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1.
J Chem Phys ; 160(19)2024 May 21.
Article in English | MEDLINE | ID: mdl-38757618

ABSTRACT

Surface tension and interfacial tension are crucial to the study of nanomaterials. Herein, we report a solubility method using magnesium oxide nanoparticles of different radii (1.8-105.0 nm, MgO NPs) dissolved in pure water as a targeted model; the surface tension and interfacial tension (and their temperature coefficients) were determined by measuring electrical conductivity and combined with the principle of the electrochemical equilibrium method, and the problem of particle size dependence is discussed. Encouragingly, this method can also be used to determine the ionic (atomic or molecular) radius and Tolman length of nanomaterials. This research results disclose that surface/interfacial tension and their temperature coefficients have a significant relationship with particle size. Surface/interfacial tension decreases rapidly with a radius <10 nm (while the temperature coefficients are opposite), while for a radius >10 nm, the effect is minimal. Especially, it is proven that the value of Tolman length is positive, the effect of particle size on Tolman length is consistent with the surface/interfacial tension, and the Tolman length of the bulk does not change much in the temperature range. This work initiates a new era for reliable determination of surface/interfacial tension, their temperature coefficients, ionic radius, and Tolman length of nanomaterials and provides an important theoretical basis for the development and application of various nanomaterials.

2.
Gene ; 908: 148281, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38360124

ABSTRACT

The upregulation of methyltransferase-like 3 (METTL3) has been associated with the progression of esophageal cancer. However, METTL3-induced N6-methyladenosine (m6A) alterations on the downstream target mRNAs in esophageal squamous cell carcinoma (ESCC) are not yet fully understood. Our study revealed that silencing METTL3 resulted in a significant decrease in ESCC cell proliferation and metastasis in vitro and in vivo. Additionally, the adhesion molecule with Ig like domain 2 (AMIGO2) was identified as a potential downstream target of both METTL3 and YTH Domain-Containing Protein 1 (YTHDC1) in ESCC cells. Functionally, AMIGO2 augmented the malignant behaviors of ESCC cells in vitro and in vivo, and its overexpression can rescue the inhibition of the proliferation and migration in ESCC cells induced by METTL3 or YTHDC1 knockdown. Furthermore, our findings revealed that knockdown of METTL3 decreased m6A modification in the 5'-untranslated regions (5'UTR) of AMIGO2 precursor mRNA (pre-mRNA), and YTHDC1 interacted with AMIGO2 pre-mRNA to regulate AMIGO2 expression by modulating the splicing process of AMIGO2 pre-mRNA in ESCC cells. These findings highlighted a novel role of the METTL3-m6A-YTHDC1-AMIGO2 axis in regulating ESCC cell proliferation and motility, suggesting its potential as a therapeutic target for ESCC.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Neoplasms/pathology , RNA Precursors/metabolism , Cell Proliferation/genetics , Up-Regulation , Methyltransferases/genetics , Methyltransferases/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , RNA Splicing Factors/genetics
3.
Open Med (Wars) ; 18(1): 20230809, 2023.
Article in English | MEDLINE | ID: mdl-37829841

ABSTRACT

Accumulating evidence shows that Schwann cells' (SCs) death caused by high glucose (HG) is involved in the pathological process of diabetic peripheral neuropathy (DPN). Ferroptosis is a novel form of regulatory cell death driven by iron-dependent lipid peroxidation. However, it is not clear whether ferroptosis is involved in the death process of SCs induced by HG. The expression of ferroptosis-related indicators in the serum of DPN patients was detected by ELISA. Subsequently, using cell counting kit­8, western blot, real-time PCR, and Ki-67 staining, we investigated the effects of HG on the ferroptosis of SCs and initially explored the underlying mechanism. The results showed that the serum levels of glutathione peroxidase 4 (GPX4) and glutathione in patients with DPN decreased, while malondialdehyde levels increased significantly. Then, we observed that erastin and HG induced ferroptosis in SCs, resulting in the decrease in cell activity and the expression level of GPX4 and SLC7A11, which could be effectively reversed by the ferroptosis inhibitor Fer-1. Mechanistically, HG induced ferroptosis in SCs by inhibiting the NRF2 signaling pathway. Our results showed that ferroptosis was involved in the death process of SCs induced by HG. Inhibition of ferroptosis in SCs might create a new avenue for the treatment of DPN.

