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.Study of the mechanism of acupuncture and moxibustion in protecting the intestinal mucosal barrier in DSS-induced UC rats based on the IL-9/IL-9R pathway
Yan HUANG ; Kexin SUN ; Jing XU ; Zhe MA ; Jimeng ZHAO ; Lingjie LI ; Chen ZHAO ; Ling YANG ; Feng LI ; Yanan LIU ; Yue ZHANG ; Luyi WU ; Rude HUANG
Journal of Acupuncture and Tuina Science 2024;22(2):91-103
Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.
3.Association between short-term exposure to atmospheric NO2 and coagulation indexes of young individuals of different weights and modification effect of temperature
Maike CHEN ; Wenlou ZHANG ; Luyi LI ; Xinbiao GUO ; Furong DENG
Journal of Environmental and Occupational Medicine 2024;41(7):721-727
Background Nitrogen dioxide (NO2) is one of the main air pollutants, and though China's NO2 pollution has been improving year by year, it maintains at a high level, threatening the health of the population. Objective To investigate the effect of short-term exposure to atmospheric NO2 on the coagulation indexes in obese and normal-weight young individuals and potential modification effect of temperature. Methods Based on a parallel control panel study design, this study recruited 53 normal-weight and 44 obese young individuals. Three prospective follow-ups were conducted. Air pollution data were obtained from the fixed monitoring station closest to the participant's residences, and personal air pollution exposure was simulated based on time-activity log and infiltration factor for the week before every follow-up. Temperature was collected from China Meteorological Data Service Center. Venous blood samples were taken to measure platelet (PLT) count, mean platelet volume (MPV), soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin), platelet aggregation rate (PAgT), and plasminogen activator inhibitor type-1 (PAI-1) during every follow-up. A linear mixed-effect model was used to assess the association between short-term atmospheric NO2 exposure and the coagulation indexes of weight grouped young individuals, and a stratified analysis was used to explore potential modification effect of temperature. Results The median [interquartile range (IQR)] of personal atmospheric NO2 exposure concentrations was 21.47 (8.01) µg·m−3. Short-term exposure to atmospheric NO2 was significantly associated the increase of sCD40L and PAgT in the obese individuals, while the most significant association appeared at 5 d lag, and for each IQR increase in the average sliding exposure concentration of atmospheric NO2 with a 5 d lag, sCD40L increased by 27.4% (95%CI: 4.2%, 56.6%) and PAgT increased by 37.5% (95%CI: 12.2%, 68.6%); short-term exposure to atmospheric NO2 was significantly associated with the decrease of PLT and PAgT in the normal-weight individuals, while the most significant association appeared at 5 d lag or 7 d lag, and for each IQR increase in the average sliding exposure concentration of atmospheric NO2 with a 5 d lag, PLT decreased by 11.8% (95%CI: −17.8%, −5.3%), and for each IQR increase in the average sliding exposure concentration of atmospheric NO2 with a 7 d lag, PAgT decreased by 16.8% (95%CI: −30.6%, −0.4%). We didn't find statistically significant association of short-term exposure to atmospheric NO2 with PLT in the obese individuals or sCD40L in the normal-weight individuals, nor statistically significant association between short-term exposure to atmospheric NO2 and PAI-1, MPV, and sP-selectin in different weight grouped individuals. The stratified analysis found that short-term exposure to atmospheric NO2 was significantly associated with PAgT in the normal-weight individuals, or with PLT, sCD40L, and sP-selectin in the obese individuals only at high temperature. Conclusions Short-term exposure to atmospheric NO2 has adverse effects on the coagulation indexes of different weight grouped young individuals, and the obese individuals are more sensitive to it than the normal-weight individuals. High temperature can enhance the adverse health effect of short-term exposure to atmospheric NO2.
