Frontiers in Pharmacology
·
2024
·
IF 4.4
Li Yan,Ge Jingping,Yin Yuanyuan,He Juan,Shang Longcheng
Background: This study aimed to explore the regulatory effect of anserine on HUVEC cell injury and thrombosis in deep venous thrombosis (DVT) rats, and to elucidate the underlying molecular mechanisms.Methods: Non-targeted metabolomics data analyses were conducted using an ultra-performance liquid chromatography system Vanquish UHPLC and mass spectrometer to detect plasma metabolism profiles. The transcriptome sequencing and gene intervention experiments were performed to verify the regulatory effect. Further in vivo and in vitro experiments were performed. Enzyme-linked immunosorbent assay was used to detect the levels of P-selectin, E-selectin, and vWF, hematoxylin-eosin (HE) staining was performed to observe thrombotic and inflammatory cell infiltration, flow cytometry and TUNEL assays were performed to detect apoptosis, and qPCR and WB assays were conducted to determine the gene and protein expression.Results: Anserine alleviated HUVECs injury, reduced adhesion molecule expression, and inflammation. It decreased P-selectin, E-selectin, vWF, THBD, TFPI levels, and apoptosis while promoting NOS3, ET-1, and NO release in HUVECs. In DVT rats, anserine reduced P-selectin, E-selectin, vWF, thrombosis, cell infiltration, apoptosis, and promoted NO release. Transcriptome sequencing and gene intervention confirmed anserine’s regulation of the PI3K-Akt pathway and coagulation via MYB. CARNMT1, a regulatory enzyme for anserine metabolism, increased anserine content, inhibiting coagulation, thrombosis, cell infiltration, and promoting NO release in rats.Conclusion: This study confirmed anserine could alleviate DVT by improving the inflammatory response, inhibiting blood agglutination, and promoting vasodilation, providing new potential therapeutic targets, important scientific evidence for the development of DVT management, and new clues for an in-depth understanding of its molecular mechanisms.
研究领域:
药理学
·
分子生物学
·
心血管疾病
·
血栓
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF NUTRITION
·
2023
·
IF 3.6
Hua Zheng,Yi-Chuang Xu,Tao Zhao,Zhi Luo,Dian-Guang Zhang,Chang-Chun Song,An-Gen Yu,Xiaoying Tan
This experiment was conducted to investigate whether dietary chenodeoxycholic acid (CDCA) could attenuate high-fat (HF) diet-induced growth retardation, lipid accumulation and bile acid (BA) metabolism disorder in the liver of yellow catfish Pelteobagrus fulvidraco. Yellow catfish (initial weight: 4·40 (sem 0·08) g) were fed four diets: the control (105·8 g/kg lipid), HF diet (HF group, 159·6 g/kg lipid), the control supplemented with 0·9 g/kg CDCA (CDCA group) and HF diet supplemented with 0·9 g/kg CDCA (HF + CDCA group). CDCA supplemented in the HF diet significantly improved growth performance and feed utilisation of yellow catfish (P < 0·05). CDCA alleviated HF-induced increment of hepatic lipid and cholesterol contents by down-regulating the expressions of lipogenesis-related genes and proteins and up-regulating the expressions of lipololysis-related genes and proteins. Compared with the control group, CDCA group significantly reduced cholesterol level (P < 0·05). CDCA significantly inhibited BA biosynthesis and changed BA profile by activating farnesoid X receptor (P < 0·05). The contents of CDCA, taurochenodeoxycholic acid and glycochenodeoxycholic acid were significantly increased with the supplementation of CDCA (P < 0·05). HF-induced elevation of cholic acid content was significantly attenuated by the supplementation of CDCA (P < 0·05). Supplementation of CDCA in the control and HF groups could improve the liver antioxidant capacity. This study proved that CDCA could improve growth retardation, lipid accumulation and BA metabolism disorder induced by HF diet, which provided new insight into understanding the physiological functions of BA in fish.