4.
Journal of Modern Urology ; (12): 654-658, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1006004

ABSTRACT

【Objective】 To investigate the feasibility of laparoscopic simple prostatectomy (LSP) in the treatment of large volume benign prostate hyperplasia (BPH). 【Methods】 Clinical and follow-up data of 30 patients with large volume BPH treated with LSP in our hospital during Feb.2019 and Dec.2021 were retrospectively analyzed. All patients underwent extraperitoneal LSP operation. The perioperative and 1-12 month postoperative follow-up data were analyzed. 【Results】 The average prostate volume was (92.4±38.9) mL, operation time (125±45) min, and weight of resected prostate (60.25±16.90) g. The hemoglobin decreased by (12.21±7.25) g/d after operation. No blood transfusion was needed. There was no need for bladder irrigation after operation in 21 cases (70%), and 9 cases (30%) had bladder irrigation time of (0.95±0.49) d. The postoperative catheter indwelling time was (6.92±2.51) d, and hospital stay (5.36±1.63) d. During the follow-up of (9.25±5.4) months, there was 1 case of postoperative intestinal obstruction (Clavien-Dindo grade II), 1 case of transient urinary incontinence (Clavien-Dindo grade I), and 1 case of delayed hematuria (Clavien-Dindo grade I). No urethral stricture occurred. The maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), International Prostate Symptom Score (IPSS) and quality of life (QoL) 3 months after operation were significantly improved compared with those before operation (P0.05). 【Conclusion】 LSP is safe and effective in the treatment of large volume BPH. It has advantages of complete resection of glands, minor bleeding and short postoperative bladder irrigation time. However, it still needs to be confirmed by a prospective control study of large samples.

5.
Pathol Res Pract ; 238: 154109, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36115333

ABSTRACT

BACKGROUND: Patients with oral squamous cell carcinoma (OSCC) have poor prognoses due to a limited understanding of the pathogenesis of OSCC. Zinc finger protein (ZNF) is the largest transcription factor family in the human genome and exert diverse and important functions. Nevertheless, the exact expression status and molecular mechanism of ZNF71 have not been described in OSCC. Therefore, this study aimed to identify the specific expression level of ZNF71 in OSCC tissues and to further interpret the potential molecular mechanism of ZNF71 in the pathogenesis of OSCC. METHODS: In-house immunohistochemical staining of 116 OSCC samples and 29 non-OSCC samples was employed to detect the expression status of ZNF71 at the protein level of OSCC tissues. Single-cell RNA sequencing data from 7 OSCC samples was used to explore the expression landscape of ZNF71 in different cell types from OSCC tissues. High-throughput RNA sequencing data and gene chips data from 893 OSCC samples and 301 non-OSCC samples were utilized to identify the specific expression level of ZNF71 at the bulk mRNA level of OSCC tissues. Here, standardized mean difference (SMD) value was applied to calculate the expression differences between OSCC group and non-OSCC group. Multiple datasets were included; hence, the results were considered to be more reliable. Sensitivity analysis was conducted to evaluate the stability of the results. Enrichment analysis and immune infiltration analysis were used to explore the underlying molecular mechanism of ZNF71 in OSCC. RESULTS: ZNF71 was significantly downregulated in OSCC tissues at the protein level (SMD = -1.96, 95 % confidence interval [95 % CI]: -2.43 to -1.50). ZNF71 was absent in various cell types from OSCC tissues including cancerous epithelial cells and tumor-infiltrating immune cells. ZNF71 was downregulated in OSCC tissues at the bulk mRNA level (SMD = -0.38, 95 % CI: -0.75 to -0.02). Enrichment analysis showed that positively and differentially co-expressed genes mainly concentrated on "herpes simplex virus 1 infection" and "regulation of plasma membrane bounded cell projection organization", and negatively and differentially co-expressed genes mainly participated in "cell cycle" and "DNA metabolic process". Moreover, the putative target genes of ZNF71 mainly participated in "cellular respiration" and "protein catabolic process". Finally, immune infiltration analysis revealed that ZNF71 expression was positively correlated with multiple immune cells including activated B cells, memory B cells, and natural killer (NK) cells, and negatively correlated with various immune cells, including CD56 bright NK cells, neutrophil, and immature dendritic cells. CONCLUSION: The downregulation of ZNF71 may influence the initiation and promotion of OSCC by reducing immune infiltration, accelerating cell cycle progression, and affecting metabolic process, and this requires further research.

