CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2019
·Vol. 47
·期 3
·372-382
·
IF 2.336
Ruili Wang,Ying Yang,Hui Wang,Ya He,Chen Li
MicroRNAs (miRNAs) have been shown to have complicated implications in the pathogenesis of Parkinson's disease (PD). However, the role of miR-29c and the underlying mechanism in the development of PD remain not well understood. In this work, the MPTP-treated mice or MPP + -intoxicated SH-SY5Y cells were established as an in vivo or in vitro PD model. Then the specific agomir of miR-29c was employed to examine its biological function on PD progress. We found that miR-29c was down-expressed but SP1 was high-expressed in substantia nigra pars compacta (SNpc) of MPTP-induced PD mice. Overexpression of miR-29c attenuated dopaminergic neuron loss and α-synuclein accumulation in SNpc of PD mice. Furthermore, the increments of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and TUNEL-positive apoptotic cells in MPTP-treated mice were ameliorated by miR-29c. Similarly, in SH-SY5Y cell models of PD, we also found that miR-29c inhibited inflammatory cytokine production, reduced apoptotic rate and suppressed pro-apoptotic regulator activity. In addition, the increased expression of SP1 in PD models was found to be inhibited by miR-29c. Luciferase reporter assay confirmed that SP1 was complementary with miR-29c. Knockdown of SP1 with siRNA restored α-synuclein accumulation, inflammation and apoptosis in MPP + -induced SH-SY5Y cells. Collectively, this current work presents that miR-29c may directly target SP1 to protect against the neuroinflammatory and apoptotic responses in PD, providing a potential biomarker for PD diagnosis and treatment.
研究领域:
神经科学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2019
·
IF 3.361
Xiao Sun,Yan Liu,Xiuli Feng,Chunyan Li,Siying Li,Zhongxi Zhao
Macrophages are the most abundant immune cells in the lung, which play an important role in COPD. The anti-inflammatory and anti-oxidation of ergosterol are well documented. However, the effect of ergosterol on macrophage polarization has not been studied. The objective of this work was to investigate the effect of ergosterol on macrophage polarization in CSE-induced RAW264.7 cells and Sprague-Dawley (SD) rats COPD model. Our results demonstrate that CSE-induced macrophages tend to the M1 polarization via increasing ROS, IL-6 and TNF-α, as well as increasing MMP-9 to destroy the lung construction in both RAW264.7 cells and SD rats. However, treatment of RAW264.7 cells and SD rats with ergosterol inhibited CSE-induced inflammatory by decreasing ROS, IL-6 and TNF-α, and increasing IL-10 and TGF-β, shuffling the dynamic polarization of macrophages from M1 to M2 both in vitro and in vivo . Ergosterol also decreased the expression of M1 marker CD40, while increased that of M2 marker CD163. Moreover, ergosterol improved the lung characters in rats by decreasing MMP-9. Furthermore, ergosterol elevated HDAC3 activation and suppressed P300/CBP and PCAF activation as well as acetyl NF-κB/p65 and IKKβ, demonstrating that HDAC3 deacetylation was involved in the effect of ergosterol on macrophage polarization. These results also provide a proof in immunoregulation of ergosterol for therapeutic effects of cultured C. sinensis on COPD patients.
研究领域:
免疫学
·
药理学
·
呼吸医学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
·
2024
·
IF 5
Yanchi Liu,Lintao Zhao,Hongyang Chen,Zimao Ye,Long Guo,Zhiqin Zhou
The study prepared and used eugenol nanoemulsion loaded with nobiletin as fungistat to study its antifungal activity and potential mechanism of Penicillium italicum (P. italicum) . The results showed that the minimum inhibitory concentration (MIC) of eugenol nanoemulsion loaded with nobiletin (EGN) was lower than that of pure eugenol nanoemulsion (EG), which were 160 μg/mL and 320 μg/mL, respectively. At the same time, the mycelial growth inhibition rate of EGN nanoemulsion (54.68 %) was also higher than that of EG nanoemulsion (9.92 %). This indicates that EGN nanoemulsion is more effective than EG nanoemulsion. Compared with EG nanoemulsion, the treatment of EGN nanoemulsion caused more serious damage to the cell structure of P. italicum . At the same time, in vitro inoculation experiments found that EGN nanoemulsion has better control and delay the growth and reproduction of P. italicum in citrus fruits. And the results reflected that EGN nanoemulsion may be considered as potential resouces of natural antiseptic to inhibit blue mold disease of citrus fruits, because it has good antifungal activity.
