1.METTL3 regulates ferroptosis and malignant progression of cervical cancer cells through mediating TRPM7 methylation
Miao FU ; Peng LIU ; Wen TIAN ; Sha WANG ; Xiaomei YIN ; Hao LIU ; Donghai WANG
Basic & Clinical Medicine 2025;45(10):1318-1325
Objective Methyltransferase 3(METTL3)mediated N6-methyladenosine(m6A)methylation modifica-tion of transient receptor potential cation channel subfamily M member 7(TRPM7)regulates ferroptosis and malig-nant progression in cervical cancer(CESC).Methods Totally 40 patients with cervical cancer were collected.Cer-vical cancer tissues and adjacent normal tissues(≥3 cm from the edge of the tumor tissue)were sampled at opera-tion and then divided into experimental group and control group,respectively.RT-qPCR and Western blot were used to detect the differences in TRPM7 mRNA and protein expression between the two groups.TRPM7-interfering cell lines were constructed to investigate the effects of TRPM7 on CESC cells.Cell proliferation and apoptosis were assessed using 5-ethynyl-2'-deoxyuridine(EdU)assay and flow cytometry,respectively.Transwell chamber assays were employed to evaluate cell invasion and migration capabilities.The levels of ferroptosis in CESC cells were measured using kits for reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH),and Fe2+.Bioinformatics tools were utilized to predict methyltransferases associated with TRPM7.The interaction between METTL3 and TRPM7 was examined through RNA immunoprecipitation(RIP)and methylated RNA immunoprecip-itation quantitative PCR(Me-RIP qPCR).The effect of METTL3 on the stability of TRPM7 expression was assessed using actinomycin D assay.Results TRPM7 was highly expressed in CESC tissue and cells.Knockdown of TRPM7 significantly inhibited cell proliferation,promoted cell apoptosis,suppressed cell migration and invasion capabilities,and enhanced ferroptosis levels(P<0.05).Bioinformatics predictions suggested that METTL3 might act as a methyltransferase for TRPM7.Interference with METTL3 gene expression significantly reduced TRPM7 pro-tein levels,decreased TRPM7 m6A modification levels,and impaired TRPM7 gene stability(P<0.05).Conclusions METTL3 regulates CESC proliferation,apoptosis,migration,invasion,and ferroptosis by m6A meth-ylation modification of the TRPM7 gene.
2.Effects of Bone Marrow Mesenchymal Stem Cell Transplantation on Neuropathic Pain in Rats with Spinal Cord Injury and Its Action on LPS-Induced Neuronal Cells
Minghui ZHANG ; Jiangtao WEN ; Xiaomei XIN ; Baohui ZHANG
Journal of Kunming Medical University 2025;46(7):74-83
Objective To investigate the effects of BMSCs treatment on neuropathic pain in rats with SCI and explore the underlying mechanism.Methods The rats were randomly divided into the following groups(n=15 per group):sham-operated(sham)group,spinal cord injury model(SCI)group,SCI+BMSCs group,and SCI+BMSCs+LY294002 group.An SCI model was established using Sprague-Dawley rats,followed by intraspinal administration of BMSCs and the PI3K inhibitor LY294002 to the injured spinal cord of SCI rats.The BBB score,pMWT,and pTWL values under thermal stimulation were measured.Hematoxylin-eosin staining was used to observe pathological changes in the injured spinal cord of rats.The effects of BMSCs transplantation on SCI rats were explored through hematoxylin-eosin staining,immunofluorescence staining,ELISA,and Western Blot experiments.RSCN were induced using LPS and co-cultured with BMSCs and their exosomes.The effects of BMSCs and their exosomes on RSCN were investigated through Annexin V-FITC/PI kit,ELISA,and Western Blot assays.Results The SCI model was considered successfully established when the following criteria were met on post-operative day 5:BBB locomotor score≤5,accompanied by a BBB score<10 on day 20,along with histopathological evidence of spinal cord tissue loosening,extensive vacuolation,and neuronal atrophy observed via HE staining.Compared with the sham group,the SCI group exhibited significantly lower BBB scores,pMWT,and pTWL values(P<0.001).Concurrently,increased immunofluorescence intensity of IBA1,elevated levels of pro-inflammatory cytokines,and pain-related factors were detected in the spinal cord(P<0.001).Furthermore,activation of the PI3K/AKT signaling pathway was significantly suppressed.BMSCs transplantation protected SCI rats by activating the PI3K/AKT pathway(P<0.001).BMSC-mediated spinal cord repair was attenuated by LY294002 administration.LPS-induced RSCNs showed increased apoptosis and pro-inflammatory cytokine release(P<0.001).Co-culture with MSCs or BMSCs-derived exosomes activated the PI3K/AKT signaling pathway,thereby reducing LPS-induced apoptosis and proinflammatory cytokine production(P<0.05).Conclusion BMSCs activate the PI3K/AKT signaling pathway in neurons through exosomes,suppressing the levels of TNF-α,SP,NE,and 5-HT,and promoting functional recovery in SCI rats.
