1.The effect of rutaecarpine on improving fatty liver and osteoporosis in MAFLD mice
Yu-hao ZHANG ; Yi-ning LI ; Xin-hai JIANG ; Wei-zhi WANG ; Shun-wang LI ; Ren SHENG ; Li-juan LEI ; Yu-yan ZHANG ; Jing-rui WANG ; Xin-wei WEI ; Yan-ni XU ; Yan LIN ; Lin TANG ; Shu-yi SI
Acta Pharmaceutica Sinica 2025;60(1):141-149
Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg-1) and a high dose (15 mg·kg-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D303)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.
2.Methodological Evaluation of Advantages of Traditional Chinese Medicine Treatment of Sjögren's Syndrome
Wenjing LIU ; Shiya WU ; Ruihua LIU ; Xinyao ZHOU ; Juan JIAO ; Ying LIU ; Zeguang LI ; Zhenbin LI ; Huadong ZHANG ; Xiaopo TANG ; Quan JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):192-197
Screening and evaluating the diseases responding specifically to traditional Chinese medicine (TCM) will help to highlight the advantages of TCM treatment, and the evaluation method should be standardized with consideration to the unique characteristics of the diseases. The incidence of Sjögren's Syndrome (SS) is increasing year by year, while the pathogenesis of this disease remains unclear. Modern therapies for this disease include biological agents and immunosuppressants, which generally have unsatisfactory efficacy. The TCM treatment of SS focuses on the harmony of the physical and mental health. The Rheumatology Branch of the China Association of Chinese Medicine organizes experts in TCM, Western medicine, and evidence-based medicine to form working groups. Delphi method and bibliometric method were used for analysis, and SS was selected as a disease responding specifically to TCM. Furthermore, the evaluation system was established for this disease, and the consensus regarding this disease was reached after seminar discussion. This paper summarized the whole process of the evaluation of the advantages of TCM treatment of SS. First, because TCM atomization is widely used in clinical practice and enriches TCM administration methods, this therapy is included after other non-drug therapies were taken as characteristic therapies. Second, the evaluation indicators of therapeutic effect should be determined with consideration to international acceptance and the current research status. Third, the expression method should be accurate, standardized, and objective, highlight the natural advantages of TCM, and avoid arbitrary extension. This paper provides a reference for clinicians to explore other diseases responding specifically to TCM.
3.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine:Fibromyalgia Syndrome
Juan JIAO ; Jinyang TANG ; Xiujuan HOU ; Mengtao LI ; Dongfeng LIANG ; Yuhua WANG ; Weixia JING ; Guangtao LI ; Qin ZHANG ; Yongfeng ZHANG ; Guangyu LI ; Qian WANG ; Yang YANG ; Jin HUO ; Mei MO ; Jihua GUO ; Xiaoxiao ZHANG ; Quan JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):216-222
Fibromyalgia syndrome (FMS) is a refractory, chronic non-articular rheumatic disease characterized by widespread pain throughout the body, for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies, and some non-drug therapies, such as acupuncture, Tai Chi, and Ba-Duan-Jin, have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine (TCM) by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine, the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine, including rheumatology, psychology, acupuncture and moxibustion, and encephalopathy, with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS, mitigation of common non-specific symptoms, preferential analgesic therapy, TCM pathogenesis and treatment advantages, and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis, poor patient participation, and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems, this paper suggests that rheumatologists should serve as the main diagnostic force of this disease, and they should improve patient participation in treatment decision-making, implement exercise therapy, and fully utilize the holistic and multidimensional features of TCM, which is effective in alleviating pain, improving mood, and decreasing adverse events. In addition, it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment, which is expected to improve the standard of diagnosis and treatment of FMS in China.
