1.Regulatory role of flavonoids in the signaling pathway of ischemic brain injury
Junlin PENG ; Zihao SHEN ; Jiamin CHEN ; Zengyu ZHANG ; Lunhui DUAN ; Ensi HONG ; Suyou ZHU
International Journal of Cerebrovascular Diseases 2025;33(1):59-66
In recent years, significant progress has been made in pharmacological research on the treatment of ischemic stroke with monomeric components of traditional Chinese medicine, among which flavonoids have shown good neuroprotective effects. This article reviews the regulatory role of flavonoids in the signaling pathway of ischemic brain injury.
2.Elemene as a binding stabilizer of microRNA-145-5p suppresses the growth of non-small cell lung cancer
Meirong ZHOU ; Jiayue WANG ; Yulin PENG ; Xiangge TIAN ; Wen ZHANG ; Junlin CHEN ; Yue WANG ; Yu WANG ; Youjian YANG ; Yongwei ZHANG ; Xiaokui HUO ; Yuzhuo WU ; Zhenlong YU ; Tian XIE ; Xiaochi MA
Journal of Pharmaceutical Analysis 2025;15(3):585-598
Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Inter-estingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17 μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated pro-tein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.
3.RBM14 enhances transcriptional activity of p23 regulating CXCL1 expression to induce lung cancer metastasis.
Wen ZHANG ; Yulin PENG ; Meirong ZHOU ; Lei QIAN ; Yilin CHE ; Junlin CHEN ; Wenhao ZHANG ; Chengjian HE ; Minghang QI ; Xiaohong SHU ; Manman TIAN ; Xiangge TIAN ; Yan TIAN ; Sa DENG ; Yan WANG ; Xiaokui HUO ; Zhenlong YU ; Xiaochi MA
Acta Pharmaceutica Sinica B 2025;15(6):3059-3072
Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.
4.Elemene as a binding stabilizer of microRNA-145-5p suppresses the growth of non-small cell lung cancer.
Meirong ZHOU ; Jiayue WANG ; Yulin PENG ; Xiangge TIAN ; Wen ZHANG ; Junlin CHEN ; Yue WANG ; Yu WANG ; Youjian YANG ; Yongwei ZHANG ; Xiaokui HUO ; Yuzhuo WU ; Zhenlong YU ; Tian XIE ; Xiaochi MA
Journal of Pharmaceutical Analysis 2025;15(3):101118-101118
Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.
5.Prediction of Tumor-Infiltrating CD8+T-Cell Expression in Glioblastoma Based on MRI Radiomics
Caiqiang XUE ; Xiaoai KE ; Qing ZHOU ; Ying WEI ; Feng SHI ; Bin ZHANG ; Peng ZHANG ; Hong LIU ; Junlin ZHOU
Chinese Journal of Medical Imaging 2025;33(10):1085-1091
Purpose To evaluate the value of preoperative MRI-based radiomic models for assessing tumor-infiltrating CD8+T-cell expression in glioblastoma patients,and to identify the most stable and efficient radiomic feature region for predicting prognosis following immunotherapy.Materials and Methods This retrospective study included 150 patients with histopathologically confirmed glioblastoma from Lanzhou University Second Hospital(January 2018 to April 2022).Tumor-infiltrating CD8+T-cell expression was quantitatively assessed using immunohistochemical staining,with patients stratified into CD8-high and CD8-low expression groups based on overall survival.A total of 1 185 radiomic features were extracted from each patient's contrast-enhanced T1C and T2WI images,covering the original tumor region and sequentially expanded peritumoral regions(2.5 mm,5.0 mm,7.5 mm,10.0 mm,12.5 mm,15.0 mm morphological dilation of tumor core+peritumoral area).Feature selection was performed using variance threshold,minimum redundancy maximum relevance,and least absolute shrinkage and selection operator methods.XGBoost classifier was employed to construct clinical,radiomic,and clinical-radiomic multimodal combined prediction models.Diagnostic performance was evaluated using receiver operating characteristic curve analysis.Results The radiomic model based on tumor expansion of 7.5 mm(tumor+peritumoral region)demonstrated optimal predictive performance.The clinical-radiomic multimodal combined model showed superior predictive capability compared to clinical and radiomic models alone,achieving an area under the curve of 0.991 and accuracy of 99.0%in the training set,and area under the curve of 0.840 with accuracy of 80.0%in the validation set.Conclusion MRI radiomics provides a feasible approach for evaluating tumor-infiltrating CD8+T-cell expression in glioblastoma patients,offering potential for preoperative prognosis prediction.
6.Prediction of Tumor-Infiltrating CD8+T-Cell Expression in Glioblastoma Based on MRI Radiomics
Caiqiang XUE ; Xiaoai KE ; Qing ZHOU ; Ying WEI ; Feng SHI ; Bin ZHANG ; Peng ZHANG ; Hong LIU ; Junlin ZHOU
Chinese Journal of Medical Imaging 2025;33(10):1085-1091
Purpose To evaluate the value of preoperative MRI-based radiomic models for assessing tumor-infiltrating CD8+T-cell expression in glioblastoma patients,and to identify the most stable and efficient radiomic feature region for predicting prognosis following immunotherapy.Materials and Methods This retrospective study included 150 patients with histopathologically confirmed glioblastoma from Lanzhou University Second Hospital(January 2018 to April 2022).Tumor-infiltrating CD8+T-cell expression was quantitatively assessed using immunohistochemical staining,with patients stratified into CD8-high and CD8-low expression groups based on overall survival.A total of 1 185 radiomic features were extracted from each patient's contrast-enhanced T1C and T2WI images,covering the original tumor region and sequentially expanded peritumoral regions(2.5 mm,5.0 mm,7.5 mm,10.0 mm,12.5 mm,15.0 mm morphological dilation of tumor core+peritumoral area).Feature selection was performed using variance threshold,minimum redundancy maximum relevance,and least absolute shrinkage and selection operator methods.XGBoost classifier was employed to construct clinical,radiomic,and clinical-radiomic multimodal combined prediction models.Diagnostic performance was evaluated using receiver operating characteristic curve analysis.Results The radiomic model based on tumor expansion of 7.5 mm(tumor+peritumoral region)demonstrated optimal predictive performance.The clinical-radiomic multimodal combined model showed superior predictive capability compared to clinical and radiomic models alone,achieving an area under the curve of 0.991 and accuracy of 99.0%in the training set,and area under the curve of 0.840 with accuracy of 80.0%in the validation set.Conclusion MRI radiomics provides a feasible approach for evaluating tumor-infiltrating CD8+T-cell expression in glioblastoma patients,offering potential for preoperative prognosis prediction.
7. Identification of the stroke type of hemorrhage and ischemic based on microwave measurement technique
Feng WANG ; Junlin BAO ; Huaiqiang LI ; Weihao PENG ; Jia XU ; Wei ZHUANG ; Jun YANG ; Haisheng ZHANG ; Xu NING ; Mingxin QIN ; Mingsheng CHEN
International Journal of Biomedical Engineering 2019;42(5):404-408
Objective:
To establish a microwave scattering parameter acquisition system to detect cerebral hemorrhage and cerebral ischemia animal models, and to study the non-contact rapid identification methods for the two stroke types.
Methods:
Rabbits were selected for modeling. Eight rabbits in the cerebral hemorrhage group were injected with autologous blood. Six rabbits in the cerebral ischemia group were treated with bilateral common carotid artery clamping and femoral artery bleeding. The measurement excitation source has a scanning frequency range of 300 kHz to 3 GHz and an intermediate frequency bandwidth of 30 kHz. The signal of the S21 phase was acquired. The collected microwave scattering signals were subjected to mean filtering, principal component analysis dimension reduction, and mean clustering and nearest neighbor analysis to realize the identification of stroke types.
Results:
The microwave scattering measurement method can reflect the changes of cerebral hemorrhage and cerebral ischemia. The phase of S21 decreases with the increase of blood loss and increases with the increase of ischemic duration. The results of the differential experiment showed that all 14 models were correctly identified.
Conclusions
The stroke identification system based on microwave scattering measurement can effectively distinguish rabbit cerebral hemorrhage model and ischemic model. This technology is low cost, portable non-invasive, simple operation and fast, which make it be a promising method for identifying pre-hospital stroke types.
8.Effects of hypoxia on adiponectin in tongue squamous cell carcinoma
Xiaohong GUO ; Chong DING ; Junlin ZHANG ; Xiaojing LAI ; Yuan PENG ; Fenghua WU ; Mingzhu YIN ; Yi LI ; Gang ZHAO
Chinese Journal of Clinical Oncology 2019;46(16):815-821
Objective: Adiponectin (APN) is an endogenous cytokine that mediates the development and progression of various tumors through its receptors (AdipoRs). The present study aimed to detect the expression and distribution of APN and its receptors (AdipoR1 and AdipoR2) in tongue squamous cell carcinoma (TSCC). Moreover, we explored whether the locoregional expression of APN was reg-ulated by HIF-1α in the hypoxic microenvironment. Methods: The expression and distribution of APN and its receptors in TSCC tissues were analyzed by immunohistochemical. Lentiviral expression vector for HIF-1α shRNA was constructed and stably transfected in TSCC cells to knock down HIF-1α expression. The mRNA and protein expression levels of APN and its receptors were detected using RT-PCR and Western blot, respectively, after hypoxic treatment. Results: The locoregional expression of APN and AdipoR1, but not AdipoR2, was upregulated at the early stages of T1, T2, and/or N0 stage, respectively, in tumor tissues compared to that in control paracancer-ous tissues (P<0.05 or P<0.01). The expression of APN and AdipoR1, but not AdipoR2, in TSCC cells was up-regulated on hypoxic treat-ment. Moreover, the expression of APN and AdipoR1 was down-regulated after shRNA knockdown of HIF-1α under hypoxia. Conclu-sions: The APN-AdipoR1 signaling pathway was activated and regulated by HIF-1α in the hypoxic environment of TSCC tissues.
9.AATYK is a Novel Regulator of Oligodendrocyte Differentiation and Myelination.
Chunxia JIANG ; Wanqing YANG ; Zhihong FAN ; Peng TENG ; Ruyi MEI ; Junlin YANG ; Aifen YANG ; Mengsheng QIU ; Xiaofeng ZHAO
Neuroscience Bulletin 2018;34(3):527-533
Oligodendrocytes (OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK (apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYK-deficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.
Animals
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Animals, Newborn
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Apoptosis Regulatory Proteins
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genetics
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metabolism
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Cell Differentiation
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drug effects
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physiology
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Cell Proliferation
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drug effects
;
genetics
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Cells, Cultured
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Cuprizone
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toxicity
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Demyelinating Diseases
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chemically induced
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metabolism
;
pathology
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Embryo, Mammalian
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Gene Expression Regulation, Developmental
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genetics
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Ki-67 Antigen
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metabolism
;
Mice
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Mice, Inbred C57BL
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Myelin Basic Protein
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metabolism
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Myelin Proteolipid Protein
;
metabolism
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Myelin Sheath
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drug effects
;
metabolism
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Oligodendroglia
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drug effects
;
metabolism
;
Protein-Tyrosine Kinases
;
genetics
;
metabolism
;
RNA, Small Interfering
;
genetics
;
metabolism
;
Rats
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Rats, Sprague-Dawley
10.Kyphoplasty with movement and secondary enlargement of balloon for compression fracture of vertebral body with im-complete posterior wall
Tiejun YANG ; Shuxia PENG ; Junlin ZHOU ; Qingxian TIAN ; Qinghe LIU ; Tie LU ; Hui ZHAO ; Yihan LI ; Lei SHAN ; Yang LIU
Chinese Journal of Orthopaedics 2017;37(1):24-30
Objective To explore the clinical efficacy and indications of kyphoplasty with movement and secondary en?largement of balloon for the compression fracture of vertebral body with ruptured posterior wall. Methods A retrospective analy?sis was carried out on the data of 29 patients (10 males, 19 females;age range:55-86 years old;mean age:71 years old;29 verte?bral bodies in total) who suffered from compression fracture of the thoracolumbar spine and below, and underwent kyphoplasty through the movement and secondary enlargement of balloon within the vertebral body and were followed up from January 2011 to November 2014. These patients had backache, accompanied by lowered support, limitation of movement, no symptom of nervous lesion on both lower extremities and no past history of balloon kyphoplasty. All fractured vertebral bodies were at T 11 or below, in?cluding 1 case at T11, 4 cases T12, 11 cases L1, 9 cases L2 and 4 cases L3. The causes of injury included fall (19 cases), car accident (8 cases) and unknown reasons (2 cases). All patients underwent kyphoplasty with the movement and secondary enlargement of bal?loon within the vertebral body. Photos were taken immediately after the surgery, at 1 month, 3 months, 6 months and 12 months, and these patients were assessed and analyzed in terms of vertebral height, Cobb angle, visual analogue score (VAS) and Oswestry disability index (ODI). Results The operation time (including the formation and solidification of bone cement) of 29 patients was 40 to 65 min and the mean time was 55 ± 7 min;the blood loss during operation was 2 to 15 ml and the mean blood loss was 5 ± 2 ml;the injected volume of bone cement was 2.5-7.5 ml and the mean volume was 5.5±0.5 ml. Post?operative pain was relieved and ambulation was performed under the protection of lumbar orthosis brace. Statstical analysis was conducted on VAS, ODI, vertebral height and Cobb angle before operation and at 1 month, 3 months, 6 months and 12 months after operation, showing statistically significant differences. X ray examination found that there was no alternation or displacement of bone cement location, and no change in vertebral morphology, the vertebral height and cobb angle remained the post?operative status, and posterior wall rupture of the vertebral body was recovered well. CT revealed that the morphology of bone cement was irregular and closely integrated with bone substance, and no cavity or fissure was seen. Conclusion Kyphoplasty with movement and secondary enlargement of bal?loon within the vertebral body has a good, definite clinical efficacy in treating compression vertebral fracture with incomplete pos?terior wall of the vertebral body without obvious displacement of fractured bone and symptom of nervous lesion on both lower ex?tremities. This surgery is easy to operate, and has an immediate analgesic effect, which could recover vertebral height as well as re?duce kyphosis deformity and improve patient’s prognosis.

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