ARCHIVES OF MEDICAL RESEARCH
·
2020
·
IF 2.093
Li-li Deng
Object Astragaloside IV (AS IV) has antioxidative and anti-apoptotic properties, however, its effects on juvenile mice with diabetic ketoacidosis (DKA) have not been determined. This study aims to explore the effect and mechanism of Astragaloside IV (AS-IV) on juvenile mice with DKA. Methods DKA model was established through intraperitoneal injection of streptozotocin (STZ) and alloxan (ALX). DKA mice were divided into Control group, DKA group, DKA+AS-IV group, DKA+AS-IV+SP600125 group, DKA+AS-IV+Anisomycin group, DKA+AS-IV+GV248 group and DKA+AS-IV+GV248-Nrf2 group. To verify the implication of JNK signal pathway, JNK inhibitor SP600125 and activator Anisomycin were injected. The effects of AS-IV on antioxidant capacity and pathologies of pancreatic tissues in DKA juvenile mice were assessed. The expression of JNK/Nrf2 signal pathway was measured by Western blot. Results DKA juvenile mouse models were successfully established, evidenced by elevated blood glucose and blood ketone, suppressed insulin and pH value, and notable injuries in pancreatic tissues. Gavage of AS-IV can enhance antioxidant capacity of pancreatic tissue and ameliorate injuries in pancreatic tissues. AS-IV increased insulin level, in addition to suppressing blood glucose in DKA juvenile mice. In pancreatic tissues of DKA juvenile mice, protein level of p-JNK/JNK in pancreatic tissue and Nrf2 in the nuclei were increased after administration of AS-IV. Inhibition on JNK/Nrf2 signal pathway would impair the favorable effect of AS-IV on DKA juvenile mice, while antioxidant capacity, insulin level and blood glucose were improved in DKA juvenile mice injected an activator of JNK/Nrf2 pathway. Conclusion Collectively, AS-IV can enhance the antioxidant capacity of DKA juvenile mice to decrease blood glucose and to increase serum insulin secretion. The mechanism of action may be realized through the JNK/Nrf2 pathway.
研究领域:
药理学
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内分泌学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2022
·
IF 7.129
Ruifen Kang,Sheng Li,Aneela Perveen,Jiakun Shen,Chunmei Li
T-2 toxin belongs to the trichothecenes group A compound, mainly produced by Fusarium fungi. It has been shown that T-2 toxin could cross the placental barrier and breast milk, thus endangering the health of offspring. The present study aimed to explore the effects of maternal T-2 toxin exposure on the integrity of the intestinal barrier and the intestinal microflora of young mice. From late pregnancy (GD 14) to lactation (LD 21), pregnant mice were given T-2 toxin daily at 0, 0.005, or 0.05 mg T-2 toxin/kg BW. Postnatal day 21 (PND21), PND28, and PND56 young mice were chosen as objects to detect the influences of maternal T-2 toxin exposure to mice on the offspring. The results showed that maternal exposure to T-2 toxin disturbed the balance of the intestinal microbial flora of the young mice. Villous adhesions and fusion of ileum were observed in T-2-treated groups. In addition, supplementation of T-2 toxin significantly decreased the gene expressions of Claudin 1 , Occludin , Tjp1 , Il10 , Il6, and Tnf in PND 21. However, in PND 28, the expressions of Tnf were significantly increased . T he expressions of Claudin 1 , Occludin , Tjp1 , Il10 , Il6 and Tnf were significantly increased after T-2 toxin treatment in PND 56. These results suggested that maternal exposure to T-2 toxin has negative influences on the intestine of young mice, which may be due to the alterations of microbial composition.
