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1.
Neural Regen Res ; 18(2): 344-349, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900428

RESUMO

The current animal models of stroke primarily model a single intracerebral hemorrhage (ICH) attack, and there is a lack of a reliable model of recurrent ICH. In this study, we established 16-month-old C57BL/6 male mouse models of ICH by injecting collagenase VII-S into the left striatum. Twenty-one days later, we injected collagenase VII-S into the right striatum to simulate recurrent ICH. Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage, delayed recovery in locomotor function, motor coordination, and movement speed, and more obvious emotional and cognitive dysfunction than mice subjected to unilateral striatal hemorrhage. These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH. These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.

2.
Biomaterials ; : 121689, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35931574

RESUMO

Spinal cord injury (SCI) represents a central nervous system disaster, resulting in the destruction of spinal cord structure and function and the formation of an adverse microenvironment at the SCI site. Various biomaterial-based therapeutic strategies have been developed to repair SCI by bridging spinal cord lesions. However, constructing a favorable biophysical microenvironment with biomaterials for spinal cord regeneration remains challenging because of the unmatched mechanical and electrical transmission properties with native spinal cords and the supra- or subtherapeutic dose release of biological molecules independent of SCI activity. Herein, we developed a new hydrogel with mechanical properties and conductivities comparable to those of native spinal cords by controlling gelatin and PPy concentrations. To endow the hydrogel with a biological function, glutathione (GSH) was conjugated on the hydrogel through gelatin-derived amine groups and GSH-derived sulfhydryl groups to prepare an MMP-responsive hydrogel with a recombinant protein, GST-TIMP-bFGF. The MMP-responsive conductive hydrogel could release bFGF on-demand in response to the SCI microenvironment and provide a favorable biophysical microenvironment with comparable mechanical and electrical properties to native spinal cords. In SCI model rats, the MMP-responsive bionic mechanical and conductive hydrogel could inhibit MMPs levels, promote axon regeneration and angiogenesis, and improve locomotion function recovery after SCI.

3.
Eur J Nutr ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913505

RESUMO

PURPOSE: Evidence from several cohorts has suggested that a higher intake of isoflavone is associated with lower risk of lung cancer in never smokers, but the association has not been investigated by histologic type of lung cancer. Adenocarcinoma is a common histologic type found in never smokers. We hypothesized that a higher intake of isoflavone is associated with a lower risk of lung adenocarcinoma among never smokers. Here, we examined the associations of isoflavone and soy food intake with lung cancer and its histologic types in never smokers. METHODS: We performed a pooled analysis using data from the Japan Public Health Center-based Prospective Study, Shanghai Women's Health Study and Shanghai Men's Study with 147,296 never smokers aged 40-74 years with no history of cancer. During 1,990,040 person-years of follow-up, 1247 lung cancer cases were documented. Dietary isoflavone and soy food intake were assessed using a food-frequency questionnaire. Multivariable Cox proportional hazards models assessed the associations between isoflavone and soy intake with incidence of lung cancer by histologic type. RESULTS: A higher intake of dietary isoflavone and soy food were associated with reduced risk of lung adenocarcinoma. The multivariable hazard ratios (HRs) (95% CI) of risk of lung adenocarcinoma for the highest versus lowest intakes of isoflavone and soy food were 0.74 (0.60-0.92) and 0.78 (0.63-0.96), respectively. The multivariable HRs of risk of lung adenocarcinoma associated with each 10 mg/day increase in isoflavone and each 50 g/day increase in soy food intake were 0.81 (0.70-0.94) and 0.84 (0.73-0.96), respectively. CONCLUSION: Higher intake of isoflavone and soy food was associated with lower risk of lung adenocarcinoma in never smokers.

4.
Front Nutr ; 9: 888317, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811962

RESUMO

Background: The association between habitual food intake in Tibet and metabolic syndrome (MetS) is largely unclear. Objective: To examine the association between Tibetan habitual food intake and MetS among Tibetan adults. Methods: A population-based cross-sectional study, named the China Multi-Ethnic Cohort (CMEC) study, was conducted between 2018 and 2019. We used data from all Tibetans in the CMEC in the current study. The participants, 1,954 men and 3,060 women aged 18-79 years, were from Lhasa, Tibet Autonomous Region, Tibet. The habitual dietary intake was assessed using a food frequency questionnaire (FFQ). MetS was defined according to ATP III guidelines. Multivariate logistic regression was used to estimate the association between five Tibetan habitual foods and MetS. Results: Tsampa, butter tea, and Qing cha intake were associated with reduced prevalence of MetS. Compared with the lowest quartile of each food, odds ratios (ORs) and their 95% confidence intervals (95% CIs) of medium and high Tsampa intake were 0.59 (0.41-0.85) and 0.53 (0.36-0.77), ORs (95% CIs) of butter tea were 0.67 (0.52-0.88) and 0.61 (0.46-0.81), and Qing cha were 0.85 (0.71-1.03) and 0.75 (0.60-0.93), respectively. When exploring the joint effects of these three foods on MetS, the adjusted ORs and their 95% CIs were 0.65 (0.49-0.87) for the middle intake group and 0.59 (0.42-0.83) for the high intake group as compared with the never/rarely group (p = 0.022 for trend). Associations of MetS with Tibetan noodles and raw beef were not observed. Conclusion: Tsampa, butter tea, and Qing cha were negatively associated with MetS. The recommendation of increasing the intake of these foods may be beneficial for MetS prevention.

