1.Effect of Biejia Decoction Pill on aerobic glycolysis in hepatocellular carcinoma by regulating the protein kinase B/mammalian target of rapamycin signaling pathway
Qinwen TAN ; Jingjing HUANG ; Ruixi ZHONG ; Yuanqin DU ; Jian XU ; Jinli NONG ; Yujiao PENG
Journal of Clinical Hepatology 2025;41(2):300-306
ObjectiveTo investigate the inhibitory effect of Biejia Decoction Pill on the proliferation, migration, and aerobic glycolysis of hepatocellular carcinoma (HCC) using cell experiments, as well as related mechanisms. MethodsHuman liver cancer cell line Huh7 was selected, and Sprague-Dawley rats were randomly divided into blank serum group, inhibitor group, and high-, middle-, and low-dose Biejia Decoction Pill groups. Rat serum containing the drug was prepared for the incubation of Huh7 cells. CCK8 assay and scratch assay were used to explore the effect of Biejia Decoction Pill on the proliferation and migration of HCC cells; glycolytic rate-limiting enzymes and metabolites were measured to explore the effect of Biejia Decoction Pill on aerobic glycolysis of liver cancer cells; RT-qPCR and Western blot were used to explore the effect of Biejia Decoction Pill on the mRNA expression, related proteins, and phosphorylation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test or the Dunnett’s T3 test were used for further comparison between two groups. ResultsCompared with the blank serum group, the Biejia Decoction Pill groups had significant reductions in OD value, migration rate during different periods of time, glycolytic rate-limiting enzymes (hexokinase, phosphofructokinase, pyruvate kinase), and glycolytic metabolites (pyruvate, lactic acid, ATP) (all P<0.05). RT-qPCR results showed that compared with the blank serum group, the high-, middle-, and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of mTOR, and the high- and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of AKT (all P<0.05). Western blot results showed that compared with the blank serum group, the high-, middle-, and low-dose Biejia Decoction Pill groups had significant reductions in the expression levels of mTOR-related proteins and phosphorylated proteins, and the high- and middle-dose Biejia Decoction Pill groups had significant reductions in the expression levels of AKT-related proteins and phosphorylated proteins (all P<0.05). ConclusionThis study preliminarily verifies that the serum containing Bijia Decoction Pill can inhibit the aerobic glycolysis of human hepatoma Huh7 cells, thereby inhibiting their proliferation and migration, possibly by inhibiting the expression of the proteins related to the AKT/mTOR signaling pathway.
2.Harmonizing tradition and technology: Liposomal nanocarriers unlocking the power of natural herbs in Traditional Chinese Medicine.
Ibrahim SHAW ; Aaron Albert ARYEE ; Yimer Seid ALI ; George Frimpong BOAFO ; Jingjing TIAN ; Ronald MLAMBO ; Songwen TAN ; Chuanpin CHEN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(6):700-713
Natural herbs demonstrate significant therapeutic potential in managing chronic and complex diseases; however, their clinical application faces limitations due to low bioavailability, instability, toxicity, and herb-drug interactions. Furthermore, insufficient standardized evidence and global acceptance impede their widespread adoption. Liposomes, nanocarriers consisting of a phospholipid bilayer enclosing an aqueous core, present a promising approach for enhancing the pharmacokinetics and therapeutic efficacy of herbal compounds. These adaptable systems can encapsulate both hydrophilic and hydrophobic agents, enabling targeted drug delivery and enhanced stability. Moreover, liposomes can be modified to carry diagnostic and imaging agents, enabling precise disease detection and monitoring. While liposomes offer potential as an innovative delivery technology for herbal remedies, their application in Traditional Chinese Medicine (TCM) remains relatively unexplored. TCM, with its holistic, energy-based approach to health and organ function, presents distinct challenges regarding formulation and delivery. This review examines the therapeutic potential of herbal medicines, emphasizing how liposomes address delivery challenges within the TCM framework. It also investigates the integration of TCM with Western medical practices, demonstrating how liposomal systems may bridge these approaches. The review analyzes key formulation techniques for TCM-loaded liposomes, particularly the microfluidic method, which demonstrates superior control over particle size and encapsulation efficiency compared to conventional methods. The analysis addresses barriers to integrating liposomal delivery systems with TCM, including physicochemical properties, scalability issues, and regulatory challenges. Finally, this review provides strategic recommendations for overcoming these obstacles and identifies future research directions to maximize the potential of liposomal technology in enhancing TCM therapies.
