1.Linagliptin synergizes with cPLA2 inhibition to enhance temozolomide efficacy by interrupting DPP4-mediated EGFR stabilization in glioma.
Dongyuan SU ; Biao HONG ; Shixue YANG ; Jixing ZHAO ; Xiaoteng CUI ; Qi ZHAN ; Kaikai YI ; Yanping HUANG ; Jiasheng JU ; Eryan YANG ; Qixue WANG ; Junhu ZHOU ; Yunfei WANG ; Xing LIU ; Chunsheng KANG
Acta Pharmaceutica Sinica B 2025;15(7):3632-3645
The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.
2.Prognostic value of SOCS6 and RORA expression in periodontal tissues in patients with periodontitis
Hui WANG ; Qixue DU ; Ruojun ZHANG ; Yang BAI
International Journal of Laboratory Medicine 2024;45(12):1501-1505,1510
Objective To explore the signal transduction of suppressor of cytokine signaling 6(SOCS6)and retinoic acid receptor related orphan nuclear receptor A(RORA)in patients with periodontitis expression of periodontal tissue,and analyze the prognosis of the patients with value.Methods A total of 224 patients with periodontitis who were treated in Jinan Hospital of Traditional Chinese Medicine from July 2021 to Janu-ary 2023 were selected as the study group,and 224 patients who needed to extract healthy teeth due to ortho-dontic treatment to the Jinan Hospital of Traditional Chinese Medicine outpatient were selected as the control group.The periodontal tissues were collected and the expression levels of SOCS6 and RORA in periodontal tissues were detected by real-time fluorescent quantitative PCR.The patients with periodontitis were followed up for 3 months,and according to the follow-up results,they were divided into good prognosis group(148 ca-ses)and poor prognosis group(76 cases).Multivariate Logistic regression analysis was used to analyze the in-fluencing factors of poor prognosis in patients with periodontitis.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of SOCS6 and RORA expression levels in periodontal tissues for poor prognosis in patients with periodontitis.Results Compared with the control group,the expression levels of SOCS6 and RORA in the periodontal tissue of the study group were decreased(P<0.05).A total of 224 patients with periodontitis were complete follow-up,the incidence of poor prognosis was 33.93%(76/224).The expression levels of SOCS6 and RORA in periodontal tissues of the poor prognosis group were lower than those of the good prognosis group(P<0.05).Multivariate Logistic regression analysis showed that the af-fected tooth located in the lower jaw,the affected tooth in the anterior teeth,the deepest probing depth of the affected tooth,the severity of periodontitis,the abnormal root morphology,the alveolar bone height,and the average attachment loss were the risk factors for the poor prognosis of patients with periodontitis(P<0.05).The expression levels of SOCS6 and RORA in periodontal tissues were protective factors(P<0.05).The area under the curve(AUC)of SOCS6 and RORA alone in predicting poor prognosis of periodontitis patients was 0.833 and 0.829,respectively.The AUC of the combination of SOCS6 and RORA(0.914)was higher than that of SOCS6 and RORA alone(Z=3.659,3.408,P<0.001).Conclusion The expression levels of SOCS6 and RORA in periodontal tissues of patients with poor prognosis of periodontitis are decreased.Both SOCS6 and RORA have a certain predictive effect on poor prognosis of patients with periodontitis,and the combina-tion of the two has a better predictive effect.
3.Identification of novel candidate genes in East Asian COPD patients by the functional summary-based imputation and the unified test for molecular signatures: a transcriptome-wide association study.
Ye TIAN ; Shufang SHAN ; Qixue BAO ; Siquan ZHOU ; Xia JIANG ; Mengqiao WANG ; Shu YIN ; Jingyuan XIONG ; Guo CHENG
Chinese Medical Journal 2023;136(13):1612-1614
4.Recent advances in molecular markers and targeted therapy in glioblastoma
Qixue WANG ; Kai ZHAO ; Chunsheng KANG
Chinese Journal of Neuromedicine 2019;18(6):629-633
Glioblastoma multiforme (GBM) is one of the most common invasive malignant tumors of the central nervous system.Molecular markers of glioblastoma are screened based on dataset,obtained through a large number of studies and algorithms,and could reflect the occurrence and development of GBM,or monitor the response to treatment.The molecular markers can effectively differentiate the subtypes,malignancy and response to radiotherapy of GBM.Here,we summarize the molecular markers of glioblastoma and discuss the prospects of targeted therapy for GBM.
