1.Mitophagy regulates bone metabolism
Hanmin ZHU ; Song WANG ; Wenlin XIAO ; Wenjing ZHANG ; Xi ZHOU ; Ye HE ; Wei LI
Chinese Journal of Tissue Engineering Research 2025;29(8):1676-1683
BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.
2.Cross - border joint prevention and control of tropical diseases in countries along the “Belt and Road” Initiative: a framework and roadmap
Yingjun QIAN ; Wei DING ; Hongmei LI ; Duoquan WANG ; Shan LÜ ; Shizhu LI ; Xiaonong ZHOU
Chinese Journal of Schistosomiasis Control 2025;37(1):8-13
Recently, there has been an increasing risk of importation of tropical diseases into China and the resultant re-transmission in the country with the in-depth implementation of the “Belt and Road” Initiative, which poses a serious threat to the national public health security. To effectively respond to the cross-border transmission risk of tropical diseases and facilitate the process towards tropical disease control and elimination in China and the countries along the “Belt and Road” Initiative, this article analyzes the current status and governance risks of major imported tropical diseases, cross-border joint prevention and control polices implemented for tropical diseases and challenges in the establishment of the joint prevention and control system for tropical diseases in China, and discusses the establishment and implementation path of the joint prevention and control system for tropical diseases in countries along the “Belt and Road” Initiative. This path covers the establishment of cross-border cooperation mechanisms, research and development and pilot production of Chinese public health products, and implementation of key cross-border tropical disease prevention and control projects. The establishment of this system will further improve Chinese prevention and control capabilities for key cross-border tropical diseases, build a demonstrative prevention and control model for tropical diseases, and promote international technical exchanges and cooperation of tropical diseases.
3.Quality evaluation of Mongolian medicine Sendeng-4 based on qualitative and quantitative analysis combined with chemical pattern recognition
Fengye ZHOU ; Jun LI ; Qian ZHANG ; Rongjie LI ; Wei ZHANG ; Jing LIU ; Fang WANG ; Shengnan LI
China Pharmacy 2025;36(9):1040-1045
OBJECTIVE To evaluate the quality of Mongolian medicine Sendeng-4 based on qualitative and quantitative analysis combined with chemical pattern recognition, in order to provide the reference for its quality control. METHODS The chemical components in Sendeng-4 were analyzed qualitatively by HPLC-Q-Exactive-MS. The contents of 16 components (methyl gallate, ethyl gallate, epicatechin, dihydromyricetin, genipin-1-O-β-D-gentiobioside, caffeic acid, catechin, corilagin, deacetylasperulosidic acid methyl ester, rutin, geniposide, luteolin, myricetin, quercetin, ferulic acid, and toosendanin) in 15 batches of Sendeng-4 (sample S1-S15) were quantitatively analyzed by HPLC-MS/MS. Cluster analysis (CA), principal component analysis (PCA), and orthogonal partial least squares discriminant analysis were conducted and variable importance projection (VIP) value greater than 1 was used as the index to screen the differential components. RESULTS A total of 73 chemical components were identified in Sendeng-4, including 20 flavonoids, 16 tannins, 14 organic acids, etc. According to the quantitative analysis, the results exhibited that the average contentsthe of above 16 components in 15 batches of Sendeng-4 were 3.683-7.730, 2.391-6.952, 2 275.538-4 377.491, 2 699.188-3 537.924, 858.266-1 377.393, 3.366-11.003, 140.624-315.683,414.629-978.334, 285.501-1 510.457, 27.799-48.325, 3 625.415-6 309.563, 0.506-0.656, 442.337-649.283, 47.093-59.736, 12.942-15.822, 127.738-326.649 μg/g, respectively. According to the results of CA and PCA, 15 batches of samples could be clustered into two categories: S1-S3, S5-S6, S9-S10 and S13 were clustered into one category; S4, S7-S8, S11-S12, S14-S15 were clustered into one category. VIP values of geniposide, epicatechin, deacetylasperulosidic acid methyl ester and genipin-1-O- β-D-gentiobioside were all greater than 1. CONCLUSIONS HPLC-Q-Exactive-MS and HPLC-MS/MS techniques are employed for the qualitative and quantitative analysis of Sendeng-4. Through chemical pattern recognition analysis, four differential components are identified: geniposide, epicatechin, deacetylasperulosidic acid methyl ester, and genipin-1-O-β-D-gentiobioside.