6.
Neoplasma ; 69(2): 292-302, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35014535

ABSTRACT

Apigenin is an edible flavonoid with anticancer properties; however, the underlying mechanisms in hepatocellular carcinoma (HCC) remain to be clarified. In the present study, we demonstrated that apigenin decreased the viability of both SMMC-7721 and SK-Hep1 cells in a dose-dependent manner, and inhibited the migration and invasion of HCC cells with different metastatic potential by regulating actin cytoskeletal rearrangements. Moreover, we showed that apigenin decreased the expression of YAP, and subsequently reduced migration and invasion by modulating the expression of the epithelial-mesenchymal transition (EMT) markers, and promoted the autophagy of HCC cells by regulating the expression of autophagy-related genes. Collectively, the present findings might provide a novel mechanism for the therapeutic application of apigenin in HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Apigenin/pharmacology , Apigenin/therapeutic use , Autophagy , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Movement/genetics , Epithelial-Mesenchymal Transition , Humans , Liver Neoplasms/genetics
7.
Neoplasma ; 69(1): 59-70, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34734530

ABSTRACT

Emerin (EMD) plays diverse roles in cellular polarity organization, nuclear stability, and cell motility, however, the biological role of EMD relevant to the migration and invasion of hepatocellular carcinoma (HCC) cells has not yet been illustrated. In the present study, we initially found that the upregulation of EMD in HCC tissues, and EMD expression was negatively correlated with the spontaneous metastatic potential of HCC cell lines. Loss of EMD in HCC cells facilitated cell migration and invasion in vitro and metastasis in vivo. Meanwhile, we demonstrated that EMD knockdown induced EMT but enhanced p21 expression in HCC cells. Notably, silencing of EMD in HCC cells increased the cytoplasmic localization of p21 protein, whereas p21 knockdown partially abrogated the migratory and invasive ability, EMT, and the actin cytoskeleton rearrangement induced by EMD knockdown in HCC cells. Our results indicated a significant role of EMD knockdown in the HCC cell motility and metastasis through upregulating the cytoplasmic p21, unveiling a novel mechanism of cell motility regulation induced by EMD.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/genetics , Cell Line , Cell Line, Tumor , Cell Movement , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Membrane Proteins , Neoplasm Invasiveness/genetics , Nuclear Proteins
8.
Chinese Journal of Urology ; (12): 626-627, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-957444

ABSTRACT

Testicular dislocation is a rare clinical presentation that occurs most commonly as a result of blunt scrotal injury or abdominopelvic injury. In this study, a rare case of testicular dislocation was reported, who was a 65-year-old man presented with a right testicle squeezed into the subcutaneous penis, and a good recovery after a successful manual restoration under ultrasound guidance was achieved. The treatment of testicular dislocation is mostly surgical, but ultrasound-guided manual restoration may provide a feasible treatment for patients with superficial dislocation based on this case report.

