1.Mechanism related to bile acids metabolism of liver injury induced by long-term administration of emodin.
Jing-Zhuo TIAN ; Lian-Mei WANG ; Yan YI ; Zhong XIAN ; Nuo DENG ; Yong ZHAO ; Chun-Ying LI ; Yu-Shi ZHANG ; Su-Yan LIU ; Jia-Yin HAN ; Chen PAN ; Chen-Yue LIU ; Jing MENG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(11):3079-3087
Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage*
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Bile Acids and Salts/metabolism*
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Animals
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Male
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Liver/injuries*
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Chemical and Drug Induced Liver Injury/genetics*
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Drugs, Chinese Herbal/adverse effects*
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Humans
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Rats, Sprague-Dawley
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Mice
;
Rats
3.Effect of the ABO Gene Variant c.917T>C on the Expression and Functional Role of B-Glycosyltransferase.
Shuang LIANG ; Fan WU ; Yan-Lian LIANG ; Tong LIU ; Li-Yan SUN ; Yu-Qing SU
Journal of Experimental Hematology 2025;33(1):269-275
OBJECTIVE:
By analyzing the correlation between genotypes and phenotypes, we explored the impact of the variant c.917T>C (p.L306P) in the ABO*B.01 allele on the expression and function of B-glycosyltransferase (GTB). This study aims to elucidate the molecular mechanisms underlying the occurrence of this subtype.
METHODS:
The study subjects included a blood donor specimen with incompatible forward and reverse ABO typing results. ABO phenotyping was determined using ABO blood group serology and GTB activity testing. Subsequently, Sanger sequencing and third-generation sequencing based on the PacBio platform were employed to sequence the ABO gene, resulting in the determination of haplotype sequences. Mutations were identified through sequence alignment. An in vitro cell expression system was established to assess the impact of the mutation site on antigen expression.
RESULTS:
The index case in this study was identified as B subtype with the allelic genotype c.917T>C in ABO*B.01/ABO*O.01.01 , which has not been previously reported. in vitro expression results revealed decreased levels of GTB expression and overall GTB activity in the mutant cells. Furthermore, the expression of the B antigen on the cell membrane was weaker in the mutant cells compared to the wild-type cells.
CONCLUSION
The p.L306P variation caused by the c.917T>C mutation in the ABO*B.01 allele may be a genetic factor contributing to the reduced expression of B antigens on the surface of red blood cells.
Humans
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ABO Blood-Group System/genetics*
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Alleles
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Genotype
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Mutation
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Glycosyltransferases/genetics*
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Haplotypes
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Phenotype
4.Predicting the potential suitable areas of Platycodon grandiflorum in China using the optimized Maxent model
Yu-jie ZHANG ; Han-wen YU ; Zhao-huan ZHENG ; Chao JIANG ; Juan LIU ; Liang-ping ZHA ; Xiu-lian CHI ; Shuang-ying GUI
Acta Pharmaceutica Sinica 2024;59(9):2625-2633
italic>Platycodon grandiflorum (Jacq.) A. DC is one of the most commonly used bulk medicinal herbs. It has important value in the fields of medicine, food and cosmetics, and its market demand is increasing year by year, and it has a good development prospect. In this study, based on 403 distribution records and 8 environmental variables, we used Maxent model to predict the potential distribution of
5.The inhibitory effect of artesunate on hepatocellular carcinoma cells by regulating expression of GADD45A and NACC1
Guan-Tong SHEN ; Jin-Yao DONG ; Jing FENG ; Nan QIN ; Gen-Lai DU ; Fei ZHU ; Ke LIAN ; Xin-Yu LIU ; Qing-Liang LI ; Xun-Wei ZHANG ; Ru-Yi SHI
Chinese Pharmacological Bulletin 2024;40(6):1089-1097
Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P<0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.