3.Diagnostic value of serum serine protease Corin in patients with chronic renal failure complicated with heart failure
Pengfei ZHOU ; Shiyu LIU ; Wen FANG ; Ruihua CHEN ; Zihan ZHOU ; Xiaomei HOU ; Yutong YAN ; Yahui HU
Chinese Journal of Laboratory Medicine 2024;47(6):610-618
Objective:To investigate the diagnostic value of serum serine protease (Corin) in chronic renal failure (CRF) complicated with heart failure.Methods:A retrospective analysis was conducted on 120 patients, (64.05±13.89) years old, 77 male (64.17%), with chronic renal failure combined with heart failure admitted to Zhengzhou People′s Hospital from January 1, 2023, to December 31, 2023. The control group consisted of 87 patients, (60.59±8.78) years old, 54 male (62.07%), with simple chronic renal failure. Clinical information, laboratory test indicators and echocardiographic parameters were collected. Serum Corin concentration was measured using enzyme-linked immunosorbent assay (ELISA). The experimental group was divided into grade Ⅱ(31 cases), grade Ⅲ(47 cases) and grade Ⅳ(42 cases) according to the New York College of Cardiology heart function classification system. Serum Corin levels were compared between the experimental group and the control group and among different cardiac function grades. Spearman correlation analysis was performed to evaluate the relationship between serum Corin and brain natriuretic peptide (BNP), D-dimer. ROC analysis was conducted to assess the predictive value of serum Corin in CRF complicated with heart failure and cardiac function classification; Binary Logistic regression was used to construct a multi-index joint prediction model, the joint prediction probability was obtained, and ROC curve was drawn to compare the diagnostic value of serum Corin and BNP in CRF combined with heart failure and the diagnostic value of serum Corin combined with D-dimer and BNP in CRF combined with heart failure.Results:The serum Corin level[2 568.97±477.70 pg/ml vs. 1 727.81±480.60 pg/ml, t=12.47, P<0.001], BNP [700.00(256.00, 2 089.75) pg/ml compared with 88.00 (43.00, 230.00) pg/ml, Z=-9.00, P<0.001], D-dimer [1 150.00(643.00, 1 874.75)μg/L compared with 556.00 (301.00, 865.00)μg/L, Z=-6.57, P<0.001] in chronic renal failure complicated with heart failure group was higher than that in simple CRF group, and the difference was statistically significant. Among patients with CRF complicated with heart failure, serum Corin[2 231.74±311.39 pg/ml vs. 2 562.09±365.30 pg/ml vs. 2 825.57±536.83 pg/ml, F=74.33, P<0.001], BNP [234.00(168.00, 612.00) pg/ml compared with 514.00(260.00, 1 455.00) pg/ml compared with 2 200.00(640.50, 4 682.75) pg/ml, H=29.42, P<0.001], D-dimer [753.00(514.00, 1 280.00) μg/L compared with 1 187.00(590.00, 1 840.00) μg/L compared with 1 603.00(810.00, 3 313.25) μg/L, H=14.98, P<0.001] increased with the increase of cardiac function grade, and the difference was statistically significant. According to Spearman correlation analysis, serum Corin was positively correlated with BNP ( r=0.409) and D-dimer ( r=0.299), P<0.001. According to the ROC analysis, the AUC of serum Corin in the diagnosis of CRF complicated with heart failure and cardiac function grade Ⅱ, Ⅲ, Ⅳ were 0.890(95% CI 0.846-0.935), 0.807 (95% CI 0.728-0.885), 0.911 (95% CI 0.864-0.959), 0.927 (95% CI 0.882-0.972) respectively; the AUC of BNP in the diagnosis of CRF complicated with heart failure was 0.867 (95% CI 0.817-0.916), the AUC of serum Corin combined with D-dimer, BNP combined with D-dimer, serum Corin combined with D-dimer and BNP in the diagnosis of CRF complicated with heart failure were respectively 0.930 (95% CI 0.897-0.962), 0.892 (95% CI 0.847-0.936), 0.952 (95% CI 0.927-0.977). Conclusions:Serum Corin expression is elevated in patients with CRF complicated with heart failure, and the degree of elevation is related to cardiac function grade. Serum Corin has a good diagnostic value for CRF complicated with heart failure and its severity. Serum Corin is expected to become a new biomarker for diagnosis of CRF complicated with heart failure.