9.
Article in English | WPRIM (Western Pacific) | ID: wpr-898728

ABSTRACT

Background and Objectives@#Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a critical role in the success of lumbar spinal fusion with autogenous bone graft. This study aims to explore the role and specific mechanism of miR-34c-5p in osteogenic differentiation of BMSCs. @*Methods@#and Results: Rabbit model of lumbar fusion was established by surgery. The osteogenic differentiation dataset of mesenchymal stem cells was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed miRNAs were analyzed using R language (limma package). The expressions of miR-34c-5p, miR-199a-5p, miR-324-5p, miR-361-5p, RUNX2, OCN and Bcl-2 were determined by qRT-PCR and Western blot. ELISA, Alizarin red staining and CCK-8 were used to detect the ALP content, calcium deposition and proliferation of BMSCs. The targeted binding sites between miR-34c-5p and Bcl-2 were predicted by the Target database and verified using dual-luciferase reporter assay. MiR-34c-5p expression was higher in rabbit lumbar fusion model and differentiated BMSCs than normal rabbit or BMSCs. The content of ALP and the deposition of calcium increased with the osteogenic differentiation of BMSCs. Upregulation of miR-34c-5p reduced cell proliferation and promoted ALP content, calcium deposition, RUNX2 and OCN expression compared with the control group. The effects of miR-34c-5p inhibitor were the opposite. In addition, miR-34c-5p negatively correlated with Bcl-2. Upregulation of Bcl-2 reversed the effects of miR-34c-5p on ALP content, calcium deposition, and the expressions of RUNX2 and OCN. @*Conclusions@#miR-34c-5p could promote osteogenic differentiation and suppress proliferation of BMSCs by inhibiting Bcl-2.

10.
Article in English | WPRIM (Western Pacific) | ID: wpr-891024

ABSTRACT

Background and Objectives@#Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a critical role in the success of lumbar spinal fusion with autogenous bone graft. This study aims to explore the role and specific mechanism of miR-34c-5p in osteogenic differentiation of BMSCs. @*Methods@#and Results: Rabbit model of lumbar fusion was established by surgery. The osteogenic differentiation dataset of mesenchymal stem cells was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed miRNAs were analyzed using R language (limma package). The expressions of miR-34c-5p, miR-199a-5p, miR-324-5p, miR-361-5p, RUNX2, OCN and Bcl-2 were determined by qRT-PCR and Western blot. ELISA, Alizarin red staining and CCK-8 were used to detect the ALP content, calcium deposition and proliferation of BMSCs. The targeted binding sites between miR-34c-5p and Bcl-2 were predicted by the Target database and verified using dual-luciferase reporter assay. MiR-34c-5p expression was higher in rabbit lumbar fusion model and differentiated BMSCs than normal rabbit or BMSCs. The content of ALP and the deposition of calcium increased with the osteogenic differentiation of BMSCs. Upregulation of miR-34c-5p reduced cell proliferation and promoted ALP content, calcium deposition, RUNX2 and OCN expression compared with the control group. The effects of miR-34c-5p inhibitor were the opposite. In addition, miR-34c-5p negatively correlated with Bcl-2. Upregulation of Bcl-2 reversed the effects of miR-34c-5p on ALP content, calcium deposition, and the expressions of RUNX2 and OCN. @*Conclusions@#miR-34c-5p could promote osteogenic differentiation and suppress proliferation of BMSCs by inhibiting Bcl-2.

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-883961

ABSTRACT

Objective:To understand the status and association of health literacy and self-management ability of hypertensive patients in the community and to provide reference for further intervention research.Methods:From June 2019 to October 2019, a random number table method was used to randomly select multiple streets or towns/townships, and then 401 residents in the community or village aged above 18 years of age diagnosed as hypertension were selected as the subjects of this study. The general data questionnaire, high blood pressure-health literacy scale into Chinese(C-HBP-HLS) and hypertension patients self-management behavior rating scale(HPSMBRS)were used to conduct one-to-one field survey. SPSS 24.0 was used to analyze the scores of health literacy and self-management behavior of patients with hypertension. SAS 9.4 was used to analyze the canonical correlation between health literacy and self-management behavior of patients with hypertension.Results:The score of health literacy and self-management ability were (38.94±17.56) points and (129.45±16.53) points, respectively.The results of canonical correlation analysis showed that the canonical correlation coefficient between health literacy and self-management behavior reached 0.57, which was mainly reflected in the great correlation between " drug label" and " diet management" .Conclusion:Attention should be paid to the positive effect of health literacy on self-management ability, and further intervention research should take the " drug label" and " written health literacy" dimensions of health literacy as entry points to effectively improve the self-management ability of hypertension patients in the community.

