serious adverse effects on human health and natural ecosystems. However, research on the mutagenicity of DBPs with different chemical structures is still limited. In the present study, we compared the mutagenicity of 8 typical DBPs in human-hamster hybrid (A L ) cells and clarified the mechanisms involved. Our data displayed that the rank order for mutagenicity was as follows: iodoacetamide (IAcAm) > iodoacetonitrile (IAN) > iodoacetic acid (IAA) > bromoacetamide (BAcAm) ≈ bromoacetonitrile (BAN) > bromoacetic acid (BAA), which was confirmed by DNA double strand breaks and oxidative DNA damage. In contrast, bromoform (TBM) and iodoform (TIM) had minimal mutagenicity. The mutation spectrum analysis further revealed that IAN, IAcAm, and IAA could induce multilocus deletions in mammalian cells. Interestingly, nitrogenous DBPs (N-DBPs) and IAA were found to cause varying degrees of iron overload and lipid peroxidation, which was mediated by the activation of the Nrf2/HO-1 signaling pathway. Moreover, the presence of deferoxamine (DFO), an iron ion inhibitor, effectively reduced γ-H2AX and 8-OHdG induced by N-DBPs and IAA. These results indicated that the variations in genotoxicity among DBPs with different structures were associated with their ability to disrupt iron homeostasis. This study provided new insights into the mechanisms underlying the structure-dependent toxicity of DBPs and established a foundation for a more comprehensive understanding and intervention of the health risks associated with DBPs.
研究领域:
环境科学
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毒理学
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分子生物学
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细胞生物学
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ACS Chemical Neuroscience
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2025
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IF 3.9
Lingbo Zhao,Chunyan Hou,Yu Gao,Hong Jin,Chun-Feng Liu,Shuwei Li,Junfeng Ma,Shuang Yang
Parkinson’s disease (PD) is a progressive neurodegenerative disorder lacking definitive diagnostic tests. To identify new diagnostic biomarkers, we employed glycoproteomics-mass spectrometry (MS) to investigate dynamic changes in protein N-glycosylation across the serum, urine, and saliva of PD patients. Our comparative analysis of differentially expressed glycoproteins (DEGs) between PD patients and healthy controls (HCs) revealed distinct patterns. Specifically, ATPase phospholipid transporter 11B (ATP11B) was significantly upregulated in the serum of PD patients, while urine and saliva showed an opposite trend. Other key findings included elevated myeloperoxidase (MPO) in urine and clusterin (CLU) in serum. Zinc-α-2-glycoprotein (AZGP1), detected in all three biofluids, displayed increased sialylation and core fucosylation in serum but decreased levels in the saliva and urine of PD patients, along with a distinct bifucosylation pattern in saliva. These glycoprotein expression changes were further validated using enzyme-linked immunoassay (ELISA). Pathway analysis indicated that these DEGs are primarily involved in inflammatory response, complement activation, and synaptic plasticity, suggesting that glycosylation dysregulation may contribute to PD progression by modulating neuroinflammation and protein homeostasis. This study represents the first comprehensive analysis of multibiofluid N-glycosylation in PD. The findings offer potential biomarkers and provide insights into the molecular mechanisms of the disease, which could ultimately inform early diagnosis and the development of targeted therapies.
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JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Yingling Luan,Kunshuang Shen,Le Yang,Jingzhe Gao,Ning Zhang,Qin Feng,Shengnan Zhu,Hui Sun,Yan Zhang,Ye Sun,Zhengcan Zhou,Ying Han,Xijun Wang
Ethnopharmacological relevance As a traditional medicine, Asini Corii Colla (E’jiao) demonstrates significant efficacy and a favorable safety profile in the treatment of Chemotherapy-induced anemia (CIA). However, its definitive hematopoietic constituents and pharmacodynamic mechanisms remain uncharacterized. Aim of the study To investigate peptides derived from E’jiao with hematopoietic activity in the cisplatin-induced anemia rat model and explore their underlying mechanisms. Methods and methods This study established a chemically induced anemia model by injecting cisplatin. The anti-anemic efficacy of E’jiao was validated through hematological analysis. Nano-liquid chromatography-mass spectrometry (Nano LC-MS) was employed to analyze peptides absorbed into blood in rats. Combined with network pharmacology and molecular weight screening, we preliminarily identified peptides exhibiting potential hematopoietic activity. Molecular docking technology was further utilized to evaluate the binding patterns and affinity of the candidate peptides with erythropoietin (EPO). Results The results demonstrated that E’jiao significantly enhanced erythropoiesis in CIA rats. Nano LC-MS identified 35 peptides absorbed into blood from E’jiao; these bioactive peptides primarily originated from collagen type I alpha 1 chain (COL1A1) and collagen type I alpha 2 chain (COL1A2). Molecular docking analysis revealed that three peptides: GEAGPAGPAGPIGPVGAR (P-GE), GPAGPTGPVGK (P-GP), and SGQPGTVGPAGVRG (P-SG) formed stable binding configurations with the α-helical domain of EPO. The study suggests that three bioactive peptides within E’jiao may exert hematopoietic functions by stabilizing the active conformation of EPO, prolonging its plasma half-life, and enhancing its biological activity. Conclusion This integrative approach combining chemotherapeutic anemia modeling, peptidomics, and molecular docking provides novel insights into the peptide-mediated hematopoietic mechanisms of E’jiao, providing evidence for elucidating the biological mechanisms by which E’jiao peptides regulate hematopoiesis and offering novel perspectives for researching active components in animal-derived medicines.