研究领域:
药理学
·
微生物学
·
食品科学
·
植物病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHYSICS AND CHEMISTRY OF SOLIDS
·
2026
·
IF 5.9
Xinyang He,Ying Lv,Dapeng Qin,Meixia Xiao,Lei Wang,Weiwei Han
The simultaneous removal of organic dyes and heavy metal ions from complex wastewater remains a formidable challenge due to the competitive redox requirements of different pollutants. In this work, we report a robust in-situ phase transformation strategy to construct a temperature-mediated S-scheme Bi 2 WO 6 /Bi 2 O 2 CO 3 heterojunction. By precisely modulating the hydrothermal temperature, the BiOCOOH phase was strategically transformed into Bi 2 O 2 CO 3 on the Bi 2 WO 6 surface, establishing an intimate interfacial contact. The resulting heterojunction induces a potent internal electric field (IEF), which dictates a high-efficiency S-scheme charge transfer pathway. This mechanism not only maximizes the spatial separation of photogenerated carriers but also preserves the powerful redox potentials of the individual components. Under visible light irradiation, the optimized BCW-2 catalyst exhibited exceptional performance, achieving near-complete removal of Rhodamine B (RhB) and Cr(VI) within 90 min, with reaction rate constants of 0.08911 min −1 and 0.06157 min −1 , respectively. Detailed experimental characterizations and density functional theory (DFT) calculations provided deep mechanistic insights into the band alignment and interfacial electronic behavior, confirming the S-scheme pathway. This study offers a transformative paradigm for the rational design of S-scheme heterojunctions with tailored redox capabilities for advanced environmental remediation.
✓ 已验证
产品关联
DOI
高影响因子
Drug Design Development and Therapy
·
2026
·
IF 6.1
Ruibin Li,Shiqi Jiang,Yan Chen,Peiqi Wang,Haoxin Fu,Jun Wu,Wenzhi Wu
Background Ilaprazole is a novel proton pump inhibitor (PPI) approved orally in China and Korea for the treatment of gastric ulcers, duodenal ulcers (DU) and erosive esophagitis. It is mainly metabolized to ilaprazole sulfone by CYP3A4.Methods The quantitative determination method of ilaprazole and its metabolite ilaprazole sulfone was optimized and fully validated by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). In addition, the effect of apatinib on ilaprazole and its metabolite ilaprazole sulfone was evaluated by in vitro and in vivo experiments using rat liver microsomes (RLM), human liver microsomes (HLM), molecular docking and Sprague-Dawley (SD) rats.Results The results of bioanalytical methodology showed that ilaprazole and ilaprazole sulfone had good linear relationship in plasma samples, and their selectivity, accuracy, precision, stability, matrix effect, recovery, carry-over, dilution integrity and re-injection reproducibility all met the needs of quantitative analysis of samples. In vitro, apatinib inhibited the metabolism of ilaprazole with half-maximum inhibitory concentration (IC50) values of 1.60 and 16.28 μM in RLM and HLM, respectively, and was a mixed inhibitor (non-competitive + competitive) in both systems. In addition, in both systems, the metabolic stability results indicated that apatinib inhibited the metabolism of ilaprazole. In vivo, under the action of apatinib, the AUC(0-t), AUC(0-∞), Cmax of ilaprazole and the AUC(0-t), AUC(0-∞), t1/2, Cmax of its metabolite ilaprazole sulfone were all significantly increased, while the CLz/F of both were significantly decreased. In vitro and in vivo studies showed that apatinib inhibited the metabolism of ilaprazole. Finally, molecular docking was performed as a supportive visualization tool and suggested possible spatial overlap within the CYP3A4 active site.Conclusion In vitro systems and SD rats, apatinib exhibited an inhibitory effect on the metabolism of ilaprazole. In addition, molecular docking provided structural context for the observed interaction. However, whether the same phenomenon exists in humans remains to be further investigated.
