1.Effects of Guben Fangxiao Beverage (固本防哮饮) on Lung Tissue Oxidative Stress and AMPK/Nrf2/HO-1 Pathway in Mice with Bronchial Asthma in Remission
Xiaohan DAI ; Xia ZHAO ; Hua YAN ; Yiwen SHAN
Journal of Traditional Chinese Medicine 2024;65(2):205-212
ObjectiveTo investigate the possible mechanism of Guben Fangxiao Beverage (固本防哮饮) for the prevention and treatment of chronic airway inflammation during asthma remission. MethodsThirty-six female Balb/c mice were randomly divided into normal group, model group, low-, medium-, and high-dose of Guben Fangxiao Beverage group and montelukast sodium group, with 6 mice in each group. Except for the normal group, ovalbumin and respiratory syncytial virus were used in other groups to establish a mouse model of bronchial asthma in remission stage. After molding, the low-, medium-, and high-dose groups of Guben Fangxiao Beverage were respectively given 12, 24, and 36 g/(kg·d), the montelukast sodium group was given montelukast sodium granule 2.6 mg/(kg·d), and the mice in the normal group and model group were given 20 ml of double-distilled water, all by gavage, once a day for 28 days. The levels of interleukin 4 (IL-4) and interleukin 5 (IL-5) in the lung tissue of mice were detected; HE staining was used to observe the pathology of the lung tissue and to score the inflammation; DHE staining was used to observe the level of reactive oxygen species (ROS) in the lung tissue, and the activities of mitochondrial respiratory chain complexes Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅴ in the lung tissue were detected; the levels of serum superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and adenosine triphosphate (ATP) were detected; the protein expression levels of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase 1 (HO-1) and cAMP responsive element binding protein (CREB) in the lung tissues of the model group were detected by Western blot. ResultsCompared with the normal group, the histopathological results of the lungs of mice in the model group showed an increase in inflammatory cells around the airways and an increase in inflammatory score; DHE staining showed an increase in the level of ROS, and an increase in the levels of IL-4 and IL-5 in the lung tissues; the levels of serum SOD, CAT, and ATP were reduced, and the level of MDA was elevated; the activities of the mitochondrial respiratory chain complexes Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅴ of the lung tissues were reduced, and the activities of p-AMPK, Nrf2, CREB protein expression decreased (P<0.05). Compared with the model group, the lung tissue inflammatory cells and inflammation scores of mice in each Guben Fangxiao Beverage dose group and montelukast sodium group were reduced; the levels of ROS, IL-4 and IL-5 in the lung tissue were reduced; the levels of CAT and ATP in the serum increased, and the content of MDA was reduced; and the activities of mitochondrial respiratory chain complexes Ⅰ and Ⅱ, as well as the expression of CREB protein, were elevated in the lung tissue (P<0.05). Compared with the high-dose group, the MDA level of the medium-dose Guben Fangxiao Beverage group decreased (P<0.05). The activity of mitochondrial respiratory chain complex V in the medium-dose group was higher than that in the montelukast sodium group, and the activity of mitochondrial respiratory chain complex Ⅳ in the medium- and high-dose groups was higher than that in the low-dose group (P<0.05). ConclusionGuben Fangxiao Beverage can inhibit oxidative stress and improve mitochondrial function to relieve chronic airway inflammation in bronchial asthma model mice during asthma remission, and its mechanism may be related to the activation of AMPK/Nrf2/HO-1 signaling pathway.
