BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Objective To investigate the impact of variations in RNA-binding motif protein 20(RBM20)and muscle-restricted coiled-coil(MURC)digenic heterozygosity variation on the structural and biological characteristics of human cardiomyocyte AC 16(an adult left ventricular myocardial cell line).Methods Cardiomyocyte AC 16 cell lines were constructed with control,negative scramble,wild-type,MURC single-gene mutant,RBM20 single-gene mutant,and RBM20 and MURC digenic mutant groups.The localization of RBM20 and MURC in cardiomyocytes,cell area,cytoskeletal arrangement,cytoskeleton-related proteins,cell polarity,and intracellular calcium concentration were observed using Western blotting,immunofluorescence staining,and reverse transcription polymerase chain reaction.Myocardial apoptosis was detected using flow cytometry.Ki-67 staining and wound healing assays were performed to detect cardiomyo-cyte proliferation and migration,respectively.Results Digenic mutations had a more pronounced impact than single-gene mutations in RBM20 or MURC on the structural and biological characteristics of cardiomyocytes,manifested by increased cell area,upregulated mRNA expression of hypertrophy-related genes,such as myosin heavy chain 7 and alpha-actin,increased cytoskeleton disturbance,decreased flu-orescence intensity of cytoskeletal proteins β-tubulin and Vinculin(all P＜0.01);increased fluorescence intensity of the polarity protein Part 6(P＜0.05);and significantly elevated cardiomyocyte apoptosis rate,decreased proliferative activity,and elevated migration rate and intracellular calcium ion concentration(all P＜0.01).Conclusion The digenic heterozygous variation in RBM20 and MURC may induce changes in the morphological structure and biological characteristics of myocardial cells,including increased cell area,cytoskeleton dis-turbance,cell polarity,increased apoptosis rate and mobility,decreased cell proliferation activity,and calcium processing ability.

Objective To explore better methods of ceramic crown design and reduce foreign body sensation of prostheses by digitally replicating the lingual morphology of the original teeth in the patient's aesthetic zone.Methods Patients with anterior tooth defects were collected from July 2022 to December 2023 at Department of Second Clinical Division of the Affiliated Stomatological Hospital,Nanjing Medical University.Patients with crown prostheses designed using automatically matched tooth morphology from the tooth shape database served as the control group.Patients with crown prostheses designed using digital technology to replicate the lingual morpholo-gy of the original teeth were used as the experimental group.Differences in occlusal evaluation and foreign body sensation evaluation of the prostheses in the two groups were compared.Results Results showed that the minimal interocclusal distance of the experimental group was greater than that of the control group,and the difference was statistically significant.The occlusal evaluation of the prostheses in the experimental group was better than that of the control group,and the difference was statistically significant.The foreign body sen-sation of the prostheses in the experimental group was also less than that of the control group.Conclusion Prostheses designed using digital technology to replicate the original lingual morphology of the teeth have a better lingual occlusal relationship with less foreign body sensation and better comfort.

Objective To study the efficacy of submucosal injection of dexamethasone in analgesia and detumescence after incremen-tal bone implantation,and to analyze the related factors of pain and swelling after incremental bone implantation.Methods Patients with dentition defect requiring bone increment(GBR or internal maxillary sinus lift)were collected from the Special Clinic of the Affilia-ted Stomatology Hospital of Nanjing Medical University from January 2023 to December 2023.Pain and swelling within 72 hours after surgery were measured and recorded,as well as possible influencing factors,including gender,age,number of implants,duration of surgery,and other factors.Oral health status,pre-FAC tension and PSQ pain sensitivity were compared between the two groups at dif-ferent time.Pearson correlation and multiple linear regression analysis were performed for the possible influencing factors.Results Pa-tients receiving dexamethasone intervention had significantly lower pain levels at 12 hours and significantly lower swelling scores at 48 hours.Correlation analysis and regression analysis showed that GBR had a significant effect on postoperative pain and swelling(r=0.348,P=0.030/r=0.441,P=0.005),and the linear regression model of pain degree was also statistically significant(R2=0.126,P=0.030).Conclusion Submucosal injection of dexamethasone can significantly relieve the pain,swelling and discomfort of patients after incremental bone implantation,and improve the comfort of diagnosis and treatment.