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Meizhu Wu,Yuting Zhou,Zhi Guo,Dawei Lian,Hong Chen,Renfeng Li,Jing Lin,Farman Ali,Aling Shen,Jun Peng
Isoliensinine, a bioactive alkaloid derived from Nelumbo nucifera Gaertn , has antihypertension effects. This study investigated its antihypertensive effect and molecular mechanism. Spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (n=6 per group) were treated with 2.5, 5 or 10 mg/kg isoliensinine or 7 mg/kg valsartan for 10 weeks. Ultrasonography, histology, immunohistochemistry, RNA-sequencing analysis, vascular tension, calcium imaging, and virtual docking were performed. Isoliensinine effectively attenuated the elevation of blood pressure, pulse wave velocity, and medial thickness of the abdominal aortas in SHRs. It reversed 253-upregulated and 161-downregulated differentially expressed transcripts in the abdominal aorta of SHRs, with enrichment in vascular smooth muscle contraction and calcium signaling pathways. Isoliensinine significantly attenuated the vasoconstriction induced by angiotensin II (Ang II), norepinephrine (NE), or potassium chloride (KCl) and maintained its inhibitory effects across increasing calcium concentrations. It promotes vasodilation in the abdominal aorta rings induced by NE or KCl independent of the endothelium and potassium ion channels but is associated with the modulation of L-type calcium channels. Isoliensinine also suppressed calcium release in vascular smooth muscle cells after KCl, Ang II, or NE stimulation. Isoliensinine upregulated the expression of MLCP but downregulated that of p-MLC2 in the abdominal aorta of SHRs. Virtual docking analysis revealed lower binding energy values for isoliensinine with MLCP, suggesting a potential interaction. Isoliensinine lowers blood pressure by regulating vascular smooth muscle contraction and relaxation, and its effects are potentially mediated by regulating calcium signaling pathways.
研究领域:
药理学
·
心血管生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 8
·950
·
IF 5.5
Wei Liu,Meihui Zhang,Huiyuan Lv,Chuanxu Yang
Background : Lipid nanoparticles (LNPs) represent one of the most effective non-viral vectors for nucleic acid delivery and have demonstrated clinical success in siRNA therapies and mRNA vaccines. While considerable research has focused on optimizing ionizable lipids and helper lipids, the impact of PEGylated lipid content on LNP-mediated mRNA delivery, especially in terms of in vitro transfection efficiency and in vivo performance, remains insufficiently understood. Methods : In this study, LNPs were formulated using a self-synthesized ionizable lipid and varying molar ratios of DMG-PEG2000. Nanoparticles were prepared via nanoprecipitation, and their physicochemical properties, mRNA encapsulation efficiency, cellular uptake, and transfection efficiency were evaluated in HeLa and DC2.4 cells. In vivo delivery efficiency and organ distribution were assessed in mice following intravenous administration. Results : The PEGylated lipid content exerted a significant influence on both the in vitro and in vivo performance of LNPs. A bell-shaped relationship between PEG content and transfection efficiency was observed: 1.5% DMG-PEG2000 yielded optimal mRNA transfection in vitro, while 5% DMG-PEG2000 resulted in the highest transgene expression in vivo. This discrepancy in optimal PEG content may be attributed to the trade-off between cellular uptake and systemic circulation: lower PEG levels enhance cellular internalization, whereas higher PEG levels improve stability and in vivo bioavailability at the expense of cellular entry. Furthermore, varying the PEG-lipid content enabled the partial modulation of organ distribution, offering a formulation-based strategy to influence biodistribution without altering the ionizable lipid structure. Conclusions : This study highlights the critical role of PEGylated lipid content in balancing nanoparticle stability, cellular uptake, and in vivo delivery performance. Our findings provide valuable mechanistic insights and suggest a straightforward formulation-based strategy to optimize LNP/mRNA systems for therapeutic applications.
