1.Prohibitin 2 exacerbates lipopolysaccharide-induced periodontal bone inflammation via the NF-κB signaling pathway
Jingxin Zhao ; Jiamin Hu ; Jike Gao ; Ming Cheng ; Youming Zhu ; Xiaoyu Sun
Acta Universitatis Medicinalis Anhui 2025;60(10):1781-1789
Objective:
To elucidate the molecular mechanism by which prohibitin 2(PHB2) mediates periodontitis-induced bone tissue inflammation through regulating the nuclear factor kappa B(NF-κB) signaling pathway and its role in irreversible alveolar bone resorption.
Methods:
Quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR) and immunohistochemistry(IHC) were used to detect the expression differences of inflammatory factors and PHB2 in healthy and inflamed alveolar bone tissues of mice in vivo. In vitro, an inflammatory model was established using lipopolysaccharide(LPS)-induced a mouse calvaria-derived preosteoblastic cell line, subclone E1(MC3T3-E1) cells. Western blot and qRT-PCR were used to clarify the regulatory relationship between PHB2 and inflammatory factors, and immunofluorescence staining was performed to observe changes in PHB2 subcellular localization. PHB2 overexpression plasmids were constructed using molecular cloning, and RNA interference was employed to knock down PHB2 expression to assess its regulatory role in inflammation. Based on RNA-seq data, differential expression analysis based on the negative binomial distribution, version 2(DESeq2) was used for differential expression analysis, and kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment along with gene ontology(GO) functional annotation were performed to identify key signaling pathways and differentially expressed genes.
Results:
In the mouse periodontitis model, PHB2 expression was significantly upregulated in alveolar bone tissues. In the in vitro inflammatory cell model, PHB2 levels positively correlated with interleukin(IL)-6, IL-1β, and tumor necrosis factor-alpha(TNF-α) levels, and its subcellular localization shifted during inflammation. RNA-seq data and the detection of the level of phosphorylation of p65 protein(p-p65) demonstrated that PHB2 exacerbated inflammatory responses through the NF-κB signaling pathway and was mechanistically linked to upregulation of the upstream chemokine C-X-C motif chemokine ligand 10(CXCL10).
Conclusion
PHB2 aggravates LPS-induced periodontitis inflammation via the NF-κB signaling pathway, providing new insights into the molecular mechanisms underlying the development of periodontitis.
2.SLAMF7 predicts prognosis and correlates with immune infiltration in serous ovarian carcinoma
Yalong DENG ; Lu ZHANG ; Changyuan DAI ; Yan XU ; Qiyu GAN ; Jingxin CHENG
Journal of Gynecologic Oncology 2024;35(6):e79-
Objective:
Signaling lymphocytic activation molecule family members (SLAMFs) play a critical role in immune regulation of malignancies. This study aims to investigate the prognostic value and function of SLAMFs in ovarian cancer (OC).
Methods:
The expression analysis of SLAMFs was conducted based on The Cancer Genome Atlas Ovarian Cancer Collection (TCGA-OV) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was further performed on tissue arrays (n=98) to determine the expression of SLAMF7. Kaplan-Meier plotter and multivariate Cox regression model were used to evaluate the correlation of SLAMF7 expression with survival outcomes of patients. The molecular function of SLAMF7 in OC was further investigated using Gene Set Enrichment Analysis (GSEA).
Results:
SLAMF7 mRNA expression were significantly upregulated in OC tumor tissue compared to normal tissue. IHC revealed that SLAMF7 expression was located in the interstitial parts of tumor tissue, and higher SLAMF7 expression was associated with favorable survival outcomes. GSEA demonstrated that SLAMF7 is involved immune-related pathways. Further analysis showed that SLAMF7 had a strong correlation with the T cellspecific biomarker (CD3) but not with the B cell (CD19, CD22, and CD23) and natural killer cell-specific biomarkers (CD85C, CD336, and CD337). Furthermore, IHC analysis confirmed that SLAMF7 was expressed in tumor-infiltrating T cells, and the IHC score of SLAMF7 was positively correlated with CD3 (r=0.85, p<0.001).