4.Relationship between stressful life events and insomnia in community-dwelling patients with schizophrenia:path analysis of psychotic symptoms and depression
Xushu CHEN ; Xin LIU ; Changjiu HE ; Chaoxinyu XIONG ; Yi GUO ; Luyi WEI ; Yuanyaun LIU ; Chunxi ZHANG ; Xiang LIU
Sichuan Mental Health 2024;37(5):439-443
Backgrounds Insomnia is frequent in schizophrenia and is found to be negatively affected by stressful life events,psychotic symptoms and depressive disorder,while the relationship among the four remains understudied in community-dwelling patients with schizophrenia.Objective To analyze the effect of stressful life events on insomnia in community-dwelling patients with schizophrenia,and to explore the mediation effect of psychotic symptoms and depression,so as to provide references for the intervention of insomnia in community-dwelling patients with schizophrenia.Methods From April to June 2023,a sample of 1 105 patients with schizophrenia attending 48 community health centers in Chengdu,Sichuan province and fulfilling the International Classification of Diseases,tenth edition(ICD-10)diagnostic criteria were included.All subjects were assessed using Stressful Life Event Scale(SLEs),Athens Insomnia Scale(AIS),Psychosis Screening Questionnaire(PSQ),and Patient Health Questionnaire Depression Scale(PHQ-9).Spearman correlation analysis was used to determine the correlation among the scales.Then the mediation model was constructed using Smart PLS 4.0,and tested with partial least squares algorithm and Bootstrap techniques.Results 332 patients(30.05%)with community schizophrenia were found to have insomnia.AIS scores in patients with schizophrenia were positively correlated with the scores on SLEs,PSQ and PHQ-9(r=0.165,0.322,0.554,P<0.01).Stressful life events indirectly contributed to insomnia through both separate mediation path and chained mediation path of psychotic symptoms and depressive disorder,and the indirect effect size of 0.102,0.372 and 0.190 was obtained,accounting for 10.46%,38.15%and 19.49%,respectively.Conclusion The stressful life events not only directly exert an impact on insomnia,but also indirectly contribute to insomnia through both the separate and chained mediation effect of psychotic symptoms and depressive disorder.
5.Investigating efficacy mechanism of electroacupuncture in treating Parkinson disease through TMT proteomics
Lu ZHU ; Guona LI ; Pin WU ; Luyi WU ; Lin SHEN ; Yu QIAO ; Jing LI ; Lingjie LI ; Zhaoqin WANG ; Yiyi CHEN ; Xiaopeng MA ; Kunshan LI ; Huangan WU ; Yanping YANG
Journal of Acupuncture and Tuina Science 2024;22(6):470-481
Objective:To explore the therapeutic mechanism of electroacupuncture(EA)in treating Parkinson disease(PD)using Tandem mass tag(TMT)quantitative proteomics technology. Methods:Forty-eight PD patients were randomly divided into a control group and an observation group,with 24 patients in each group.The control group received routine drug treatment,while the observation group received EA in addition to the routine drug treatment.EA was administered for 30 min per session,3 times a week,for a total of 12 weeks.Nine patients from each group were randomly selected to provide peripheral blood serum samples before and after treatment for TMT quantitative proteomics analysis.Differentially expressed proteins between the two groups were compared,and bioinformatics analysis was performed.The screened differentially expressed proteins were validated using enzyme-linked immunosorbent assay(ELISA). Results:In the observation group,scores on the unified Parkinson disease rating scale(UPDRS),UPDRS Ⅱ,and UPDRS Ⅲ were significantly reduced after treatment(P<0.05).In the control group,these scores tended to increase,but the changes were not statistically significant(P>0.05).After treatment,the UPDRS and UPDRS Ⅲ scores in the observation group were significantly lower than those in the control group(P<0.05).The observation group showed 62 differentially expressed proteins,while the control group had 36.Compared to the control group,the observation group had 142 differentially expressed proteins.These proteins were primarily involved in the cyclic adenosine monophosphate(cAMP)signaling pathway,T helper(Th)1 and Th2 cell differentiation,ATP-binding cassette transporter,vascular endothelial growth factor signaling pathway,and high-affinity immunoglobulin E receptor(FcεRI)signaling pathway.ELISA verification indicated that after EA treatment,the levels of α-Synuclein(αSyn)and heat shock protein beta 1(HSPB1)in the observation group were significantly lower than those in the control group(P<0.05),while the regulator of G-protein signaling 10(RGS10)level was significantly higher(P<0.05). Conclusion:EA,combined with routine drug therapy,can significantly improve clinical symptoms of PD,potentially through the regulation of the cAMP signaling pathway and the contents of differentially expressed proteins of αSyn,HSPB1,and RGS10.
