OBJECTIVES: To reprogram human placental fibroblasts (HPFs) into chemically induced epithelioid-like cells (ciEP-Ls) using a combination of small-molecule compounds. METHODS: HPFs cultured under normoxic conditions were identified using immunofluorescence assay, PCR and chromosomal karyotyping. Under hypoxic conditions (37 ℃, 5% O₂), HPFs were cultured in a medium containing small-molecule compounds C6TSEDRVAJZ (CHIR99021, 616452, TTNPB, SAG, EPZ5676, DZNep, Ruxolitinib, VTP50469, Afuresertib, JNK-IN-8, and EZM0414), and the cell morphology was observed daily. The expression levels of epithelial cell markers in the induced cells were detected by immunofluorescence, Western blotting and PCR. Chromosomal karyotyping of the induced cells was performed and the induction efficiency was calculated. RESULTS: Before induction, HPFs showed positive expressions of fibroblast surface markers CD34 and vimentin and were negative for epithelial surface markers. PCR results showed high expressions of fibroblast-specific genes S100A4 and COL1A1 in HPFs with a normal human diploid karyotype. After one day of induction, the HPFs underwent morphological changes from a multinodular spindle shape to a round or polygonal shape, which was morphologically characteristic of ciEP-Ls. On day 4 of induction, the cells exhibited high expressions of the epithelial cell markers E-cadherin and Lin28A. RT-qPCR results also showed that the cells expressed the epithelial markers Smad3, GLi3, PAX8, WT1, KRT19, and KRT18 with significantly down-regulated expressions of all the fibroblast surface markers and a normal human diploid karyotype. The reprogramming efficiency of HPFs into ciEP-Ls ranged from (64.53±2.8)% to (68.10±3.6)%. CONCLUSIONS The small-molecule compound combination C6TSEDRVAJZ is capable of inducing HPFs into ciEP-Ls under hypoxic conditions with a high induction efficiency.
Humans ; Fibroblasts/drug effects* ; Pregnancy ; Female ; Cell Differentiation/drug effects* ; Pyrimidines/pharmacology* ; Placenta/cytology* ; Cells, Cultured ; Pyridines/pharmacology* ; Pyrazoles/pharmacology* ; Epithelial Cells/cytology*

Migraine is a common neurological disorder with a complex pathogenesis that is currently not fully understood;however,the role of mitochondrial function in migraine pathogenesis has recently attracted widespread attention.This review considers the latest research progress on the relationship between mitochondrial dysfunction and migraine,including mitochondrial energy metabolism,oxidative stress,calcium homeostasis,and neuroinflammation.We introduce the epidemiological and clinical characteristics of migraine,and provide a detailed exploration of the key role of mitochondria in these processes.Mitochondrial dysfunction may lead to increased neuronal excitability,abnormal vasoconstriction,and inflammatory responses,thereby inducing migraine.Based on the evidence of mitochondrial involvement in the pathogenesis of migraine,we propose future research directions and potential treatment strategies,with the aim of providing new ideas for the prevention and treatment of migraine.

Migraine is a common neurological disorder with a complex pathogenesis that is currently not fully understood;however,the role of mitochondrial function in migraine pathogenesis has recently attracted widespread attention.This review considers the latest research progress on the relationship between mitochondrial dysfunction and migraine,including mitochondrial energy metabolism,oxidative stress,calcium homeostasis,and neuroinflammation.We introduce the epidemiological and clinical characteristics of migraine,and provide a detailed exploration of the key role of mitochondria in these processes.Mitochondrial dysfunction may lead to increased neuronal excitability,abnormal vasoconstriction,and inflammatory responses,thereby inducing migraine.Based on the evidence of mitochondrial involvement in the pathogenesis of migraine,we propose future research directions and potential treatment strategies,with the aim of providing new ideas for the prevention and treatment of migraine.