Liposomes/chemistry*
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Drugs, Chinese Herbal/administration & dosage*
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Humans
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Medicine, Chinese Traditional/methods*
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Drug Delivery Systems
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Drug Carriers/chemistry*
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Animals
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Nanoparticles/chemistry*
3.The relationship between D-loop region single nucleotide polymorphism and copy number of mitochondrial DNA with the risk of developing dermatomyositis
Zirui Tan ; Jingjing Zhang ; Yuanyuan Jia ; Chenxing Peng ; Yufe Zhao
Acta Universitatis Medicinalis Anhui 2025;60(1):130-135
Objective :
To explore the relationship between single nucleotide polymorphisms ( SNPs) in D-loop region of mitochondrial DNA ( mtDNA) and mtDNA copy number and the risk of dermatomyositis ( DM) ,and its in- fluencing factors.
Methods :
74 patients with DM and 92 healthy controls were included in the study. Genomic DNA was extracted from peripheral blood and the target fragment of mtDNA D-loop region was amplified by PCR technique,and the products were subsequently sequenced.Serum levels of ROS were assessed using a high-sensi- tivity reactive oxygen species detection kit.The expression levels of cytokines,interleukin ( IL) -5,IL-13,inter- feron-γ ( IFN-γ) ,IL-2,IL-6,IL-10,tumor necrosis factor-α ( TNF-α) and IL-4 were measured using Flow Fluo- rescence Immunmicrobeads Assay.Wilcoxon rank-sum test was used to assess the potential correlation between cy- tokines and SNPs associated with DM risk.The relative copy number of mtDNA was measured using quantitative re- al-time polymerase chain reaction ( qPCR) analysis.
Results :
Two SNPs ( 16304T / C,16519T / C) were found to be associated with the risk of developing DM,and alleles 16304C ( χ2 = 4. 937,P = 0. 026) and 16519C ( χ2 = 4. 405,P = 0. 036) in the mitochondrial D-loop region were confirmed to be associated with DM development risk. The DM risk-associated allele 16304C was significantly associated with lower IL-4 expression ( P = 0. 016) .The mtDNA copy number was significantly higher in DM patients than in controls ( P <0. 001) .
Conclusion
Mitochondrial D-loop SNPs can be potential biomarkers for DM risk,and SNPs may be involved in DM by influencing cytokines.DM shows high expression of mtDNA copy number,and the increase in mtDNA copy number may lead to mitochondrial dysfunction,which triggers the pathogenesis of DM.
4.Association of stage 1 hypertension defined by the 2017 ACC/AHA guideline with cardiovascular events and mortality in Chinese adults
Qiannan GAO ; Liuxin LI ; Jingjing BAI ; Luyun FAN ; Jiangshan TAN ; Shouling WU ; Jun CAI
Chinese Medical Journal 2024;137(1):63-72
Background::The 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) guideline lowered the threshold defining hypertension to 130/80 mmHg. However, how stage 1 hypertension defined using this guideline is associated with cardiovascular events in Chinese adults remains unclear. This study assessed the association between stage 1 hypertension defined by the 2017 ACC/AHA guideline and clinical outcomes in the Chinese population.Methods::Participants with stage 1 hypertension ( n = 69,509) or normal BP ( n = 34,142) were followed in this study from 2006/2007 to 2020. Stage 1 hypertension was defined as a systolic blood pressure of 130–139 mmHg or a diastolic blood pressure of 80–89 mmHg. None were taking antihypertensive medication or had a history of myocardial infarction (MI), stroke, or cancer at baseline. The primary outcome was a composite of MI, stroke, and all-cause mortality. The secondary outcomes were individual components of the primary outcome. Cox proportional hazards models were used for the analysis. Results::During a median follow-up of 11.09 years, we observed 10,479 events (MI, n = 995; stroke, n = 3408; all-cause mortality, n = 7094). After multivariable adjustment, the hazard ratios for stage 1 hypertension vs. normal BP were 1.20 (95% confidence interval [CI], 1.13–1.25) for primary outcome, 1.24 (95% CI, 1.05–1.46) for MI, 1.45 (95% CI, 1.33–1.59) for stroke, and 1.11 (95% CI, 1.04–1.17) for all-cause mortality. The hazard ratios for participants with stage 1 hypertension who were prescribed antihypertensive medications compared with those without antihypertensive treatment during the follow-up was 0.90 (95% CI, 0.85–0.96). Conclusions::Using the new definition, Chinese adults with untreated stage 1 hypertension are at higher risk for MI, stroke, and all-cause mortality. This finding may help to validate the new BP classification system in China.