6.Seminoma characterized by thickening of the pituitary stalk:A case report
Bing PENG ; Xingtian WANG ; Yuhuan DENG ; Yu LIAN ; Yanling ZHENG ; Jianren KUANG ; Jinyu QIAN ; Jie LIANG ; Yanlin ZHANG
Journal of Central South University(Medical Sciences) 2024;49(6):863-869
Intracranial seminoma is a rare malignant tumor originating from the germ cells,usually occurring in the pineal gland or pituitary gland.In June 2020,the Department of Endocrinology at the First Affiliated Hospital of Army Military Medical University admitted a 20-year-old male patient with an intracranial germ cell tumor and spinal metastases.The patient presented with headache,dizziness,and visual impairment.Enhanced magnetic resonance imaging(MRI)of the head indicated thickening of the pituitary stalk.After multidisciplinary consultation,the patient underwent endonasal transsphenoidal resection of the tumor,with the pathological diagnosis confirming germ cell tumor.The patient received regular radiotherapy postoperatively.One year later,the tumor recurred and metastasized,leading to a second surgery for tumor resection in the thoracic spinal canal,followed by continued chemotherapy.The patient's clinical symptoms,such as headache and visual disturbances,improved,but he continued to experience panhypopituitarism and required long-term hormone replacement therapy.Early diagnosis of intracranial germ cell tumors is challenging,and they are prone to metastasis and highly sensitive to radiotherapy and chemotherapy.Early diagnosis and multidisciplinary comprehensive treatment can help improve the quality of life and prognosis for patients.
7.Methodological establishment of PTV and PRV margins for MRI guided online adapt-to-position radiotherapy for intracranial tumors
Qiu GUAN ; Nan LIU ; Xin LIAN ; Tingting DONG ; Yunliang SUN ; Hao LIANG ; Wei TIAN ; Lang YU ; Bo YANG ; Jie QIU
Chinese Journal of Radiation Oncology 2024;33(12):1106-1111
Objective:To establish a method for obtaining planning target volume (PTV) and planning risk volume (PRV) margins caused by rotation in the use of adapt-to-position (ATP) modality of magnetic resonance linear accelerator (MRL) for patients with intracranial tumors.Methods:Clinical data of 6 patients with intracranial tumors (150 fractions in total) who received MRI-guided online ATP radiotherapy in Peking Union Medical College Hospital from November 2023 to January 2024 were retrospectively analyzed. The pre-planned CT structure was copied onto each segmented MR image and then the structures were traced back to the CT image according to the three-dimensional registration relationship. The anisotropic distance of the structure based on the original CT structure was calculated to obtain the variation range of the target and the organs at risk. The maximum anisotropic value was taken as the result of the PTV and the relationship between the results and intracranial location of different patients was analyzed. Group comparison was performed by Chi-square test. Two group comparison was conducted by post-hoc Wilcoxon signed-rank test. Results:After the rotation deviation was included, the range of target changes in the six directions of left and right (L/R), anterior and posterior (A/P) and superior and inferior (S/I) of the 6 patients were: (1.24± 0.86) mm/(1.91± 1.07) mm, (2.02± 1.26) mm/(1.66± 1.07) mm, (1.84± 1.84) mm /(2.94±1.93) mm, respectively. The results in the SI direction were significantly different, and the values in the I direction in 2 patients exceeded 4 mm, the margins suitable for all patients were 3.01 mm/2.4 mm(A/P), 1.9 mm/2.93 mm(L/R) and 3.14 mm/4.62 mm(S/I) in different directions, respectively. The L/R direction of the lens and the S/I direction of the optic nerve were significantly changed, and the A/P direction of the brain stem was (3.99± 4.64) mm. Larger values might be required when the target was in the posterior brain (left-down area, right-down area).Conclusions:The rotation deviation, organ movement and intracranial location affect the PTV and the organs at risk PRV in the MRI-guided ATP modality in intracranial tumors patients. The margin generation method based on image fusion can help to quantify the margin value reasonably.