Objective To determine the expression and clinical significance of pseudogene FMO6P in gastric cancer,and explore its functions and underlying molecular mechanism in regulating the invasion and metastasis of gastric cancer cells.Methods The expression level of FMO6P in gastric cancer tissues and cell lines was detected by quantitative real time polymerase chain reaction(qRT-PCR).The migration and invasion abilities of gastric cancer cells were detected by transwell assay.The effect of FMO6P on the tumor formation and peritoneal dissemination of gastric cancer cells were evaluated by injecting FMO6P-overexpressing gastric cancer cells into the subcutaneous or peritoneal cavity of nude mice respectively.The expression levels of epithelial-mesenchymal transition(EMT)markers,including E-cadherin,N-cadherin,ZEB1,MMP2,and the activation of AKT/mTOR pathway in FMO6P-overexpressing or knockdown gastric cancer cells were measured by Western blot.Results The expression of FMO6P was significantly reduced in tumor tissues compared to its adjacent non-tumor tissues of gastric cancer,FMO6P expression level in tumor tissues was correlated with tumor size and TNM stage.Overexpression of FMO6P significantly inhibited the invasion and migration abilities of gastric cancer cells,while downregulation of FMO6P expression promoted the invasion and migration ability of gastric cancer cells.Overexpression of FMO6P in gastric cancer cells significantly inhibited the subcutaneous tumor formation and peritoneal dissemination of gastric cancer cells in nude mice.Moreover,overexpression of FMO6P promoted the expression of E-cadherin,and inhibited the expression of N-cadherin,ZEB1,and MMP2 in gastric cancer cells.The phosphorylation levels of AKT and mTOR were also downregulated in gastric cancer cells overexpressing FMO6P.Conclusions All these findings suggested that pseudogene FMO6P suppresses the invasion and migration potential of gastric cancer cells in vitro and in vivo,which is possibly through the inhibition of the AKT/mTOR signaling pathway.

Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.

Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.

Objective To investigate and analyze the impact of three personalized surgical design schemes for SPT trans PRK on postoperative visual quality and higher-order aberrations in individuals with myopic astigma-tism,aiming to provide a foundation for more rational selection of personalized design schemes.Methods The 96 cases(96 eyes)with myopic astigmatism were divided into three groups based on three personalized design schemes and a conventional mode.Specifically,24 eyes were assigned to the personalized group 1,which focused on coma elimination;another 24 eyes belonged to personalized group 2,where the aim was to minimize spherical aberration elimination;and the remaining 24 eyes were further categorized into personalized group 3 based on a model that aimed at minimizing spherical aberration.Additionally,there were also 24 eyes in the control group treated using the conventional mode.The study compared and analyzed various parameters including best corrected visual acuity,spherical aberration,coma,total higher-order aberration of the anterior corneal surface,as well as differences in corneal ablation thickness between personalized and conventional schemes within the surgical design software.Results(1)The postoperative visual acuity of the personalized group was significantly superior to that of the control group(P＜0.05);(2)Among the personalized groups,Group 2 exhibited a reduced amount of cor-neal tissue ablation compared to other groups(P＜0.01);(3)Group 2 demonstrated lower values than the other groups after surgery(P＜0.05).(4)Coma:The control group showed a significantly higher level of coma com-pared to preoperative measurements(P＜0.01).No significant differences were observed between Groups 1,2,and 3 after surgery(P＞0.05).(5)Total higher-order aberrations:All groups experienced a significant increase in total higher-order aberrations following surgery(P＜0.01).Group 2 exhibited lower values than the other groups postoperatively(P＜0.05).Conclusion For myopic astigmatism,SPT trans PRK incorporates the personalized surgical scheme with a focus on minimizing spherical aberration elimination mode,resulting in enhanced optimiza-tion of postoperative high-order aberration and improved visual quality,while preserving corneal tissue.

Objective To investigate and analyze the impact of three personalized surgical design schemes for SPT trans PRK on postoperative visual quality and higher-order aberrations in individuals with myopic astigma-tism,aiming to provide a foundation for more rational selection of personalized design schemes.Methods The 96 cases(96 eyes)with myopic astigmatism were divided into three groups based on three personalized design schemes and a conventional mode.Specifically,24 eyes were assigned to the personalized group 1,which focused on coma elimination;another 24 eyes belonged to personalized group 2,where the aim was to minimize spherical aberration elimination;and the remaining 24 eyes were further categorized into personalized group 3 based on a model that aimed at minimizing spherical aberration.Additionally,there were also 24 eyes in the control group treated using the conventional mode.The study compared and analyzed various parameters including best corrected visual acuity,spherical aberration,coma,total higher-order aberration of the anterior corneal surface,as well as differences in corneal ablation thickness between personalized and conventional schemes within the surgical design software.Results(1)The postoperative visual acuity of the personalized group was significantly superior to that of the control group(P＜0.05);(2)Among the personalized groups,Group 2 exhibited a reduced amount of cor-neal tissue ablation compared to other groups(P＜0.01);(3)Group 2 demonstrated lower values than the other groups after surgery(P＜0.05).(4)Coma:The control group showed a significantly higher level of coma com-pared to preoperative measurements(P＜0.01).No significant differences were observed between Groups 1,2,and 3 after surgery(P＞0.05).(5)Total higher-order aberrations:All groups experienced a significant increase in total higher-order aberrations following surgery(P＜0.01).Group 2 exhibited lower values than the other groups postoperatively(P＜0.05).Conclusion For myopic astigmatism,SPT trans PRK incorporates the personalized surgical scheme with a focus on minimizing spherical aberration elimination mode,resulting in enhanced optimiza-tion of postoperative high-order aberration and improved visual quality,while preserving corneal tissue.

