FISH PHYSIOLOGY AND BIOCHEMISTRY
·
2023
·
IF 2.9
Pan En-Zhuang,Xin Yue,Li Xue-Qing,Wu Xin-Yu,Tan Xue-Lian,Dong Jing-Quan
The aim of this study was to investigate the splenic tissue damage of environmental biological drug avermectin to freshwater cultured carp and to evaluate the effect of silybin on the splenic tissue damage of carp induced by avermectin. A total of 60 carp were divided into 4 groups with 15 carp in each group, including the control group fed with basic diet, experimental group fed with basal diet and exposed to avermectin (avermectin group), experimental group fed with basal diet supplement silybin (silybin group), and experimental group fed with basal diet supplement silybin and exposed to avermectin (silybin + avermectin group). The whole test period lasted for 30 days, and spleen tissue was collected for analysis. In this study, H&E staining, mitochondrial purification and membrane potential detection, ATP detection, DHE staining, biochemical tests, qPCR, immunohistochemistry, and apoptosis staining were used to evaluate the biological processes of spleen tissue injury, mitochondrial function, oxidative stress, apoptosis, and endoplasmic reticulum stress. The results show that silybin protected carp splenic tissue damage caused by chronic avermectin exposure, decreased mitochondrial membrane potential, decreased ATP content, ROS accumulation, oxidative stress, apoptosis, and endoplasmic reticulum stress. Silybin may ameliorate the splenic tissue damage of cultured freshwater carp caused by environmental biopesticide avermectin by alleviating mitochondrial dysfunction and inhibiting PERK-ATF4-CHOP-driven mitochondrial apoptosis. Adding silybin into the diet becomes a feasible strategy to resist the pollution of avermectin and provides a theoretical basis for creating a good living environment for freshwater carp. Graphical Abstract
研究领域:
水产养殖
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毒理学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Chao Liu,Yuhao Jiang,Wenliang Xue,Jinyu Liu,Zihao Wang,Jianhong Luo,Xinsong Li
Lipid nanoparticles (LNP) have shown great promise in clinical applications for delivering mRNA. Targeted delivery of mRNA to particular tissues or organs is essential for precise therapeutic outcomes and minimized side effects in various disease models. However, achieving targeted delivery beyond the liver is a challenge based on current LNP formulations. In this report, we synthesized four ionizable cholesterol analogs by attaching two tertiary amine groups onto the head of a cholesterol-like structure and incorporated them as a fifth component into conventional commercial LNPs based on ALC-0315 or SM-102. Selective targeting delivery of mRNA is achieved by adjusting the proportion of the fifth component in the LNP. Specifically, a spleen-targeted 0315-Ergo-40% formulation demonstrated an impressive 95% delivery efficiency, while a lung-targeted 102-Sito-40% formulation achieved up to 78%. Moreover, when this strategy is applied to a self-developed ionizable lipid named U-101 instead of ALC-0315 or SM-102, the targeting delivery efficiencies to the spleen and lungs reach 96 and 71%, respectively. Multiple assessments suggest that inclusion of the fifth component does not compromise LNP stability, as indicated by consistent particle size, polydispersity index (PDI), and encapsulation efficiency. Furthermore, the test results of liver and kidney function and immunogenicity reveal no increase of toxicity in vivo following the introduction of the fifth component. Additional studies on in vitro cytotoxicity, lysosomal escape, and cellular transfection efficiency confirm that the fifth component does not diminish delivery performance. Taken together, the incorporation of ionizable cholesterol analogs leads to targeting of LNP delivery, which features strong organ selectivity, high safety, and suitability for further evaluation.