12.
Chinese Journal of School Health ; (12): 829-833, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-881266

ABSTRACT

Objective@#To analyze changes of school canteen construction and canteen meal provision in surveilled schools after the initiation of the National Nutrition Improvement Program for Rural Compulsory Education Student (NNIPRCES), therefore to provide data basis for improving efficacy of school canteen meals.@*Methods@#From 2012 to 2017, among the 699 trial counties in 22 provinces under NNIPRCES, at least 10% of elementary schools and middle schools with each food supply model (canteen meals, enterprise meals, and family meals) were randomly selected in each county in each year. Questionnaire survey was conducted to collect school canteen construction and meal provision information. The sample size were around 8 000 to 11 000 schools every year.@*Results@#From 2012 to 2017, the proportion of schools that have canteens only, have both canteen and dining room, as well as those have canteen and dining room with tables and chairs significantly increased with years(χ 2=3 043.95, 6 383.85, 6 731.17, P<0.01). The proportion of schools having canteen increased from 59.5% in 2012 to 87.0% in 2017. The proportion of schools with canteen providing breakfast, lunch or dinner varied across years(χ 2=51.85, 144.96, 189.19, P<0.01). The varieties of food groups of three meals all significantly increased during 2012, 2014 and 2017(χ 2=702.30, 892.38, 550.55, P<0.01). The canteen construction indicators, proportion of canteens providing three meals, and food groups included in three meals all significantly differed between elementary schools and middle schools, also between schools of central area and western area(P<0.05). The changing patterns with year were significantly different in elementary schools and middle schools, and in schools of central area and western area(P<0.05).@*Conclusion@#After the implementation of NNIPRCES, canteen construction and food variety in canteen meals significantly improved during 2012 to 2017. However, there are still gaps between changes of canteen construction and canteen meal provision. It is necessary to overcome obstacles to further increase the proportion of schools with canteen offering meals and the variety of food of meals.

13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1015926

ABSTRACT

Objective In this study, electroacupuncture (EA) was used to analyze the expression changes of related proteins in neuroglobin (NGB), PI3K/AKT and apoptotic pathways in the temporal cortex of bilirubin encephalopathy (BE) rats, so as to investigate the therapeutic effect of EA on BE and the relevant mechanism of NGB in this process. Totally 39 seven-day-old SD rats were divided into Sham, BE model and BE+EA groups. The neonatal BE model was established by injecting bilirubin solution (10 μg UCB/g Weight) into the cerebellomedullary cistern, Sham group was injected with the same amount of normal saline. BE rats were treated with EA at Baihui (GV20) and Quchi (LI11) acupoints with the frequency of 2/15 Hz for 15 min. Treatment was performed 12 h before modeling, followed by treatment every 12 h, in a total of three times. HE, Nissl staining and electron microscopy (TEM) were used to observe the pathological and ultrastructural changes of nerve cells in each group. Results showed that EA treatment reduced the damage of cortical neurons of BE rats and increase the number of Nissl bodies. TEM confirmed that EA treatment could alleviate the degree of mitochondria edema. Immunofluorescence staining was used to detect the expression sites and cell types of NGB. Results showed that NGB was mainly expressed in cortical neurons. Western blotting showed that EA treatment increased the expression of NGB, PI3K (p110 alpha), pAKT (Ser473) (P< 0. 05, P< 0. 05 and P< 0. 01, respectively) and the ratio of apoptosis-related protein Bcl-2/Bax (P < 0. 001), decreased the expression of Cleaved Caspase-3 (P< 0. 05) in the temporal cortex of rats. TUNEL staining showed that EA reduced the number of apoptotic cells (BE group 186. 00±13. 86 vs BE+EA group 78. 67±11. 85, P< 0. 01) . This study confirms that EA can promote the expression of NGB in the temporal cortex of BE rats, then activate the PI3K/AKT pathway to exert its neuroprotective function and inhibit the occurrence of apoptosis. EA may become a potential treatment method for BE.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-876186