研究领域:
水产养殖
·
营养学
·
生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PROTEOME RESEARCH
·
2021
·
IF 4.466
Peng Ma,Zijing Wang,Yisa Wang,Biyu Hou,Jialin Sun,He Tian,Bowen Li,Guanghou Shui,Xiuying Yang,Xinyu Yang,Guifen Qiang,Chong Wee Liew,Guanhua Du
Once protein synthesis is excessive or misfolded protein becomes aggregated, which eventually overwhelms the capacity of the endoplasmic reticulum (ER), a state named ER stress would be reached. ER stress could affect many tissues, especially the liver, in which nonalcoholic fatty liver disease, liver steatosis, etc. have been reported relative. However, there is still a lack of systematic insight into ER stress in the liver, which can be obtained by integrating metabolomics and transcriptomics of the tissue. Here, tunicamycin was utilized to induce ER stress in C57BL/6N mice. Microarray and untargeted metabolomics were performed to identify the genes and metabolites significantly altered in liver tissues. Surprisingly, apart from the predictable unfolded protein response, liver lipid, arginine, and proline metabolisms were affirmed to be related to ER stress. Also, the ketone body metabolism changed most prominently in response to ER stress, with few studies backing. What is more, succinate receptor 1 (Sucnr1) may be a novel marker and therapeutical target of liver ER stress. In this study, the combination of the metabolome and transcriptome provided reliable information about liver pathological processes, including key relative pathways, potential markers, and targets involved in ER stress of the liver.
研究领域:
分子生物学
·
生物化学
·
系统生物学
·
肝病学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Xinrui Feng,Ran Wang,Jingnan Lu,Qingfei Du,Kezhou Cai,Bao Zhang,Baocai xu
Umami peptides are valuable taste substances due to their exceptional taste and beneficial properties. In this study, purification of fermented goose bone broth was performed using continuous chromatography and sensory analysis, and after identification through nano-LC-MS/MS, four umami peptides were screened out by umami activity prediction and molecular docking, which are VGYDAE, GATGRDGAR, GETGEAGER, and GETGEAGERG derived from collagen. Sensory analysis indicated that they were also umami-enhancing, with thresholds ranging from 0.41 to 1.15 mmol/L, among which GER9 was the best. Combining the results of docking and molecular dynamics simulation, it was known that hydrogen bond and electrostatic interactions were vital in driving the umami formation. Moreover, Glu, Ser, and Asp of umami receptor T1R1/T1R3 were the key residues for the binding between four umami peptides and T1R1/T1R3. These findings provide novel insights into the high-value utilization of goose bones and offer profound theoretical guidance for understanding the umami mechanism.
研究领域:
食品科学
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分子生物学
·
化学工程
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL RESEARCH
·
2024
·Vol. 57
·期 1
·1-12
·
IF 4.3
Ma Lin-Wei,Liu Yu-Fan,Zhang Hui,Huang Chang-Jun,Li Ang,Qu Xin-Zhe,Lin Jia-Piao,Yang Yan,Yao Yong-Xing
Studies have suggested that endoplasmic reticulum stress (ERS) is involved in neurological dysfunction and that electroacupuncture (EA) attenuates neuropathic pain (NP) via undefined pathways. However, the role of ERS in the anterior cingulate cortex (ACC) in NP and the effect of EA on ERS in the ACC have not yet been investigated. In this study, an NP model was established by chronic constriction injury (CCI) of the left sciatic nerve in rats, and mechanical and cold tests were used to evaluate behavioral hyperalgesia. The protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that glucose-regulated protein 78 (BIP) and inositol-requiring enzyme 1α (IRE-1α) were co-localized in neurons in the ACC. After CCI, BIP, IRE-1α, and phosphorylation of IRE-1α were upregulated in the ACC. Intra-ACC administration of 4-PBA and Kira-6 attenuated pain hypersensitivity and downregulated phosphorylation of IRE-1α, while intraperitoneal injection of 4-PBA attenuated hyperalgesia and inhibited the activation of P38 and JNK in ACC. In contrast, ERS activation by intraperitoneal injection of tunicamycin induced behavioral hyperalgesia in naive rats. Furthermore, EA attenuated pain hypersensitivity and inhibited the CCI-induced overexpression of BIP and pIRE-1α. Taken together, these results demonstrate that EA attenuates NP by suppressing BIP- and IRE-1α-mediated ERS in the ACC. Our study presents novel evidence that ERS in the ACC is implicated in the development of NP and provides insights into the molecular mechanisms involved in the analgesic effect of EA.
