المؤلفون: Zhao, Jiang-Man, Su, Zhi-Hui, Han, Qiu-Ying, Wang, Miao, Liu, Xin, Li, Jing, Huang, Shao-Yi, Chen, Jing, Li, Xiao-Wei, Chen, Xia-Ying, Guo, Zeng-Lin, Jiang, Shuai, Pan, Jie, Li, Tao, Xue, Wen, Zhou, Tao

المصدر: Nutrition & Metabolism; 1/2/2024, Vol. 21 Issue 1, p1-13, 13p

مصطلحات موضوعية: DISEASE progression, AUTOANTIBODIES, CATARACT, CYTOKINES, PANCREAS, INFLAMMATION, ANIMAL experimentation, TYPE 1 diabetes, BLOOD sugar, RNA, INTERFERONS, RATS, INSULIN, ENZYME-linked immunosorbent assay, RESEARCH funding, POLYMERASE chain reaction, DIABETIC nephropathies

مستخلص: Background: Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes. Methods: Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-β were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining. Results: In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1^−/− rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-β, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic β cells. Conclusions: Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies. [ABSTRACT FROM AUTHOR]

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المؤلفون: Lu, Yuan, Pan, Jie, Zhu, Xiaoqing, Zhang, Shuai, Liu, Chunhua, Sun, Jia, Li, Yueting, Chen, Siying, Huang, Jing, Cao, Chuang, Wang, Yonglin, Li, Yongjun, Liu, Ting

المصدر: BMC Pharmacology & Toxicology; 9/6/2021, Vol. 22 Issue 1, p1-8, 8p

مصطلحات موضوعية: DOXORUBICIN, DRUG-herb interactions, RATS, INJECTIONS, HEPATOCELLULAR carcinoma, LIQUID chromatography-mass spectrometry

مستخلص: Background: Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC. Methods: Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results: Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI. Conclusions: Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI. [ABSTRACT FROM AUTHOR]

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المؤلفون: Xu, De Lai, Pan, Jie

المصدر: 3 Biotech; 3/9/2021, Vol. 11 Issue 4, p1-9, 9p

مصطلحات موضوعية: TRANSCRIPTION factors, RHEUMATOID arthritis, AUTOPHAGY, RATS, PROTEIN expression

مستخلص: This study investigated the effect of autophagy-related gene transcription factor EB (TFEB) on the rheumatoid arthritis (RA) and explored whether TFEB regulated RA by autophagy. The Sprague–Dawley rats were divided into two groups (n = 6). The rats were stimulated with the mixture of the type II collagen and Freund's adjuvant or PBS at the root of the tail. Results showed that swollen and deformed joints were discovered, the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were elevated, and hematoxylin and eosin staining showed the inflammatory cells infiltrate the synovial tissue in the RA rats, compared to the control group. Immunohistochemistry displayed that the expressions of TFEB and LC3B increased in the synovial tissues of RA rats, whereas p62 decreased. The silence of TFEB in the RA-fibroblast-like synoviocytes (RA-FLS) decreased the protein expressions of LC3B, compared to the siRNA NC group. Meanwhile, the activity of FLS was raised, whereas the levels of TNF-α and IL-6 decreased in RA-FLS with TFEB knockdown. In conclusion, our study revealed that TFEB plays a crucial role in the progress of RA by regulating autophagy, which might provide novel targets for the therapy of RA. [ABSTRACT FROM AUTHOR]

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المؤلفون: Li, Yuhuan, Wang, Nina, Pan, Jie, Wang, Xinrui, Zhao, Yanling, Guo, Zongjun

المصدر: Neuropsychiatric Disease & Treatment; Feb2021, Vol. 17, p389-399, 11p

مصطلحات موضوعية: HIPPOCAMPUS (Brain), RATS, CELLULAR signal transduction, PROTEIN expression, BRAIN-derived neurotrophic factor

مستخلص: Background: Depression is the common mental disorder in the world. However, the pathophysiology mechanism underlying depression remains elusive. It has been reported that aberrant expression of miR-144 is closely related to depression. This study was to investigate whether and how miR-144 involves in depressive-like behaviors in a chronic unpredictable mild stress (CUMS) animal model. Methods: A rat model of CUMS was established, and qRT-PCR was performed to detect the expression of miR-144 in the hippocampus of a depressed rat. The lentiviral vector carried miR-144 (LV-miR-144) was injected into the hippocampus of the CUMS rat to investigate the effects of miR-144 on the behaviors and PTP1B/TrkB/BDNF signal transduction in the hippocampus of the rat. The interaction between miR-144 and PTP1B was investigated by biological analyses and dual-luciferase reporter assay. Results: The results showed that CUMS rats had typical depressive behaviors, and the expression of miR-144 in the hippocampus of CUMS rats was significantly lower than that of the control group. In addition, PTP1B protein expression was significantly up-regulated, while the expression of pTrkB and BDNF protein was significantly down-regulated in the hippocampus of CUMS rats. Moreover, PTP1B was a direct target of miR-144, and miR-144 could activate the downstream TrkB/BDNF signaling pathway by inhibiting the expression of PTP1B in primary hippocampus neurons. Conclusion: MiR-144 played an anti-depressive role in hippocampus dysfunction by inhibiting PTP1B and activating the TrkB/BDNF signaling pathway in the hippocampus of CUMS rats. [ABSTRACT FROM AUTHOR]