4.Effect of Linggui Zhugantang on Mitochondrial Fusion-fission and Sirt3/ AMPK Signaling Pathway in Chronic Heart Failure Rats After Myocardial Infarction
Juan YAO ; Rui DING ; Xiangyang LI ; Tongjuan TANG ; Wanwan WU ; Kedong WEI ; Shaohua XU ; Liang WANG ; Peng ZHOU ; Jinling HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):1-9
ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3(Sirt3)/adenosine monophosphate dependent protein kinase (AMPK) signaling pathway in chronic heart failure (CHF) rats after myocardial infarction (MI). MethodSD rats randomly divide into sham operation group (normal saline ,thread only without ligature), model group (normal saline, ligation of the left anterior descending coronary artery proximal to the heart), Linggui Zhugantang group (4.8 g·kg-1) and Captopril group (0.002 57 g·kg-1), with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin (HE) staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species (ROS). JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate (ATP), superoxide dismutase (SOD), malondialdehyde (MDA), mitochondrial respiratory chain complex activity (Ⅰ-Ⅳ). TdT-mediated dUTP nick end labeling (TUNEL) staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3, phosphorylated AMPK (p-AMPK), phosphorylated dynamic-related protein 1(p-Drp1), mitochondrial fission protein 1(Fis1), mitochondrial fission factor (MFF), optic atrophy protein 1(OPA1). ResultCompared to the sham group, the left ventricular end diastolic diameter (LVIDd) and left ventricular end systolic diameter (LVIDs) were significantly increased in model group (P<0.01), while the left ventricular short axis shortening rate (LVFS) and left ventricular ejection fraction (LVEF) were significantly decreased (P<0.01). There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS, MDA levels and myocardial cell apoptosis rate were significantly increased (P<0.01), SOD level, ATP content, and membrane potential were significantly decreased (P<0.01). The activity of mitochondrial respiratory chain complexes (Ⅰ-Ⅳ) was significantly decreased (P<0.01). Levels of p-Drp1, Fis1, MFF proteins were significantly up-regulated (P<0.01), while Sirt3, p-AMPK, OPA1 proteins level were significantly down-regulated (P<0.01). Compared with model group, LVIDd and LVIDs were significantly decreased (P<0.01), LVEF and LVFS were significantly increased (P<0.01). Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS, MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group (P<0.01), SOD level, ATP content, and membrane potential significantly increased (P<0.01). The activity of mitochondrial respiratory chain complexes (Ⅰ-Ⅳ) increased significantly (P<0.01),and p-Drp1, Fis1, MFF protein levels were significantly down-regulated (P<0.01), Sirt3, p-AMPK, OPA1 protein were significantly up-regulated (P<0.01). ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells, maintain mitochondrial function stability, and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.
5.Short-term effects of air pollutants on outpatient volume of respiratory diseases in Guiyang
Juan DU ; Yingping TANG ; Ping HE ; Li JIANG
Journal of Environmental and Occupational Medicine 2024;41(1):62-69
Background Affected by concentration, composition, and population tolerance of air pollutants, the relationship between air pollutants and population health has regional differences. There is still a research gap in Guiyang. Objective To explore the short-term effects of air pollutant concentrations in low-pollution areas on the outpatient volume of respiratory diseases. Methods Spearman correlation analysis was used to evaluate the correlation between air pollutants, meteorological factors, and respiratory outpatient volume from January 1, 2013 to December 31, 2020 in Guiyang City. A single pollutant distribution lag nonlinear model and a multi-pollutant interaction model were established based on Poisson distribution. A three-dimensional diagram was drawn to display the relationship between air pollutants and respiratory outpatient volume. Quantitative analysis was conducted on the attribution risk and lag effect of air pollutant concentration on outpatient volume of respiratory diseases in Guiyang City. Results The results of the single pollutant model showed that fine particulate matter (PM2.5), nitrogen dioxide (NO2), carbon monoxide (CO), and sulfur dioxide (SO2) elevated the outpatient volume of respiratory diseases. The maximum relative risk (RR) and 95%CI values of PM2.5, NO2,CO, and SO2 appeared on Day 2, 0, 5, and 6, respectively, which were 1.019 (1.015, 1.023), 1.146 (1.122, 1.171), 1.129 (1.116, 1.143), and 1.046(1.040, 1.052), respectively. For every quartile concentration increment of PM2.5, NO2, CO, or SO2, the outpatient volume of respiratory diseases increased by 0.943% (0.111%, 1.782%), 4.050% (3.573%, 4.529%), 0.595% (0.317%, 0.874%), or 0.667% (0.235%, 1.100%), respectively. The maximum RR (95%CI) of O3 was 1.015 (1.007, 1.023) and appeared on Day 0. The results of multi-pollutant model showed that PM2.5, NO2, CO, SO2, and O3 all elevated the outpatient volume of respiratory diseases. The maximum RR values of PM2.5, NO2, CO, SO2 and O3 appeared on Day 14, 0, 5, 7 and 0, respectively, which were 1.027 (1.021, 1.034), 1.213 (1.179, 1.248), 1.059 (1.043, 1.074), 1.016 (1.005, 1.026), and 1.024 (1.015, 1.033), respectively. Compared with the single pollutant model, the RR values of PM2.5, NO2, and O3 on the outpatient volume of respiratory diseases in the multi-pollutant model showed an upward trend, while the RR values of CO and SO2 in the multi-pollutant model showed a downward trend. Conclusion The impact of low concentrations of PM2.5, NO2, CO, and SO2 on human health cannot be ignored.