研究领域:
药学
·
纳米技术
·
基因递送
·
生物医学工程
·
RNA治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pathogens
·
2025
·Vol. 14
·期 10
·1069
·
IF 3.3
Xianqi Peng,Xialian Bu,Weisong Ma,Jinbiao Jiao,Xiaohong Huang,Yu Zhao,Jian Zhu,Lei Huang,Jing Chen,A’qin Zheng,Huantao Qu,Jiayun Yao
White spot disease, caused by the parasiticIchthyophthirius multifiliis, induces mortality exceeding 80% in intensive aquaculture systems, resulting in global annual losses of >$1 billion. Current chemical controls (e.g., formaldehyde) face environmental persistence and drug resistance challenges. This study developed a synthetic isoquinoline derivative, BHTCA (s)-2-tert-butoxycarbonyl-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid), as a biodegradable alternative againstI. multifiliisin grass carp (Ctenopharyngodon idella). In vitro assays revealed stage-selective efficacy: theronts exhibited higher susceptibility (EC50= 0.10 mg/L at 4 h) than tomonts (EC50= 0.40 mg/L at 24 h), with BHTCA disrupting ciliary structures and compromising cyst integrity. In vivo trials (0.6 mg/L) reduced parasite loads by 78.1% and host mortality by 66.7% versus untreated controls. Acute toxicity tests confirmed a high therapeutic index (LC50= 16.75 mg/L; >167× effective concentration). With demonstrated efficacy, low production cost, and minimal eco-toxicity, BHTCA presents a sustainable strategy for Ichthyophthiriasis management in aquaculture.
✓ 已验证
DOI
PubMed
高影响因子
APPLIED CATALYSIS B-ENVIRONMENTAL
·
2025
·
IF 21.1
Teng Zong,Ming Tian,Chaojie Wang,Nanxin Wang,Jiachen Yang,Lin Li,Yujia Han,Xiaodong Wang
It is of great significance but challenge to achieve superior H 2 O splitting performance by tailoring active sites in novel Fe-based mixed oxides in order to boost H 2 O activation to achieve the oxidation of metallic Fe to Fe 3+ back into parent substrate rather than thermodynamically more favourable Fe 2+ (Fe-O v ) usually exhibiting low H 2 O activation in chemical looping water splitting (CLWS). Herein, we for the first time reported the performance of Ga-doped garnets (Y 3 Fe 2 Ga x Al 3-x O 12 abbreviated as YF 2 G x Al 3-x , x = 1 and 2) for CLWS which surpassed most of the state-of-the-art Fe-based oxides by virtue of marvelous peak H 2 production rate of 195.3 mL min −1 g −1 , H 2 productivity of 60.7 mL g −1 , 100 % H 2 purity and outstanding redox stability for YF 2 G 2 A 1 . It was clarified that Ga doping led to the formation of an interface with Fe 0 and Ga δ+ -O v in garnets, which synergistically improved H 2 O dissociation, leading to the direct oxidation of Fe 0 to Fe 3+ back into garnets and thus accounting for its prominent performance.
研究领域:
材料科学
·
能源化学
·
无机化学
·
催化化学
·
清洁能源技术
✓ 已验证
产品关联
DOI
高影响因子
FOOD HYDROCOLLOIDS
·
2025
·
IF 12.4
Wenxin Ma,Fangling Du,Tongcheng Xu,Xiuxiu Wang,Baorui Li,Hao Yue,Min Jia,Aizhen Zong
Baicalin, a flavonoid compound with various health benefits, faces significant limitations in its application due to poor solubility. Identifying a nontoxic, biodegradable, and readily available solubilizer is therefore critical for improving the solubility of baicalin and related analogues. This study aimed to evaluate the potential of citrus pectin and its acid-hydrolyzed derivatives to improve baicalin solubility, elucidating the underlying mechanisms of solubilization. Three fractions, MCP-1, MCP-2, and MCP-3, were obtained via partial acid hydrolysis followed by anion exchange chromatography. The results demonstrated that MCP-3, composed of 91.2 % galacturonic acid and 8.8 % rhamnose, exhibited the highest efficacy in enhancing baicalin solubility. Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermodynamic, molecular dynamics (MD) simulation confirmed that MCP-3 adopted a helical structure in solution, encapsulating baicalin within its helical cavity through hydrogen bonding between carboxyl and hydroxyl groups, as well as hydrophobic interactions and van der Waals forces. The MCP-3/baicalin complex exhibited good pH and temperature stability. Pharmacokinetic studies demonstrated that MCP-3 significantly enhanced the in vivo bioavailability of baicalin by 1.95-fold, and the complex exhibited low cytotoxicity. This study offers a promising strategy for the development of more effective flavonoid-based products.
