Frontiers in Behavioral Neuroscience
·
2021
·
IF 3.558
Yin Ying,Qian Shiyu,Chen Yifan,Sun Yan,Li Yuqiao,Yu Yongfei,Li Jianqing,Wu Zhangjie,Yu Xinlang,Ge Rui,Han Jia,Sun Dongdong,Wu Haoxin,Liu Lanying,Xue Wenda,Wang Wei
Previous studies have demonstrated that Yueju-Ganmaidazao (YG) decoction induces rapid antidepressant-like effects, and the antidepressant response is mostly dependent on the suppression of nitric oxide-cyclic guanosine monophosphate signaling in male mice. This study aimed to investigate the sex difference mediated by calcium/calmodulin-dependent protein kinase II (CaMKII)-neuronal nitric oxide synthase (nNOS) signaling involved in the antidepressant-like effect of YG in mice. We found that the immobility times in the tail suspension test (TST) were found to be decreased after the single injection of YG in male and female mice with the same dosage. Additionally, chronic administration for 4 days of subthreshold dosage of YG and escitalopram (ES) also significantly decreased the immobility time in mice of both sexes. Chronic subthreshold dosage of YG and ES in LPS-treated mice and in chronic unpredictable stress (CUS) mice both decreased the immobility time, which was increased by stress. Meanwhile, in CUS-treated mice, sucrose preference test, forced swimming test, and open field test were applied to further confirm the antidepressant-like effects of YG and ES. Moreover, CUS significantly decreased the expression of nNOS and CaMKII, and both YG and ES could enhance the expression in the hippocampus of female mice, which was opposite to that in male mice, while endothelial nitric oxide synthase expression was not affected by stress or drug treatment neither in male mice nor in female mice. Finally, subthreshold dosage of YG combined with 7-nitroindazole (nNOS inhibitor) induced the antidepressant-like effects both in female and in male mice, while the single use of YG or 7-NI did not display any effect. However, pretreatment with KN-93 (CaMKII inhibitor) only blocked the antidepressant-like effect of high-dosage YG in female mice. Meanwhile, in CUS mice, chronic stress caused NR1 overexpression and inhibited cAMP response element binding protein action, which were both reversed by YG and ES in male and female mice, implying that YG and ES produced the same antidepressant-like effect in mice of both sexes. The study revealed that chronic treatment with a subthreshold dose of YG also produced antidepressant-like effects in female mice, and these effects depended on the regulation of the CaMKII-nNOS signaling pathway.
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Biomed Research International
·
2016
·
IF 2.134
Gai Xue,Xiaolei Han,Xin Ma,Honghai Wu,Yabin Qin,Jianfang Liu,Yuqin Hu,Yang Hong,Yanning Hou
Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are considered to be an ideal cell source for cell therapy of many diseases. The aim of this study was to investigate the contribution of the microenvironment to the hepatic differentiation potential of hUCMSCs in vitro and in vivo and to explore their therapeutic use in acute liver injury in rats. We established a new model to simulate the liver tissue microenvironment in vivo using liver homogenate supernatant (LHS) in vitro. This induced environment could drive hUCMSCs to differentiate into hepatocyte-like cells within 7 days. The differentiated cells expressed hepatocyte-specific markers and demonstrated hepatocellular functions. We also injected hUCMSCs into rats with CCl4-induced acute hepatic injury. The hUCMSCs were detected in the livers of recipient rats and expressed the human hepatocyte-specific markers, suggesting that hUCMSCs could differentiate into hepatocyte-like cells in vivo in the liver tissue microenvironment. Levels of biochemistry markers improved significantly after transplantation of hUCMSCs compared with the nontransplantation group (). In conclusion, this study demonstrated that the liver tissue microenvironment may contribute to the differentiation of hUCMSCs into hepatocytes both in vitro and in vivo.
