1.Mechanism of action of the nuclear factor-kappa B signaling pathway in liver diseases and its potential as a therapeutic target
Wenqian FENG ; Yang DU ; Dewen MAO ; Weiyu CHEN ; Lei FU ; Luyi YAN ; Chun YAO ; Yanmei LAN
Journal of Clinical Hepatology 2025;41(9):1949-1955
Nuclear factor-kappa B (NF-κB) is an important intracellular transcription factor widely involved in the processes such as immune response, inflammatory response, cell proliferation, and apoptosis. The abnormal activation of the NF-κB signaling pathway plays a pivotal role in various liver diseases including chronic hepatitis, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. Extensive studies have shown that inhibiting NF-κB activity may effectively reduce inflammation and fibrosis and improve metabolic disorders. Several natural compounds, such as matrine and salvianolic acid B, have shown the potential in suppressing NF-κB activity, thereby exerting anti-inflammatory, anti-fibrotic, and anti-tumor effects. This article systematically reviews the critical role of the NF-κB signaling pathway in liver diseases and its potential as a therapeutic target, in order to highlight its potential as a therapeutic target for liver diseases and provide new directions for the treatment of liver diseases.
2.Prevotella nigrescens exacerbates periodontal inflammation and impairs cognitive function in mice.
Qi CHEN ; Tiantian XIA ; Yongqiang ZHOU ; Mingyang CHANG ; Nan HU ; Yanmei YANG ; Zhong LI ; Yue GAO ; Bin GU
Journal of Southern Medical University 2025;45(3):453-460
OBJECTIVES:
To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice.
METHODS:
Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining.
RESULTS:
After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups.
CONCLUSIONS
Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals
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Periodontitis/microbiology*
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Mice
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Mice, Inbred C57BL
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Cognition
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Alveolar Bone Loss
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Hippocampus/pathology*
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Male
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Inflammation
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Maze Learning
3.Synthesis and Cytotoxicity Evaluation of Panaxadiol Derivatives
Hong PU ; Chengmei DONG ; Cheng ZOU ; Qing ZHAO ; Wenyue DUAN ; Yanmei CHEN ; Lianqing ZHANG ; Jianlin HU
Chinese Journal of Modern Applied Pharmacy 2024;41(13):1765-1774
OBJECTIVE
To obtain stronger cytotoxic activity of panaxadiol derivatives.
METHODS
The 3-amino panaxadiol was prepared by the bioelectronic isosteric principle, and then 18 derivatives of cinnamic acid, NO donor and other types of panaxadiol derivatives were synthesized, among them, 12 compounds had not been reported in the literature, and their structures had been confirmed by 1H-NMR, 13C-NMR and mass spectrometry. These compounds were evaluated for their cytotoxic activity by MTS assay against human leukemia cell line HL-60, liver cancer cell line SMMC-7721, lung cancer cell line A-549, breast cancer cell line MCF-7, and colon cancer cell line SW480.
RESULTS
These results showed that compounds 6c, 7 as well as 7j exhibited potent inhibitory activities against all five tumor cells, especially the IC50 values of compound 7 against HL-60 and SMMC-7721cells were 3.41 and 4.51 μmol·L−1, respectively. It was significantly superior to panaxadiol in cytotoxicity.
CONCLUSION
These results show that 7 and 7j can be used as promising lead compounds for further research.