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المؤلفون: Pan, Jie, Lu, Yuan, Zhang, Shuai, Li, Yueting, Sun, Jia, Liu, Hua Chunhua, Gong, Zipeng, Huang, Jing, Cao, Chuang, Wang, Yonglin, Li, Yongjun, Liu, Ting

المصدر: Xenobiotica; Oct2020, Vol. 50 Issue 10, p1251-1257, 7p

مصطلحات موضوعية: DOXORUBICIN, RATS, LIVER cells, DRUG toxicity, HEPATOCELLULAR carcinoma, INTRAVENOUS therapy

مستخلص: Hepatocellular carcinoma (HCC) is a malignancy of liver cells. Recent studies have shown that HCC patients often have changes in the activities of transporters and metabolic enzymes, which can considerably affect drug pharmacokinetics and lead to drug toxicity. Doxorubicin (DOX) has been frequently administered in chemotherapy for HCC, but to our knowledge, the effects of HCC on the pharmacokinetics of DOX are unknown. In the present study, following intravenous administration of DOX in diethylnitrosamine-induced HCC rats, the plasma concentration was determined by a UPLC/MS/MS method. The expression of metabolic enzyme and transporters (p-gp, cbr1 and slc22a16) was analyzed by qRT-PCR and western blot. The results showed that the pharmacokinetic parameters AUC, T1/2, K12 and K21 of DOX were markedly increased, the K10 and CL were significantly decreased in HCC rats. The expression of cbr1 and slc22a16 was markedly decreased, while p-gp was significantly upregulated in HCC rats. These findings suggest that HCC could significantly alter the pharmacokinetic profile of DOX, which may be associated with the decreased expression of cbr1 and slc22a16 rather than the upregulation of p-gp expression. [ABSTRACT FROM AUTHOR]

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المؤلفون: Yuan, Li, Chen, Hao, Ma, Xue, Pan, Jie, Gong, Zi-Peng, Chen, Si-Ying, Li, Yue-Ting, Wang, Ai-Min, Zheng, Lin, Huang, Yong

المصدر: Evidence-based Complementary & Alternative Medicine (eCAM); 8/18/2020, p1-9, 9p, 6 Charts, 3 Graphs

مصطلحات موضوعية: ANIMAL experimentation, COMBINATION drug therapy, HERBAL medicine, LIQUID chromatography, MASS spectrometry, DRUG-herb interactions, MEDICINAL plants, CHINESE medicine, QUINOLONE antibacterial agents, RATS, PLANT extracts

مصطلحات جغرافية: CHINA

مستخلص: Polygonum capitatum has unique curative effects on the urinary system. In fact, many Polygonum capitatum-based preparations are currently used in the clinic. In China, the combination of levofloxacin (LVFX) with a Chinese herbal preparation derived from Polygonum capitatum has been used for the clinical treatment of urinary system diseases, which can improve the curative effects and reduce the side effects of LVFX. However, the herb-drug interaction (HDI) between these drugs has not been reported and the effect of Polygonum capitatum on the in vivo process of LVFX is unclear. In this article, a sensitive ultraperformance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) method was developed to evaluate the effects of the combined application of LVFX and the Polygonum capitatum extract on tissue distribution and excretion. Thereafter, the method was validated for selectivity, accuracy, precision, linearity, lower limit of quantification (LLOQ), dilution integrity, recovery, and matrix effect. Based on tissue distribution, LVFX could diffuse into all of the tested tissues, with significant differences in the content of each tissue between the coadministration group and single administration group. At 48 h after the combination was orally administered, the urinary cumulative excretion of LVFX decreased from 20.69% to 11.84% while its fecal cumulative excretion decreased from 26.08% to 13.28%. Our results suggest that a drug interaction exists between the two drugs in the process of distribution and excretion. This study provides important experimental evidence for further studies on the clinical efficacy and mechanism of the Polygonum capitatum extract and LVFX. [ABSTRACT FROM AUTHOR]