研究领域:
纳米技术
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药学科学
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分子生物学
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治疗学
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Qiang Li,Linmao Ke,Dandan Yu,Han Xu,Zixuan Zhang,Rilei Yu,Tao Jiang,Yue-Wei Guo,Mingzhi Su,Xin Jin
Mitogen-activated protein kinase-interacting protein kinases (MNKs) and phosphorylate eukaryotic initiation factor 4E (p-eIF4E) play a critical role in regulating mRNA translation and protein synthesis associated with the development of cancer, metabolism, and inflammation. This study undertakes the modification of a 4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)pyridine structure, leading to the discovery of 4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)-1H-pyrrolo[2,3-b]pyridine (D25) as a potent and selective MNK inhibitor. D25 demonstrated inhibitory activity, with IC50 values of 120.6 nM for MNK1 and 134.7 nM for MNK2, showing exceptional selectivity. D25 inhibited the expression of pro-inflammation cytokines in RAW264.7 cells, such as inducible NO synthase, cyclooxygenase-2, and interleukin-6 (IL-6). In the lipopolysaccharide-induced sepsis mouse model, D25 significantly reduced p-eIF4E in spleen tissue and decreased the expression of tumor necrosis factor α, interleukin-1β, and IL-6, and it also reduced the production of reactive oxygen species, resulting in improved organ injury caused by inflammation. This suggests that D25 may provide a potential treatment for sepsis and sepsis-associated acute spleen injury.
研究领域:
药理学
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免疫学
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传染病
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2020
·
IF 3.004
Li Huang,Mingzhu Ye,Jiacai Wu,Wuping Liu,Hongyuan Chen,Wen Rui
Honey-processed Astragalus is a dosage form of radix Astragali processed with honey, which is deemed to contain better qi-tonifying effects in traditional Chinese medicine theroy. Our previous study has demonstrated that honey-processed Astragalus exhibited a better effect on reinforcing qi (vital energy) and immune improvement toward spleen qi deficiency compared with radix Astragali. However, the detailed mechanisms related to qi-tonifying effects of honey-processed Astragalus is still unclear. In this study, we evaluated the qi-tonifying effects of honey-processed Astragalus on spleen qi deficiency rats and predicted the mechanisms by aggregating metabonomics, lipidomics and network pharmacology. The results revealed that body weights, symptom scores, the levels of red blood cell, white blood cell, lymphocyte, spleen and thymus indexes, and three cytokines (TNF-α, IL-6, IFN-γ) in honey-processed Astragalus treated rats were improved in comparison with spleen qi deficiency rats. In parallel, based on the 26 biomarkers screened in metabonomics and lipidomics, we inferred that glycerophospholipid metabolism significantly regulated in pathway analysis was connected with qi-tonifying effects. Moreover, the network pharmacology analysis concluded that the compounds targets of honey-processed Astragalus CDK2, NOS3, MAPK14, PTGS1 and PTGS2 interacted with markers targets PLA2G(s) family and LYPLA1 could be responsible for regulation of glycerophospholipid metabolism to develop qi-tonifying effects. What’s more, the above processes were possibly through VEGF signaling and MAPK signaling pathways.
研究领域:
中医药
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药理学
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代谢组学
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脂质组学
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网络药理学
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产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
·
2019
·
IF 3.119
Liting Wu,Enxu Zhou,Along Gao,Linghe Kong,Siwei Wu,Xia Bian,Yuan Li,Bingxi Li,Shengli Fu,Zheng Guo,Jianmin Ye
B lymphocyte-induced maturation protein 1 (Blimp-1), a transcription factor containing zinc finger , is required and sufficient to trigger terminal differentiation of B cells in mammals. The Blimp-1 ( OnBlimp-1 ) from Nile tilapia ( Oreochromis niloticus ) was identified and characterized its expression pattern during B cell activation and maturation. The cDNA of OnBlimp-1 open reading frame is 2547 bp encoding a protein of 848 amino acids and the predicted molecular weight is 93.36 kDa. OnBlimp-1 contains a SET domain and five ZnF_C2H2 domains, which shares high homology with that of other species. OnBlimp-1 transcription was detected in all examined tissues with high expression in the spleen (SPL). Analysis of sorted lymphocyte populations , including IgM + and IgM − cells from peripheral blood (PBL), SPL and anterior kidney (AK), indicated that the OnBlimp-1 transcription was highly expressed in the IgM + B cells. Upon LPS stimulation, OnBlimp-1 expression was up-regulated in tissues of PBL, SPL and AK significantly. The expression of OnBlimp-1 , as well as the secreted IgM , was significantly up-regulated in the SPL and AK leukocytes stimulated with anti-OnIgM monoclonal antibody and LPS in vitro , respectively. Above results suggest that OnBlimp-1, a cytokine regulating the terminal differentiation of activated B cells to antibody-secreting cells, is likely to play important roles in B cell activation and maturation in Nile tilapia.