研究领域:
民族药理学
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生药学
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肽类研究
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血液学
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中医药
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药物作用机制
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FOOD CHEMISTRY
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2025
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IF 9.8
Chongxin Liu,Simona Grasso,Nigel Patrick Brunton,Minghui Gu,Mengyu Shang,Shaobo Li,Li Chen,Dequan Zhang
The authenticity of food origin labelling is a critical concern for consumers. This study analysed the protein profiles of Tan lambs from three different regions using 4D-DIA quantitative proteomics. Using least absolute shrinkage and selection operator (LASSO), 16 potential protein markers were identified. Six machine learning algorithms were employed to train predictive models, with leave-one-out cross-validation. Significant regional differences in protein composition and abundance were revealed by the results. Fourteen protein markers selected using λ min demonstrated superior predictive accuracy compared to the λ 1se group, likely due to its reduced information loss. Logistic regression was identified as the optimal model based on the receiver operating characteristic curve performance. Further analysis using the SHapley Additive Explanations method highlighted W5PF65, W5PQE5 and W5Q501 as key markers for origin identification. This study provides an in-depth analysis of the protein composition of Tan lamb across different regions. It also presents a method for verifying the origin of lamb products and enhancing food traceability.
研究领域:
食品科学与技术
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蛋白质组学
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机器学习
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食品真实性
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分析化学
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FOOD CHEMISTRY
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2025
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IF 9.8
Chaonan Sun,Aijing Jia,Hongwei Luan,Ying Bu,Wenhui Zhu,Xuepeng Li
This paper aimed to explore salt-enhancing peptides from the hydrolysates of Manila clam. Firstly, 265 peptides were identified in the hydrolysates of Manila clams. Then, 26 bioactive peptides were selected for molecular docking with the TMC4 receptor. Finally, peptides LF9 (−120.41 kcal/mol), EM9 (−118.10 kcal/mol), and SH9 (−112.49 kcal/mol) showed better docking affinities. Van der Waals forces and hydrogen bonding were the main binding forces, with ARG583 and GLU286 identified as key residues. E -tongue showed that the three peptides had salt-enhancing effects: SH9 (8.93) > EM9 (3.77) > LF9 (3.22). The SH9-TMC4, EM9-TMC4, and LF9-TMC4 complexes reached equilibrium within 50 ns in molecular dynamics simulations. The quantum chemistry analysis revealed that the active sites of LF9, SH9, and EM9 are C24C25, C56C57, and C58S59, corresponding to HIS, GLN, and GLU, respectively. The discovery of three salt-enhancing peptides contributed to the development of novel salt enhancers and provided new theoretical insights.