研究领域:
药剂学
·
药物代谢
·
天然产物化学
·
生物药剂学
·
计算药理学
·
材料科学
·
中医药学
✓ 已验证
产品关联
DOI
高影响因子
Food Bioscience
·
2026
·
IF 5.9
Mohammad Imtiyaj Khan,Monika Kumari,Hidam Bishworjit Singh,Danni Zhang
Betalainic plants accumulate biosynthetically related betacyanins such as betanidin, betanin (betanidn-5- O -glucoside), and amaranthin [betanidin-5- O -(2′- O -glucuronyl)-glucoside]. In such plants, these pigments are involved in stress tolerance and other physiological roles. These pigments are pharmacoactive and also used as food colorants, smart indicators in packaging films, and others. Herein, we investigated the effects of incremental substitution in their structures using density functional theory (DFT), in vitro antioxidant activity, cytotoxicity, and seedlings of Brassica campestris L., which is a betalain-devoid crop plant. The results showed betanin’s better electron-donating potential, amaranthin’s better in vitro antioxidant activity, and synergistic in vitro cytotoxic effect of all the three above-mentioned betacyanins. Individual betacyanins or in combinations of two of them were not cytotoxic. Betanin (50 mmol/L) produced comparable growth-promoting effect with 24-epibrassinolide (EBR; 10 μmol/L), a brassinosteroid. EBR and betanin did not affect total chlorophylls, but amaranthin enhanced them. Betanin enhanced tyrosine and ascorbic acid in B. campestris seedlings. Amaranthin neither produced a significant growth-promoting effect nor a comparable tyrosine-enhancing effect with betanin. Taken together, our findings establish that betanin is a physiologically more effective compound in planta , particularly in betalain-devoid B. campestris . Considering the importance of tyrosine and ascorbic acid in our diet and betanin’s ability to enhance them in B. campestris , pre-harvest treatment with betanin or betanin-containing formulations may be recommended to enhance the nutritional quality.
✓ 已验证
产品关联
DOI
高影响因子
DRUG AND CHEMICAL TOXICOLOGY
·
2026
·
IF 1.9
Wenxin Wang,Shuhua Xi,Yue Wang
N-nitrosodimethylamine (NDMA), as a disinfection by-product of drinking water, has been detected in various water. Epidemiological investigations have found that exposure to NDMA can exacerbate the development of diseases related to insulin resistance. In this study, male C57BL/6 mice were exposed to 0.5 and 12.5 mg/L NDMA by drinking water for 12 weeks. The mice in 12.5 mg/L NDMA group appeared fasting blood glucose elevation, and glucose tolerance and insulin sensitivity decreased. NDMA exposure enhanced hepatic gluconeogenesis and suppressed glycolysis of mice, but not affecting glycogen synthesis. In addition, NDMA exposure inhibited the phosphorylation of AMPK and FoxO1 as well as GLUT2 protein expression, and increased PGC-1α protein levels. GLUT2 protein decreasing could reduce glucose uptake of hepatocyte and enhance blood glucose concentration. Dephosphorylated FoxO1 might translocate to the nucleus, binding promoters of gluconeogenesis key enzymes PEPCK and G6Pase to upregulate their expression and promote gluconeogenesis. PGC-1α could also stimulate the expression of PEPCK and G6Pase. Furthermore, human normal liver cells (MIHA) were treated with NDMA for 24 hours. AMPK as a central energy sensor, regulates hepatic glucose production, uptake, and the process of glycolmetabolism. Therefore, AMPK agonist AICAR was used to explore the mechanism of NDMA causing hyperglycemia. AICAR reversed p-FoxO1, PGC-1α, GLUT2, PEPCK and G6Pase proteins expression and improved the glycolysis and glucose uptake capacity in NDMA treated MIHA cells. In conclusion, NDMA in drinking water led to fasting blood glucose enhancing, impairment of glucose tolerance and insulin sensitivity, increasing hepatic gluconeogenesis via AMPK signaling.
✓ 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）