Objective:To investigate the inhibitory effect of ferulic acid on the retina of diabetic mice and high glucose-induced human retinal pigment epithelium (RPE) cell injury and the mechanism.Methods:Thirty 8-week-old SPF male type 2 diabetic db/db mice were selected and divided into a model group and a ferulic acid group by the random number table method, with 15 mice in each group.Another 15 db/m mice of the same age were selected as a control group.The model and control groups received normal saline (5 ml/kg) by gavage daily, and the ferulic acid group received ferulic acid solution (0.05 g/kg) by gavage daily.After two months of treatment, the mice were sacrificed and the eyeballs were removed.The morphological changes of mouse retinal tissues were observed by hematoxylin-eosin staining.The fluorescence intensity and expression levels of mitochondrial calcium uniporter (MCU), p38 mitogen-activated protein kinase (p38 MAPK) and phosphorylated p38 MAPK (p-p38 MAPK) in mouse retinal tissues were detected by immunofluorescence staining and Western blot.Human RPE cells were divided into control group, dimethyl sulfoxide (DMSO) group, high glucose group and high glucose+ ferulic acid group.The control group received no treatment, and the other cell groups were cultured with the corresponding reagents for 24 hours.The reactive oxygen (ROS) level of RPE cells in each group was detected with the ROS detection kit.The mitochondrial membrane potential level of RPE cells was detected with the a mitochondrial membrane potential detection kit (JC-1).The MCU and microfilament fluorescence intensity of RPE cells were detected with the a microfilament green fluorescent probe.To explore the regulatory relationship between MCU, p38 MAPK and p-p38 MAPK, the MCU protein level was silenced and overexpressed by lentivirus transfection technology.The fluorescence intensity and expression levels of MCU, p38 MAPK and p-p38 MAPK proteins in RPE cells were detected by immunofluorescence staining and Western blot.The use and feeding of experimental animals followed the 3R principle and the Statement of the Association for Research in Vision and Ophthalmology on the Use of Animals in Ophthalmology and Vision Research.This study protocol was approved by the Ethics Committee of Ningxia Eye Hospital, People's Hospital of Ningxia Hui Autonomous Region (No.2019085).Results:The intercellular space of the outer nuclear layer, inner nuclear layer and ganglion cell layer of the retinal tissue in the model group was increased and the cell arrangement was disordered compared with the control group, and the retinal tissue in the ferulic acid group was significantly improved.Compared with the control group, the fluorescence intensity of MCU, p-p38 MAPK and MCU+ p-p38 MAPK protein of mouse retinal tissue in model group and ferulic acid group was significantly increased (all at P<0.05).Compared with the model group, the fluorescence intensity of MCU, p-p38 MAPK and MCU+ p-p38 MAPK protein of mice retinal tissue in ferulic acid group was significantly decreased (all at P<0.05).Compared with the control group, the relative expression levels of MCU, p38 MAPK and p-p38 MAPK proteins of mouse retinal tissue in model group were significantly increased (all at P<0.05).Compared with the model group, the relative expression levels of MCU, p38 MAPK and p-p38 MAPK proteins of mice retinal tissue in ferulic acid group were significantly decreased (all at P<0.05).The ROS fluorescence intensities in the control group, DMSO group, high glucose group and high glucose+ ferulic acid group were 0.22±0.02, 0.22±0.03, 0.30±0.02 and 0.24±0.02, respectively, and the overall difference was statistically significant ( F=7.845, P<0.01).The ROS fluorescence intensity was significantly higher in the high glucose group than in the control and DMSO groups, and it was significantly lower in the high glucose+ ferulic acid group than in the high glucose group (all at P<0.05).The mitochondrial membrane potential was significantly lower in high glucose group and high glucose+ ferulic acid group than in control and DMSO groups, and significantly higher in high glucose+ ferulic acid group than in high glucose group (all at P<0.05).Compared with the control group and DMSO group, the fluorescence intensity of MCU was higher in the high glucose group, accompanied by the decrease and thinning of cell microfilaments, and the fluorescence intensity of MCU protein was significantly decreased in high glucose+ ferulic acid group, with the number of microfilaments increased significantly.Compared with the control group and DMSO group, the fluorescence intensity and relative expressions of MCU, p38 MAPK and p-p38 MAPK proteins were significantly increased in the high glucose group (all at P<0.05).Compared with the high glucose group, the fluorescence intensity and relative expressions of MCU, p38 MAPK and p-p38 MAPK proteins were significantly decreased in the high glucose+ ferulic acid group (all at P<0.05).Compared with the control group and the empty vector group, the relative expressions of MCU, p38 MAPK and p-p38 MAPK proteins were significantly increased in the MCU overexpression group and significantly decreased in the MCU shRNA group and the MCU overexpression+ ferulic acid group (all at P<0.05).Compared with MCU overexpression group, the relative expressions of MCU, p38 MAPK and p-p38 MAPK proteins were significantly decreased in MCU shRNA group and MCU overexpression+ ferulic acid group, and the differences were statistically significant (all at P<0.05). Conclusions:Ferulic acid can regulate oxidative stress and mitochondrial dysfunction, thereby ameliorating retinal damage and high glucose-induced RPE cell injury in diabetic mice, which may play a protective role through MCU and p38MAPK signaling pathways.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC. METHODS: Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages. RESULTS: Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively). CONCLUSIONS This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Prognosis ; Gene Expression Profiling ; Transcriptome ; Tumor Microenvironment ; Receptors, G-Protein-Coupled/therapeutic use* ; Tetraspanins/genetics* ; Protein Kinases ; Integrin beta1/therapeutic use*