4.Research and application progress of gingival mesenchymal stem cells in oral diseases
Caitao ZHAO ; Xiaomei XIE ; Wen YIN ; Rui CHEN ; Zhen FAN ; Chunbo HAO
STOMATOLOGY 2024;44(7):556-560
Gingival mesenchymal stem cells(GMSCs)are a population of mesenchymal stem cells found in the lamina propria of gingi-val tissue and can be isolated not only from healthy gingival tissue but also from hyperplastic or even inflamed gingival tissue.GMSCs have become a hot topic of research in oral disease treatment because of their abundant sources,easy availability,unique immunomod-ulatory properties and multi-directional differentiation potential.GMSCs have been used in the treatment of periodontitis,gingival reces-sion,oral cancer,mandibular defects,peripheral nerve injury repair and so on.To prevent and treat oral diseases,this study will re-view the recent progress of research on the application of GMSCs in oral diseases.
5.Clinical Advantages of Traditional Chinese Medicine in Treatment of Pediatric Diseases
Yingke LIU ; Hong CUI ; Jian YANG ; Junhong WANG ; Liqun WU ; Xiaohua JI ; Bing AN ; Xiaomei LIU ; Weilin WAN ; Hong WANG ; Gaojun ZHOU ; Wen ZHANG ; Liyi QIU ; Kai GUO ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):224-231
The traditional Chinese medicine (TCM) in pediatric care has a long history,proven efficacy,and distinctive characteristics.The China Association of Chinese Medicine has organized a series of youth salons to discuss the clinical advantages of treating diseases.Experts at this seminar proposed that the superior disease categories in pediatric TCM are significant for showcasing the unique strengths and advantages of TCM in the treatment of pediatric diseases,enhancing diagnostic and treatment levels,inheriting TCM knowledge,promoting the integration of TCM and Western medicine,and meeting patients' needs.The strengths of pediatric TCM are summed up as "having what others do not,excelling at what others have,being special in what others excel at,and ensuring safety in what others specialize in." The scope of superiority in pediatric TCM covers multiple systems,including respiratory,digestive,endocrine,psychological,and dermatological systems.This article summarized the advantages of TCM in treating 13 diseases discussed in the salon,such as upper respiratory tract infections,coughs,pneumonia,allergic rhinitis,bronchial asthma,atopic dermatitis,functional dyspepsia,functional constipation,enuresis,marginal short stature,simple obesity,attention deficit hyperactivity disorder,and tic disorders.The overall advantages were reflected in three aspects:First,the holistic concept and treatment based on syndrome differentiation in TCM highlight the advantage of treating the root causes of diseases,making the treatment methodical and precise.Second,most traditional Chinese herbs are natural and have strong safety profiles.Third,TCM treatment methods are abundant,especially the external treatment methods,which are widely used in pediatrics,highly accepted by parents,and have definite efficacy,as well as good safety and compliance.