研究领域:
免疫学
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分子生物学
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鱼类生理学
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产品关联
DOI
PubMed
高影响因子
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2020
·Vol. 84
·期 2
·411-420
·
IF 1.516
Miao Zhonghua,Cheng Ruyue,Zhang Yujie,Liang Huijing,Jiang Fengling,Shen Xi,Chen Gong,Zhang Qisheng,He Fang,Li Ming
This study assessed whether antibiotics could alter gut microbiota to affect host growth and the possibility of alleviation by lactobacilli. We divided four-week-old BABL/c mice into control (Ctrl), antibiotic exposure (Abx), Lactobacillus plantarum PC-170 (PC), and Lactobacillus rhamnosus GG (LGG) group and the Abx, LGG, and PC group received an one-week antibiotic/antibiotic + probiotic treatment. The fecal microbiota and the expression of splenic cytokines were determined. Following the ceftriaxone treatment, the body weight gain of Abx was delayed compared with others. The ceftriaxone treatment significantly decreased the alpha-diversity of the fecal microbiota and altered the fecal microbiota but LGG and PC can partly alleviate the effect. At the end of the study, the microbial community of LGG and PC group were more similar to Ctrl compared with Abx group. The results indicated that ceftriaxone could significantly alter intestinal microbiota. Lactobacilli might alleviate the side effects of antibiotics by stabilizing the intestinal microbiota.
研究领域:
微生物学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2022
·
IF 4.622
Sheng Luo,Li-Cong Wang,Zhi-Han Shuai,Guan-Jun Yang,Jian-Fei Lu,Jiong Chen
Peptidoglycan recognition proteins (PGRPs) belong to a member of pattern-recognition receptors (PRRs), which proposed as antibacterial protein . The present study investigated the antibacterial effect of BpPGRP5 in great blue-spotted mudskipper ( Boleophthalmus pectinirostris ). BpPGRP5 transcript was detected in all tested tissues with the highest expression level in spleen , and its expression was significantly upregulated in spleen, intestine, and kidney following Aeromonas veronii infection. rBpPGRP5 was found to interact with several polysaccharides and bacteria, including Gram-negative bacteria ( Escherichia coli and A. veronii ) and Gram-positive bacteria ( Listeria monocytogenes and Staphylococcus aureus ). rBpPGRP5 inhibited the proliferation of E. coli , S. aureus , L. monocytogenes , and A. veronii in a Zn 2+ -dependent manner. Furthermore, in vivo studies revealed that intraperitoneal injection of rBpPGRP5 improved the survival rate of A. veronii -infected B. pectinirostris , accompanied by decreased bacterial load in the blood, kidney, intestine, and spleen. Taken together, our results indicated that BpPGRP5 is an antimicrobial protein that protects B. pectinirostris against bacterial infection.