6.Cognition about emergency management of avulsed incisor in children among dentists in Guangdong province.
Li ZHANG ; Jing XIE ; Ying CHEN ; Shuman DENG ; Luyi CHEN ; Qi GAO
West China Journal of Stomatology 2023;41(3):323-332
OBJECTIVES:
This study aimed to evaluate and analyze the current situation of dentists in Guangdong pro-vince regarding the management of avulsed incisors, thereby providing a reference for making treatment strategies for avulsed incisors in the future.
METHODS:
A total of 712 dentists with different educational backgrounds and working conditions in Guangdong province were randomly selected to conduct an online questionnaire survey on the cognition of children with avulsed incisors from April 2022 to May 2022. The data were recorded by Excel software and statistics were analyzed on Stata/SE 15.1.
RESULTS:
A total of 712 dentists were investigated and 701 questionnaires were collected (98.46%). In addition, 65.9% of investigators came from the Department of Stomatology in a First-class Hospital or Stomatological Hospital. The results showed that the average number of avulsed teeth consulted by dentists was less than 20 per year. Although 99.7% of respondents considered normal saline as a suitable storage medium, 3.1% and 23.8% of them had a misunderstanding that the tap/alcohol could be used for root cleaning. Moreover, 93.4% was the correct selection rate of the treatment plan for processing on root surfaces before replanting by investigators. The correct selection rate of the duration using elastic fixation was only 10.7%. Meanwhile, 42.9% of investigators refused to inoculate tetanus immunoglobulin after teeth replanting. Emergency management of dental avulsion (EM) and clinical management of dental avulsion (CM) answered correctly with average scores of 14.60±11.85 and 14.48±2.67, respectively. Multivariate linear regression analysis revealed that working years were negatively correlated with EM and CM scores (P<0.05). There was a positive correlation between CM and EM scores with the number of avulsion cases treated by physicians each year (P<0.05). In terms of the EM score of dentists' learning attitude, investigators who had received enough knowledge were higher than those who had not and insufficient knowledge reserved, and the difference was statistically significant (P<0.05). The scores of investigators who thought they had a certain degree of knowledge about dental trauma were higher than those who thought they "did not understand", and the difference was statistically significant (P<0.05). In terms of CM scores, investigators who thought the knowledge of dental trauma was "very helpful" had higher scores than those who thought it was "not helpful", and the difference was statistically significant (P<0.05). The scores of the investigators who thought they had "relatively sufficient knowledge" of dental trauma were higher than those who thought they had "no knowledge" or "insufficient know-ledge", and the difference was statistically significant (P<0.05).
CONCLUSIONS
The overall accuracy of the management of avulsed incisors among dentists was low in Guangdong province. Dentists were more likely to have a higher rate of accuracy choice in treatment options for luxation injury and avulsion to enhance the prognosis of replanted teeth.