Conclusion
SLAMF7 is expressed in the interstitial components of clinical OC tissue, and higher SLAMF7 expression indicated a favorable prognosis for patients with OC.Additionally, SLAMF7 is involved in T-cell immune infiltration in OC.
3.SLAMF7 predicts prognosis and correlates with immune infiltration in serous ovarian carcinoma
Yalong DENG ; Lu ZHANG ; Changyuan DAI ; Yan XU ; Qiyu GAN ; Jingxin CHENG
Journal of Gynecologic Oncology 2024;35(6):e79-
Objective:
Signaling lymphocytic activation molecule family members (SLAMFs) play a critical role in immune regulation of malignancies. This study aims to investigate the prognostic value and function of SLAMFs in ovarian cancer (OC).
Methods:
The expression analysis of SLAMFs was conducted based on The Cancer Genome Atlas Ovarian Cancer Collection (TCGA-OV) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was further performed on tissue arrays (n=98) to determine the expression of SLAMF7. Kaplan-Meier plotter and multivariate Cox regression model were used to evaluate the correlation of SLAMF7 expression with survival outcomes of patients. The molecular function of SLAMF7 in OC was further investigated using Gene Set Enrichment Analysis (GSEA).
Results:
SLAMF7 mRNA expression were significantly upregulated in OC tumor tissue compared to normal tissue. IHC revealed that SLAMF7 expression was located in the interstitial parts of tumor tissue, and higher SLAMF7 expression was associated with favorable survival outcomes. GSEA demonstrated that SLAMF7 is involved immune-related pathways. Further analysis showed that SLAMF7 had a strong correlation with the T cellspecific biomarker (CD3) but not with the B cell (CD19, CD22, and CD23) and natural killer cell-specific biomarkers (CD85C, CD336, and CD337). Furthermore, IHC analysis confirmed that SLAMF7 was expressed in tumor-infiltrating T cells, and the IHC score of SLAMF7 was positively correlated with CD3 (r=0.85, p<0.001).
Conclusion
SLAMF7 is expressed in the interstitial components of clinical OC tissue, and higher SLAMF7 expression indicated a favorable prognosis for patients with OC.Additionally, SLAMF7 is involved in T-cell immune infiltration in OC.
4.SLAMF7 predicts prognosis and correlates with immune infiltration in serous ovarian carcinoma
Yalong DENG ; Lu ZHANG ; Changyuan DAI ; Yan XU ; Qiyu GAN ; Jingxin CHENG
Journal of Gynecologic Oncology 2024;35(6):e79-
Objective:
Signaling lymphocytic activation molecule family members (SLAMFs) play a critical role in immune regulation of malignancies. This study aims to investigate the prognostic value and function of SLAMFs in ovarian cancer (OC).
Methods:
The expression analysis of SLAMFs was conducted based on The Cancer Genome Atlas Ovarian Cancer Collection (TCGA-OV) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was further performed on tissue arrays (n=98) to determine the expression of SLAMF7. Kaplan-Meier plotter and multivariate Cox regression model were used to evaluate the correlation of SLAMF7 expression with survival outcomes of patients. The molecular function of SLAMF7 in OC was further investigated using Gene Set Enrichment Analysis (GSEA).
Results:
SLAMF7 mRNA expression were significantly upregulated in OC tumor tissue compared to normal tissue. IHC revealed that SLAMF7 expression was located in the interstitial parts of tumor tissue, and higher SLAMF7 expression was associated with favorable survival outcomes. GSEA demonstrated that SLAMF7 is involved immune-related pathways. Further analysis showed that SLAMF7 had a strong correlation with the T cellspecific biomarker (CD3) but not with the B cell (CD19, CD22, and CD23) and natural killer cell-specific biomarkers (CD85C, CD336, and CD337). Furthermore, IHC analysis confirmed that SLAMF7 was expressed in tumor-infiltrating T cells, and the IHC score of SLAMF7 was positively correlated with CD3 (r=0.85, p<0.001).