5.Effect of amino acid metabolic reprogramming on immune microenvironment of hepatocellular carcinoma
Xiaoli LIU ; Qinwen TAN ; Jian XU ; Huanling CHEN ; Jie YU ; Lu LU ; Mingkan DAI ; Jingjing HUANG ; Hongna HUANG ; Dewen MAO
Journal of Clinical Hepatology 2024;40(12):2531-2537
Tumor immune microenvironment is a local external tumor environment composed of tumor immune cells and the cytokines secreted by these cells, and it plays a regulatory role in the development and progression of tumors. In the treatment of hepatocellular carcinoma, amino acid metabolism and its reprogramming of proliferating cell metabolism have attracted more and more attention, showing potential in regulating the tumor immune microenvironment. Although amino acid metabolic reprogramming is regarded as a novel approach for tumor therapy, its specific mechanism remains unclear in the regulation of tumor immunity in hepatocellular carcinoma. This article discusses the mechanism of action of amino acid metabolism in the tumor immune microenvironment of hepatocellular carcinoma and its application prospect in clinical practice, in order to provide new ideas for immunotherapy for liver cancer.
6.Oxidized lipoprotein(a)induces endothelial cell pyroptosis by inhibiting the expres-sion of cytochrome b
Zitong CAO ; Yanjun CHEN ; Shiming TAN ; Yuzhu RAO ; Jingjing WANG ; Zeming CAI ; Zuo WANG
Chinese Journal of Arteriosclerosis 2024;32(7):558-566
Aim To explore the mechanism of oxidized lipoprotein(a)(oxLp(a))inducing pyroptosis of vascu-lar endothelial cells.Methods After incubating human umbilical vein endothelial cells(HUVEC)with 100 mg/L ox-Lp(a)for 24 hours,Western blot and RT-qPCR was used to detect pyroptosis related proteins,pro-inflammatory cytokines,mitochondrial related proteins NRF1,NRF2,PGC-1α and mitochondrial gene cytochrome b(CYTB),ELISA was used to detect the levels of inflammatory factors,scanning electron microscopy was used to detect cell membrane rup-ture,transmission electron microscopy was used to detect mitochondrial morphology,Hoechst33342/PI staining was used to detect cell apoptosis,MitoSOX probe was used to detect mitochondrial reactive oxygen species(mtROS),Flu-4AM probe was used to detect calcium ions,JC-1 probe was used to detect mitochondrial membrane potential(MMP),and Calcein AM staining was used to detect mitochondrial permeability transition pore(mPTP).Transfecting HUVEC with CYTB overexpressing lentivirus and analyzing its effects on oxLp(a)induced pyroptosis and mitochondrial function.Results After treatment with oxLp(a),the expression of NLRP3,pro-Caspase-1,Caspase-1,GSDMD and GSDMD-N proteins re-lated to pyroptosis were significantly increased(P<0.05);the protein and mRNA levels of CYTB and pro-inflammatory cy-tokine IL-1β,IL-18 were significantly increased(P<0.05).Small pores appeared on the cell membrane,the percentage of PI stained positive cells significantly increased(P<0.05).OxLp(a)significantly inhibited the expression of mito-chondrial related proteins NRF1,NRF2 and PGC-1α,and the expression of mitochondrial gene CYTB,promoted an in-crease in mtROS generation,Ca2+overload,a decrease in ATP levels,a decrease in MMP,an increase in mPTP values,and abnormal mitochondrial morphology.After transfection with pHelper 2.0 lentivirus vector overexpressing CYTB,it was found that oxLp(a)induced HUVEC pyroptosis and mitochondrial morphological and functional abnormalities were par-tially reversed by overexpression of CYTB.Conclusion oxLp(a)promotes mitochondrial morphological and functional abnormalities and induces HUVEC pyroptosis by downregulating CYTB.
7.Research progress of matrix metalloproteinase-28 in pulmonary disease
Ling TAN ; Xue MA ; Jingjing WANG ; Fengfeng LEI
The Journal of Practical Medicine 2024;40(20):2949-2953
Matrix metalloproteinase-28(MMP-28)is widely expressed in vertebrates and plays diverse biological roles,participating in the regulation of various pathophysiological processes in the body.Increased expression of MMP-28 has been observed in chronic obstructive pulmonary disease,pulmonary fibrosis,and other lung diseases.Studies have demonstrated that MMP-28 promotes chronic inflammation and tissue remodeling by regulating macrophage recruitment and M2 polarization,and is involved in the pathogenesis of lung diseases by promoting cell proliferation and epithelial-mesenchymal transition.This article provides a review of the relationship between the basic characteristics of MMP-28 and pulmonary diseases.