研究领域:
神经科学
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疼痛管理
·
分子生物学
·
针灸
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产品关联
DOI
PubMed
高影响因子
POLYMERS FOR ADVANCED TECHNOLOGIES
·
2020
·Vol. 31
·期 11
·2676-2686
·
IF 2.578
Yingying He,Xinyue Liu,Xiaojun Qi,Yupeng Guan,Shuai Li,Hongxia Liu,Li Zhou,Chun Wei,Chuanbai Yu
Both poly(methyl methacrylate) (PMMA) and polystyrene (PS) have excellent transparency, but a blend of the two typically has low mechanical properties and poor transparency owing to phase separation. Herein, oil-in-water Pickering emulsion gel technology was combined with the hot pressing process to prepare cellulose nanofibrils (CNFs) reinforced PMMA/PS binary blend composite film materials (CNFs/PMMA/PS). The CNFs/PMMA/PS composites with a pebble-shaped structure had a unique three-dimensional crosslinked network structure and endowed the composite film with better thermal stability, and excellent transparency and mechanical properties. Particularly, the derivative thermogravimetry and differential scanning calorimetry results revealed that the compatibility between the PMMA and the PS phases in the composite film is remarkably improved. The optimal tensile strength (58 MPa) and maximum strain (4.2%) were obtained when the content of CNFs was 52%, which represented approximately 3-fold and 2-fold improvements, respectively, than those of the PMMA/PS blend films. Moreover, the C-CNFs/PMMA/PS composite films maintained an excellent light transmittance of approximately 80% in the wavelength range of 600 to 800 nm. The facile preparation method is proposed to achieve an excellent dispersion of unmodified CNFs in hydrophobic and binary polymer mixture, which constitutes a new approach for using CNFs to enhance the high performance of polymer materials.
研究领域:
材料科学
·
高分子科学
·
纳米技术
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产品关联
DOI
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2020
·Vol. 42
·期 3
·393-403
·
IF 5.064
Tian Jia-hui,Wu Qian,He Yong-xiang,Shen Qi-ying,Rekep Mubarak,Zhang Gui-ping,Luo Jian-dong,Xue Qin,Liu Ying-hua
Endoplasmic reticulum stress (ER stress) plays a key role in the development of cardiac hypertrophy and diabetic cardiomyopathy (DCM). Zonisamide (ZNS) was originally developed as an antiepileptic drug. Studies have shown that ZNS suppresses ER stress-induced neuronal cell damage in the experimental models of Parkinson’s disease. Herein, we investigated whether ZNS improved DCM by attenuating ER stress-induced apoptosis. C57BL/6J mice were fed with high-fat diet (HFD) and intraperitoneally injected with low-dose streptozotocin (STZ) to induce type 2 diabetes mellitus (T2DM), and then treated with ZNS (40 mg·kg −1 ·d −1 , i.g.) for 16 weeks. We showed that ZNS administration slightly ameliorated the blood glucose levels, but significantly alleviated diabetes-induced cardiac dysfunction and hypertrophy. Furthermore, ZNS administration significantly inhibited the Bax and caspase-3 activity, upregulated Bcl-2 activity, and decreased the proportion of TUNEL-positive cells in heart tissues. We analyzed the hallmarks of ER stress in heart tissues, and revealed that ZNS administration significantly decreased the protein levels of GRP78, XBP-1s, ATF6, PERK, ATF4, and CHOP, and elevated Hrd1 protein. In high glucose (HG)-treated primary cardiomyocytes, application of ZNS (3 μM) significantly alleviated HG-induced cardiomyocyte hypertrophy and apoptosis. ZNS application also suppressed activated ER stress in HG-treated cardiomyocytes. Moreover, preapplication of the specific ER stress inducer tunicamycin (10 ng/mL) eliminated the protective effects of ZNS against HG-induced cardiac hypertrophy and ER stress-mediated apoptosis. Our findings suggest that ZNS improves the cardiac diastolic function in diabetic mice and prevents T2DM-induced cardiac hypertrophy by attenuating ER stress-mediated apoptosis.