6.Expression of brain-derived neurotrophic factor in hippocampal tissue of central obese mice induced by sodium glutamate
Peng-Juan CAO ; Jia-Yuan TANG ; Mei-Zi YANG ; Yuan-Yuan LI ; Li-Ting HUANG ; Wen-Wen MENG ; Yong-Jun JIN ; Jian-Xun MO
The Chinese Journal of Clinical Pharmacology 2024;40(15):2227-2230
Objective To explore whether the cognitive function of central obese mice is decreased by affecting the expression of brain-derived neurotrophic factor(BDNF)in hippocampus.Methods Healthy mice at the neonatal stage were divided into normal group and model group at random.To obtain the obese models,model group mice were injected at cervical subcutaneous with 10%L-monosodium glutamate(MSG;3 mg·g-1·d-1)for 5 days.The normal group was injected with the same dose of 0.9%NaCl.In addition,mice were removed according to the requirements.Finally,we got 8 mice in each group.The following parameters were compared:body weight,Lee's index and levels of the serum lipid.The BDNF expression levels in hippocampal tissue were measured using western blotting.Results At the 8th weekend,the body weight of the model and normal groups was(49.01±2.47)and(41.27±3.28)g;the Lee's indexes were(357.14±9.24)and(330.15±7.37)g1/3·cm-1;triglyceride levels were(1.37±0.52)and(0.73±0.31)mmol·L-1;total cholesterol levels were(2.98±0.18)and(1.98±0.30)mmol·L-1;low-density lipoprotein levels were(0.31±0.03)and(0.24±0.02)mmol·L-1;high-density lipoprotein levels were(2.70±0.15)and(1.98±0.40)mmol·L-1;the differences were statistically significant(P<0.05,P<0.01),which were consistent with the characteristics of the central obesity model.The BDNF protein expression levels in the hippocampus of the model and normal groups were 6.02 x 104±626.53 and 7.04 x 104±1 440.81,which has statistically significant(P<0.01).Conclusion The cognitive function of central obese mice may be decreased by down-regulating the expression of BDNF in hippocampus.
7.The diagnostic value of miR-571 levels in blood from the peripherals in liver fibrosis
Juan TANG ; Yi LI ; Liqiong ZHAI ; Shaowen LIU ; Yong SHEN ; Shuo CONG ; Yongmei LIU
The Journal of Practical Medicine 2024;40(5):653-657
Objective To study the diagnostic value of miR-571 for liver fibrosis by detecting miR-571 expression in the peripheral blood of patients with liver fibrosis.Methods From December 2022 to September 2023,40 patients with liver fibrosis,40 patients with chronic hepatitis,and 40 healthy controls were chosen as research subjects.The expression level of miR-571 in peripheral blood was detected using a real-time quantitative polymerase chain reaction,and the relative expression of miR-571 in each group was evaluated.The Spearman correlation method was utilized to examine the relationship between miR-571 and clinical detection indices.To assess the capacity of miR-571 and the multivariate diagnostic model to identify liver fibrosis,binary logistic regression was used to create a multivariate diagnostic model,and ROC curves were generated.Results The expression of miR-571 was significantly higher in the liver fibrosis group than in the healthy control and hepatitis groups,and the difference was statistically significant(P<0.001).The expression level of miR-571 was positively connected with ALT,APRI score,and FIB-4 index(r = 0.23,0.30,0.22,P<0.05)and negatively correlated with PLT(r =-0.19,P<0.05)according to Spearman correlation analysis.Logistic regression research revealed that miR-571 and the FIB-4 index were independent risk factors for liver fibrosis.The AUC for miR-571 to diagnose fibrosis was 0.91(95%CI:0.85~0.96),while the AUC for miR-571 paired with the FIB-4 index was 0.94(95%CI:0.90~0.98).Conclusion MiR-571 expression was shown to be considerably higher in the peripheral blood of hepatic fibrosis patients,and the combined FIB-4 index offers some clinical diagnostic value for hepatic fibrosis.
