1.Effect of Juglone on Proliferation Inhibition and RIPK1/RIPK3/MLKL Expression in Acute Myeloid Leukemia Cells.
Chun-Yi LYU ; Xue-Wei YIN ; Zong-Hong LI ; Chen HAN ; Yan WANG ; Zhen-Zhen WANG ; Lyu-Ye LIU ; Rui-Rong XU
Journal of Experimental Hematology 2025;33(4):980-985
OBJECTIVE:
To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia (AML) cells.
METHODS:
Juglone and AML targets were collected from public databases, and the intersecting target clusters were taken for functional enrichment analysis to explore the potential mechanism of juglone in the treatment of AML. Then wet experiments were performed to verify. AML cell lines including KG-1a, MV-411, THP-1 and MOLM-13 were treated with different concentrations of juglone for 24 h. MTT assay was used to detect cell viability and determine the IC50, and the most sensitive cell line was screened for subsequent experiments. Flow cytometry was used to detect the apoptosis of cells treated with different concentrations of juglone. Western blot was performed to check the expression of relevant proteins.
RESULTS:
Eleven targets were obtained as potential targets for juglone in the treatment of AML, and the top ten significantly enriched pathways were intrinsic pathway of apoptosis, programmed cell death, cytochrome c-mediated apoptotic response, apoptosis, apoptotic factor-mediated response, regulated necrosis, cytokine signaling in immune system, signaling by interleukins, oncogene induced senescence, and signal transduction. The cell viability of KG-1a, MV-411, THP-1 and MOLM-13 was decreased with increasing juglone concentration after 24 h of juglone treatment (r =-0.992, -0.886, -0.956, -0.910). Among them, MOLM-13 was the most sensitive to juglone. The results of flow cytometry showed that the apoptosis rate of MOLM-13 tended to significantly increase with the increasing concentration of juglone (r =0.99). At the same time point, p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLK were decreased in each juglone concentration group compared with control group.
CONCLUSION
Juglone inhibits the viability of KG-1a, MV-411, THP-1 and MOLM-13 cells, and induces apoptosis of MOLM-13 cells, the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.
Humans
;
Naphthoquinones/pharmacology*
;
Apoptosis/drug effects*
;
Cell Proliferation/drug effects*
;
Leukemia, Myeloid, Acute/pathology*
;
Cell Line, Tumor
;
Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*
;
Protein Kinases/metabolism*
;
Signal Transduction
;
Cell Survival/drug effects*
2.Research progress on carrier-free and carrier-supported supramolecular nanosystems of traditional Chinese medicine anti-tumor star molecules
Zi-ye ZANG ; Yao-zhi ZHANG ; Yi-hang ZHAO ; Xin-ru TAN ; Ji-chang WEI ; An-qi XU ; Hong-fei DUAN ; Hong-yan ZHANG ; Peng-long WANG ; Xue-mei HUANG ; Hai-min LEI
Acta Pharmaceutica Sinica 2024;59(4):908-917
Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.
3.The material basis and mechanism of action of anti-inflammatory effects of simplified Zhiqin Decoction
Kun WANG ; Yang LIU ; Yue YIN ; Xiao XIAO ; Xue-jiao ZHOU ; Zhi-ying YUAN ; Liang-hong YE ; Xiao-yu XU
Acta Pharmaceutica Sinica 2024;59(8):2245-2254
The anti-inflammatory effect of simplified Zhiqin Decoction was observed by using lipopolysaccharide (LPS)-induced inflammation mouse model. The main chemical constituents and the main mechanism of action of simplified Zhiqin Decoction were predicted by network pharmacology. Animal experiments verified the anti-inflammatory mechanism of simplified Zhiqin Decoction (this experiment was approved by the Animal Experiment Ethics Committee of Southwest University, approval number: IACUC-20210825-02). Simplifying Zhiqin Decoction has a significant anti-inflammatory effect on inflammatory mice, can significantly improve the overall macro shape of mice, reduce body temperature, water intake, increase the number of autonomous activities; alleviate liver, lung, spleen, thymus inflammation and pathological damage; decrease tumor necrosis factor-
4.Key Components of Fishy Smell of Eupolyphaga Steleophaga by Head Space-Solid Phase Microextraction-GC-MS and Odor Activity Value
Hongyan MA ; Hong FAN ; Qian LIU ; Xue LI ; Hui YE ; Dingkun ZHANG ; Yongmei GUAN ; Ming YANG ; Houlin XIA
Chinese Journal of Modern Applied Pharmacy 2024;41(1):88-96
To determine the main components of the fishy smell of the Eupolyphaga Steleophaga, and to provide a theoretical basis for deodorizing the Eupolyphaga Steleophaga.