6.Computed tomographic images analysis of frontal recess anatomy based on three-dimension reconstruction.
Peng WANG ; Xiaodong HAN ; Gui YANG ; Yanhong ZHANG ; Jianping LAN ; Hailiang ZHAO ; Shuqi QIU ; Hongtao ZHEN ; Qixue GAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2014;28(17):1305-1310
OBJECTIVE:
To observe the CT three-dimensional imaging features of the frontal recess region with advanced three-dimensional reconstruction, and develop the real image of the important anatomical structures around the region to conduct surgery.
METHOD:
Thirty patients were undergone spiral CT by 16 line high speed spiral CT, and multiplanar reconstruction images using standard three-dimensional reconstruction protocol on a computer workstation. The structure of the frontal recess, the agger nasi cell and adhere style of the uncinate process were observed. The parameter of the important anatomic structure of frontal recess was measured precisely.
RESULT:
After the reconstruction, we get the three-dimensional model very close to the true state of the nasal cavity-sinuses cell, in which parts of the frontal recess can clearly identify the agger nasi cell, frontal cell and other important structures. In these patients, the height, width and depth of the agger nasi and frontal sinus were (9.45 ± 3.60)mm, (8.08 ± 3.37)mm, (26.98 ± 6.82)mm and (26.86 ± 9.45)mm, respectively.
CONCLUSION
This study tried to develop the standardized techniques and measurements from three-dimensional reconstructed images of the frontal sinus and to ascertain the usefulness of the frontal sinus in identification of patients. The project results in better preoperative patient counselling and in predicting postoperative improvement in clinical status.
Ethmoid Sinus
;
diagnostic imaging
;
Frontal Sinus
;
diagnostic imaging
;
Humans
;
Image Processing, Computer-Assisted
;
methods
;
Imaging, Three-Dimensional
;
Nasal Cavity
;
Paranasal Sinuses
;
diagnostic imaging
;
Tomography, Spiral Computed
;
methods
7.3D computed tomographic analysis of frontal recess region.
Peng WANG ; Yanhong ZHANG ; Xiaodong HAN ; Gui YANG ; Jianping LAN ; Hailiang ZHAO ; Shuqi QIU ; Hongtao ZHEN ; Qixue GAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2014;28(5):311-317
OBJECTIVE:
The purpose of the study was to observe the three-dimensional (3D) CT imaging features of the frontal recess region with 3D reconstruction, and obtain the real image of the important anatomical structures of the region to conduct surgery.
METHOD:
Five patients were undergone spiral CT by 16 line high speed spiral CT, and multiplanar reconstruction images using standard 3D reconstruction protocol on a computer workstation. The structure of the frontal recess, the agger nasi cell and adhere style of the uncinate process were observed. The parameter of the important anatomic structure of frontal recess was measured precisely.
RESULT:
After the reconstruction, we get the 3D model very close to the true state of the nasal cavity--sinuses cell, in which parts of the frontal recess can clearly identify the agger nasi cell, frontal cell and other important structures. In this patient, the height, width and depth of the agger nasi and frontal sinus were 12.3 mm, 12.1 mm, 38.5 mm, respectively.
CONCLUSION
This study tried to develop the standardized techniques and measurements from 3D reconstructed images of the frontal sinus and to ascertain the usefulness of the frontal sinus in identification of patients. The results in better preoperative patient counselling and in predicting postoperative improvement in clinical status.
Adolescent
;
Adult
;
Aged
;
Female
;
Frontal Sinus
;
diagnostic imaging
;
Humans
;
Imaging, Three-Dimensional
;
Male
;
Middle Aged
;
Tomography, Spiral Computed
;
Young Adult
8.A case of malignant melanoma on the left side of the maxillary sinus.