4.Cardio-metabolic risk and adverse pregnancy outcomes in the first trimester: findings from the Shenzhen birth cohort study
Yixuan CHEN ; Linlin WU ; Xiaoxia WU ; Yanmei WAN ; Xuna HUANG ; Jianmin NIU
Chinese Journal of Cardiology 2024;52(2):158-164
Objective:To investigate the relationship between cardio-metabolic abnormalities in the first trimester and adverse pregnancy outcomes (APO).Methods:This cohort study recruited singleton pregnancies in the first trimester (6-13 +6 weeks of gestation) from Shenzhen Maternal and Child Health Care Hospital between January 1, 2021, and October 31, 2022. Cardiometabolic markers, including body mass index (BMI), blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were recorded during the first trimester. Incidence of APO, including gestational hypertension, preeclampsia, gestational diabetes mellitus, preterm birth, fetal growth restriction, small for gestational age infant, and placental abruption, was documented. Cardiovascular metabolic abnormalities in the first trimester were defined as meeting one or more of the following criteria: elevated BMI (BMI≥24 kg/m2), elevated TG (TG≥1.7 mmol/L), decreased HDL-C (HDL-C<1.0 mmol/L), elevated blood pressure (systolic pressure≥130 mmHg (1 mmHg=0.133 kPa) and/or diastolic pressure≥85 mmHg), elevated FPG (FPG≥5.6 mmol/L). Enrolled women were categorized into abnormal cardio-metabolic and normal cardio-metabolic groups. Poisson regression was employed to analyze the association between cardio-metabolic abnormalities in the first trimester and APO. Results:The study included 14 197 pregnant women with an age of (32.0±4.1) years. There were 8 139 women in the normal cardio-metabolic group and 6 058 women in the abnormal cardio-metabolic group. Women with cardio-metabolic disorders in the first trimester had a younger gestational age and higher incidence rates of preterm birth, gestational hypertension, preeclampsia, and gestational diabetes mellitus (all P<0.05). In multivariable Poisson regression, elevated BMI ( RR=1.22, 95% CI 1.15-1.29), elevated FPG ( RR=1.59, 95% CI 1.38-1.82), elevated TG ( RR=1.22, 95% CI 1.13-1.31), and elevated blood pressure ( RR=1.50, 95% CI 1.39-1.63) were independent risk factors for APO, while decreased HDL-C ( RR=0.93, 95% CI 0.70-1.23) was not. Elevated blood pressure ( RR=5.57, 95% CI 4.58-6.78), elevated BMI ( RR=1.71, 95% CI 1.40-2.09), and elevated TG ( RR=1.38, 95% CI 1.10-1.74) had the greatest impact on the risk of developing preeclampsia. Elevated FPG ( RR=1.70, 95% CI 1.45-1.99) had the greatest impact on the risk of gestational diabetes. Conclusions:Elevated blood pressure, BMI, TG and FPG in the first trimester are closely related to APO.
5.Drug resistance characteristics and treatment strategies of TB patients in three age groups in Guangdong Province from 2014 to 2020
Wenji ZHUO ; Ran WEI ; Yanmei CHEN ; Xunxun CHEN ; Meiling YU ; Huixin GUO ; Hongdi LIANG ; Jing LIANG ; Xiaoyu LAI
The Journal of Practical Medicine 2024;40(5):702-707
Objective To evalute the drug resistance characteristics of tuberculosis(TB)patients of all ages in Guangdong Province during 2014-2020,and provide prevention and treatment strategies of tuberculosis.Method We used 39,048 clinical isolates of Mycobacterium tuberculosis(MTB)belonging to patients with confirmed TB from 2014 to 2020,from 32 TB drug-resistant surveillance sites in Guangdong Province,and we retrospectively analyzed the laboratories data of patients with drug-resistant TB,and grouped patients by age and region,to explore the trend of drug-resistance of MTB clinical isolates,the trend and incidence differences of multi-resistant TB(including monodrug-resistant TB(MR-TB),polydrug-resistant TB(PDR-TB),multidrug-resistant TB(MDR-TB)and exten-sively drug-resistant TB(XDR-TB)),and resistance characteristics of MTB clinical isolates to drugs in focus(rifam-picin and ofloxacin).Result The differences in the resistance rates of MTB clinical isolates to nine antituberculosis drugs among patients at 32 TB drug resistance surveillance sites in Guangdong Province from 2014 to 2020 were not statistically significant(P>0.05).The rates of MR-TB,PDR-TB,MDR-TB,XDR-TB,and total resistance isolates of MTB clinical isolates were 14.46%,5.16%,5.16%,4.58%,and 1.29%,respectively.he pediatric group had a higher MR rate(15.4%)than the adult and geriatric groups,while the adult and geriatric groups had higher MDR rates(5.0%and 5.0%,respectively).The geriatric group also had a higher XDR rate(2.1%),with statistically significant differences(P<0.001).The rates of MR-TB(14.8%),PDR-TB(5.3%),MDR-TB(4.7%),XDR-TB(1.4%),ofloxacin resistance(11.33%)and rifampicin resistance(6.92%)of MTB clinical isolates were higher in patients from the Pearl River Delta than in other regions of Guangdong Province,with statistically significant differ-ences(P<0.001).Conclusion According to the data from the surveillance sites,the epidemiological trend of drug-resistant TB in Guangdong Province is leveling off during the period 2014-2020.However,the incidence of drug-resistant TB is higher in specific populations(e.g.children and the elderly),and the incidence of drug-resistant TB and the rate of drug resistance to drugs in focus are higher in the Pearl River Delta than in other regions of Guang-dong Province,necessitating further investigation and the development of novel prevention and control strategies.