8.Research progress on the role of microglia polarization in neuropathic pain
Jingjing CHEN ; Zhangsong NONG ; Liangyuan TAN ; Peipei YANG ; Yingye LIANG ; Hongliang TANG ; Kailong WANG
Tianjin Medical Journal 2024;52(9):1000-1003
Neuropathic pain(NPP)is a recurrent and intractable pain syndrome,and microglial polarization is closely related to it.Recent studies have shown that after cell polarization,M1 pro-inflammatory and M2 anti-inflammatory types could be formed,and M1 and M2 microglial cells are involved in NPP through the modulation of inflammatory responses.The two types of microglial cells have different roles in NPP,just like a double-edged sword.M1 pro-inflammatory type plays an injurious role in NPP through the release of pro-inflammatory factors and noxious substances,whereas M2 anti-inflammatory type plays a protective role by secreting anti-inflammatory factors.In this article,the role of microglia polarization on NPP are reviewed.
9.Genetic characteristics of human infection with Brucella melitensis in Nanjing from 2017 to 2022
Weixiang WANG ; Lu ZHOU ; Jingjing SU ; Nan ZHANG ; Jie HONG ; Weizhong ZHOU ; Changjun BAO ; Zhongming TAN
Chinese Journal of Endemiology 2024;43(10):775-782
Objective:To study the distribution of species type, biotype and genotype of human Brucella isolated and identified in Nanjing. Methods:A total of 89 strains of human Brucella were collected from microbiology laboratories of three sentinel hospitals in Nanjing from 2017 to 2022. The species type was identified using biological methods and Brucella nucleic acid detection (BCSP31-PCR and AMOS-PCR). Further biotyping of Brucella melitensis isolates was conducted by serological results of A and M factors. Meanwhile, genotype analysis was performed using multiple-locus variable number tandem repeat analysis (MLVA), multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP). Results:From 2017 to 2022, 89 strains of Brucella isolated and identified in Nanjing were all Brucella melitensis. Among them, Brucella melitensis biotype 3 accounted for 82.02% (73/89), and biotype 1 accounted for 17.98% (16/89). MLVA typing showed that 89 strains of Brucella melitensis belong to the "Eastern Mediterranean" cluster and could be divided into 50 MLVA genotypes; among which panel 1 had 3 genotypes, namely Type 42 (84.27%, 75/89), Type 63 (8.99%, 8/89) and Type 43 (6.74%, 6/89). The results of MLST-9 and MLST-21 were both ST8, and the core genome multilocus sequence typing (cgMLST) classified 89 strains into 11 genotypes. SNP analysis revealed a total of 4 013 SNP loci, with SNPs ranging from 0 to 409 across different strains, involving 59 SNP genotypes. Conclusions:The human Brucella strains isolated and identified in Nanjing are all Brucella melitensis, mainly biotype 3. The MLVA cluster is the "Eastern Mediterranean" cluster. The traditional MLST-9 and MLST-21 typing results are all ST8 type, while cgMLST divides all the strains into 11 genotypes with higher resolution.
10.Clinical application study on capillary electrophoresis-based gene diagnosis of hyperphenylalaninemia
Jianxin TAN ; Yun SUN ; Binbin SHAO ; Yanyun WANG ; Yuguo WANG ; Yan WANG ; Jingjing ZHANG ; Zhengfeng XU
Chinese Journal of Applied Clinical Pediatrics 2024;39(2):94-97
Objective:To evaluate the clinical value of a capillary electrophoresis-based method for gene diagnosis of hyperphenylalaninemia.Methods:In this single-center prospective study, 40 newborns with suspected hyperphenylalaninemia detected by neonatal liquid chromatography-tandem mass spectrometry screening at Nanjing Maternity and Child Health Care Hospital from February 2021 to February 2023 were included, with 22 males, 18 females and a mean age at diagnosis of 21.93 days.Capillary electrophoresis was used to detect 85 variants of the phenylalanine hydroxylase ( PAH) gene in 40 newborns with suspected hyperphenylalaninemia.The PAH gene of undiagnosed patients was further analyzed by Sanger sequencing.The detection rate, sensitivity and specificity of capillary electrophoresis were calculated. Results:Among these 40 newborns with suspected hyperphenylalaninemia, 71 PAH variants were detected by capillary electrophoresis, 32 patients were clearly diagnosed, only 1 pathogenic variant was found in 5 patients, and no pathogenic variant was found in the last 3 patients.Therefore, the detection rate, sensitivity and specificity of capillary electrophoresis for analysis of the PAH gene were 80.00%, 88.75% and 100%, respectively. Conclusions:The capillary electrophoresis-based method can rapidly, efficiently and accurately detect PAH gene variants at lower cost and is a promising gene detection method for hyperphenylalaninemia in clinical practice.


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