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

Hereditary thyroxine protein amyloidosis (ATTRv) is one of the most common forms of systemic and ocular amyloidosis, characterized by autosomal dominant inheritance, incomplete penetrance, and diverse manifestations. ATTRv deposition leads to visual impairment and even irreversible visual loss, which has a negative impact on the quality of life of patients. The diagnostic rate of pathological examination and genetic testing in ATTRv patients is low, and the detection rate of systemic amyloid lesions is low. We need to increase our awareness of this disease and gain a deeper understanding of its systemic manifestations and corresponding examination methods; genetic testing is conducted on the proband's family to investigate the relationship between different gene mutations and eye manifestations. In the future, multidisciplinary consultations can be conducted to jointly diagnose and treat patients with ATTRv eye involvement, conducting large-scale and long-term follow-up studies on the early clinical characteristics, treatment plans, efficacy, possible complications, and early prevention, in order to improve clinical diagnosis rate, reduce misdiagnosis rate, and improve patient prognosis.

Objective:To measure the partial parameters of the soft tissues of upper eyelid in young women with single eyelid in Shantou City, Guangdong Province, and to explore the asymmetry rate of the left and right palpebral fissure and its regularity.Methods:From March 2018 to July 2019, the Medical Cosmetology Center of the First Affiliated Hospital of Shantou University Medical College measured 108 young women with single eyelid, aged 18-35 years, with an average age of 24.6 years. Before operation, palpebral fissure width (PFW), palpebral fissure height (PFH), palpebral fissure inclination (PFI) and central eyebrow height (CEH) were measured. The resected intra-orbital septum fat pad during the procedure was weighed. Both direct measurement and the photo measurement were used to obtain the average value of the two sets of data for final analysis. We calculated out the incidence rate of asymmetry of each palpebral item.Results:The paired t-test showed that the mean value of PFW was (25.76±1.50) mm on the left and (26.04±1.55) mm on the right ( t=2.93); the mean value of PFH was (9.70±1.15) mm on the left and (9.49±1.05) mm on the right ( t=3.12); the mean value of PFI was (9.77±2.57)° on the left and (9.67±2.28)° on the right ( t=2.01); the mean value of CEH was (12.05±1.61) mm on the left and (12.32±1.69) mm on the right ( t=-2.66); the mean value of the weight of the intra-orbital septum fat pad was (0.20±0.11) g on the left and (0.22±0.12) g on the right ( t=2.29). There were significant differences between the two sets of data (all P<0.05). Conclusions:The asymmetric phenomenon of the upper eyelid is commonly found in Shantou young female undergraduates, in which the PFH in the left is higher than that in the left; the PFW, the CEH, the weight of the intra-orbital septum fat pad in the right more commonly found than that in the left.. This study provides a certain reference for the clinical evaluation of the operation.

Hypertension is a common cardiovascular disease. Chinese guidelines for the management of hypertension, the global practice guidelines for hypertension of the International Hypertension Society (ISH) and the guidelines for the treatment of adult hypertension drugs of the World Health Organization have been issued successively, which play an important role in guiding the clinical medication of hypertension. Calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), angiotensin receptor neprilysin inhibitor (ARNI), thiazide diuretics and β-receptor blockers are commonly used in clinical antihypertensive drugs. The goal of hypertension drug control, the application timing of hypertension drugs, the selection of combined medication scheme, the drug selection of hypertension complicated with other diseases, and the medication of gestational hypertension are all problems that clinicians need to master.