6.Effectiveness of cold-air anesthesia during fractional carbon-dioxide laser treatment
Lidan ZHANG ; Xiaolei QIN ; Yanmei WANG ; Mengjiao CHEN ; Kai LI
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(3):292-295
Objective:To evaluate the impact of cold-air anesthesia on patients′ comfort and side effects during ablative fractional carbon-dioxide (CO 2) laser treatment for acnescars. Methods:Eighteen patients with atrophic acne scars treated with CO 2 laser were used as split-face comparative study with a cold-air device combined with 5% lidocaine cream on the left side of the face, and the right side as a control group treated with 5% lidocaine cream only. Symptoms and signs of patients were observed during treatment, immediately after treatment, 15 minutes, 30 minutes and 1 month after treatment. The score of patient′s comfort and incidence of adverse events was evaluated. Results:The results were obvious difference between each group. The surface temperature in combined group (33.1±1.3) showed significantly better results compared with other groups (36.9±0.4) during the operative period while the same result after the treatment immediately shown in the combined group (35.1±1.3) compared with other groups (36.4±0.2). The score of erythema shown that combined group (48.7±8.4) was significantly lower than that of the control group (54.8±8.0) ( P<0.05) as the score of exudation in combined group (6.2±1.6) was lower than that in the control group (7.8±1.6). There was significant statistical difference regarding scores of erythema between combined group (46.9±6.6) and control group (51.8±6.9) a month after the treatment. The pigmentation score revealed the same result that the combined group (48.9±8.8) was lower than the other groups (51.4±7.0). No patients had severe adverse events. Conclusions:The cold-air cooling application is safe and effective to reduce the surface temperature, pain and side effects during fractional carbon-dioxide laser treatment.
7.Rapid Analysis of Chemical Constituents from Ethanol Extracts of Yuye Detoxification Particle Based on UPLC-Q-TOF-MS/MS and Molecular Network Technology
Xiaolong FENG ; Yuan CAI ; Penghui LI ; Jun CHEN ; Kaiyi CHEN ; Hongping LONG ; Yanmei PENG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(10):1581-1592
Objective UPLC-Q-TOF-MS integrated molecular network strategy was used to rapidly analyze and identify the chemical components of Yuye detoxification Particle. Methods The secondary mass spectrometry data of compounds were obtained using mass spectrometry scanning in both positive and negative ion mode. The similarity of MS/MS fragmentation patterns was calculated to create the global natural product social molecular networking (GNPS) platform. The major components in Yuye detoxification Particle were quickly identified according to the molecular clusters with similar structures in GNPS. Manual analysis and identification of other compounds were performed according to the mass fragment ion information of the primary and secondary mass spectrum data and related references by using the molecular feature extraction (MFE) function of Agilent Masshunter Qualitative Analysis workstation and traditional Chinese Medicine composition database (TCM-DATA). Results A total of 89 compounds in Yuye detoxification Particle were identified by LC-MS,including 22 phenoliacids,21 flavonoids and their glycosides,6 iridoid glycosides,28 triterpenoid saponins and 12 other types of ingredients. Conclusion UPLC-Q-TOF-MS/MS integrated molecular network technology can be used for rapid and systematic identification of chemical components of Yuye detoxification Particle,which provides theoretical basis for its quality control and clinical application. The established molecular network can provide reference for rapid qualitative analysis of components of traditional Chinese medicine compound.
8.Predictive value of 18F-FDG PET/CT radiomics for BCL-2/IgH fusion gene expression status in follicular lymphoma
Xiaohe GAO ; Yanmei LI ; Jie CHEN ; Jian SUN ; Zeying WEN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(10):577-582
Objective:To explore the clinical application value of 18F-FDG PET/CT radiomics in predicting B-cell lymphoma-2 (BCL-2)/immunoglobulin heavy chain (IgH) fusion gene expression status in follicular lymphoma (FL) patients. Methods:A retrospective analysis was conducted on the clinical and imaging data of 90 FL patients (46 males and 44 females, age (48.7±10.5) years) who underwent 18F-FDG PET/CT examinations at Henan Cancer Hospital from January 2016 to August 2023. According to the expression status, patients were divided into positive group and negative group. Patients were randomly divided into training set ( n=62) and validation set ( n=28) at a ratio of 7∶3. PET and CT radiomics features were extracted by LIFEx 7.3.11 software. After using least absolute shrinkage and selection operator (LASSO) regression and ten-fold cross-validation for feature selection, PET and CT radiomics models were constructed. Univariate and multivariate analyses were used to select important clinical features and construct clinical model. Finally, a combined model was established by combining the radiomics features with clinical features. ROC curve and AUC were used to evaluate the predictive performance of models, and Delong test was used to compare the differences in AUCs. Results:After features selection, a total of 3 PET radiomics features, 3 CT radiomics features and 2 clinical features were selected for the construction of radiomics model and clinical model respectively. Multivariate analysis of clinical data showed that pathological grade (odds ratio ( OR)=0.201, 95% CI: 0.052-0.699, P=0.014) and maximum diameter of the maximum lesion (D max) ( OR=1.033, 95% CI: 1.009-1.065, P=0.017) were associated with BCL-2/IgH expression status. In the training set, the AUCs of clinical model, PET radiomics model, CT radiomics model and combined model were 0.84, 0.80, 0.80 and 0.91 respectively. In the validation set, the AUCs of the four models were 0.55, 0.61, 0.66 and 0.71 respectively. The combined model exhibited a trend toward higher in AUC than other three models in both the training and validation sets ( z values: 0.50-1.71, P values: 0.087-0.620). Conclusion:It is valuable to predict BCL-2/IgH fusion gene expression status based on PET/CT radiomics combined with clinical features.