4.Clinical Efficacy of Zhuyuwan in Treatment of Hyperlipidemia with Syndrome of Phlegm Turbidity and Obstruction
Lele YANG ; Danmei LUO ; Jiao CHEN ; Xiaobo ZHANG ; Wei SONG ; Wenyu ZHU ; Xin ZHOU ; Xueping LI ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):29-37
ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study, hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine (TCM) from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally, 162 valid cases were included, encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets, and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery, blood lipid levels, TCM syndrome distribution, efficacy in terms of TCM syndrome, and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery, the total response rate in the observation group was 86.36% (76/88) and that in the control group was 86.49% (64/74), with no statistically significant difference between the two groups. After treatment, both groups showed declines in levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (P<0.05) and elevations in the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05). Moreover, the observation group outperformed the control group in recovering the levels of TG, LDL-C, and HDL-C (P<0.05, P<0.01). In terms of TCM syndrome, hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% (55/63), which was higher than that (63.46%, 33/52) in the control group (χ2=9.102, P<0.01). After treatment, the scores of total TCM symptoms, primary symptoms, and secondary symptoms decreased in both groups (P<0.05), and the observation group had lower scores than the control group (P<0.01). The observation group was superior to the control group in alleviating obesity, chest tightness, and low food intake (P<0.05). In terms of safety, the level of aminotransferase was slightly elevated in the control group, and no obvious adverse reaction was observed in the observation group, with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.
5.Mahoniae Caulis Alkaloids Ameliorate Depression by Regulating Synaptic Plasticity via cAMP Pathway
Junhui HE ; Chunlian JIA ; Kedao LAI ; Guili ZHOU ; Rongfei ZHOU ; Yi LI ; Dongmei LI ; Jiaxiu XIE ; Guining WEI ; Juying ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):132-140
ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids (MA) in ameliorating depression by network pharmacology, molecular docking, and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. Protein-protein interaction (PPI) network was constructed by protein interaction analysis (STRING) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed through Bioinformatics (DAVID) database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone (CORT) once a day for 35 consecutive days. Sixty mice were randomly allocated into control (0.9% normal saline), model (CORT, 20 mg·kg-1), positive control (fluoxetine hydrochloride, 3.6 mg·kg-1), and MA (10, 5, and 2.5 mg·kg-1) groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling (TUNEL) was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor (BDNF), dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in mice. The mRNA levels of cyclic adenosine monophosphate (cAMP) pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 (Cx43). ResultsA total of 434 component targets and 545 depression targets were obtained, including 84 common targets, among which 10 core targets were screened out. GO analysis predicted 34 biological processes, 15 cell components, and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group, CORT prolonged the immobility time of mice in forced swimming and tail suspension tests (P<0.01), lowered the serum levels of NE, BDNF, and 5-HT (P<0.05), up-regulated the mRNA levels of nuclear factor-κB (NF-κB) and interleukin-6 (IL-6) in the brain tissue (P<0.05), and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein (CREB) and BDNF (P<0.05) and the protein levels of protein kinase (PRKACA), phosphorylation (p)-CREB/CREB, BDNF, and Cx43 (P<0.05) in the brain tissue. Compared with the model group, high-dose MA reduced the immobility time of mice in forced swimming (P<0.05) and tail suspension (P<0.01) tests, raised the serum levels of NE, BDNF, and 5-HT (P<0.01), down-regulated the mRNA level of NF-κB (P<0.01), and up-regulated the mRNA level of BDNF (P<0.01) and protein levels of PRKACA, p-CREB/CREB, BDNF, and Cx43 (P<0.05). ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway, improving synaptic plasticity and gap junction function, and reducing neuroinflammation.