研究领域:
免疫学
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微生物学
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分子生物学
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海洋生物学
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产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Enzhuang Pan,Huizhen Chen,Xinyu Wu,Nana He,Jiajie Gan,Huimiao Feng,Yong Sun,Jingquan Dong
Avermectin pollution is an important problem that cannot be ignored in aquatic system in recent years. It has brought great trouble to freshwater aquaculture, especially fishery aquaculture. Plant-derived quercetin has anti-inflammatory and antioxidant properties and is widely used as a dietary additive, but its protective effect on immune damage induced by avermectin in freshwater carp remains unclear. This study evaluated the role of dietary additive quercetin supplementation in chronic avermectin exposure of carp spleen. Sixty carp were divided into 4 groups ( n = 15/ group), including control group, avermectin treatment group, quercetin treatment group, quercetin and avermectin co-treatment group. Carp were exposed to a 1/10 96 h LC 50 dose of avermectin for 30 d and fed a carp diet containing 400 mg/kg quercetin twice a day (3% body weigh/ carp). The results showed that chronic avermectin exposure caused the loose parenchymal structure of carp spleen tissue and the increase of inflammatory cells, accompanied by increased transcription levels of pro-inflammatory il-1β , il-6 , tnf-α and decreased levels of anti-inflammatory factors il-10 and tgf-β1 , ROS accumulation in spleen tissue. MDA content increased and T-AOC, CAT and GSH levels decreased. Quercetin down-regulates the NF-κB pathway by inhibiting the expression of iNOS and activating p38 MAPK, blocking the transcription of inflammatory factors, and alleviating the inflammation of carp spleen caused by chronic avermectin exposure. In addition, quercetin inhibits the over-activation of Nrf2/Keap-1 signaling axis, blocks ROS accumulation, and restores the spleen REDOX homeostasis. In conclusion, quercetin, as a dietary additive for carp feed, can effectively improve the immune damage caused by avermectin pollution in aquatic environment, resist spleen inflammation and oxidative stress, and provide a theoretical basis for clinical development of freshwater carp feed.
研究领域:
水产养殖
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免疫学
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毒理学
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药理学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Haiyu Ni,Shuwen Xu,Pengfei Gu,Adelijiang wusiman,Yue Zhang,Tianxin Qiu,Zhenguang Liu,Han Ni,Yuanliang Hu,Jiaguo Liu,Yi Wu,Deyun Wang
This study aimed to optimize the preparation conditions for cetyltrimethylammonium bromide-modified Polygonatum sibiricum polysaccharide cubosomes (CTAB-modified PSP-Cubs) by response surface methodology (RSM). Glyceryl-monooleate (GMO) was used as the lipid base for the cubosomes. The optimal preparation conditions of CTAB-modified PSP-Cubs were as follows: the mass percentage of PSP to GMO (X 1 ), Poloxamer 407 (F127) to GMO (X 2 ) and water to GMO (X 3 ) was 1.4%, 9% and 50%, respectively. The encapsulation efficiency (EE) of CTAB-modified PSP-Cubs under the experimental conditions was 62.4 ± 3.6%, which was close to our predicted value. The particle size, polydispersity index (PDI) and zeta potential of CTAB-modified PSP-Cubs were 427.7 ± 8.0 nm , 0.236 ± 0.024 and 19.2 ± 0.4 mV, respectively. Specific modifications were able to slow down in vitro release behaviors and reduce cytotoxicity to some extent. The effects of CTAB-modified PSP-Cubs on splenic lymphocytes were also investigated. When splenic lymphocytes were treated with CTAB-modified PSP-Cubs together with LPS or PHA , the results showed more favorable effects on cellular proliferation than blank cubosomes or free PSP at certain concentrations.
研究领域:
药剂学
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免疫学
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生物技术
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产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF HAEMATOLOGY
·
2021
·Vol. 195
·期 2
·267-275
·
IF 6.998
Zaoke He,Xiaoqin Sun,Shixiang Wang,Dongsheng Bai,Xiangyu Zhao,Ying Han,Piliang Hao,Xue-Song Liu
Summary The expression of GGCT (γ-glutamyl cyclotransferase) is upregulated in various human cancers. γ-glutamyl cyclotransferase enzyme activity was originally purified from human red blood cells (RBCs), but the physiological function of GGCT in RBCs is still not clear. Here we reported that Ggct deletion in mice leads to splenomegaly and progressive anaemia phenotypes, due to elevated oxidative damage and the shortened life span of Ggct −/− RBCs. Ggct −/− RBCs have increased reactive oxygen species (ROS), and are more sensitive to H 2 O 2 -induced damage compared to control RBCs. Glutathione (GSH) and GSH synthesis precursor l -cysteine are decreased in Ggct −/− RBCs. Our study suggests a critical function of Ggct in RBC redox balance and life span maintenance through regulating GSH metabolism.