ABSTRACT

Objective To investigate the effects of parental support for the moderate-to-vigorous physical activity (MVPA) of their children and to promote physical activity for children and adolescents. Methods A total of 622 students were selected by stratified clustering sampling methods.Physical activity and parental support factors were assessed by self-report questionnaire survey.Logistic regression was used to analyze determinants of physical inactivity. Results Nearly 58.7% of the parents purchased sports equipment for their children and 57.6% of the parents accompanied their children to do exercise.The rate of parental explicit modeling was 22.8%.The students who received parental logistic support and explicit modeling did longer MVPA on weekends.The students with parental logistic support were prone to be in activity (OR=1.51, 95%CI:1.01-2.27). Conclusion Family-based interventions from parental logistic support and explicit modeling could promote middle-to-high-intensity activities for junior high school students.

15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-905496

ABSTRACT

Objective:To observe the effect of electroacupuncture at Baihui (DU20) and Shenshu (BL23) acupoints on learning-memory ability and expression of the relative protein of P35/P25-cyclin-dependent kinase 5 (CDK5)-Tau phosphorylation signaling pathway in the prefrontal cortex (PFC) in rats with Alzheimer's disease (AD), so as to reveal its potential mechanisms in treating AD. Methods:Male adult Sprague-Dawley rats were randomly divided into normal control group, sham group, model group and treatment group with six rats in each group. The AD model was constructed by bilateral hippocampal injection of Aβ25-35 in latter two groups. Equal amount of normal saline was injected into the sham group. The treatment group was acupunctured at Baihui and Shenshu once a day for ten days. All the rats were tested with Morris Water Maze. Immunohistochemistry staining and Western blotting were used to detect the related protein of P35/P25-CDK5-Tau protein phosphorylation in the PFC. Results:Compared with the normal control group and the sham group, the escape latency and escape length increased (P < 0.05) and the times crossing the platform reduced (P < 0.05) in the model group; compared with the model group, the escape latency and escape length reduced (P < 0.05), and the times crossing the platform increased (P < 0.05) in the treatment group. The optical density of P35/P25 and CDK5 were significantly higher in the model group than in the normal control group and the sham group (P < 0.01), and they were lower in the treatment group than in the model group (P < 0.001). The relative expression of P35/P25, CDK5, Tau[pS199] and Tau[pS202] were higher in the model group than in the normal control group and the sham group (P < 0.05), and the expression of the above proteins was lower in the treatment group than in the model group (P < 0.05). Conclusion:Electroacupuncture could improve the learning-memory and spatial exploration ability, which associate with inhabiting the P35/P25-CDK5-Tau protein phosphorylation signaling pathway in the PFC to delay the development of AD.

16.
Pathol Res Pract ; 215(6): 152378, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30871913

ABSTRACT

The severe damage to health and social burden caused by head and neck squamous cell carcinoma (HNSCC) generated an urgent need to develop novel anti-cancer therapy. Currently, drug repositioning has risen in responses to the proper time as an efficient approach to invention of new anti-cancer therapies. In the present study, we aimed to screen candidate drugs for HNSCC by integrating HNSCC-related pathways from differentially expressed genes (DEGs) and drug-affected pathways from connectivity map (CMAP). We also endeavored to unveil the molecular mechanism of HNSCC through creating drug-target network and protein-to-protein (PPI) network of component DEGs in key overlapping pathways. As a result, a total of 401 DEGs were obtained from TCGA and GTEx mRNA-seq data. Taking the intersection part of 27 HNSCC-related Kyoto Encyclopedia of Genes and Genomes pathways and 33 drug-affected pathways, we retained 22 candidate drugs corresponding to two key pathways (cell cycle and p53 signaling pathways) of the five overlapping pathways. Two of the hub genes (PCNA and CCND1) identified from the PPI network of component DEGs in cell cycle and p53 signaling pathways were defined as the critical targets of candidate drugs with increased protein expression in HNSCC tissues, which was reported by the human protein atlas (HPA) database and cBioPortal. Finally, we validated via molecular docking analysis that two drugs with unknown effects in HNSCC: MG-262 and bepridil might perturb the development of HNSCC through targeting PCNA. These candidate drugs possessed broad application prospect as medication for HNSCC.