6.Clinical Efficacy of Zhuyuwan in Treatment of Hyperlipidemia with Syndrome of Phlegm Turbidity and Obstruction
Lele YANG ; Danmei LUO ; Jiao CHEN ; Xiaobo ZHANG ; Wei SONG ; Wenyu ZHU ; Xin ZHOU ; Xueping LI ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):29-37
ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study, hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine (TCM) from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally, 162 valid cases were included, encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets, and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery, blood lipid levels, TCM syndrome distribution, efficacy in terms of TCM syndrome, and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery, the total response rate in the observation group was 86.36% (76/88) and that in the control group was 86.49% (64/74), with no statistically significant difference between the two groups. After treatment, both groups showed declines in levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (P<0.05) and elevations in the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05). Moreover, the observation group outperformed the control group in recovering the levels of TG, LDL-C, and HDL-C (P<0.05, P<0.01). In terms of TCM syndrome, hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% (55/63), which was higher than that (63.46%, 33/52) in the control group (χ2=9.102, P<0.01). After treatment, the scores of total TCM symptoms, primary symptoms, and secondary symptoms decreased in both groups (P<0.05), and the observation group had lower scores than the control group (P<0.01). The observation group was superior to the control group in alleviating obesity, chest tightness, and low food intake (P<0.05). In terms of safety, the level of aminotransferase was slightly elevated in the control group, and no obvious adverse reaction was observed in the observation group, with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.
7.Mahoniae Caulis Alkaloids Ameliorate Depression by Regulating Synaptic Plasticity via cAMP Pathway
Junhui HE ; Chunlian JIA ; Kedao LAI ; Guili ZHOU ; Rongfei ZHOU ; Yi LI ; Dongmei LI ; Jiaxiu XIE ; Guining WEI ; Juying ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):132-140
ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids (MA) in ameliorating depression by network pharmacology, molecular docking, and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. Protein-protein interaction (PPI) network was constructed by protein interaction analysis (STRING) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed through Bioinformatics (DAVID) database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone (CORT) once a day for 35 consecutive days. Sixty mice were randomly allocated into control (0.9% normal saline), model (CORT, 20 mg·kg-1), positive control (fluoxetine hydrochloride, 3.6 mg·kg-1), and MA (10, 5, and 2.5 mg·kg-1) groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling (TUNEL) was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor (BDNF), dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in mice. The mRNA levels of cyclic adenosine monophosphate (cAMP) pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 (Cx43). ResultsA total of 434 component targets and 545 depression targets were obtained, including 84 common targets, among which 10 core targets were screened out. GO analysis predicted 34 biological processes, 15 cell components, and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group, CORT prolonged the immobility time of mice in forced swimming and tail suspension tests (P<0.01), lowered the serum levels of NE, BDNF, and 5-HT (P<0.05), up-regulated the mRNA levels of nuclear factor-κB (NF-κB) and interleukin-6 (IL-6) in the brain tissue (P<0.05), and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein (CREB) and BDNF (P<0.05) and the protein levels of protein kinase (PRKACA), phosphorylation (p)-CREB/CREB, BDNF, and Cx43 (P<0.05) in the brain tissue. Compared with the model group, high-dose MA reduced the immobility time of mice in forced swimming (P<0.05) and tail suspension (P<0.01) tests, raised the serum levels of NE, BDNF, and 5-HT (P<0.01), down-regulated the mRNA level of NF-κB (P<0.01), and up-regulated the mRNA level of BDNF (P<0.01) and protein levels of PRKACA, p-CREB/CREB, BDNF, and Cx43 (P<0.05). ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway, improving synaptic plasticity and gap junction function, and reducing neuroinflammation.