研究领域:
食品科学
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肽化学
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分子营养学
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生物信息学
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计算生物学
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Food Chemistry: Molecular Sciences
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2025
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IF 4.7
Liangde Kuang,Yunduan Wang,Min Lei,Xueer Mu,Lin Huang,Bin Wang,Jingwei He,Rui Yang,Rongxia Li,Congyan Li,Wei Fu
Understanding the molecular basis of rabbit meat quality is essential for genetic improvement. We compared Sichuan White (S) and New Zealand White (N) rabbits using carcass phenotyping ( n = 20), longissimus dorsi transcriptomics ( n = 3), and 4D-DIA proteomics ( n = 3). Differentially expressed genes (DEGs) were identified using |log₂FoldChange| ≥ 0.3 and p < 0.05, and differentially expressed proteins (DEPs) were determined using fold change ≥1.3 or ≤ 0.8 and p < 0.05. S rabbits exhibited lower drip loss and shear force but higher intramuscular fat (IMF) content, despite N rabbits displaying greater carcass yield. Integrated omics analysis revealed 848 differentially expressed genes and 140 differentially expressed proteins. The IMF accumulation in S rabbits was driven by upregulated lipid biosynthesis and suppressed fatty acid oxidation. Enrichment of oxidative phosphorylation and thermogenesis indicated enhanced mitochondrial coupling and redox balance, supporting water-holding capacity. Upregulation of ECM-related integrin β-subunits was correlated with improved tenderness. Sixty-eight KEGG pathways were co-enriched across omics layers, highlighting the interplay of lipid metabolism, mitochondrial function and ECM remodeling. Integrated transcriptomic and proteomic analyses revealed that upregulated lipid biosynthesis, suppressed fatty acid oxidation, and enhanced ECM–receptor signaling jointly contribute to superior meat quality in S rabbits. These findings provide candidate molecular targets for improving native rabbit meat quality and offer a foundation for future marker-assisted selection after validation in independent populations.
研究领域:
动物科学
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遗传学
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蛋白质组学
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转录组学
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肉类科学
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分子生物学
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World Journal of Cardiology
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2025
·Vol. 17
·期 12
·112062
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IF 2.8
Yu-Bao Zhao,Zhi-Hong Bao,Ya Tu,Xia Qiu,Yin-Lan Bao,Min Su,Hai-Jun Qi,Quan Wan
BACKGROUND Myocardial infarction (MI) occupies a very high mortality and morbidity rate, and the search for effective pharmacological treatments has far-reaching implications for clinical research. AIM To explore the protective effects of Mongolian medicine Agari-5 on rats with MI. METHODS Sprague-Dawley rats were used, and both the Agari-5 and model groups had their coronary arteries clamped to induce MI. Proteomics was used to research the potential mechanism of action while ELISA, hematoxylin and eosin, and Masson’s staining were used to preliminarily investigate the protective impact of Agari-5 on rats with MI. RESULTS The current study has shown that Agari-5 might enhance cardiac function indicators, including echocardiography results of rats and creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase, in rats that had MI. According to the results of pathological staining, Agari-5 may lessen inflammatory cell infiltration and cardiomyocyte fibrosis, among other things. The proteome analysis revealed that there were 60 distinct proteins in total, four of which were associated with the heart. The expression of PSAT1, PDK1, SMAD4, and SDF2 proteins may be linked to the mechanism of their protective effects. CONCLUSION Potential therapeutic effects of Agari-5 for MI and its mechanism of action may be related to PSAT1, PDK1, SMAD4, and SDF2.
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Food & Function
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2025
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IF 5.4
Yuhui Ye,Xiaoyi Jiang,Yijun Jiang,Longteng Zhang,Binsong Han,Yulong Wang,Pengyan Liu,Xin Lu,Cun-Zheng Zhang
Although often regarded as compromising the fruit’s sensory quality, pear peel is an edible component that enhances the nutritional and functional value of pears within a whole food diet. Rich in diverse polyphenols with demonstrated bioactivity, the pear peel represents a valuable dietary source of health-promoting compounds, however, its role in ulcerative colitis (UC) remains underexplored. In this study, the protective effect of pear peel polyphenols (PPP) against UC was investigated using both in vitro and in vivo models. PPP markedly suppressed proinflammatory cytokine and enzyme expressions in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. In dextran sulfate sodium (DSS) induced colitis mice, PPP significantly mitigated UC symptoms, suppressed serum inflammatory cytokine production, and ameliorated histological damage in colon tissues. Moreover, PPP modulated the gut microbiota by reshaping microbial diversity, enriching beneficial taxa such as Akkermansia, and suppressing proinflammatory taxa including Bacteroides, Enterobacteriaceae, and Parabacteroides. Proteomic analysis further demonstrated that PPP modulated mucosal immunity, particularly by rebalancing immunoglobulin-related processes (IgM, IgD, and IgA) and attenuating antigen presentation responses involving major histocompatibility complex (MHC) class II molecules and cluster of differentiation (Cd40) signaling. Together, these findings suggest that PPP exerts a protective effect against colitis through the coordinated regulation of gut microbiota and mucosal immunity, highlighting its potential as a functional food ingredient for intestinal health.
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危险品化学品经营许可证（带存储）