8.Effect of dapagliflozin on oxidative stress and left ventricular hypertrophy in patients with type 2 dia-betes mellitus and chronic heart failure
Yun LI ; Yu-Lian LIANG ; Chuan-Song LI
Chinese Journal of cardiovascular Rehabilitation Medicine 2024;33(4):455-460
Objective:To explore effect of dapagliflozin on oxidative stress and left ventricular hypertrophy in patients with type 2 diabetes mellitus(T2DM)and chronic heart failure(CHF).Methods:A total of 114 T2DM+CHF pa-tients treated in our hospital from January 2020 to October 2020 were included.They were divided into routine group(traditional medication)and dapagliflozin group(dapagliflozin oral therapy based on routine group)by ran-dom number table method,with 57 cases in each group.After 6-month treatment,left ventricular hypertrophy de-gree,indexes of oxidative stress,left ventricular remodeling and glucose metabolism were compared between two groups before and after treatment.Results:After 6-month treatment,15 cases were lost and 99 patients were fi-nally included,including 47 patients in the routine group and 52 patients in the dapagliflozin group.After 6-month treatment,compared with routine group,there was significant rise in superoxide dismutase(SOD)level[(33.17±6.05)U/L vs.(37.43±6.22)U/L](P<0.001),and significant reductions in reactive oxygen species(ROS)[(613.63±36.50)U/ml vs.(597.12±39.85)U/ml],left ventricular end-diastolic volume index(LVEDVI)[(49.31±2.58)ml/m2 vs.(47.60±2.53)ml/m2],left ventricular end-systolic volume index(LVESVI)[(31.18±2.37)ml/m2 vs.(29.44±2.26)ml/m2],left ventricular mass index(LVMI)[(107.93±6.46)g/m2 vs.(104.85±6.19)g/m2],incidence rate of left ventricular hypertrophy(19.15%vs.5.77%),levels of fasting blood glucose(FBG)[(6.33±1.56)mmol/L vs.(5.65±1.42)mmol/L],2h postprandial glucose(2hPG)[(7.35±1.11)mmol/L vs.(6.46±2.10)mmol/L]and glycosylated hemoglobin A1e(HbA1c)[(7.30±1.41)%vs.(6.62±1.29)%]in dapagliflozin group,P<0.05 or<0.01.Conclusion:Dapagliflozin on the basis of traditional medication can further im-prove blood glucose,inhibit oxidative stress,delay the process of left ventricular remodeling,and reduce the incidence of left ventricular hypertrophy in patients with type 2 diabetes mellitus and chronic heart failure.
9.Quality status of Bombyx Batryticatus and suggestions for Chinese Pharmacopoeia (2025).
Yong-Hong YANG ; Mei WANG ; Ye-Min CHONG ; Hong-Mei DENG ; Meng-Lian JIANG ; Zhuan-Zhen YANG ; Yu-Hao YAN ; Jing-Liang QI ; Min LI ; Yan GOU
China Journal of Chinese Materia Medica 2023;48(15):4087-4096
To understand the current quality status and rearing situation of Bombyx Batryticatus, the authors collected 102 batches of Bombyx Batryticatus from different main producing areas and five major Chinese medicine markets from 2016 to 2018, and measured the properties and quality of the silk gland, to clarify the quality status of Bombyx Batryticatus from different producing areas and markets. In addition, 35 batches of Bombyx Batryticatus from 2019 to 2022 were used to verify the silk gland after revision. Moreover, Beauveria Bassiana was inoculated in the silkworm of 4-5 instars, and standardized rearing was carried out until they die. The death rate and the quality of Bombyx Batryticatus were measured to determine the differences in Bombyx Batryticatus of different instars, and explore the rationality of the infection age of Bombyx Batryticatus in Chinese Pharmacopoeia(2020). The results revealed that in the 102 batches of Bombyx Batryticatus, the qualification rate of silk gland was low; the content of total ash far exceeded the standard; the content of beauvericin varied greatly. The qualification rate of the silk gland of the 35 batches of Bombyx Batryticatus was only 47.49%, which could be increased to 73.00% if the number of silk gland was 2 to 4. The death rate of Bombyx Batryticatus at different infection ages was quite different, with uneven quality. Generally, the yield of Bombyx Batryticatus inoculated on the first day of the fifth instar was high with good quality. Therefore, in combination with the quality and actual production of Bombyx Batryticatus, the following suggestions were proposed for revision of Bombyx Batryticatus in Chinese Pharmacopoeia(2025): The number of silk gland should be revised as 2-4 bright brown or bright black silk glands, after which, the quality of Bombyx Batryticatus could be guaranteed, and the "quality identification based on character" could also be reflected scientifically; the content determination index that the content of beauvericin shall not be less than 0.017% should be added to better control the quality of Bombyx Batryticatus; the infection age should be revised as the first day of the fifth instar to narrow the age span, which could better fit the actual production and ensure the quality of Bombyx Batryticatus.