研究领域:
药理学
·
心脏病学
·
糖尿病
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 10
·5794-5806
·
IF 6.317
Wenshuai Wang,Xiaoxu Li,Yaohan Zhang,Jianjun Zhang,Le Jia
Nonylphenol (NP) exposure has become a crucial inducement of male reproductive disorders in the world. Therefore, it is urgent to seek solutions to alleviate the toxicity of NP. This study was oriented toward studying the protective effects of Macrolepiota procera mycelium polysaccharides (MMP) on NP-induced reproductive impairments. After NP administration, declined sperm amounts and testis index, increased the deformity rate of sperms, aberrant hormone secretion and testicular pathological injury were observed, corporately leading to reproductive capacity attenuation. Importantly, MMP significantly reversed the foregoing changes in NP-treated mice. Notably, it has been observed that the MMP therapy remarkably improved oxidative stress, apoptosis, autophagy and inflammatory responses, and suppressed the Akt/mTOR signaling pathway in testicular tissues. These results manifested that MMP might be a promising treatment strategy for ameliorating the biotoxicity of NP.
研究领域:
毒理学
·
生殖生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Lipids in Health and Disease
·
2025
·Vol. 24
·期 1
·1-16
·
IF 4.2
Li Lishuang,Ren Xing,Gao Xinyu,Zhao Yujia,Ma Yuman,Gong Junxiao,Yang Shuo,Sun Yanan,Wang Yi
Objective This study aimed to investigate the regulatory role and mechanisms of chenodeoxycholic acid (CDCA) on lipid metabolism, and to evaluate its therapeutic potential in lipid metabolism-related diseases such as acne, seborrheic alopecia, and prostate cancer, with the aim of identifying safer and more sustainable treatment alternatives. Methods Lipid-overproduction models were established using RM-1 (murine prostate cancer cells) and primary sebaceous gland cells, stimulated by linoleic acid (LA) and dihydrotestosterone (DHT), respectively. CDCA’s mechanisms were explored using transcriptomics, proteomics, and fatty acid-targeted metabolomics. In vivo validation was conducted via intradermal injection of CDCA into the sebaceous gland area of golden hamsters to assess its effect on sebaceous lipid metabolism. Results CDCA significantly reduced intracellular lipid accumulation in both murine prostate cancer cells (RM-1) and primary sebaceous gland cells, and suppressed the expression of the androgen receptor (AR), along with the downregulation of key lipogenic enzymes (SREBF1, FASN, FADS2). Mitochondrial membrane potential was restored in CDCA-treated cells. Multi-omics analyses revealed that CDCA modulated fatty acid biosynthesis and degradation, energy metabolism, mitochondrial function, and Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) signaling. Lipidomic profiling demonstrated a shift from saturated to unsaturated fatty acid dominance after CDCA treatment. In vivo, CDCA decreased sebaceous lipid accumulation and downregulated PPAR-γ expression in golden hamsters. Conclusion CDCA exerted multifaceted regulatory effects on lipid metabolism, hormone signaling, and mitochondrial dynamics. These effects contributed to the maintenance of sebaceous gland homeostasis and supported the development of innovative and potentially more biocompatible therapies for lipid-related disorders.
研究领域:
生物化学
·
分子生物学
·
药理学
·
皮肤科学
·
肿瘤学
·
内分泌学
·
系统生物学
·
代谢组学
·
转录组学
·
蛋白质组学
✓ 已验证
DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2021
·Vol. 105
·期 9
·3573-3586
·
IF 4.813
Liu Zhiyong,Zhang Rongzhen,Zhang Wenchi,Xu Yan
Abstract NAD(H)-dependent 7α-hydroxysteroid dehydrogenase catalyzes the oxidation of chenodeoxycholic acid to 7-oxolithocholic acid. Here, we designed mutations of Ile258 adjacent to the catalytic pocket of Brucella melitensis 7α-hydroxysteroid dehydrogenase. The I258M variant gave a 4.7-fold higher k cat , but 4.5-fold lower K M , compared with the wild type, resulting in a 21.8-fold higher k cat / K M value for chenodeoxycholic acid oxidation. It presented a 2.0-fold lower K M value with NAD + , suggesting stronger binding to the cofactor. I258M produced 7-oxolithocholic acid in the highest yield of 92.3% in 2 h, whereas the wild-type gave 88.4% in 12 h. The I258M mutation increased the half-life from 20.8 to 31.1 h at 30 °C. Molecular dynamics simulations indicated increased interactions and a modified tunnel improved the catalytic efficiency, and enhanced rigidity at three regions around the ligand-binding pocket increased the enzyme thermostability. This is the first report about significantly improved catalytic efficiency, cofactor affinity, and enzyme thermostability through single site-mutation of Brucella melitensis 7α-hydroxysteroid dehydrogenase. Key points • Sequence and structure analysis guided the site mutation design. • Thermostability, catalytic efficiency and 7 - oxo - LCA production were determined . • MD simulation was performed to indicate the improvement by I258M mutation .