8.Role of complement C3 in early predicting pregnancy outcomes of frozen-thawed embryo transfer
Zhixia TANG ; Shuangying MA ; Ying ZHAGN ; Jiajia SHENG ; Juan LI ; Jingjing HE ; Henghua XUAN ; Min-Gyun HONG
The Journal of Practical Medicine 2024;40(7):924-929
Objective To investigate the role of complement C3 in early predicting pregnancy outcomes of frozen-thawed embryo transfer(F-ET).Methods A total of 378 F-ET cycles were prospectively collected and divided into group A(complement C3≤1.05,120 cycles)and group B(complement C3>1.05,258 cycles)based on the best cutoff value of complement C3 for predicting F-ET pregnancy outcomes.The outcomes of the two groups were compared,and the best cutoff value of complement C3 for predicting F-ET spontaneous abortion was analyzed in group B.Results Age was a risk factor for successful F-ET pregnancy(P<0.05),and complement C3 and embryo type were protective factors for successful F-ET pregnancy(P<0.05).The area under the receiver-operating characteristic curve(ROC)of complement C3 for predicting F-ET pregnancy outcome was 0.702,and the best cutoff value was 1.05 g/L,with a clinical pregnancy sensitivity of 87.60%and a specificity of 52.00%.The clinical pregnancy rate and embryo implantation rate in group B were both significantly higher than those in group A(67.05%vs.52.75%,P<0.05).The best cutoff value of complement C3 for predicting spontaneous abortion after F-ET was 1.32 g/L,with an area under the ROC curve of 0.760,a sensitivity of 69.00%,and a specificity of 81.20%.Conclusions Complement C3 is of significance in the early prediction of F-ET pregnancy outcome.When complement C3 exceeds the level of 1.32 g/L,it may lead to an increase in the rate of spontaneous abortion.
9.GPCR-Gs mediates the protective effects of ginsenoside Rb1 against oxygen-glucose deprivation/re-oxygenation-induced astrocyte injury
Xi Wang ; Ying Liu ; Juan Li ; Jiayu Xie ; Yi Dai ; Minke Tang
Journal of Traditional Chinese Medical Sciences 2024;11(1):33-43
Objectives:
To investigate whether the protective actions of ginsenoside Rb1 (Rb1) on astrocytes are mediated through the Gs-type G-protein-coupled receptor (GPCR-Gs).
Methods:
Primary astrocyte cultures derived from neonatal mouse brain were used. Astrocyte injury was induced via oxygen-glucose deprivation/re-oxygenation (OGD/R). Cell morphology, viability, lactate dehydrogenase (LDH) leakage, apoptosis, glutamate uptake, and brain-derived neurotrophic factor (BDNF) secretion were assessed to gauge cell survival and functionality. Western blot was used to investigate the cyclic adenosine monophosphate (cAMP) and protein kinase B (Akt) signaling pathways. GPCR-Gs-specific inhibitors and molecular docking were used to identify target receptors.