Animals
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Bombyx
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Medicine, East Asian Traditional
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Silk
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Larva
10.Comparison of Plerixafor or Cyclophosphamide Combined with G-CSF in Mobilization of Peripheral Blood Stem Cells in Multiple Myeloma.
Wan-Ting LI ; Liang-Ming MA ; Yu LIAN ; Quan-Gang WANG ; Zhong-Jie GAO ; Shuang ZHAO
Journal of Experimental Hematology 2023;31(5):1403-1409
OBJECTIVE:
To compare the efficacy of plerixafor (PXF) combined with granulocyte colony-stimulating factor (G-CSF) (PXF+G-CSF) and cyclophosphamide (Cy) combined with G-CSF (Cy+G-CSF) in the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma (MM).
METHODS:
The clinical data of 41 MM patients who underwent PBSC mobilization using PXF+G-CSF (18 cases) or Cy+G-CSF (23 cases) in Shanxi Bethune Hospital from January 2019 to December 2021 were retrospectively analyzed, including the count of collected CD34+ cells, acquisition success rate, failure rate, and optimal rate. The correlation of sex, age, disease type, DS staging, ISS staging, number of chemotherapy cycle, disease status before mobilization, and mobilization regimen with the collection results was analyzed, and the adverse reactions, length of hospital stay, and hospitalization costs were compared between the two mobilization regimens.
RESULTS:
The 41 patients underwent 97 mobilization collections, and the median number of CD34+ cells collected was 6.09 (0-34.07)×106/kg. The acquisition success rate, optimal rate, and failure rate was 90.2%, 56.1%, and 9.8%, respectively. Univariate analysis showed that sex, age, disease type, and disease stage had no significant correlation with the number of CD34+ cells collected and acquisition success rate (P >0.05), but the patients with better disease remission than partial remission before mobilization were more likely to obtain higher CD34+ cell count (P <0.05). The PXF+G-CSF group had a larger number of CD34+ cells and higher acquisition success rate in the first collection than Cy+G-CSF group (both P <0.05), and had lower infection risk and shorter length of hospital stay during mobilization (both P <0.05), but the economic burden increased (P <0.05).
CONCLUSION
PXF+G-CSF used for PBSC mobilization in MM patients has high first acquisition success rate, large number of CD34+ cells, less number of collection times, and short length of hospital stay, but the economic cost is heavy.
Humans
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Antigens, CD34/metabolism*
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Cyclophosphamide/therapeutic use*
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Granulocyte Colony-Stimulating Factor/therapeutic use*
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Hematopoietic Stem Cell Mobilization/methods*
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Hematopoietic Stem Cell Transplantation
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Heterocyclic Compounds/therapeutic use*
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Multiple Myeloma/drug therapy*
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Peripheral Blood Stem Cells/metabolism*
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Retrospective Studies

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