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Evidence-based Complementary and Alternative Medicine
·
2022
·
IF 2.65
Haijun Gao,Yan Zhang,Xiaojin Mo,Lele Huo,Yanping Luo,Ting Zhang,Xingming Ma,Wei Hu,Tao Jing
Background. Liver cancer, particularly hepatocellular carcinoma (HCC), is the fourth leading cause of cancer-related death worldwide. Sorafenib is a crucial drug for the treatment of advanced HCC, but it is difficult to meet the challenge of increasing clinical demands due to its severe side effects and drug resistance. Hence, development of novel antitumor drugs is urged. Previous studies showed that pseudolaric acid B (PAB) could reduce the expression of protein kinase B (PKB/Akt), a downstream effector of Notch signaling, facilitating cell apoptosis in HCC. The disruption of Notch signaling was verified to exacerbate malignant progression and drug resistance, however, the antitumor effect of PAB on Notch signaling in HCC remains unclear. Thus, this study aims to investigate the anti-HCC effect of PAB in association with the regulation of Notch1/Akt signaling. Methods. CCK-8 assay and transwell assay were used to examine the cell proliferation and invasion in Huh7 cells after treatment with PAB and a Notch inhibitor DAPT. Moreover, the cell cycle of Huh7 cells after treatment with PAB was analyzed using flow cytometry. Finally, the changes of Notch1, Jagged1, Hes1, and Akt expression at the protein and mRNA level in Notch1/Akt signaling in Huh7 cells after treatment with PAB and DAPT were analyzed using immunofluorescence assay and real-time qPCR. Results. The proliferation rate of Huh7 cells exposed to PAB of 0.5, 1, 2, 4, 8, 10, 20, 40, 80, 100, and 200 μmol/L revealed a time-and dose-dependent decrease in vitro, showing cell cycle arrest at G2/M phase . Furthermore, compared with the untreated group, at the concentration of 40 μmol/L, the proliferation rate and invasion rate of Huh7 cells in PAB, DAPT, and PAB-DAPT combination (PAB + DAPT) group were significantly decreased , but the PAB + DAPT showed no synergistic antiproliferation and anti-invasion effect in comparison with PAB treatment alone . In addition, compared with the untreated group, PAB and DAPT alone significantly downregulated the expression of Notch1, Jagged1, Hes1, Akt mRNA, or/and protein in Huh7 cells , but there was no significant difference in synergistic downregulated effect between the PAB + DAPT group and the PAB group . Conclusion. PAB can suppress proliferation and invasion of HCC cells through downregulating the expression of Notch1/Akt signaling protein and mRNA, and may be a potential novel antitumor drug candidate for the clinical treatment of HCC in the future.
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Molecular Medicine Reports
·
2021
·Vol. 23
·期 3
·1-1
·
IF 2.952
Zhen Xiong,Jiali Xu,Xin Liu
Oxymatrine (OMT) is the primary active component of Sophora flavescens Ait., and is widely used for the treatment of diabetic complications. The present study aimed to investigate the effects of OMT on acute lung injury (ALI) in diabetic rats subjected to myocardial ischemia/reperfusion (I/R). ALI in a myocardial I/R model was established in streptozocin‑induced diabetic rats. Enzyme‑linked immunosorbent assays were used to evaluate the levels of creatine kinase isoenzyme MB and lactate dehydrogenase, and the inflammatory response was assessed via leukocyte counts and the levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑8 in the bronchoalveolar lavage (BAL) fluid. Hematoxylin and eosin staining was used to determine pathological changes to the lung tissue, and the autophagy‑related proteins LC‑3II/LC‑3I, Beclin‑1, autophagy protein 5 (Atg5) and p62 were detected by western blotting. Diabetic rats subjected to myocardial I/R showed increased levels of ALI with a higher lung injury score and WET/DRY ratio, and lower partial pressure of oxygen. This was accompanied by aberrant autophagy, indicated by an increased LC‑3II/LC‑3I ratio, decreased p62 expression levels, increased Atg5 and beclin‑1 expression levels, decreased superoxide dismutase activity and increased 15‑F2t‑isoprostane formation in lung tissues, as well as increased levels of leukocytes, TNF‑α, IL‑6 and IL‑8 in the BAL fluid. Administration of the autophagy inducer rapamycin significantly accelerated these alterations, while the autophagy inhibitor 3‑Methyladenine exerted the opposite effects. These results indicated that diabetic lungs are more vulnerable to myocardial I/R, which was associated with aberrant autophagy. Furthermore, oxymatrine was observed to reverse and alleviate ALI in diabetic rats with myocardial I/R in a concentration‑dependent manner, the mechanism of which may be associated with the inhibition of autophagy.