METHODS
Head space-solid phase microextraction-gas chromatography-mass spectrometry was used to identify the components of 10 batches of Eupolyphaga Steleophaga, and area normalization method and chemometrics method were used to analyze the smelly gas of different batches. Odor activity value(OAV) was used to evaluate the contribution of odor components and identify key odor components.
RESULTS
A total of 87 volatile odor components were identified, the key fishy smell compounds(OAV≥1) were m-methylphenol, dimethyltrisulfide, 4-methylphenol, 2-methyliso-borneol, 2-etzol, 4-methylvaleric acid, iso-valeric acid, etc. Modified fishy gas composition(0.1
5.Exploration and practice of humanistic care in children's fever clinics from the perspective of narrative medicine
Yutao CAI ; Xue CHEN ; Xiulan WEN ; Liyan YE ; Handan HONG ; Canying LI ; Xian CAI ; Qiumei YANG ; Yansong SU
Chinese Medical Ethics 2024;37(5):586-591
To explore the application of humanistic care in children's fever clinics,the children's fever clinics of Guangzhou Women and Children's Medical Center conducted relevant research using narrative medicine as a guiding concept.This paper elaborated on the medical humanistic dilemmas and narrative care needs in children's fever clinics,and focused on exploring the practice paths of narrative medicine in pediatric with Chinese characteristics from five dimensions,including the cultivation of nursing staff's abilities of professional narrative and humanistic care,the establishment of health lectures featuring narrative patient education,the alleviation of medical anxiety for children and their families,related support of narrative nursing,and caring services.The aim was to improve the narrative care ability of nurses in children's fever clinics,develop methods for pediatric patients that can eliminate the fear of seeking medical treatment,and protect children's physical and mental health.A carrier of care,support,and emotional expression can be provided for parents.The foundation for nursing staff to achieve professional growth through narrative reflection can be laid.Thus,it can assist in establishing a life narrative community relationship between doctors and patients,and jointly explore the meaning of life.
6.Huaiqihuang Granules Affect Differentiation of Th17 Cells in IgA Vasculitis Nephritis Mice by Regulating AMPK/ACC Pathway
Xinglan YE ; Keying LI ; Jiaxuan LI ; Juan BAI ; Wencheng XU ; Hong LIU ; Xue XUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):78-86
ObjectiveTo observe the intervention effect of Huaiqihuang granules (HQH) on immunoglobulin A vasculitis nephritis (IgAVN) mice and explore the underlying therapeutic mechanism. MethodFifty SPF-grade male Kunming mice were randomly divided into a normal group, an IgAVN model group, a dexamethasone group (2.5 mg·kg-1·d-1), a low-dose HQH group (4 g·kg-1·d-1), and a high-dose HQH group (8 g·kg-1·d-1). The mouse model was established using oral administration of gliadin combined with intravenous injection of India ink. After successful modeling, the mice were euthanized after 4 weeks of gastric gavage according to groups. The 24 h urinary total protein (24 h UTP), urine β2-microglobulin (β2-MG), serum total protein, albumin, IgA, etc. were detected in each group. Flow cytometry was used to determine the proportion of T helper 17 (Th17) cells in spleen cell suspension. Western blot was employed to detect the expression of adenosine 5'-monophosphate-activated protein kinase α (AMPKα), phosphorylated AMPKα (p-AMPKα), acetyl-CoA carboxylase 1 (ACC1), and phosphorylated ACC1 (p-ACC1) in Th17 cells. Pathological changes in the spleen and kidneys were observed. ResultCompared with the normal group, the IgAVN model group showed significant increases in 24 h UTP, urine β2-MG, total cholesterol (P<0.05), serum interleukin-17 (IL-17), IgA, Th17 proportion in the spleen cell suspension, and IL-17 expression in the spleen tissue (P<0.01), and significantly decreased serum total protein, albumin, p-AMPKα/AMPKα, and p-ACC1/ACC1 expression of Th17 cells (P<0.01). Compared with the IgAVN model group, in the 4th week, the 24 h UTP, urine β2-MG, serum IL-17, IgA levels, and renal IgA deposition were significantly reduced in each treatment group (P<0.01), and the Th17 proportion and IL-17 expression in spleen tissue were significantly decreased (P<0.05, P<0.01). Serum albumin levels significantly increased (P<0.05). Compared with the IgAVN model group, the dexamethasone group and the high-dose HQH group showed increases in serum total protein (P<0.01), p-AMPKα/AMPKα, and p-ACC1/ACC1 expression of Th17 cells (P<0.05, P<0.01). The high-dose HQH group showed a significant decrease in total cholesterol level (P<0.05). Various treatment groups showed different degrees of improvement in spleen and kidney pathological changes. ConclusionHQH may affect Th17 cell differentiation by regulating the AMPK/ACC pathway, correcting immune inflammatory disorders, and exerting therapeutic effects on IgAVN.