Subject(s)
Antineoplastic Agents , Bepridil , Boronic Acids , Drug Repositioning/methods , Squamous Cell Carcinoma of Head and Neck , Computational Biology/methods , Gene Expression Profiling/methods , Gene Regulatory Networks , Humans , Molecular Docking Simulation/methods , Proliferating Cell Nuclear Antigen/drug effects
17.
Pathol Res Pract ; 215(5): 963-976, 2019 May.
Article in English | MEDLINE | ID: mdl-30904360

ABSTRACT

BACKGROUND: The role of miR-99a-3p in Head and neck squamous cell carcinoma (HNSCC) has not been reported. Therefore, in this study, we examined the expression level and its molecular mechanisms of miR-99a-3p in HNSCC. MATERIALS AND METHODS: MiR-99a-3p-related miRNA-chip and miRNA-sequencing data were collected. We then carried out meta-analyses to pool the standard mean difference (SMD) value and generate a summarized receiver operating characteristic (sROC) curve. MiR-99a-3p mimic was transfected into FaDu cells and those genes influenced by miR-99a-3p were gathered. The target genes were also predicted from 12 tools through miRwalk2.0, and combined with differentially expressed genes in HNSCC from the The Cancer Genome Atlas and Genotype-Tissue Expression sequencing databases. FunRich and DAVID were used for the pathway signaling analyses for the potential targets of miR-99a-3p in HNSCC. RESULTS: The SMD was -0.30 (95% CI: -0.51, -0.08) in the fixed-effect model and -0.28 (95% CI: -0.67, 0.10) in the random-effect model (I2 = 60%), indicating a reduced expression level of miR-99a-3p in HNSCC tissues based on 1167 cases. In the sROC curve, the area under the curve (AUC) was 0.77 (95% CI: 0.73, 0.81). The 251 potential targets of miR-99a-3p were enriched in several pathways related to cancer, with the "Pathways in cancer" standing at the top. vascular endothelial growth factor A was selected as an example with up-regulated trend in HNSCC tissues. CONCLUSION: MiR-99a-3p exhibits a significant lower expression status in HNSCC, and this reduced or deletion status promotes the malignant progression of HNSCC. However, its molecular mechanism is still unclear and requires further investigation.


Subject(s)
MicroRNAs/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Disease Progression , Gene Expression Profiling , Humans , Oligonucleotide Array Sequence Analysis , Squamous Cell Carcinoma of Head and Neck/pathology
18.
Chinese Journal of Nephrology ; (12): 494-498, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-756079

ABSTRACT

Objective To analyze the incidence and risk factors of hypocalcemia after total parathyroidectomy without autotransplantation. Methods A total of 783 maintenance hemodialysis patients who underwent TPTX in the Second Affiliated Hospital of Nanjing Medical University from September 2008 to September 2017 were included in the study. The preoperative blood biochemical examination, preoperative iPTH, total mass of parathyroid gland (M) and postoperative iPTH and electrolyte results were collected. The incidence of severe hypocalcemia after TPTX were analyzed retrospectively. Binary logistic regression model was used to analyze the risk factors of severe hypocalcemia after TPTX. Results The age of 783 patients with TPTX was (46.90±10.78) years old, and the average dialysis age was (91.36±41.75) months. Postoperative severe hypocalcemia occurred in 235 cases (30.01%). Binary logistic regression analysis showed that higher preoperative blood iPTH (OR=7.56, 95%CI: 1.55-36.79, P=0.01), higher blood alkaline phosphatase (OR=36.71, 95%CI:14.75-91.36, P<0.01), blood phosphorus (OR=1.74, 95%CI: 1.11-2.71, P=0.02) and greater mass of resected glands (OR=1.18, 95% CI: 1.06-1.31, P<0.01) were the risk factors for post-hypocalcemia. The higher preoperative serum calcium can reduce the risk of postoperative hypocalcemia (OR=0.02,95%CI: 0.01-0.07, P<0.01). Conclusions The incidence of hypocalcemia after TPTX treatment for SHPT is very high. Blood iPTH, alkaline phosphatase, phosphorus, and total mass of intraoperative parathyroid gland excision are the independent risk factors for severe hypocalcemia after surgery.