8.Population genetic structure of sandflies in China based on mitochondrial DNA
Zhongqiu LI ; Zixin WEI ; Zhengbin ZHOU ; Yi ZHANG
Chinese Journal of Schistosomiasis Control 2025;37(2):144-151
Objective To investigate the genetic diversity of sandfly populations in endemic areas of visceral leishmaniasis in China, so as to provide references insights into management of visceral leishmaniasis and the vector sandflies. MethodsSixteen sampling sites were selected from main endemic foci of visceral leishmaniasis in China from June to September 2024, including Shanxi Province, Shaanxi Province, Henan Province, Gansu Province, Sichuan Province, and Xinjiang Uygur Autonomous Region. Sandflies were captured using light traps and manual aspirators from sheep pens, chicken coops, cave dwellings, bovinesheds, and pig pens at each sampling site. A single sandfly sample was washed in phosphate-buffered saline (PBS), and genomic DNA was extracted from sandfly samples. Cytochrome oxidase subunit 1 (COI) gene was amplified using PCR assay with universal primers, and analyzed and retrieved with the nucleotide sequence analysis tool (BLAST) software, and the sequence of COI gene was aligned with the ClustalX 1.83 and MEGA 7.0 software. The base composition and variation site of the COI gene sequence were analyzed using the software MEGA 7.0, and the number of haplotypes, total number of segregating sites, haplotype diversity, nucleotide diversity, and average nucleotide differences were calculated in the COI gene sequence using the software DnaSP 5.10, followed by Tajima’s D test for neutrality. Haplotypes were screened using the software DnaSP 5.10, and the haplotype network map of sandfly samples was plotted using the software Network 5.0. MEGA 7.0 software was employed for gene sequence editing and alignment, and calculation of genetic distances among sandfly species sampled from different regions, and a phylogenetic tree was built with a neighbor-joining method. Results A total of 466 sandflies were captured from 16 sampling sites in China from June to September 2024, and 430 gene sequences were yielded following PCR amplification and sequencing of the COI gene, with 652 to 688 bp in the length of amplification fragments. The captured sandfly samples were characterized as Phlebotomus chinensis, Sergentomyia squamirostris, Se. koloshanensis, Ph. sichuanensis, and Ph. longiductus following the COI gene sequence alignment in BLAST. A total of 251 haplotypes were identified in the 430 gene sequences from sandfly samples (50.5%), and the average haplotype diversity, nucleotide diversity and average number of nucleotide difference were 0.885, 0.257 and 160.761, respectively. The Tajima’s D values were -0.92 for sandfly populations from Yangquan City, Shanxi Province and -1.73 for sandfly populations from Sanmenxia City, Henan Province, and were all more than 0 for sandfly populations from other sampling sites. Haplotype analysis identified 50 haplotypes, which were classified into two haplogroups. Heplogroup 1 included 29 haplotypes, which had a high homology, and heplogroup 2 included 21 haplotypes. The average genetic distance was 0.000 to 0.604 among sandfly samples from different sampling sites, and phylogenetic analysis revealed that the five sandfly species were clustered into distinct clades, all with 100% clade confidence. Conclusions There is a high genetic polymorphism in the COI gene from five sandfly populations in main endemic foci of visceral leishmaniasis in China, and COI gene may serve as a marker gene for analysis of the genetic structure of sandfly populations.
9.Combined anterior and posterior miniscrews increase apical root resorption of maxillary incisors in protrusion and premolar extraction cases
Zhizun WANG ; Li MEI ; Zhenxing TANG ; Dong WU ; Yue ZHOU ; Ehab A. ABDULGHANI ; Yuan LI ; Wei ZHENG ; Yu LI
The Korean Journal of Orthodontics 2025;55(1):26-36
Objective:
Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors.
Methods:
Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1).
Results:
The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group.
Conclusions
In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.
10.PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma
Ranran FENG ; Yilin GUO ; Meilin CHEN ; Ziying TIAN ; Yijun LIU ; Su JIANG ; Jieyu ZHOU ; Qingluan LIU ; Xiayu LI ; Wei XIONG ; Lei SHI ; Songqing FAN ; Guiyuan LI ; Wenling ZHANG
Journal of Pathology and Translational Medicine 2025;59(1):68-83
Background:
Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.
Methods:
We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).
Results:
We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.
Conclusions
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

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