研究领域:
毒理学
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微生物学
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发育生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND FUNCTION
·
2023
·
IF 3.6
Jing Luo,Yijue Deng,Yi Ding,Chenguang Tang,Mengqing Wang
This study aimed to determine the effects of Xiebai Zengye decoction (XBZY) on airway inflammation and respiratory function in rats with postinfectious cough (PIC), and its regulatory effects on the extracellular signal-regulated kinase (ERK) signaling pathway. Compared with the normal group, the rats from the PIC group had significantly shortened expiratory time (TE) and enhanced pause (EEP), increased resistance (RT), and enhanced pause (Penh), along with increased levels of serum interleukin-4 (IL-4) and IL-6, and decreased levels of IL-10. The lung and colon tissues of rats from the PIC group showed histopathological changes, including inflammatory cell infiltration, damaged mucosal epithelium, and crypt structure, with significantly increased ERK mRNA and protein expression levels. Treatment with XBZY and montelukast sodium (MAS) improved the respiratory function and serum cytokine levels, reduced tissue inflammation, and decreased ERK mRNA and protein expression levels in the lung and colon tissues. In the lung tissues, XBZY treatment significantly decreased the expression of phosphorylated-ERK (p-ERK) protein, as well as p-MEK1/2, p-ERK1/2, and p-c-Fos proteins, while in the colon tissues, XBZY significantly decreased the expression of p-ERK1/2 and p-c-Fos proteins. However, MAS treatment only showed significant improvement in the lung tissue inflammation score, and the expression level of p-ERK protein in the lung tissue was decreased. In conclusion, the present study suggests that XBZY has a potential therapeutic effect on PIC by improving respiratory function and attenuating inflammation, and this effect may be associated with the inhibition of the ERK signaling pathway. These findings could provide a new direction for the development of treatments for PIC. However, further research is needed to elucidate the underlying molecular mechanisms of XBZY and to confirm its safety and efficacy in clinical trials. Significance statement Postinfectious cough (PIC) accounts for 21.73% of the causes of chronic cough in Chinese children and has a higher incidence rate in preschool children. This study aims to observe the effects of Xiebai Zengye decoction (XBZY) on airway inflammation and reactivity in young rat model of PIC cough, and to explore its regulatory effects on the ERK signaling pathway, to preliminarily elucidate the mechanism of XBZY in treating PIC.
研究领域:
药理学
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呼吸病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2021
·Vol. 85
·期 4
·798-804
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IF 2.043
Yang Yanfei,Li Yabin,Han Jinli,Wang Yanfen
Gastrodin has shown the potential as an anticonvulsant. Epilepsy is a neurological disease with significant effects in children. In the current study, the therapeutic potential of gastrodin in handling pediatric epilepsy was explored by focusing on the AMPK/PPARα pathway. Three-week-old Sprague–Dawley rats were subjected to lithium-pilocarpine method to induce epileptic symptoms and then administrated with gastrodin. The effects of gastrodin on rats were first assessed using electroencephalogram (EEG) recording, Racine classification, Morris water maze test, and histological staining. The levels of BDNF and NGF, and the activity of AMPK/PPARα were measured. Based on the results of EEG, behavior analyses, and histological staining, epileptic symptoms were significantly alleviated by gastrodin. Moreover, the administration of gastrodin also suppressed the levels of BDNF and NGF, and activated the AMPK/PPARα pathway. In conclusion, our results demonstrated that gastrodin contributed to the alleviation of pediatric epilepsy by activating AMPK/PPARα signaling transduction.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
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IF 7.6
Lihua Feng,Yuanyuan Lang,Leke Sun,Weihong Shi,Xiangxiang Chen,Yanan Xia,Hengyi Xu,Yang Liu
Titanium dioxide nanoparticles (TiO 2 NPs) are widely used in children’s daily necessities and foods, and their health hazards to children have attracted particular attention. Childhood is a critical time for accelerated bone growth and development. Current studies revealed that TiO 2 NPs exposure causes bone damage in juvenile rats; however, the underlying mechanism is unknown. Ghrelin is a polypeptide hormone that is considered to be a candidate factor for regulating bone growth and development. In this research, 3-week-old juvenile male rats were administered 0, 100 or 200 mg/kg TiO 2 NPs and 50 μg/kg ghrelin for 4 weeks to explore the underlying mechanism of TiO 2 NPs-induced bone damage, and the protective effect of ghrelin. Our results revealed that TiO 2 NPs resulted in decreased synthesis of bone growth-related hormones, disturbed bone metabolism, and destruction of bone structure. Further mechanism studies showed that TiO 2 NPs inhibited Wnt/β-catenin pathway, reduced collagen synthesis, inhibited chondrocyte proliferation and differentiation, promoted chondrocyte apoptosis, and inhibited endochondral osteogenesis, ultimately leading to long bone longitudinal growth retardation and osteoporosis. Ghrelin alleviated the negative effects of TiO 2 NPs-induced bone growth in juvenile rats by upregulating the Wnt/β-catenin signaling pathway. This study provided a reference for the clinical treatment of growth retardation and idiopathic short stature in juvenile children caused by environmental pollutants.