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BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2015
·Vol. 38
·期 8
·1142-1149
·
IF 1.828
Kexin Wang,Yu Sun,Peng Lin,Jun Song,Ruxing Zhao,Wenjuan Li,Xinguo Hou,Chuan Wang,Lingshu Wang,Ping Zhu,Li Chen
β-Cell insufficiency plays an important role in the development of diabetes. Environmental factors, including lifestyle, play a critical role in β-cell dysfunction. Modern lifestyles affect the inherent circadian clock in central and peripheral organs. Recent studies have demonstrated that the normal intrinsic circadian clock in islets was essential for the viability of β cells and their insulin secretory function. Overall, however, the data are inconclusive. Our study demonstrated that the disrupted circadian rhythm of islets in streptozotocin induced type1 diabetic mice may be associated with impaired β-cell function and glucose intolerance. Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, could partially restore the normal circadian rhythm and activate the 5′ AMP-activated protein kinase (AMPK) signaling pathway. Our study provided evidence demonstrating that Liraglutide might restore β-cell function and protect against the development of diabetes in a mouse model by attenuating the disruption of the intrinsic circadian rhythm in islets and by activating AMPK signaling.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
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2021
·
IF 4.219
Long Ma,Yingying Lu,Yaqin Li,Zhizhen Yang,Yu Mao,Yi Wang,Shuli Man
Adenosine, as a naturally occurring nucleoside , plays an important role in human health maintenance. In recent years, many studies have shown that adenosine has the effect of cancer inhibition, and some of its analogs have been successfully marketed as anticancer drugs . This report mainly describes the anti-colon cancer activities and mechanism of a novel halogenated adenosine analog named 5′-bromodeoxyadenosine (5’-BrDA). As a result, 5’-BrDA concentration-dependently inhibited colon cancer cells proliferation , induced autophagy without disruption of lysosomal stability, and promoted autophagy-independently cellular mitochondrial apoptosis by increasing the accumulation of reactive oxygen species . Furthermore, 5’-BrDA inhibited the tumor growth of colon cancer in CT26 inbred mice without affecting the body weight in vivo . Collectively, the above-mentioned mechanisms contributed to the anticancer activity of 5’-BrDA. It is rare to discover novel anticancer adenosine analogs during the past couple of decades. We believe that our work will enrich the understanding of adenosine analogs, also, pave the way for adenosine analogs product based anticancer drug development.
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AMB Express
·
2022
·Vol. 12
·期 1
·1-15
·
IF 4.126
Liu Shasha,She Pengfei,Li Zehao,Li Yimin,Yang Yifan,Li Linhui,Zhou Linying,Wu Yong
According to a 2019 report from the Centers of Disease Control and Prevention (CDC), methicillin-resistant Staphylococcus aureus (MRSA) was listed as one of the “serious threats” that had become a global public challenge in hospitals and community. Biofilm-associated infections and refractory persisters of S. aureus also impede the effectiveness of conventional antibiotics that have greatly increased difficulty in clinical therapy. There is an urgent need to develop new antimicrobials with antibiofilm and anti-persister capacities, and drug repurposing is the most effective and most economical solution to the problem. The present study profiles the antimicrobial activity of ceritinib, a tyrosine kinase inhibitor, against S. aureus in vitro and in vivo. We investigated the antimicrobial efficacy of ceritinib against planktonic and persistent S. aureus by a time-killing kinetics assay. Then, antibiofilm effect of ceritinib was assessed by crystal violet staining and laser confocal microscope observation. Ceritinib showed biofilm inhibition and mature biofilm eradication, and possesses robust bactericidal activity against S. aureus persisters. We also evaluated antimicrobial efficacy in vivo using a subcutaneous abscess infection model. Ceritinib ameliorated infection in a subcutaneous abscess mouse model and only showed negligible systemic toxicity in vivo. Mechanism exploration was conducted by transmission electron microscopy, fluorescently labeled giant unilamellar vesicle assays, and a series of fluorescent dyes. In conclusion, we find ceritinib represents potential bactericidal activity against MRSA by disrupting cell membrane integrity and inducing reactive oxygen species production, suggesting ceritinib has the potential to treat MRSA-related infections.
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JOURNAL OF FOOD ENGINEERING
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2021
·
IF 5.354
Anlei Ge,Shahid Iqbal,Xiao Dong Chen
In this study, three different types of O/W emulsions were prepared by dispersing 20 wt% soybean oil in aqueous continuous phases, consisting 4 wt % SPI and 0.5 wt% polysaccharide (pectin, iota carrageenan , or kappa carrageenan) composition. The emulsions were heated to thermal denaturation temperature of SPI (90 °C, 30 min), and their rheology, microstructure, and particle size was deeply examined and compared with unheated systems. The results showed that the shear stress, viscosity, shear modulus, and the droplet size of heated emulsions were higher than those of unheated systems. This behavior suggested that thermal treatment exposes the positively charged and hydrophobic regions of SPI in acidic medium (pH 4), which allowed to attach the anionic polysaccharide strongly by electrostatic and hydrophobic interactions, especially in SPI-kappa carrageenan emulsion. This study may be useful for the creation of highly viscous O/W products having higher rheology and stability, but reduced total fat contents.