Conclusion
SLAMF7 is expressed in the interstitial components of clinical OC tissue, and higher SLAMF7 expression indicated a favorable prognosis for patients with OC.Additionally, SLAMF7 is involved in T-cell immune infiltration in OC.
5.Protective effect of vitamin D3 on alcohol⁃induced liver inj ury in mice
Huihui Wang ; Xiaoyu Wang ; Weiyi Gong ; Wenxiu Cheng ; Jingxin Gao ; Chunqiu Hu
Acta Universitatis Medicinalis Anhui 2023;58(5):707-710,717
Objective:
To investigate the protective effect of vitamin D3 on alcoholic liver injury in mice.
Methods:
Forty mice were randomly divided into 4 groups : normal Control (Control) group , vitamin D3 (VitD3 ) group , alcohol model (EtOH) group and alcohol + vitamin D3 (EtOH + VitD3 ) group. The mice were fed with the DeCarlialcohol liquid diet to establish alcoholic liver injury model. Serum levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) and liver index were detected. HE staining was used to observe the pathological changes of liver. The relative expression levels of tumor necrosis factor α (TNF⁃α ) , transforming growth factor β (TGF⁃β) , interleukin⁃6 (IL⁃6) and interleukin⁃1β (IL⁃1β) mRNA were detected by quantitative real⁃time PCR (qRT⁃PCR) . The expressions of nuclear factor⁃kappa B (NF⁃κB) p65 and NF⁃κB p50 in liver were detected by Western blot.
Results:
The serum ALT , AST vitality , liver index and hepatic TNF⁃α , TGF⁃ β , IL⁃6 and IL⁃1β mRNA in
EtOH group were significantly higher than those in Control group. EtOH group disorganized hepatocyte and hepatic lobules boundary was not clear, and the hepatocytes showed apparent inflammatory cells infiltration of liver cells and fat cavitation. NF⁃κB p65 and NF⁃κB p50 protein expression increased significantly. Compared with EtOH group ,the serum ALT , AST vitality , liver index and hepatic TNF⁃α , TGF⁃ β , IL⁃6 and IL⁃1β mRNA in EtOH + VitD3 group decreased significantly. The pathological staining results showed that inflammatory cells infiltration and decrease in the number of fat vacuoles , and the liver cells returned to normal liver cell structure. At the same time the NF⁃κB p65 and NF⁃κB p50 protein expression level decreased significantly.
Conclusion
Vitamin D3 has a certain protective effect on alcohol⁃induced liver injury in mice , and its main mechanisms are related to the inhibition of NF⁃κB pathway and the reduction of inflammatory response.
6.Oncologic outcomes of early stage cervical cancer performed operation by different laparoscopic surgical procedures: analysis of clinical data from mutiple centers
Kaijian LING ; Yanzhou WANG ; Hui ZHANG ; Xuyin ZHANG ; Junjun YANG ; Chengyan LUO ; Bin SONG ; Wenxi ZHANG ; Li DENG ; Gongli CHEN ; Yudi LI ; Qunying HU ; Yong CHEN ; Xin WANG ; Jun ZHANG ; Jingxin DING ; Tong REN ; Shan KANG ; Keqin HUA ; Yang XIANG ; Wenjun CHENG ; Zhiqing LIANG
Chinese Journal of Obstetrics and Gynecology 2020;55(9):617-623
Objective:To evaluate the oncologic outcomes of different laparoscopic radical hysterectomy.Methods:From January 2011 to December 2014, the laparoscopic operation cases of cervical cancer at stage Ⅰb1, Ⅰb2, Ⅱa1 and Ⅱa2, including the histologic subtypes of squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma, were collected in five clinical centers. The data were divided into two groups according to the surgical procedures, that is, modified laparoscopic-vaginal radical hysterectomy (mLVRH) and total laparoscopic radical hysterectomy (TLRH). The overall survival rate (OS), disease-free survival rate (DFS) at 5 years were retrospectively analyzed in this study.Results:There were 674 cases in total, including 377 cases of mLVRH, 297 cases of TLRH. (1) The OS at 5 years: the mLVRH was 96.1% and the TLRH was 92.0%, and the mLVRH was higher than that of TLRH ( P=0.010). Stratify analysis, including stage of disease (Ⅰb1 and Ⅱa1), histologic subtypes (squamous-cell carcinoma, adenocarcinoma), lymph node metastasis, revealed that, ① Stage of disease: in stage Ⅰb1, the OS