9.The predictive value of heparin-binding protein combined with pediatric sequential organ failure assessment score in the prognosis of sepsis in children
Xiaoshun WANG ; Yimin ZHU ; Shuqiong LIU ; Pei WU ; Yinggang PENG ; Huimin ZHU ; Yanmei CHEN ; Saizhen ZENG
Chinese Pediatric Emergency Medicine 2024;31(8):614-618
Objective:To investigate the predictive value of heparin binding protein(HBP) combined with pediatric sequential organ failure assessment(pSOFA) in children with sepsis.Methods:Children with sepsis admitted to PICU of Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University) from January 2021 to June 2022 were selected as study group,while those who underwent elective surgery for inguinal hernia and assessment of precocious puberty and short stature during the same period were selected as control group.All children with sepsis were divided into sepsis group and septic shock group according to their severity as well as survival group and death group according to prognosis.The study group was monitored for HBP on the 1st,3rd,and 7th day of admission,while the control group was monitored for HBP on the 1st day of admission.Patients in the sepsis group received pSOFA scores immediately after admission.The laboratory results and HBP concentrations were compared between groups,and a joint model was established in combination with pSOFA to observe its predictive performance in sepsis prognosis.Results:A total of 50 children with sepsis were included in study group,including 45 children with sepsis and five children with septic shock.There were 27 males and 23 females,aged 1 month~13 years(median age two years).There were 7 deaths in this study,including two patients with sepsis and five patients with septic shock.The HBP concentration in the study group was significantly higher than that in the control group on the 1st day,and the HBP concentration in the group gradually decreased with the prolongation of hospital stay.The concentration of HBP on the first day of septic shock group was higher than that of sepsis group,and the difference was statistically significant( P<0.001).The concentration of HBP on the 1st day in the sepsis death group was significantly higher than that in the sepsis survival group( P=0.023).The receivor operator characteristic curve analysis showed that HBP and pSOFA had good predictive value for the death of children with sepsis,and the joint model of HBP and pSOFA(75.1×pSOFA-0.1×HBP)had the best predictive performance for the death of children with sepsis,but there was no significant difference with the pSOFA. Conclusion:The HBP level significantly increases in children with sepsis,and gradually decreases with the length of hospital stay,and HBP has great value in predicting the outcome of death in children with sepsis,and the combination of pSOFA could improve its predictive ability of death,but not better than pSOFA.
10.MiR-379-5p inhibits proliferation,invasion,and migration of mouse breast cancer 4T1 cells
Yanmei SONG ; Ningxin SUN ; Chen LIU ; Yifen SONG ; Hongli LI ; Chonggao YIN
Chinese Journal of Comparative Medicine 2024;34(3):85-92
Objective By investigating the effects of miR-379-5p on the proliferation,invasion and metastasis of mouse breast cancer 4T1 cells,we aimed to provide new therapeutic targets for the clinical inhibition of breast cancer proliferation,invasion,and metastasis.Methods After plasmid transfection,4T1 cells were utilized to detect the expression of miR-379-5p using fluorescence quantitative PCR.While 5-ethynyl-2'doxyuridine(EdU)cell proliferation and Transwell assays were employed to detect changes in the proliferation and invasion ability of 4T1 cells in each group.The migration ability of 4T1 cells after overexpression and knockdown of miR-379-5p was examined by scratch healing assay.A transplanted tumor model of breast cancer was established in BABL/c mice,and the effects of overexpressing miR-379-5p on tumor growth and the number and size of lung metastases were observed.Results EdU result showed that knocking down miR-379-5p enhanced the proliferation ability of the cells compared with the control group cells,and miR-379-5p overexpression reduced the capacity of breast cancer cells to proliferate(P<0.05).Transwell and wound healing assays showed that miR-379-5p knockdown enhanced,while miR-379-5p overexpression significantly inhibited,the invasion and migratory ability of breast cancer cells(P<0.01).An in vivo tumorigenesis experiment with BABL/c mice showed that miR-379-5p overexpression significantly slowed the tumor growth rate(P<0.05)and inhibited lung metastasis(P<0.01).Conclusions MiR-379-5p plays a role in tumor gene suppression in breast cancer and inhibits the proliferation,invasion,and migration of mouse breast cancer 4T1 cells.


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