Results:
Rb1 at concentrations ranging from 0.8 to 5 μM did not significantly affect the viability, glutamate uptake, or BDNF secretion in normal astrocytes. OGD/R reduced astrocyte viability, increasing their LDH leakage and apoptosis rate. It also decreased glutamate uptake and BDNF secretion by these cells. Rb1 had protective effects of astrocytes challenged by OGD/R, by improving viability, reducing apoptosis, and enhancing glutamate uptake and BDNF secretion. Additionally, Rb1 activated the cAMP and Akt pathways in these cells. When the GPCR-Gs inhibitor NF449 was introduced, the protective effects of Rb1 completely disappeared, and its activation of cAMP and Akt signaling pathways was significantly inhibited.
Conclusion
Rb1 protects against astrocytes from OGD/R-induced injury through GPCR-Gs mediation.
10.Safety and efficacy of mitomycin nanoparticles in inhibiting scar proliferation after glaucoma filtration surgery
Ying LI ; Juan TANG ; Changfen LI ; Qilin FANG ; Xingde LIU ; Dan ZHANG ; Tingting ZHANG ; Xiaoli WU ; Tao LI
International Eye Science 2024;24(11):1708-1714
AIM: To prepare a nanodrug MMC-ATS-@PLGA using polylactic acid hydroxyacetic acid copolymer(PLGA)as a carrier and mitomycin C(MMC)loaded on PLGA, and to analyse the biological safety and treatment effect of this nanodrug on inhibiting the proliferation of filtering bleb scarring after glaucoma surgery in vivo.METHODS: The thin-film dispersion hydration ultrasonic method was used to prepare the MMC-ATS-@PLGA, and its physical and chemical properties were detected. The effect of MMC-ATS@PLGA on rabbit corneas was analysed through corneal fluorescence staining and HE staining, and tear film rupture time(BUT), Schirmer test and intraocular pressure data were collected to analyse ocular surface biosafety. A slit lamp was used to observe and calculate the filtration bubble size, and the tissue morphological changes were analysed by conjunctival HE staining. In addition, immunohistochemistry and Elisa were used to compare the anti-inflammatory effects of Flumiolone Eye Drops(FML), MMC, and MMC-ATS-@PLGA nanoparticles on inhibiting the formation of filtering bleb scarring after glaucoma surgery from multiple perspectives via comparative proteomic analysis.RESULTS: The average particle size and zeta potential of MMC-ATS-@PLGA were 128.78±2.54 nm and 36.49±4.25 mV, respectively, with an encapsulation efficiency and a drug loading rate of(78.49±2.75)% and(30.86±1.84)%, respectively. At 33°C(the ocular surface temperature), the cumulative release rate of the MMC-ATS-@PLGA nanoparticles reached(76.58±2.68)% after 600 min. Moreover, corneal fluorescence staining, HE, BUT, Schirmer, and intraocular pressure results showed that MMC-ATS-@PLGA had good biocompatibility with the ocular surface of rabbits. At 3 wk after surgery, the area of filtering blebs in the MMC-ATS-@PLGA group was significantly larger than that in the FML group and MMC group, and the filtering blebs in the control group had basically disappeared. Pathological tissue analysis of the conjunctiva in the filtering blebs area of the eyes of the rabbits revealed that compared with that in the normal group, the morphology of the collagen fibres in the MMC-ATS-@PLGA group was relatively regular, the fibres were arranged neatly, and the tissue morphology was similar to that of the normal group. Immunohistochemistry and Elisa confirmed that compared with those in the normal group, the expression levels of α-SMA, CTGF, and type Ⅲ collagen fibre antibodies were significantly increased in the control group. After FML, MMC, or MMC-ATS-@PLGA treatment for 3 wk, the expression of inflammatory factors gradually decreased. Among the groups, the MMC-ATS-@PLGA group showed the most significant decrease(P<0.05).CONCLUSION: This study successfully synthesized a nanomedicine(MMC-ATS-@PLGA)that inhibits scar proliferation after glaucoma filtration surgery. The drug had stable physicochemical properties, good biocompatibility, and better anti-inflammatory effects by inhibiting the expression of α-SMA, CTGF, and type Ⅲ collagen fibres, which can prevent the formation of scarring in the filtering blebs area, thereby improving the success rate of glaucoma filtering surgery.


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