at five years of mLVRH was higher than that in TLRH group (98.6% vs 93.6%, P=0.012). In stage Ⅱa1, there was significant difference between the two groups, the OS at five years of mLVRH and TLRH were 93.6% and 77.6% ( P=0.007). ② Histologic subtypes: for the OS at five years of squamous-cell carcinoma, mLVRH and TLRH were 96.1% and 92.3%, and there was significant difference ( P=0.046); for adenocarcinoma, the OS at five years were 91.0% and 88.6%, and there was no difference between two groups ( P=0.230). ③ Lymph node metastasis: the mLVRH and TLRH with lymph node metastasis, the OS at five years were 98.6% and 96.4%; the mLVRH and TLRH without lymph node metastasis, the OS at five years were 89.3% and 80.8%. There were no significant differences between the two groups,respectively ( P=0.156, P=0.093). (2) The DFS at 5 years: there was no significant difference between mLVRH and TLRH (94.1% vs 90.9%, P=0.220). Stratify analysis for stage of disease, the mLVRH group was higher than that in the TLRH group in stage Ⅰb1 (97.0% vs 92.8%, P=0.039). However, for stage Ⅱa1, there was no significant difference between mLVRH and TLRH group (88.2% vs 75.8%, P=0.074). Conclusions:The results of this retrospective study indicated that different laparoscopy surgical procedures had diverse oncologic outcomes. The OS at 5 years of the mLVRH is superior to the TLRH. The DFS at 5 years in Ⅰb1 stage, the mLVRH is higher than the TLRH. Therefore, the modified laparoscopy is still an alternative surgery for early cervical cancer patients when following the principle of no-tumor-exposure.
7.Comparison of the therapeutic effect of TGF-β1 gene therapy and traditional nonsurgical treatment on the rat model of postpartum stress urinary incontinence
Mingjun CHENG ; Yungui CAO ; Jingxin DING ; Jian HUANG
Acta Laboratorium Animalis Scientia Sinica 2016;24(4):408-413
Objective To study the effect of TGF?β1 gene therapy on the rat model of postpartum stress urinary incontinence and explore a novel non?operative treatment of this disease. Methods Two hundred and forty 6?month old SD female rats were used to prepare the model of postpartum stress urinary incontinence by vaginal dilation with a water sac. 148 rats from the 185 successfully prepared model rats were selected, and randomly divided into 5 groups: the TGF?β1 gene therapy, clentuterol treatment, electric stimulation therapy, injection of empty vector plasmid, and non?treated groups. In addition, 20 normal rats were selected as blank control group. Sneeze test and urodynamic test were conducted, the pelvic floor pubococcygeus muscle contractile force/muscle weight ratio was calculated, serum TGF?1 was detected by ELISA, and TGF?1 protein was detected by immunohistochemistry at 1, 21, 42 and 63 days after the treatment. Results At 21 days after treatment, all the maximum bladder capacity, leak point pressure, and urine or contractile force / muscle weight ratio of the TGF?β1 gene therapy group showed even better effects than those of the electrical stimulation group, but the differences were statistically not significant ( P>0?05 ) . Conclusions TGF?β1 gene therapy shows good therapeutic effect on the rat models of postpartum stress urinary incontinence, suggesting that TGF?β1 gene therapy may become a new type of non?surgical treatment for this disease.
8.Research of Project Management Working Mode of National Drug Reference Standards
Jingxin XIE ; Mingli LIU ; Cheng LI ; Lihua XIAO ; Xinyue XIAO ; Bo LI
China Pharmacist 2015;(8):1370-1371,1425
To explore the establishment of a scientific and innovative working mode of the national drug reference standards. Methods:Project management was adopted. Results and Conclusion: The project management mode can effectively ar-range the work of the national drug reference standards including raw material collection, research, review, subpackage, package and so on, which exhibits guiding significance for the development direction and improving products supplement.