19.
Chinese Journal of Geriatrics ; (12): 934-938, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-755447

ABSTRACT

Objective To study the changes in protein expression levels of 8 oxide of guanine in the temporal and frontal lobes in SAMP8 (senescence accelerated mice)mice versus SAMR1 (control mice).Methods In the study,we collected 12 SAMP8 mice and 12 SAMR1 mice at different month stage(1m,4m,8m,12m)(n=6,each group).After anesthesia,mice were sacrificed.The temporal and frontal lobe tissues of mice were labeled according to the stereotactic anatomical map of mouse brain and taken up for study.After paraffin sections were made,the expression level of 8 oxide of guanine in brain tissues was detected by immunohistochemical method.Results In the same age group at 1 month in the same temporal lobe,the average optical density of 8-oxodG was slightly higher in SAMP8 mice(0.086)than in SAMR1 mice(0.061,t =1.541,P>0.05).There were significant differences in the mean optical density of 8-oxodG in temporal lobe in 4,8 and 12 months groups between SAMP8 and SAMR1 group(0.101 vs.0.081,0.147 vs.0.109 and 0.176 vs.0.120,t =2.405,2.612 and 5.019,respectively,P <0.05).There was no significant difference in the average optical density levels of 8-oxodG in frontal lobe in 1 and 4 months groups between SAMP8 and SAMR1 mice (0.044 vs.0.030,0.062 vs.0.046,t =1.843 and 1.163,respectively,P > 0.05),while the average optical density levels of 8-oxodG in 8 and 12 months groups(0.090 and 0.138)were higher than those of SAMR1 mice in the same age group(0.049 and 0.063)(t =5.327 and 4.88,P<0.01).There was no significant difference in the average optical density of 8-oxoG in temporal lobe in 1 month group between SAMP8 and SAMR1 mice(0.099 vs.0.066,t =1.956,P >0.05).There were significant differences in the average optical density levels of 8-oxoG in temporal lobe in 4,8 and 12 months groups between SAMP8 and SAMR1 mice(0.119 vs.0.076,0.148 vs.0.094 and 0.173 vs.0.101,t =4.033,3.042 and 5.328,respectively,P<0.01).There was no significant difference in the average optical density levels of 8-oxoG in frontal lobe in 1 month and 4 months groups between SAMP8 and SAMR1 mice(0.049 vs.0.039,0.058 vs.0.056,t =0.713 and 0.172,respectively,P >0.05).The average optical density of 8-oxoG in frontal lobe in 8 months and 12 months groups had significant differences between SAMP8 and SAMR1 mice(0.087 vs.0.058,0.12 vs.0.063,t =2.261 and 4.185,P <0.05).In addition,we also found that the average optical density of 8 oxide of guanine in same SAMP8 mice at the same age was higher in temporal lobe than in frontal lobe.Conclusions The protein levels of 8-oxodG and 8-oxoG are increased with age,and the damage caused by nucleic acid oxidation is more severe in temporal lobe than in frontal lobe in SAMP8 mice.

20.
Cancer Med ; 7(8): 3848-3861, 2018 08.
Article in English | MEDLINE | ID: mdl-29956500

ABSTRACT

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.


Subject(s)
DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic , Immunomodulation/genetics , Mutation , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/immunology , Alleles , Case-Control Studies , Cell Line, Tumor , Female , Gene Expression Profiling , Genotype , High-Throughput Nucleotide Sequencing , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Male , Nasopharyngeal Carcinoma/pathology , Neoplasm Staging , Polymorphism, Single Nucleotide , Tripartite Motif Proteins , Ubiquitin-Protein Ligases
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