6.Management strategies of scientific research projects based on SWOT analysis
Lijuan WEN ; Ang CHEN ; Xiaomei WANG ; Yingrou YANG ; Qiongqing XIAO ; Meixin HUANG
Modern Hospital 2024;24(2):314-316
SWOT analysis is used to identify the strengths and external opportunities of scientific research management in hospitals.It facilitates the establishment of a systematic and rational approach to scientific research project management,help-ing hospitals to mitigate internal weaknesses and address external threats.This article chooses Y Hospital to carry out a case stud-y.SWOT analysis was done to investigate the hospital's strengths,weaknesses,opportunities,and threats.Based on the analysis results,it proposes targeted management strategies of"SO,""WO,""ST,"and"WT".After the use of the strategies in the management,the number of funded scientific research projects,published papers,registered invention patents,and achievements transferred from the scientific research remarkably increases,driving the improvement of research quality.
7.Association between Helicobacter pylori infection and albuminuria among physical examination population
Wen GAO ; Zhengce WAN ; Yuchai HUANG ; Xiaomei LEI ; Yuancheng HUANG ; Liu HU
Chinese Journal of Health Management 2023;17(8):598-602
Objective:To investigate the correlation between Helicobacter pylori ( H.pylori) infection and albuminuria inphysical examination population. Methods:It was a cross-sectional study. All the adults who received physical examination and underwent 13C-urea breath test at the Physical Examination Center in Tongji Hospital in 2021 were selected as the study subjects. General data (such as demographic information and past medical history) were documented. The physical measurement and blood biochemical indicators were checked too. Multivariate analysis was used to analyze the relationship between H. pylori infection and albuminuria. Results:A total of 30 311 subjects were included in this analysis. There were 17 123 males and 13 188 females with an age of (44.51±12.17) years. The positive rate of H. pylori infection was 27.3%. The incidence of albuminuria in subjects with H. pylori infection was 6.7%, and it was 6.1% in the subjects without H. pylori infection ( P=0.031). After adjusting for the confounding factors such as gender, age, diabetes and hypertension, H. pylori infection was independently associated with the risk of albuminuria (odds ratio ( OR)=1.133, 95% CI: 1.018-1.261, P=0.022). Conclusion:H. pylori infection is positively correlated with the occurrence of albuminuria in the physical examination population.
8.Recommendations for the diagnosis and treatment of Sj?gren′s syndrome in China
Wen ZHANG ; Zhu CHEN ; Xiaomei LI ; Jie GAO ; Yan ZHAO
Chinese Journal of Internal Medicine 2023;62(9):1059-1067
Sj?gren′s syndrome (SS) is a chronic systemic autoimmune disease characterized by lymphocyte proliferation and progressive exocrine gland damage. In addition to the impairment of salivary and lacrimal gland function, SS can present with multi-system and multi-organ involvement, accompanied by autoantibodies in serum and hyperimmunoglobulinemia. SS can be divided into primary and secondary forms based on the absence or presence, respectively, of concurrent connective tissue diseases such as systemic lupus erythematosus and rheumatoid arthritis. Based on evidence and guidelines from China and other countries, the Chinese Rheumatology Association drafted standardized criteria for the diagnosis and treatment of primary SS. The objectives were to standardize the detection and interpretation of key indicators for the diagnosis of SS, including serum anti-SSA antibody and labial gland pathology, suggest the use of the widely accepted European League Against Rheumatism (EULAR)-SS disease activity index for the evaluation of the disease, and standardize the rational management of SS patients with topical and systemic therapies.
10.KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer.
Cancan ZHENG ; Xiaomei YU ; Taoyang XU ; Zhichao LIU ; Zhili JIANG ; Jiaojiao XU ; Jing YANG ; Guogeng ZHANG ; Yan HE ; Han YANG ; Xingyuan SHI ; Zhigang LI ; Jinbao LIU ; Wen Wen XU
Acta Pharmaceutica Sinica B 2023;13(10):4217-4233
Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

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