研究领域:
生物化学
·
酶学
·
微生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Siyu Zheng,Afei Liu,Xianhui Zhang,Wenhui Wu,Lihui Chen,Chunmei Lai,Yuekun Lai,Kai Liu
Most hydrogels rely heavily on cryoprotectants to enhance their anti-freezing capabilities; however, this approach is often accompanied by disadvantages such as altered network structures and the risk of cryoprotectant leakage in aqueous conditions. Given these challenges, an environmentally resilient diode-like hydrogel is developed, featuring a double-layer coating design inspired by the physiological characteristics of penguins. This design is achieved through plasma treatment and immersion in 3-aminopropyltriethoxysilane/butyl acetate and perfluoropolyether carboxylic acid/butyl acetate solutions, constructing a double-layer coating with stable interfacial strength. The coating not only enhances anti-dehydration performance but also imparts anti-freezing properties via N,N-dimethylformamide solution. By carefully regulating the coating thickness and polymerization duration, it has optimized the mechanical and electrical attributes of hydrogel, culminating in robust performance even at −80 °C. The hydrogel exhibits exceptional water retention capabilities, with a mere 33.4% water loss rate following 7 days of air drying. Moreover, the hydrogel demonstrates stable piezoionic output performance across various low-temperature environments, with tensile and compressive strengths of 1156 kPa and 3.45 MPa, respectively. This study presents a novel solution for the application of conductive hydrogels in smart wearable devices, underscoring their potential for use in extreme environments.
研究领域:
材料科学
·
柔性电子学
·
可穿戴传感器
·
能量收集
·
仿生材料
✓ 已验证
产品关联
DOI
高影响因子
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
·
2024
·
IF 3.2
Yuan Gao,Jiao Xu,Kaichuan He,Qi Guo,Lin Xiao,Sheng Jin,Danyang Tian,Xu Teng,Cuixia An,Hongmei Xue,Yuming Wu
Previous studies showed that hyperhomocysteinemia (HHcy) induced endothelial dysfunction by endoplasmic reticulum (ER) stress induction and autophagy stimulation. This study aimed to determine the effect of hydrogen sulfide (H 2 S) in homocysteine (Hcy)-induced endothelial dysfunction and observe the possible mechanism involved.Male Wistar rats (160-180g) were used and randomly divided into four groups: Control group, HHcy group, HHcy+Sodium hydrosulfide (NaHS) group and NaHS group. Rats were fed with 2% high methionine diet for 8 weeks to set up HHcy model. Plasma concentration of Hcy was measured by ELISA.Endothelium-dependent and non-endothelium-dependent vasodilation of rat renal arteries were determined by myograph.The protein expression of cystathionine-γ-lyase (CSE), ER stress-and autophagy-related proteins in renal arteries or human umbilical vein endothelial cells (HUVECs) were analyzed by western blotting. The endothelial function was impaired in HHcy rats and HUVECs. NaHS supplementation could improve the ACh-induced vasodilation, however it was eliminated by ER stress inducer Tunicamycin (TM) or autophagy inducer Rapamycin. Western blotting in renal arteries showed that Glucose-regulated protein 78 (GRP78) and three branches of ER stress (p-IRE1α, p-PERK, ATF6, GRP78) and p-JNK1+p-JNK2 was downregulated by NaHS administration, simultaneously the autophagy marker Beclin1, LC3BII/LC3BI ratio was decreased and p62 was increased in HHcy rats. In HUVECs, IRE1α-JNK induced autophagy was involved in HHcy-induced endothelial dysfunction, while NaHS stimulation decreased the protein expression in IRE1α/JNK-autophagy pathway with Hcy incubation. This study might suggest that endothelial dysfunction induced by HHcy might be correlate with IRE1α-JNK-autophagy axis pathway, which was suppressed by exogenous supplementation of H 2 S donor NaHS.
研究领域:
心血管疾病
·
分子生物学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）