2.Generation of traditional Chinese medicine prescription driven by generative artificial intelligence GPT-4
Qitao CHEN ; Jingwen NI ; Jun XU ; Xiaohan GAO ; Lizhen XIA
China Pharmacy 2023;34(23):2825-2828
OBJECTIVE To evaluate the safety and suitability of traditional Chinese medicine prescriptions generated by generative artificial intelligence (AIGC), and to provide research ideas for empowering the traditional Chinese medicine industry with AIGC. METHODS Using the 2020 edition of Chinese Pharmacopoeia and the 5th edition of Traditional Chinese Medicine as corpus, GPT-4 and the real-time networking model developed based on GPT-4 (referred to as the “networking model”) were used for deep learning. The clinical cases included in the consensus of traditional Chinese medicine experts in recent years were extracted manually to regenerate prescriptions based on diagnosis using the GPT-4 model and networking model; traditional Chinese medicine experts conducted blind evaluation and scoring of GPT-4 generated prescriptions, networking model generated prescriptions, and expert consensus prescriptions. At the same time, Turing testing was used to evaluate whether the GPT-4 model and networking model had the same ability as human intelligence. RESULTS The average score of traditional Chinese medicine prescriptions generated by the GPT-4 model showed no statistically significant difference compared to manual prescriptions (P>0.05), while the average score of prescriptions generated by the networking model showed no statistically significant difference compared to traditional Chinese medicine prescriptions generated by the GPT-4 model (P>0.05). The proportion of model-generated prescriptions mistakenly judged as manual prescriptions in the Turing test was 51.11%. CONCLUSIONS The traditional Chinese medicine prescriptions generated by the GPT-4 model have reached a certain level of safety and suitability, and the GPT-4 model has passed the Turing test. The introduction of AIGC in the diagnosis and treatment process may provide technical support for the rational use of clinical traditional Chinese medicine.
3.Implementation and application of telephone recruitment for apheresis platelet donors: based on the whole process information management of blood collection and supply
Xiaohan XIA ; Chunyan LI ; Yue ZHENG ; Xiahua ZHAN ; Caixia LIN ; Qing FENG
Chinese Journal of Blood Transfusion 2021;34(10):1130-1133
【Objective】 To develop and implement a precise and efficient telephone recruitment strategy for apheresis platelet donors based on the information management of blood collection and supply process. 【Methods】 A telephone recruitment strategy based on the whole process information management of apheresis platelet donors (hereinafter referred to as telephone recruitment) was formulated From January 1, 2019, apheresis platelet donors in Hangzhou, registered in the intelligent blood donor recruitment system(hereinafter referred to as the recruitment system), were recruited by telephone calls or (and) SMS reminders to inform re-donation interval, key points of recruitment consultation, blood donation appointment time and other precautions. Response rate, pass rate and blood donation rate of donors before(in 2018) and after( in 2019) the implementation of telephone recruitment, as well as the above three rates during the COVID-19 epidemic in 2020 in Hangzhou were collected and analyzed by χ2 test. 【Results】 The response rate, pass rate, and blood donation rate of apheresis platelet donors in Hangzhou before /after the implementation of telephone recruitment and during the COVID-19 epidemic were 28.52%(3 901/13 678)vs 30.52%(4 429/14 511)vs 39.36%(4 064/10 326), 73.80%(2 879/3 901)vs 77.83%(3 447/4 429)vs 78.20%(3 178/4 064)and 6.77%(2 879/42 553)vs 7.77%(3 447/44 366)vs 8.13%(3 178/39 077, respectively(P<0.05). In 2020, 85.94%(3 178/3 698) of apheresis donors were recruited by telephone(P<0.05). The proportion of apheresis donations successfully recruited by telephone in 2018 and 2019 accounted for 11.74% (2 879/24 519) and 12.48% (3 447/27 628), respectively(P<0.05), contributing 10.59% (4 030 U/38 040 U) and 11.38% (4 875 U/42 853 U) of units(P<0.05) that issued to the clinical. Due to the COVID-19 epidemic, the number of blood donors recruited by telephone and its proportion in 2020 decreased significantly as compared with those before the implementation of telephone recruitment (2019). 【Conclusion】 The telephone recruitment strategy based on the whole-process information management (system) of blood collection and supply can effectively improve the targeted recruitment of apheresis platelet donors and enhance its proportion of apheresis collection that issued to the clinical.
4.Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting Mafa
Shenghan SU ; Qingrui ZHAO ; Lingfeng DAN ; Yuqing LIN ; Xuebei LI ; Yunjin ZHANG ; Chunxiao YANG ; Yimeng DONG ; Xiaohan LI ; Romano REGAZZI ; Changhao SUN ; Xia CHU ; Huimin LU
Endocrinology and Metabolism 2022;37(6):901-917
Background:
Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse β-cells and elucidated the possible role of microRNAs in this process.
Methods:
β-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated β-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked β-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs.
Results:
Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR- 8114 expression in both mouse islets and β-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced β-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected β-cells.
Conclusion
These data demonstrate that melatonin protects against stearic acid-induced β-cell senescence by inhibiting miR-146a- 5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced β-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression.