1.Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma
Wenwen YU ; Yubo SHI ; Xiaoqiong BAO ; Xiangxiang CHEN ; Yangyang NI ; Jincong WANG ; Hua YE
The Korean Journal of Physiology and Pharmacology 2025;29(3):337-347
Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.
2.Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma
Wenwen YU ; Yubo SHI ; Xiaoqiong BAO ; Xiangxiang CHEN ; Yangyang NI ; Jincong WANG ; Hua YE
The Korean Journal of Physiology and Pharmacology 2025;29(3):337-347
Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.
3.Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma
Wenwen YU ; Yubo SHI ; Xiaoqiong BAO ; Xiangxiang CHEN ; Yangyang NI ; Jincong WANG ; Hua YE
The Korean Journal of Physiology and Pharmacology 2025;29(3):337-347
Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.
4.Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma
Wenwen YU ; Yubo SHI ; Xiaoqiong BAO ; Xiangxiang CHEN ; Yangyang NI ; Jincong WANG ; Hua YE
The Korean Journal of Physiology and Pharmacology 2025;29(3):337-347
Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.
5.Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma
Wenwen YU ; Yubo SHI ; Xiaoqiong BAO ; Xiangxiang CHEN ; Yangyang NI ; Jincong WANG ; Hua YE
The Korean Journal of Physiology and Pharmacology 2025;29(3):337-347
Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.
6.Immunogenicity, protective efficacy and preliminary protective mechanism of KPC-2, a drug resistance target from Klebsiella pneumoniae
Xiaoqiong WANG ; Guangyang MING ; Zhifu CHEN ; Qiang GOU ; Yue YUAN ; Liqun ZHAO ; Jinyong ZHANG ; Renjian HU
Chinese Journal of Microbiology and Immunology 2024;44(1):2-10
Objective:To develop a recombinant protein vaccine based on KPC-2, a drug resistance target in Klebsiella pneumoniae, and evaluate its immunogenicity, protective efficacy and mechanism in a mouse model of pneumonia. Methods:KPC-2 was expressed in Escherichia coli and purified using GST affinity chromatography. A recombinant protein vaccine was prepared with KPC-2 and used to immunize New Zealand rabbits through subcutaneous injection. Serum samples were isolated from cardiac blood and Protein G chromatography was used to purify polyclonal antibodies against KPC-2. Opsonophagocytic killing assay was used to assess the bactericidal activity of the polyclonal antibodies in vitro. Female BALB/c mice were immunized three times with the recombinant protein vaccine, and the titers of specific IgG antibodies in serum were measured by indirect ELISA. One week after the last vaccination, the mice were infected with Klebsiella pneumoniae strain SRT through tracheal intubation, and received a single intravenous dose of meropenem (0.1 mg) 1 h later. The protective efficacy of the KPC-2 recombinant protein vaccine was evaluated by comparing the survival rates, bacterial colonization and histopathological changes between vaccine group and adjuvant group as well as the survival rates between meropenem group and normal saline group. Moreover, the protective efficacy of polyclonal antibodies against KPC-2 was evaluated through passive immunization. Results:The level of specific IgG antibodies in serum was significantly higher in the vaccine group than in the adjuvant group ( t=4.325, P<0.05). The survival rate in the vaccine group was also higher than that of the adjuvant group [70% (7/10) vs 10% (1/10), P<0.05]. Furthermore, lung inflammation was less severe and bacterial burden was reduced in the vaccine group as compared with those of the control group ( t=3.127, P<0.05). Both active and passive vaccination strategies demonstrated strong protective efficacy against Klebsiella pneumoniae infection, and had a synergistic effect when used in combination with antibiotic therapy. The polyclonal antibodies against KPC-2 had bactericidal activity in vitro ( t=5.427, P<0.05). Conclusions:The prepared KPC-2 vaccine has better immunogenicity and protective efficacy. It can induce strong humoral immune responses. This study suggest that drug resistance target may be used as a candidate antigen for future vaccine development.
7.Identification of banana ADA1 gene family members and their expression profiles under biotic and abiotic stresses.
Qiqi ZHAO ; Wenhui REN ; Huifei ZHU ; Qiuzhen WU ; Chunyu ZHANG ; Xiaoqiong XU ; Binbin LUO ; Yuji HUANG ; Yukun CHEN ; Yuling LIN ; Zhongxiong LAI
Chinese Journal of Biotechnology 2024;40(1):190-210
The Spt-Ada-Gcn5-acetyltransferase (SAGA) is an ancillary transcription initiation complex which is highly conserved. The ADA1 (alteration/deficiency in activation 1, also called histone H2A functional interactor 1, HFI1) is a subunit in the core module of the SAGA protein complex. ADA1 plays an important role in plant growth and development as well as stress resistance. In this paper, we performed genome-wide identification of banana ADA1 gene family members based on banana genomic data, and analyzed the basic physicochemical properties, evolutionary relationships, selection pressure, promoter cis-acting elements, and its expression profiles under biotic and abiotic stresses. The results showed that there were 10, 6, and 7 family members in Musa acuminata, Musa balbisiana and Musa itinerans. The members were all unstable and hydrophilic proteins, and only contained the conservative SAGA-Tad1 domain. Both MaADA1 and MbADA1 have interactive relationship with Sgf11 (SAGA-associated factor 11) of core module in SAGA. Phylogenetic analysis revealed that banana ADA1 gene family members could be divided into 3 classes. The evolution of ADA1 gene family members was mostly influenced by purifying selection. There were large differences among the gene structure of banana ADA1 gene family members. ADA1 gene family members contained plenty of hormonal elements. MaADA1-1 may play a prominent role in the resistance of banana to cold stress, while MaADA1 may respond to the Panama disease of banana. In conclusion, this study suggested ADA1 gene family members are highly conserved in banana, and may respond to biotic and abiotic stress.
Musa/genetics*
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Phylogeny
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Fungal Proteins
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Cell Nucleus
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Histones
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Stress, Physiological/genetics*
8.Application of visual rigid laryngoscope in nasotracheal intubation for patients simulated difficult airway with cervical spine immobilization
Rongmu LIN ; Jiaxiang CHEN ; Rui ZHANG ; Peng HE ; Xiaoqiong XIA ; Zhiguo TAO
The Journal of Clinical Anesthesiology 2024;40(8):830-835
Objective To compare the effects of visual rigid laryngoscope and visual laryngoscope in nasotracheal intubation(NTI)for patients with cervical spine immobilization simulated difficult airway.Methods Ninety patients scheduled for selective surgery under general anesthesia requiring NTI,52 males and 38 females,aged 18-64 years,BMI 18.5-25.0 kg/m2,ASA physical status Ⅰ or Ⅱ,were scheduled for selective surgery under general anesthesia requiring NTI.Before anesthesia induction,the spinal surgeon selected an appropriate cervical collar and adjusted it to fix patient's neck to establishing difficult airway sim-ulation model.All patients were randomly assigned into two groups:visual rigid laryngoscope(group R)and common visual laryngoscope(group C),45 patients in each group.NTI was performed using either visual rigid laryngoscope or visual laryngoscope in groups R and C,respectively.The nasal passage time,glottic exposure time,intubation time,number of successful first intubation attempts,and intubation attempts were recorded.Glottic exposure was assessed using the Cormack-Lehane(C-L)grading system,and the intuba-tion condition was quantitatively evaluated using the modified nasal intubation difficulty scale(NIDS).The blood pressure and heart rate were measured at baseline(T1),immediately after intubation(T2),and at 1 minute(T3)and 3 minutes(T4)after intubation.The occurrence of intubation-related complications(nasal bleeding,sore throat,hoarseness)was recorded.Results Compared with group C,the nasal passage time and proportion of successful intubations without difficulty were significantly increased in group R,and the glottic exposure time and intubation time were significantly decreased in group R(P<0.05).Compared with group C,the HR and MAP at T2 and T3 were significantly decreased in group R(P<0.05).Com-pared with group C,group R had significantly lower incidence rates of nasal bleeding,sore throat,and hoarseness(P<0.05).There were no statistically significant differences in the first intubation success rate,number of intubation attempts,or C-L grade between the two groups.Conclusion Patients with cer-vical spine immobilization simulated difficult airway,both visual rigid laryngoscope and visual laryngoscope can be performed safely and effectively in NTI.Compared with visual laryngoscope,visual rigid laryngoscope can provide faster glottic exposure,shorter intubation time,lower intubation difficulty,less hemodynamic impact,and lower incidence of complications.