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المؤلفون: Sun, Hui-Yuan, Zheng, Lin, Gong, Zi-Peng, Li, Yue-Ting, Yang, Chang, Pan, Jie, Wang, Yong-Lin, Wang, Ai-Min, Li, Yong-Jun, Huang, Yong

المصدر: Evidence-based Complementary & Alternative Medicine (eCAM); 5/2/2019, p1-9, 9p, 1 Diagram, 6 Charts, 2 Graphs

مصطلحات موضوعية: ANIMAL experimentation, GLYCOSIDES, HIGH performance liquid chromatography, MASS spectrometry, METHANOL, MOLECULAR structure, ORGANIC compounds, RATS, PHYTOCHEMICALS, ACYCLIC acids

مستخلص: A rapid, reliable, and sensitive HPLC-electrospray ionization-tandem mass spectrometry (HPLC-MS/MS) method was established and validated for simultaneous determination of militarine and its three metabolites (gastrodin, α-isobutylmalic acid, and gymnoside I) in rat plasma. Plasma was acidified with formic acid, and protein was precipitated with methanol. MS/MS with ESI and multiple reaction monitoring at m/z 725.3→457.3, 457.1→127, 304.3→107.2, 189→129, and 417.1→267.1 was used for determination of militarine, gastrodin, α-isobutylmalic acid, gymnoside I, and puerarin (internal standard), respectively. Chromatographic separation was conducted using an ACE UltraCore SuperC18 (2.1 × 100 mm, 2.5 μm) column with gradient mobile phase (0.1% formic acid in water and acetonitrile). The lower limits of quantitation for militarine, gastrodin, α-isobutylmalic acid, and gymnoside I were 1.02, 2.96, 1.64, and 0.3 ng/mL, respectively. The relative standard deviations of intra- and interday measurements were less than 15%, and the method accuracy ranged from 87.4% to 112.5%. The extraction recovery was 83.52%-105.34%, and no matrix effect was observed. The three metabolites (gastrodin, α-isobutylmalic acid, and gymnoside I) were synchronously detected at 0.83 h, suggesting that militarine was rapidly transformed to gastrodin, α-isobutylmalic acid, and gymnoside I. Moreover, the area under the curve (AUC) and Cmax of militarine were significantly lower than those of gastrodin and α-isobutylmalic acid, showing that militarine was largely metabolized to gastrodin and α-isobutylmalic acid in vivo. The studies on pharmacokinetics of militarine and its three metabolites were of great use for facilitating the clinical application of militarine and were also highly meaningful for the potential development of militarine. [ABSTRACT FROM AUTHOR]

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المؤلفون: Lu, Yuan, Gong, ZiPeng, Xie, YuMin, Pan, Jie, Sun, Jia, Li, YueTing, Chen, SiYing, Li, YongJun, Wang, YongLin, Huang, Yong

المصدر: Evidence-based Complementary & Alternative Medicine (eCAM); 9/4/2016, Vol. 2016, p1-6, 6p, 2 Charts, 2 Graphs

مصطلحات موضوعية: ANIMAL experimentation, CIPROFLOXACIN, HERBAL medicine, DRUG-herb interactions, CHINESE medicine, RATS, SULFAMETHOXAZOLE, TRIMETHOPRIM, PHARMACOKINETICS

مستخلص: Relinqing granule (RLQ) is the best-selling Chinese patent drug for treatment of urinary system diseases. In this study, the effects of RLQ on the pharmacokinetics of ciprofloxacin, sulfamethoxazole, and trimethoprim in SD rats were investigated. Rats were randomly divided into control group 1, control group 2, RLQ group 1, and RLQ group 2. RLQ group 1 and RLQ group 2 were treated orally with RLQ for 7 days, and rats were treated with the same volume of water in control group 1 and control group 2. Then, RLQ group 1 and control group 1 were given intragastrically ciprofloxacin on day 8, while RLQ group 2 and control group 2 were given intragastrically sulfamethoxazole and trimethoprim on day 8. Blood samples were collected and determined. There was no significant influence of pharmacokinetic parameters of trimethoprim on two groups. But some pharmacokinetic parameters of ciprofloxacin and sulfamethoxazole in RLQ pretreated rats were evidently altered (P < 0.05), which indicated that absorption of ciprofloxacin and sulfamethoxazole in RLQ pretreated rats was significantly affected. It indicated the coadministration of RLQ would have an influence on the efficacy of ciprofloxacin and sulfamethoxazole, and the doses of ciprofloxacin tablet and compound sulfamethoxazole tablet need adjustment. [ABSTRACT FROM AUTHOR]

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