Objective To determine the feasibility of neck vessel wall imaging technology with three?dimensional variable?flip?angle turbo spin?echo (3D T1w?SPACE) for the detection of carotid atherosclerotic disease before revascularization. Methods Thirty?one patients who underwent carotid endarterectomy (CEA) and fifty?three patients who underwent carotid stenting (CAS) were enrolled prospectively. Neck vessel wall imaging examination were performed in all patients whilecarotid artery DSA were performed in all CAS patients. Quantitative measurements including stenosis, lesion length, and the presence or absence of plaque ulceration obtained with 3D T1w?SPACE and DSA were independently determined. And images of the 3D T1w?SPACE were compared with corresponding histology to identify major plaque components including intraplaque hemorrhage (IPH), lipid rich necrotic core (LRNC), and calcification (CA). The consistency rate, sensitivity, specificity, positive predictive value and negative predictive value were used to assess diagnostic value. Bland?Altman plots, intraclass correlation coefficient (ICC), and Cohen Kappa were determined. Results DSA was served as the reference standard. There was an excellent correlation between 3D T1w?SPACE and DSA images in measuring stenosis (r=0.984, P<0.01) and luminal stenosis [ICC=0.98 (95% confidence interval: 0.96-0.99)]. Bland?Altman plots showed that the two examinations were in good consistency in evaluating the extent of stenosis. Sensitivity (89.5%) and specificity (95.1%) was high in 3D T1w?SPACE images compared to DSA for the detection of ulcers. The consistency rate between 3D T1w?SPACE images and histological results for IPH, LRNC and CA detection were 85.7%, 82.1% and 92.9%, respectively. Sensitivity and specificity were 90.0% and 75.0% for IPH;83.3% and 80.0% for LRNC; 91.3% and 100.0% for CA respectively. However, lesion length measurements by using 3D T1w?SPACE were longer than those measured by using DSA (P<0.01).Conclusion Neck vessel wall imaging technology with 3D T1w?SPACE is a noninvasive and accurate technique for the diagnosis of carotid artery atherosclerotic disease before revascularization.

Objective: To investigate the expression of Flotillin-2 (Flot-2) protein in gastric cancer tissues and its relationship with clinicopathological features and prognosis of gastric cancer (GC) patients. Methods: 112 samples of gastric cancer tissue and the corresponding paracancerous tissue that resected at the gastrointestinal surgery department of the Second Affiliated Hospital of Nanchang University between January 2009 andApril 2010 were collected for this study. The expression of Flot-2 protein in tumor tissues was detected by immunohistochemistry. The survival data were analyzed by Kaplan-Meier and Log-Rank test, and the survival curve was plotted. Spearman correlation analysis was used to examine the relationship between Flot-2 protein expression and clinicopathological characteristics and prognosis of GC patients. Results: In gastric cancer tissues, Flot-2 was primary stained in cytoplasm. Level of Flot-2 was significantly higher in gastric cancer tissues compared with that in paracancerous tissues (53.57% vs 46.43%, P<0.05). Expression of Flot-2 in tumor tissues was significantly associated with tumor size, depth of invasion, lymph node metastasis, distant metastasis and AJCC stage (all P<0.01), but not with gender, age, differentiation degree and tumor location (P>0.05). Moreover, survival analysis showed that the overall survival of patients with low Flot-2 expression was significantly higher than that of the patients with high level (P<0.01). Cox regression analysis indicated that distant metastasis, AJCC stage and Flot-2 expression were the independent risk factors for the prognosis of GC patients. Conclusion: Flot-2 protein was highly expressed in gastric cancer tissues and closely correlated with the poor prognosis of GC patients; Flot-2 is an independent risk factor for GC prognosis and may be served as a potential therapeutic target for gastric cancer.