Humans
;
Child
;
Tooth Avulsion/therapy*
;
Incisor
;
Tooth Replantation/methods*
;
Surveys and Questionnaires
;
Dentists
;
Cognition
;
China
;
Health Knowledge, Attitudes, Practice
7.Predictive value of dual-source stone energy spectrum CT for uric acid stones
Wang LI ; Qiang FU ; Rong CHEN ; Hong XIE ; Hui GUO ; Jiemin SI ; Miao XIE ; Luyi YANG ; Ranxing YANG
Chinese Journal of Urology 2023;44(6):459-462
Objective:To investigate the predictive value of stone composition prediction method based on dual-source stone energy spectrum CT for uric acid stones.Methods:The clinical data of 204 patients with urinary stones, 159 males and 45 females, admitted to Shanghai Sixth People's Hospital from July 2020 to July 2022 were retrospectively analyzed. The average age was (50.7±14.3) years. There were 187 cases of upper urinary tract (kidney, ureter) stones and 17 cases of lower urinary tract (bladder, urethra) stones. All patients underwent preoperative dual-source stone energy spectroscopy CT, measuring CT values at 150 kV and 100 kV, respectively, and the calculated dual energy ratio (Ratio) was used to predict stone composition. Of the 204 cases in this group, 33 cases underwent percutaneous nephrolithotomy and 171 cases underwent ureteroscopic lithotripsy. Postoperative stone specimens were analyzed for stone composition by infrared spectroscopy. Subject work characteristic (ROC) curves were used to analyze the efficacy of preoperative dual-source stone energy spectrum CT to predict uric acid stones.Results:In 204 patients, preoperative CT predicted 28 cases of uric acid stones and 176 cases of non-uric acid stones, including 136 cases of calcium oxalate stones, 38 cases of hydroxyapatite, and 2 cases of cystine stones. Postoperative IR spectral analysis detected 26 cases of uric acid stones and 178 cases of non-uric acid stones, including 129 cases of calcium oxalate stones, 47 cases of hydroxyapatite, and 2 cases of cystine stones. Compared with the preoperative CT results, there were 2 false positives and no false negatives in the classification of uric acid stones. The ROC curve showed that the sensitivity of the CT value for predicting uric acid stones at 100 kV was 96.2%, the specificity was 99.5%, and the area under the ROC curve (AUC) was 0.995, with the best prediction value of 620 HU.The sensitivity of the CT value for predicting uric acid stones at 150 kV was 96.2%, specificity was 85.5%, AUC was 0.916, and the best predictive value was 597.5 HU. The sensitivity of using Ratio values for predicting uric acid stones was 100.0%, specificity was 97.9%, AUC was 0.996, and the best predictive value was 1.14. The CT values for uric acid stones at 100 kV and 150 kV were (558.58±77.07) HU and (521.12±83.54) HU, CT values for calcium oxalate stones were (1 335.26±301.82) HU and (878.21±200.21) HU, CT values for hydroxyapatite were (1 104.09±203.61) HU and (710.38±178.44) HU, respectively.The CT values of cystine stones were (684.5±67.18) HU and (573.5±67.10) HU, respectively, and the differences between uric acid stones and other components were statistically significant ( P<0.01). The Ratio values of uric acid stones, calcium oxalate stones, hydroxyapatite, and cystine stones were 1.08±0.06, 1.52±0.08, 1.62±0.40, and 1.19±0.02, respectively, and the differences were statistically significant ( P<0.01) when comparing uric acid stones with other components. Conclusion:The CT and Ratio values of dual-source stone energy spectrum CT can effectively distinguish uric acid stones from other types of stones, and the accuracy, sensitivity, and specificity of this method for predicting uric acid stones are high.
8.Prenatal diagnosis of fetal diencephalic-mesencephalic junction dysplasia: a case report
Peiwei ZHAO ; Luyi CHEN ; Lei ZHANG ; Xuelian HE
Chinese Journal of Perinatal Medicine 2023;26(8):684-686
We report a case of fetal diencephalic-mesencephalic junction dysplasia (DMJD) diagnosed prenatally. Prenatal ultrasound at 24 gestational weeks showed that the fetus was small, about the size at 22 weeks' gestation, with short biparietal diameter and enhanced echo at the anterior border of thalamus. Fetal MRI showed short T2 signal shadow in the left choroid plexus, and hemorrhage and midbrain dysplasia were suspected. A pathogenic homozygous mutation variant in protocadherins 12 gene (c.1558C>T) was found in this fetus by whole exome sequencing and both parents carried the same heterozygous variation revealed by Sanger sequencing. All of the above information lead to the diagnosis of fetal DMJD, and the pregnancy was terminated after genetic counseling.