研究领域:
毒理学
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内分泌学
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儿科
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骨骼生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
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2022
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IF 6.59
Zhenhui Chen,Ziyu Tang,Jingjing Kong,Lixuan Chen,Jiaxin Liu,Yunting Li,Wanwen Huang,Wendan Li,Junlin Wu,Wei Zhao,Xiaojing Meng,Hongying Fan
Pb poisoning affects infant growth and development. However, dimercaptosuccinic acid (DMSA) as the current therapy for Pb poisoning exerts relatively significant toxic side effects in infants. Therefore, identifying a non-toxic treatment in this regard is particularly important. In this study, we aimed to investigate the therapeutic effect of an infant feces-derived probiotic strain, Lactobacillus casei SYF-08 (SYF-08), on Pb poisoning in young mice. The Pb levels in the organisms were detected via inductively coupled plasma mass spectrometry, while the therapeutic effect of SYF-08 on Pb-induced neural system damage was explored via the Morris water maze test, hematoxylin-eosin staining, and immunohistochemistry. Additionally, the molecular mechanisms underlying the protective effects of SYF-08 against Pb-induced intestinal damage were also explored via histological staining, 16S rRNA sequencing, untargeted metabolomics, qRT-PCR, and western blotting. In vivo experiments revealed that SYF-08 reduced blood and bone Pb levels and increased urinary Pb excretion. Additionally, SYF-08 alleviated Pb-induced pathological damage to the brain and ultimately improved the learning and cognitive abilities of the young mice. This treatment also restored intestinal microflora dysbiosis, regulated bile acid metabolism, and inhibited the FXR-NLRP3 signaling pathway. It also resulted in fewer adverse events than the DMSA treatment. In conclusion, our results provided valuable insights into the therapeutic role of SYF-08 in Pb poisoning and also suggested that its administration can significantly alleviate the Pb-induced damage.
研究领域:
微生物学
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毒理学
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神经科学
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代谢组学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
·
IF 4.8
Yanjun Yang,Zhouyang Qian,Chenhui Wu,Yue Cheng,Bing Yang,Jianguo Shao,Jing Zhao,Xiangjun Zhu,Xiaobin Jia,Liang Feng
Ethnopharmacological relevance Pudilan Xiaoyan Oral Liquid (PDL) is a proprietary Chinese medicinal preparation approved by the State for treating acute pharyngitis in both adults and children (Approval No. Z20030095). It is worth noting that children exhibit unique physiopathological characteristics compared to adults. However, the in vivo regulatory characteristics of PDL in treating acute pharyngitis in children remain incompletely understood. Aim of the study The differential absorption and metabolism characteristics of the main pharmacological components in PDL in young and adult rats were investigated with a view to providing a reference for preclinical data of PDL in medication for children. Materials and Methods This study utilized UPLC-Q-TOF-MS to investigate the pharmacodynamic material basis of PDL. The focus was on the gastrointestinal digestion and absorption characteristics of organic acid components in PDL (PDL-OAC), known as the primary pharmacodynamic components in this formulation. The research combined in vitro dynamic simulation and a Quadruple single-pass intestinal perfusion model to examine these characteristics. The permeability properties of PDL-OAC were evaluated using an artificial parallel membrane model. Additionally, an acute pharyngitis model was established to evaluate the histopathological condition of the pharynx in young rats using H&E staining. The levels of IL-1 β , TNF- α , IL-6, and IL-10 in blood and pharyngeal tissue homogenates of young rats were quantified using ELISA kits. Results A total of 91 components were identified in PDL, including 33 organic acids, 24 flavonoids, 14 alkaloids, 5 terpenoids and coumarins, 3 sugars, and 12 amino acids. The PDL-OAC exhibited a significant reduction in IL-1 β , TNF- α , IL-6, and IL-10 levels in the pharyngeal tissues of young rats with acute pharyngitis. Results from dynamic simulation studies of gastrointestinal fluids revealed that the PDL-OAC (Specifically chlorogenic acid (CGA), gallic acid (GA), chicoric acid (CRA), and caffeic acid (CA)) were effectively stabilized in the gastrointestinal fluids of both children and adults in vitro . Young rats, characterized by thinner intestinal walls and higher permeability, efficiently absorbed the four organic acids across the entire intestinal segment. The absorption of CGA, GA, and CRA followed a concentration-dependent pattern, with CGA and GA absorption being influenced by exocytosis. Conclusion The efficacy of the PDL-OAC in treating acute pharyngitis was demonstrated in young rats. The absorption rate of these components was observed to be faster in young rats compared to adult rats, underscoring the need for dedicated studies on the drug's usage in children. This research provides valuable insights for the appropriate clinical use of PDL in pediatric patients.