9.Feasibility of predicting expression of Ki-67 in lung adenocarcinoma via multi-parameter of duallayer spectral detector CT
Yiting CHEN ; Xiaoqiong NI ; Liang XU ; Guohua FAN ; Dan JIN
Journal of Practical Radiology 2024;40(10):1597-1600,1610
Objective To explore the feasibility of predicting expression level of Ki-67 in lung adenocarcinoma via multi-parameter of spectral CT.Methods The data of 226 patients with lung adenocarcinoma confirmed by pathology were analyzed retrospectively.The conventional and spectral CT parameters of the lesions were analyzed.According to Ki-67 expression level,all patients were divided into low expression group and high expression group.The parameters with statistical significance were identified as independent variables for multivariate logistic regression analysis to establish a logistic regression model for predicting the expression level of Ki-67.Receiver operating characteristic(ROC)curve was used to assess the diagnostic performance for each model,respectively.Results There were significant differences in the clinical factors of gender,smoking and chest pain between high and low Ki-67 expression groups.In spectral CT parameters,CT40 keV,CT100 keV,Z-effective(Zeff)and iodine concentration(IC)in the high expression group in arterial phase were significantly higher than those in the low expression group.Logistic regression analysis showed that CT100 keV was the independent risk factor for Ki-67 expression level.Both the spectral CT model and the combined model had high value in predicting the expression level of Ki-67 in lung adenocarcinoma,and the combined model had better diagnostic efficacy.Conclusion Spectral CT parameters combined with clinical factors have a certain value in predicting the expression level of Ki-67 in lung adenocarcinoma.
10.Antitumor effect and mechanism of total alkaloids of Gelsemium elegans and sempervirine in vitro
Huixian CHEN ; Wenyi WANG ; Xinghui TAN ; Gaopan LI ; Xiaoqiong ZHANG ; Desen LI ; Shuisheng WU
China Pharmacy 2023;34(12):1437-1442
OBJECTIVE To explore the antitumor effect and mechanism of total alkaloids of Gelsemium elegans (TA) and sempervirine (SPV) in vitro. METHODS The effects of low, medium and high concentrations of TA (50, 100, 200 μg/mL) and SPV (10, 30, 50 μmol/L) on the morphology of human hepatoma cells (HepG2, Bel-7402), human lung cancer cells (A549) and human colon cancer cells (HCT-8) were observed, and the toxicity of TA and SPV to four tumor cells was monitored. The effects of TA and SPV on the contents of caspase-3 and caspase-9 in the supernatant of HCT-8 cells, the protein expressions of phosphorylated protein kinase B (p-Akt) (Thr308, Ser473), B-cell lymphoma 2 (Bcl-2), Bcl-2-related X protein (Bax), survivin, C/EBP-homologous protein (CHOP), immunoglobulin binding protein (Bip) and microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ) in HCT-8 cells were detected. RESULTS After the intervention of TA and SPV, the volume reduction and nuclear shrinkage were founded in four tumor cells; the cell activity decreased to varying degrees, among which TA and SPV had the best inhibitory effect on HCT-8 cells. After the intervention of TA and SPV, the contents of caspase-3 and caspase-9 in the supernatant of HCT-8 cells, the protein expressions of Bax, CHOP, Bip and LC3Ⅱ all increased to different degrees, while the protein expressions of p-Akt (Thr308, Ser473), Bcl-2 and survivin in HCT-8 cells all decreased to different degrees. CONCLUSIONS TA and SPV have inhibitory effects on the above four tumor cells, and the inhibitory effect on HCT-8 cells is the best. The mechanism of their action on HCT-8 cells may be related to promoting apoptosis, activating endoplasmic reticulum stress and autophagy.

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