研究领域:
血液学
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分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF VETERINARY MEDICAL SCIENCE
·
2024
·
IF 1.1
Nianyuan CHEN,Qingxiu CAI,Shujing WANG,Qingyang SONG,Ying XIE,Huijuan SHI,Hongmei LI,Xiaomin ZHAO,Ningning ZHAO,Xiao ZHANG
Protozoan parasites such as Eimeria tenella and Toxoplasma gondii pose significant health challenges in livestock and humans. The limited treatment options and rising drug resistance underscore the urgent need for new therapies. This study investigates myrcene, a monoterpene hydrocarbon classified for its antiprotozoal potential against E. tenella and T. gondii infections. Initially, we examined its effect on the sporulation process of E. tenella oocysts in vitro and its anti-E. tenella activity in vivo. Myrcene significantly reduced the sporulation rate of E. tenella oocysts at 3 and 4 mg/kg. In vivo experiments demonstrated that treatment with 4 mg/kg myrcene significantly reduced E. tenella load and oocyst output, as well as cecal lesion and weight loss caused by E. tenella infection, showing moderate anti-E. tenella activity, with an Anticoccidial Index (ACI) of 161.4. Furthermore, we investigated the anti-T. gondii activity of myrcene both in vitro and in vivo. In vitro studies showed that treatment with myrcene effectively inhibited the invasion rate and intracellular proliferation ability of T. gondii tachyzoite in DF-1 cells in a dose-dependent manner. In vivo administration prolonged the survival time in T. gondii-infected mice, suggesting notable protective effects. Additionally, it mitigated T. gondii-induced hepatosplenic toxicity by reducing parasite load in the liver and spleen, and ameliorating liver function as evidenced by decreased serum transaminase levels. In conclusion, the findings demonstrate promising anti-E. tenella and anti-T. gondii activity exhibited by myrcene warranting further exploration into its mechanisms and potential therapeutic applications.
研究领域:
兽医学
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寄生虫学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Parasites & Vectors
·
2024
·Vol. 17
·期 1
·1-11
·
IF 3
Li Xin,Jiang Ning,Li Qilong,Zheng Kexin,Zhang Yiwei,Sang Xiaoyu,Feng Ying,Chen Ran,Chen Qijun
Background Artemisinin (ART) is a frontline drug for the treatment of malaria; however, the emergence of ART-resistant Plasmodium strains necessitates increasing ART sensitivity. Given that taurine (TAU) has been shown to have immunomodulatory activity, we investigated the effects of TAU as an adjunct therapy to ART in mice infected with Plasmodium berghei . Methods Mice infected with P. berghei ANKA strain ( P. berghei ANKA) were treated with TAU alone, ART alone or a combination of TAU and ART (TAU + ART), and their survival time and parasitaemia were recorded. The cytotoxic effects of TAU and ART were subsequently assessed. The expression levels of inflammasome-related genes and inflammatory factors in mice infected with P. berghei ANKA were analysed in relation to those in mice treated with TAU alone, ART alone or the TAU + ART combination. The therapeutic effects were further evaluated by histological analysis and measurement of the spleen index. Results Compared with the control mice, P. berghei ANKA-infected mice treated with ART in combination with TAU presented significantly lower parasitaemia and prolonged survival. The combined treatment resulted in significant reductions in the expression levels of inflammasome-related genes in the spleen, including absent in melanoma 2 ( AIM2 ), caspase-1, NOD-, LRR- and pyrin domain-containing protein 3 ( Nlrp3 ), Nlrp1b , Nlrp1b , NLR family CARD domain containing 4 ( Nlrc4 ), Nlrp6 , nucleotide binding oligomerization domain containing 1 ( NOD1 ) and NOD2 , and decreases in the levels of inflammatory cytokines in the serum, including interleukin (IL)-12p70, tumour necrosis factor-alpha, monocyte chemoattractant protein-1, IL-10 and IL-6. Histopathological analysis confirmed that TAU + ART combination treatment reduced spleen pathology caused by P. berghei ANKA infection. Conclusions The findings indicate that TAU potentiates ART efficacy by modulating the immune response in P. berghei -infected mice. Graphical
研究领域:
免疫学
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寄生虫学
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药理学
·
疟疾研究
✓ 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）