研究领域:
药理学
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民族药理学
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儿科
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
·
IF 6.6
Lixin Xie,Lihua Feng,Xiaomin Tang,Yunping Xu,Hengyi Xu,Yang Liu
Purpose To evaluate the therapeutic effect of oral administration of Lactiplantibacillus plantarum P101 (P101) on skeletal injury in young rats exposed to titanium dioxide nanoparticles (TiO2 NPs), and explore the potential mechanism.Methods Four-week-old male rats were orally administration to TiO2 NPs and supplemented with P101 2 hours later for 4 weeks. The growth and development, food intake, bone metabolism and serum inflammatory markers of the rats were evaluated. Their tibias were observed and evaluated using microcomputed tomography (micro-CT), tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR). We observed the tibia growth plate using safranin and fast green staining. 16S rDNA sequence analysis of fecal samples was performed to observe changes in the gut microbiota.Results Our results showed that TiO2 NPs can lead to bone growth inhibition and osteoporosis, induce intestinal flora imbalance, and induce inflammation in young rats. Further mechanistic studies suggested that TiO2 NPs disrupts intestinal flora and increases serum IL-1β levels, which increased the expression of RANKL in bone, thereby enhancing osteoclast differentiation and function, leading to bone loss. Through a P101 supplementation experiment, we found that P101 ameliorated the inflammation and osteoporosis on bone caused by TiO2 NPs.Conclusion This study showed that the mechanism by which P101 alleviates bone damage caused by TiO2 NPs may be through restoring intestinal microbial homeostasis and inhibiting inflammatory response.
研究领域:
微生物学
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免疫学
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骨骼生物学
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纳米技术
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2019
·
IF 4.527
Yue Ma,Yinsheng Guo,Hailing Ye,Kaiqin Huang,Ziquan Lv,Yuebin Ke
Wide use of titanium dioxide nanoparticles (TiO 2 NPs) as white pigments induces unintentionally release in environment which increases concerns about their adverse health effects on respiratory system. So it is crucial to get a deep understanding of the disease process and molecular mechanism. Epigenetic mechanisms, such as DNA methylation, have been found to play a role in the development of lung diseases by affecting expression of key genes. In addition, there could be potential different toxic effects of TiO 2 NPs between young and adult. Thus, the comparative toxicity of TiO 2 NPs in 5-week (young) and 10-week (adult) old NIH mice is investigated in this study following nasal inhalation of TiO 2 NPs at dose of 20 mg/kg (body weight)/day for 30 days. Global DNA methylation and hydroxymethylation in lung were measured. Promoter methylation of inflammatory genes ( IFN-γ and TNF-α ) and tissue fibrosis gene ( Thy-1 ) were determined. Additional, RNA-sequencing runs were performed on the pulmonic libraries. We found the induced pulmonary inflammation and fibrosis were more severe in young mice. Decreased global methylation and hydroxymethylation were only found in the young group. The altered methylation in promoter of TNF-α and Thy-1 were found to play a role in the inflammatory response and fibration. RNA-sequencing showed that in pathways in cancer expression of 197 genes was up-regulated in the young mice more that in the adult mice. All these results suggested that the young ages are more sensitive to TiO 2 NP exposure and the potential of abnormal DNA methylation might be used as biomarkers of both exposure and disease development.