7.Phenotypic evaluation of Ttc37 knockout mouse as type Ⅰ tricho-hepato-enteric syndrome model
Ming-Ya LI ; Xue-Lin WANG ; Ye WEI ; Pei-Hong YANG ; Lei SUN
Fudan University Journal of Medical Sciences 2024;51(2):249-256
Objective To establish a mouse model of type Ⅰ tricho-hepato-enteric syndrome(THES)induced by Ttc37 deficiency.Methods Ttc37 flox strain was established by site-specifically inserted loxP sites into Ttc37 gene via CRISPR/CAS9 technology.Ubiquitously expressed CAG-Cre was introduced for all-tissue removal of Ttc37 in Ttc37flox/flox;CAG-Cre mice.The knock-out effect was confirmed by fluorescence quantitative PCR and Western blot.Phenotypic evaluations were conducted in 8-week-old mice including hematoxylin-eosin staining of skin,spleen,liver,bladder,and gastrointestinal tract(GI),serum enzyme activity assay of aspartate aminotransferase(AST)and alanine aminotransferase(ALT),measurement of serum hemoglobin level,and ELISA for IgG and IgM level upon antigen immunization.Results Similar to type Ⅰ THES patients,Ttc37flox/flox;CAG-Cre mice exhibited impaired development of hair shaft,epidermis,B cell and eyes,while liver,GI,bladder and serum hemoglobin level seemed normal under unstressed condition.Conclusion A novel mouse model of typeⅠ THES was constructed successfully,which was applicable for pathological study.
8.Analysis of key genes in the development from colon adeno-ma to carcinoma through high-throughput RNA sequencing
Jie BIAN ; Tao WANG ; Chang-Chun YE ; Gen-Wang GAO ; Chun-Hong MA ; Xue-Jun SUN ; Qi SUN
Chinese Journal of Current Advances in General Surgery 2024;27(4):286-291
Objective:To analyze and compare the difference of gene expression profiles in normal colon tissues,colon adenoma and carcinoma tissues by RNA sequencing technology,and re-veal the key genes and potential mechanisms in the development from colon adenoma to carcinoma.Methods:RNA sequencing analysis was carried out on normal colon tissues,colon adenomas and carcinoma tissues of the same patient,and differential genes that were significantly expressed in colon cancer and not significantly expressed in adenoma tissues were obtained,and the GO and KEGG function enrichment analysis was performed.Results:There are 4307 differential genes that are significantly expressed in colon cancer and not significantly expressed in adenoma.The GO and KEGG function enrichment analysis of these genes found that they were mainly enriched in bi-ological processes such as biological process regulation,cell process regulation,protein binding and cancer pathway,PI3K Akt signal pathway MAPK signal pathway.Conclusion:There are many genes involved in the development process from colon adenoma to carcinoma.These genes have the potential to become therapeutic targets for colorectal cancer,providing a new direction for fol-low-up research on colorectal cancer.
9.Comparison of anterior lateral ligament reconstruction and anterior lateral complex repair in the treatment of anterior cruciate ligament combined with anterior lateral ligament injury with high-grade pivot shift.
Xue-Feng JIA ; Qing-Hua WU ; Tong-Bo DENG ; Xiao-Zhen SHEN ; Jian-Ping YE ; He FANG ; Rong-Chang ZHOU ; Yang CAO ; You-Fen CHEN ; Qi-Ning YANG ; Guo-Hong XU
China Journal of Orthopaedics and Traumatology 2024;37(11):1101-1106
OBJECTIVE:
To retrospectively analyze the clinical efficacy of anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex repair and ACL reconstruction combined with ALL reconstruction in the treatment of anterior cruciate ligament injuries with high-grade pivot shift.