9.Effect of IGF-1 gene and electric stimulation therapy on the rat model of postpartum stress urinary incontinence
Jian HUANG ; Mingjun CHENG ; Yisong CHEN ; Jingxin DING ; Keqin HUA
Acta Laboratorium Animalis Scientia Sinica 2015;(6):617-621
Objective To study the effect of IGF-1 gene therapy and electric stimulation therapy on the rat models of postpartum stress urinary incontinence, and explore the ideal treatment for this disease.Methods 240 SD female rats were used to establish the model of postpartum stress urinary incontinence by water sac vaginal dilation.148 model rats were randomly selected from 185 successful models and divided into 5 groups:IGF-1 gene therapy, clenbuterol treatment, electric stimulation therapy, injection of empty vector plasmid, and untreated groups.Besides, 20 non-modeled rats were used as blank control group.Urodynamic test was performed, pelvic floor pubococcygeus muscle/muscle weight ratio was calculated, and serum biochemical indices (LDH, CK) were detected, and the morphological changes of pubococcygeus muscle fibers were observed by light microscopy at 1, 21, 42 and 63 days after treatment.Results At 21 days after treat-ment, the maximum bladder capacity, leak point pressure, the contractile force/muscle weight ratio in the IGF-1 group and electric stimulation treatment group were significantly better (P>0.05), and the differences between the IGF-1 group and electric stimulation group were not significant ( P>0.05 ) .Conclusions The effect of IGF-1 gene therapy and electric stimulation on the rat models of postpartum stress urinary incontinence is better than that in the drug therapy group and oth-er groups.
10.Screening and functional analysis of microRNA expression in HPV16-positive squamous carcinoma of the cervix in the Uygur of southern Xinjiang.
Min YUAN ; Jingxin CHENG ; Yaxin LIU ; Wei SU ; Yu ZHANG ; Yi ZHANG
Journal of Central South University(Medical Sciences) 2015;40(7):701-709
OBJECTIVE:
To explore the differential expression of microRNA (miRNA) in HPV16-positive squamous carcinoma of the cervix in the Uygur of southern Xinjiang and to predict the target genes of the miRNAs.
METHODS:
Samples of HPV16-positive squamous carcinoma of the cervix from 5 Uygurs were collected for miRNA microarray assay. The differentially expressed miRNAs were selected for further verification by real-time quantitative RT-PCR. The software, including targetscan, miRwalk, miRanda and pictar, were used to predict the target genes of the verified miRNAs.
RESULTS:
Eighteen differentially expressed miRNAs were identified by miRNA microarray assay. The significantly differentially expressed miRNA-138 and miRNA-720 were verified by real-time quantitative RT-PCR. According to the prediction, the target genes for miRNA-138 were EZH2, LYPLA1, ARHGEF3, CLNS1A, EIF4EBP1, GNAI2, LIMK1, RHOC, ROCK2, SLC20A1, TERT, and H2AFX, while for miRNA-720 were EZH2, AGAP2, SPOCK2, FGF14, HNRNPA2B1, QKI, FOXG1, ACVR1B, DNMT3A, EPHB2, LATS2, KRAS, CCND2, NBN, ENAM, AMELX, PRNP, and CALB1.
CONCLUSION
miR-138 and miR-720 are the down-regulated target miRNAs in HPV16-positive squamous carcinoma of the cervix in the Uygur of southern Xinjiang. The common target gene for miR-138 and miR-720 is EZH2, which might be related to cervical squamous carcinoma invasion and metastasis.
Carcinoma, Squamous Cell
;
metabolism
;
virology
;
China
;
Down-Regulation
;
Female
;
Human papillomavirus 16
;
isolation & purification
;
Humans
;
MicroRNAs
;
metabolism
;
Papillomavirus Infections
;
metabolism
;
Real-Time Polymerase Chain Reaction
;
Uterine Cervical Neoplasms
;
metabolism
;
virology


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