9.Exploring the mechanism by which acupuncture and moxibustion reduce colonic mucosal inflammation in rats with ulcerative colitis(UC)based on the P2X7R-NLRP3 inflammasome pathway
Zhenzhen FANG ; Huangan WU ; Luyi WU ; Yanan LIU ; Ling YANG ; Chen ZHAO ; Zhe MA ; Yan HUANG ; Wenjia WANG
Journal of Acupuncture and Tuina Science 2023;21(5):356-367
Objective:To explore the mechanism of acupuncture and moxibustion for ulcerative colitis(UC)from the perspective of the P2X7 receptor(P2X7R)-nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome pathway. Methods:Sprague-Dawley rats were randomly assigned to a normal(N)group,a model(M)group,a herb-partitioned moxibustion(HM)group,and an electroacupuncture(EA)group.For modeling,the rats drank 4%dextran sulfate sodium for 7 d.Rats in the HM group and EA group received 7 consecutive days of HM or EA at bilateral Tianshu(ST25),respectively.The histopathological change in colon tissue was observed by hematoxylin-eosin(HE)staining;immunofluorescence staining was used to detect the protein expression of related molecules in the colon tissue,and enzyme-linked immunosorbent assay was used to detect the concentrations or contents of related molecules in the serum and colon tissue.Wild-type(WT)and P2X7R gene knockout(KO)mice were used to construct UC models,histopathological changes in the colon tissue were observed by HE staining,and the NLRP3 protein expression in the colon tissue was observed by immunohistochemistry. Results:Compared with the N group,the colon histopathological score in the M group was significantly increased,and the protein expression of P2X7R,NLRP3,apoptosis-associated speck-like protein containing CARD(ASC),Caspase-1,interleukin-1β(IL-1β),and interleukin-18(IL-18)in the colon tissue and the protein levels of IL-1β and IL-18 in the serum were significantly increased(P<0.05).Compared with the M group,the histopathological scores of the colon in the HM group and the EA group were significantly decreased,and the protein expression levels of P2X7R,NLRP3,ASC,Caspase-1,IL-1β,and IL-18 in the colon tissue and the protein level of IL-18 in the serum were significantly decreased(P<0.05).After UC modeling,the colonic mucosal epithelial damage and inflammatory cell infiltration in P2X7R KO mice were less than those in WT mice,and the NLRP3 protein expression in the colon was also decreased compared with that in WT mice(P<0.05). Conclusion:HM and EA at Tianshu(ST25)may inhibit the protein activities of P2X7R,NLRP3,ASC,and Caspase-1 in the colon tissue of rats with UC,thereby reducing the downstream molecules IL-1β and IL-18 in the P2X7R-NLRP3 inflammasome pathway to relieve UC inflammation.
10.NEDD8-conjugating enzyme E2 UBE2F confers radiation resistance by protecting lung cancer cells from apoptosis.
Lisha ZHOU ; Changsheng DONG ; Zhuoming XU ; Xinran WANG ; Luyi ZHANG ; Siyuan CHEN ; Jiahao CHEN ; Yingying ZHU
Journal of Zhejiang University. Science. B 2021;22(11):959-965
Lung cancer, which is exacerbated by environmental pollution and tobacco use, has become the most common cause of cancer-related deaths worldwide, with a five-year overall survival rate of only 19% (Siegel et al., 2020; Yang et al., 2020; Yu and Li, 2020). Nearly 85% of lung cancers are non-small cell lung cancers, of which lung adenocarcinoma is the most common subtype accounting for 50% of non-small cell lung cancer cases. At present, radiotherapy is the primary therapeutic modality for lung cancer at different stages, with significant prolongation of survival time (Hirsch et al., 2017; Bai et al., 2019; Shi et al., 2020). Irradiation can generate reactive oxygen species (ROS) through the radiolysis reaction of water and oxygen, cause DNA damage and oxidative stress, and subsequently result in cancer cell death (Kim et al., 2019). Nevertheless, radioresistance seriously hinders the success of treatment for lung cancer, owing to local recurrence and distant metastasis (Huang et al., 2021). Compared with small cell lung cancer, non-small cell lung cancer shows more tolerance to radiotherapy. Therefore, it is of great importance to decipher key mechanisms of radioresistance and identify effective molecular radiosensitizers to improve patient survival.

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