METHODS:
From January 2018 to June 2022, 49 patients combined ACL and ALL injuries with high-grade pivot shift were retrospectively studied from three hospitals, 29 of them underwent ACL reconstruction with anterolateral complex repair (repair group), including 23 males and 6 females with an average age of (27.5±4.8) years old, ranged from 20 to 37 years old;the injured sides were 13 on the left and 16 on the right, and 11 patients were suffered with meniscus injury. The other 20 patients underwent ACL and ALL reconstruction (reconstruction group) including 17 males and 3 females with the mean age of (27.1±4.5) years old, ranged from 20 to 38 years old;the injured sides were 8 on the left and 12 on the right, and 6 patients were suffered with meniscus injury. Knee stability (pivot shift test, KT-2000), range of motion, knee function (Lysholm scoring scale, Cincinnati sports activity scale (CSAS) scoring scale, and Tegner activity level score between two groups were compared.
RESULTS:
A total of 49 patients were followed up, the repair group receiving 13 to 20(15.3±1.8) months and the reconstruction group receiving 12 to 21(16.0±2.2) months. There was no statistically significant difference in the preoperative pivot shift test grading distribution between two groups (P>0.05). At the last postoperative follow-up, there were 24 patients with grade 0 and 5 patients with grade 1 in the repair group, and there were 18 patients with grade 0 and 2 patients with grade 1 in the reconstruction group, there is no significant difference in the distribution of axial shift test grading between two groups(P>0.05). The preoperative KT-2000 tibial displacement of two groups were (9.39±0.77) mm (repair group) and (9.14±0.78) mm (reconstruction group) respectively, with no statistically significant difference (P>0.05). At the final postoperative follow-up, there were 24 patients with KT-2000 tibial displacement <3 mm and 5 patients with 3 to 5 mm in the repair group, while 18 patients with <3 mm and 2 patients with 3 to 5 mm in the reconstruction group, KT-2000 tibial displacement distribution of two groups was no significant difference (P>0.05), but the KT-2000 tibial displacement in the reconstruction group (1.30±0.86) mm was significantly smaller than that in the repair group (1.99±1.11) mm (P<0.05). The final postoperative follow-up range of motion of the contralateral side knee between two groups was no significant difference (P>0.05). The range of motion of the suffering knee in the repair group was less than that in the reconstruction group (P<0.05). There was no significant difference in preoperative Lysholm and CSAS scores between two groups (P>0.05). At the final postoperative follow-up, both groups showed significant improvement in Lysholm and CSAS scores, while the Lysholm and CSAS scores of the reconstruction group were better than those of the repair group, and the difference was statistically significant (P<0.05). Significant differences was found in Tegner scores between two groups, which 16 patients in the repair group returned to their pre-injury activity level, and 17 patients in the reconstruction group returned to their pre-injury level (P<0.05).
CONCLUSION
Compared to anterolateral complex repair, combined ACL and ALL reconstruction in the treatment of ACL injuries with high-grade pivot shift results in better knee joint function and stability. This is advantageous in reducing the risk of ACL reconstruction failure.
Humans
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Male
;
Female
;
Adult
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Anterior Cruciate Ligament Reconstruction/methods*
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Anterior Cruciate Ligament Injuries/surgery*
;
Young Adult
;
Retrospective Studies
;
Anterior Cruciate Ligament/surgery*
;
Range of Motion, Articular
10.Activation of renal outer medullary potassium channel in the renal distal convoluted tubule by high potassium diet.
Xue LI ; Peng-Hui LI ; Yu XIAO ; Kun ZHAO ; Hong-Ye ZHAO ; Chang-Zhu LU ; Xiao-Juan QI ; Rui-Min GU
Acta Physiologica Sinica 2023;75(2):188-196
Renal outer medullary potassium (ROMK) channel is an important K+ excretion channel in the body, and K+ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K+ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na+-Cl- cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.
Potassium Channels, Inwardly Rectifying/metabolism*
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Kidney Tubules, Distal/metabolism*
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Potassium/metabolism*
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Epithelial Sodium Channels/metabolism*
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Diet


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