Wanqing NIAN ; Heng WANG ; Qixue GAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2014;28(4):279-280
The clinical manifestations of the disease lacked specificity,and the clinical symptoms were nasal obstruction, any blood in snively and slightly swelling pain on face. The neoplasm with unsmooth surface looked taupe and maroon, and was brittle and easy blooding. Paranasal sinus CT:crumbly mass lesion within the shadow filled in the left side of the maxillary sinus,and the sinus stopped up,sinus wall bone was absorpt and thinned, front and rear wall and inner wall bone were boundedness broken off, knuckle partly to the nasal cavity. Direct reinforcement MRI:in addition to the result of paranasal sinus CT,enhance examination found obviously asymmetrical intensify of the focus. The pathological diagnosis of postoperation was malignant melanoma on the left side of the maxillary sinus.
Humans
;
Male
;
Maxillary Sinus Neoplasms
;
Melanoma
;
Middle Aged
9.Inhibitory Effects of Glucocorticoids on the Tenascin C Expression in Nasal Polyp
Heng WANG ; Zheng LIU ; Xiang LU ; Xuejun YOU ; Qixue GAO ; Yonghua CUI
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2009;38(6):756-759
Objective To investigate the effect of glucocortieoids on tenasein C(TNC) expression in nasal polyp tissues and airway epithelia,and explore the possible mechanism of glucocorticoids inhibiting remodeling of nasal polyp tissue.Methods The enzyme linked immunosorbent assay(ELISA) was used to detect the protein levels of tenascin C and transforming growth factor-β1(TGF-β1) in nasal polyp tissues from intranasal glucocorticoids (Budesonide,BUD) treated group and untreated group.The cell culture,real-time RT-PCR and in situ ELISA were employed to investigate the regulatory effects of budesonide on the TNC mRNA and protein expression in BEAS-2B immortalized human bronchial epithelial cells.Results The protein levels of TNC and TGF-β1 were decreased in nasal polyp tissues from intranasal BUD-treated group as compared with untreated group(P<0.01).There was a significantly positive correlation between TNC and TGF-β1 protein levels in nasal polyp tissues (r =0.68,P<0.01).After preincubation with BUD,TNC mRNA and protein expression induced by TGF-β1 in BEAS-2B cells was significantly decreased(P<0.01).Conclusion Glucocorticoids might participate in the regulation of tissue remodeling in nasal polyp by inhibiting the TGF-β1 expression in nasal polyp tissue and suppressing the induction of TGF-β1 to up-regulatie the TNC expression in airway epithelia.
10.Computed tomographic analysis of frontal recess region.
Peng WANG ; Xunhua XU ; Ping ZHAO ; Hongtao ZHEN ; Qixue GAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2009;23(5):214-218
OBJECTIVE:
The purpose of the study was to observe the CT imaging features of the frontal recess regional.
METHOD:
Eighty-two patients were undergone spiral computed tomography (CT). Then multiplanar reconstruction images were made using standard triplanar reconstruction protocol on a computer workstation.
RESULT:
The prevalence of agger nasi cell was 87.8% (144/164). One hundred and forty-five (89%, 145/164) uncinate processes had one superior attachment for each uncinate process. The others had two superior attachments for each uncinate process. The uncinate process' single superior attachment of into the surrounding structures was identified to have the following distribution: 90/164 (54.9%): to the lamina papyracea, 50/164 (30.5%) to the middle turbinate, and 5/164 (3.0%) to the skull base. Of all the frontal cells were identified in 144 (87.8%) sides of frontal recesses, the prevalence of type I II, type III IV, were 30.5% and 9.8% respectively.
CONCLUSION
T Agger nasi cell and uncinate process play an important role in endoscopic frontal sinus surgery.
Adolescent
;
Adult
;
Aged
;
Child
;
Female
;
Frontal Lobe
;
diagnostic imaging
;
Frontal Sinus
;
diagnostic imaging
;
Humans
;
Image Processing, Computer-Assisted
;
Male
;
Middle Aged
;
Nasal Cavity
;
diagnostic imaging
;
Tomography, X-Ray Computed
;
Turbinates
;
diagnostic imaging
;
Young Adult

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