研究领域:
毒理学
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表观遗传学
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呼吸系统
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2020
·Vol. 40
·期 9
·1284-1296
·
IF 2.997
Zhangjian Chen,Shuo Han,Pai Zheng,Shupei Zhou,Guang Jia
Titanium dioxide nanoparticles (TiO 2 NPs) were usually consumed with a high content of sugar, and children were identified as having the highest exposures due to sweet food preferences. Research on the combined effect of ingested TiO 2 NPs and glucose has great significance, particularly in young people. We examined young Sprague-Dawley rats administered TiO 2 NPs (0, 2, 10 and 50 mg/kg) orally with and without glucose (1.8 g/kg) for 90 days. Blood glucose homeostasis was assessed by monitoring blood glucose and detecting glycoproteins. Glucose tolerance was also evaluated by the oral glucose tolerance test. The levels of blood glucose-related hormones such as insulin, C-peptide and glucagon were measured. We found that subchronic co-exposure of TiO 2 NPs and glucose caused slight imbalance of blood glucose homeostasis in vivo. Mild and temporary hypoglycemia, impaired glucose tolerance and changes of glucose-regulating hormones were shown in the exposure groups. The combined effect of TiO 2 NPs and glucose was more apparent than that of TiO 2 NPs alone, which may be due to the effects of excess glucose and the interactions between TiO 2 NPs and glucose. The antagonistic effect of TiO 2 NPs with glucose did exist in the level of glycosylated hemoglobin in female rats. Gender differences were apparent in these effects induced by TiO 2 NPs and glucose. Female rats seemed to be more susceptible for blood glucose disorders. Co-exposure of TiO 2 NPs and excessive glucose could induce gender-dependent imbalance of blood glucose homeostasis in rats. It may be the reason that these consumers face greater health risks glycosylated hemoglobin.
研究领域:
毒理学
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内分泌学
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营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Wenshu Cheng,Xinyue Xu,Yuanyuan Lang,Zugen Cheng,Mohammad Rizwan,Xiaomin Tang,Lixin Xie,Yanling Liu,Hengyi Xu,Yang Liu
Purpose To evaluate the effects of anatase and rutile TiO2 nanoparticles (NPs) on the growth and development of bones in young rats and explore their possible mechanisms.Methods Three-week-old male rats were orally administered anatase TiO2 NPs and rutile TiO2 NPs for 28 days. The indicators of rat growth and development, liver function, bone metabolism, and insulin-like growth factor-1 (IGF-1) levels were evaluated. Micro-computed tomography (micro-CT) and immunohistochemistry were used to evaluate the tibia.Results No significant differences were observed among growth and development indicators in young rats. Significant differences were found in IGF-1 levels, phosphorus levels, and liver function. Micro-CT revealed osteoporosis in the bones. The micro-CT data supported the same result. Bone immunohistochemistry results showed that the expression of osteoprotegerin (OPG) was decreased and the expression of receptor activator of nuclear factor-κB ligand (RANKL) and cathepsin K (CTSK) was increased.Conclusion This study demonstrated that TiO2 NPs can damage bones via the IGF-1/OPG/RANKL/CTSK pathway in young rats. Furthermore, rutile TiO2 NPs damaged the bones more seriously than anatase TiO2 NPs.
研究领域:
纳米技术
·
生物材料
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骨骼生物学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2020
·Vol. 10
·期 1
·1-11
·
IF 3.998
Wang Yue,Xiao Han,Yang Lei,Jia Xiaojing,Guo Xuan,Zhang Zhaobin
p -Alkoxyphenols (AOPs) are a class of ethers that are widely used in industrial and agricultural productions and daily necessities. p -Phenoxyphenol (PhOP) and p -pentyloxyphenol (PeOP) belong to this class and have been reported to be estrogenic in vitro. However, their in vivo estrogenic activities have rarely been of concern. In this study, we performed an immature mouse uterotrophic assay and studied the estrogenic effects of these two compounds in mice. The results revealed that the uterine weights of the animals treated with PhOP significantly increased at doses of 30 and 300 mg kg -1 bw day -1 for 3 days ( P < 0.05), while no significant uterotrophic effects were observed in the mice treated with PeOP. Using next-generation transcriptome sequencing (RNA-seq), we also analyzed the gene expression in the uterine tissue of mice treated with PhOP and PeOP. The observed gene regulation patterns of the PhOP- and PeOP-treated specimens were similar to those of the 17 β -estradiol (E 2 )-treated specimens. In particular, some estrogen-responsive genes, such as the Sprr2 gene family, Apoa1 , Prap1 , and Ahsg , displayed a regulation trend similar to that of E 2 . In addition, molecule docking analysis revealed that both PhOP and PeOP could be well docked into the active site of hERα, with potential of mean force (PMF) values of − 58.68 and − 52.67 kcal mol -1 for PhOP and PeOP, respectively. The results of this study indicate that PhOP exhibits relatively strong in vivo estrogenic activity, which could be of future concern.
研究领域:
毒理学
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分子生物学
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内分泌学
✓ 已验证
DOI
PubMed
高影响因子
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