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Current Computer-Aided Drug Design
·
2023
·Vol. 21
·期 1
·50-66
·
IF 1.7
Hongyi Liang,Guoliang Yin,Guangxi Shi,Xiaofei Liu,Zhiyong Liu,Jingwei Li
AimsBreast cancer (BC) is by far seen as the most common malignancy globally, with 2.261 million patients newly diagnosed, accounting for 11.7% of all cancer patients, according to the Global Cancer Statistics Report (2020). The luminal A subtype accounts for at least half of all BC diagnoses. According to TCM theory, Bushen Huoxue Decoction (BSHXD) is a prescription used for cancer treatment that may influence luminal A subtype breast cancer (LASBC).ObjectivesTo analyze the clinical efficacy and underlying mechanisms of BSHXD in LASBC.Materials and MethodsNetwork pharmacology and in vitro experiments were utilized to foresee the underlying mechanism of BSHXD for LASBC.ResultsAccording to the bioinformatics analysis, BSHXD induced several proliferation and apoptosis processes against LASBC, and the presumed targets of active components in BSHXD were mainly enriched in the HIF-1 and PI3K/AKT pathways. Flow cytometry assay and western blotting results revealed that the rate of apoptosis enhanced in a dose-dependent manner with BSHXD concentration increasing, respectively. BSHXD notably downregulated the expressions of HIF-1α, P-PI3K, PI3K, P-AKT and AKT proteins. However, adding an HIF-1α agonist restored those protein levels.ConclusionThe study proved that the mechanism of BSHXD in LASBC may be connected to suppressing proliferation by inhibiting the activity of the HIF-1α/PI3K/AKT signaling pathway and promoting apoptosis via the Caspase cascade in LASBC cells.
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FOOD CHEMISTRY
·
2019
·
IF 5.399
Shen-Zhi Wang,Hui-Qian Dai,Ke-Xian Chen,Juan Li,Zhong-Xiu Chen
Control of lipid digestibility by various food components has received great attention in recent decades. However, there is limited literature on investigating the synergistic effect of exogenous emulsifiers and endogenous sodium cholate (SC) on lipid digestion in a simulated physiological crowded medium. In this work, the synergistic interaction of Tween80 and SC according to the regular solution theory, and the hydrolysis of lipid emulsions containing tricaprylin, glyceryltrioleate or soybean oil in crowding medium was studied. The results show that emulsions stabilized by a combination of Tween80 and SC showed higher digestion rate and transformation than those with Tween80 or SC. The digestion rate could be increased by polyethylene glycols (PEGn) with varying crowding degree. The denaturation temperature of the lipase was increased in macromolecular crowded medium. This work allows for better understanding of the interaction between the amphiphiles and the macromolecular crowding effect on lipase digestion in the physiological environment.
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Environmental Systems Research
·
2024
·Vol. 13
·期 1
·1-10
·
IF 0
Du Hairong,Zhu Xiaoling,Yao Yunying,Yao Wei
Neonicotinoid insecticides (NNIs), as a new type of insecticide, are widely used in agriculture and daily life. Because of the low volatility of NNIs, few studies have evaluated them in atmospheric particulate matter. In this study, 101 outdoor PM 2.5 samples were collected from the Wuhan urban area from 2019 to 2021, leading to the detection of seven NNIs and three of their metabolites. The detection frequencies of all 10 substances were more than 60%, with DIN (dinotefuran) and IMI (imidacloprid) reaching 100%. DIN (52.4 pg/m 3 ) and IMI (43.0 pg/m 3 ) had higher median concentrations than other substances. Concentration distributions of the four substances ACE (acetamiprid), DIN, IMI, and 5-OH-IMI (5-Hydro-Imidacloprid) exhibited statistically significant differences ( P < 0.05) across the four seasons. Concentration levels of ACE, CLO (clothianidin), and IMI were statistically different between the three years ( P < 0.05). The median concentration of imidacloprid-equivalent total neonicotinoids (IMIeq: generated by the relative potency factor method) was 256.1 pg/m 3 . Finally, the estimated daily intake (EDI) of NNIs via respiration was greater in infants and young children than in the rest of the population, suggesting that infants and young children were more likely to be exposed to the health effects of airborne residual PM 2.5 .
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Nature Communications
·
2024
·Vol. 15
·期 1
·1-11
·
IF 14.7
Feng Chao,Liu Zhi,Ju Huanxin,Mavrič Andraž,Valant Matjaz,Fu Jie,Zhang Beibei,Li Yanbo
The buried interface tens of nanometers beneath the solid-liquid junction is crucial for photocarrier extraction, influencing the overall efficiency of photoelectrochemical devices. Precise characterization of the interfacial properties is essential for device optimization but remains challenging. Here, we directly probe the in situ transformation of a Cu x O interlayer at the NiO/n-Si interface by hard X-ray photoelectron spectroscopy. It is found that Cu(I) in the Cu x O interlayer gradually transforms to Cu(II) with air exposure, forming an energetically more favorable interface and improving photoanode’s efficiency. Based on this finding, a reactive e-beam evaporation process is developed for the direct deposition of a CuO interlayer, achieving a half-cell solar-to-hydrogen efficiency of 4.56% for the optimized NiO/CuO/n-Si heterojunction photoanode. Our results highlight the importance of precision characterization of interfacial properties with advanced hard X-ray photoelectron spectroscopy in guiding the design of efficient solar water-splitting devices.
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