5.
ACS Nano ; 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35775975

RESUMO

PdSe2 has a layered structure with an unusual, puckered Cairo pentagonal tiling. Its atomic bond configuration features planar 4-fold-coordinated Pd atoms and intralayer Se-Se bonds that enable polymorphic phases with distinct electronic and quantum properties, especially when atomically thin. PdSe2 is conventionally orthorhombic, and direct synthesis of its metastable polymorphic phases is still a challenge. Here, we report an ambient-pressure chemical vapor deposition approach to synthesize metastable monoclinic PdSe2. Monoclinic PdSe2 is shown to be synthesized selectively under Se-deficient conditions that induce Se vacancies. These defects are shown by first-principles density functional theory calculations to reduce the free energy of the metastable monoclinic phase, thereby stabilizing it during synthesis. The structure and composition of the monoclinic PdSe2 crystals are identified and characterized by scanning transmission electron microscopy imaging, convergent beam electron diffraction, and electron energy loss spectroscopy. Polarized Raman spectroscopy of the monoclinic PdSe2 flakes reveals their strong in-plane optical anisotropy. Electrical transport measurements show that the monoclinic PdSe2 exhibits n-type charge carrier conduction with electron mobilities up to ∼298 cm2 V-1 s-1 and a strong in-plane electron mobility anisotropy of ∼1.9. The defect-mediated growth pathway identified in this work is promising for phase-selective direct synthesis of other 2D transition metal dichalcogenides.

6.
Biomed Res Int ; 2022: 7567447, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774273

RESUMO

Background: Gastric cancer (GC) is the fifth most common malignant tumor and the third leading cause of cancer-related deaths. Because GC has the characteristics of high heterogeneity, unclear mechanism, limited treatment methods, and low five-year survival rate, it is necessary to find the prognostic biomarkers of GC and explore the mechanism of GC. Methods: We first identified differentially expressed genes (DEGs) between gastric cancer and normal gastric cells through expression analysis. A protein-protein interaction (PPI) network was constructed to find tightly connected modules. We performed survival analysis on the DEGs in the modules to identify genes with prognostic significance. Gene set enrichment analysis (GSEA) was used to identify gene enrichment pathways. Finally, we used our own collected clinical samples of 119 gastric adenocarcinoma (STAD) tissues and 40 normal gastric tissues to perform immunohistochemical (IHC) staining to verify the differential expression of COL8A1 in STAD tissues and normal gastric tissues and its correlation with epithelial-mesenchymal transition- (EMT-) related factors. Results: We identified 356 DEGs through differential expression analysis. Through PPI analysis and survival analysis, we determined that the collagen type VII alpha-1 chain (COL8A1) gene has prognostic significance. GSEA analysis showed that COL8A1 was significantly enriched in the EMT. IHC results showed that COL8A1 was upregulated in STAD tissues and could be used as an independent prognostic factor and was related to EMT. Conclusion: This study shows that COL8A1 is related to the prognosis of GC patients and might affect the progress of GC through the EMT pathway. Therefore, COL8A1 may be a biomarker for predicting the prognosis of GC.


Assuntos
Neoplasias Gástricas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Transição Epitelial-Mesenquimal/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Neoplasias Gástricas/patologia
7.
Dis Markers ; 2022: 4466776, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783010

RESUMO

Background: MCM3AP antisense RNA 1 (MCM3AP-AS1) is a newly identified potential tumor biomarker. Nevertheless, the prognostic value of MCM3AP-AS1 in cancer has been inconsistent in the available studies. We performed this meta-analysis to identify the prognostic role of MCM3AP-AS1 in various cancers. Methods: We searched PubMed, Web of Science, EMBASE, and the Cochrane Library databases to screen relevant studies. Hazard ratios (HR) or odds ratios (OR) and corresponding 95% confidence intervals (CI) were used to evaluate the relationship between aberrant MCM3AP-AS1 expression and survival and clinicopathological features (CFS) of cancer patients. A meta-analysis was performed using STATA 12.0 software. Additionally, results were validated by an online database based on The Cancer Genome Atlas (TCGA). Subsequently, we analyzed the MCM3AP-AS1-related genes and molecular mechanisms based on the MEM database. Results: Our results showed that overexpression of MCM3AP-AS1 was related to poor overall survival (OS) (HR = 2.00, 95% CI, 1.52-2.64, P < 0.001) and relapse-free survival (RFS) (HR = 3.28, 95% CI 1.56-6.88, P = 0.002). In addition, MCM3AP-AS1 overexpression was associated with TNM stage, differentiation grade, and lymph node metastasis, but not significantly with age, gender, and tumor size. In addition, MCM3AP-AS1 overexpression was verified by the GEPIA online database to be associated with poorer survival. The further functional investigation suggested that MCM3AP-AS1 may be involved in several cancer-related pathways. Conclusions: The overexpression of MCM3AP-AS1 was related to poor survival and CFS. MCM3AP-AS1 may be considered a novel prognostic marker and therapeutic target in various cancers.


Assuntos
Síndrome de Fadiga Crônica , RNA Longo não Codificante , Acetiltransferases/genética , Biologia Computacional , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Recidiva Local de Neoplasia , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
8.
Food Res Int ; 158: 111512, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35840220

RESUMO

Geographic-label is a remarkable feature for Chinese tea products. In this study, the UHPLC-Q/TOF-MS-based metabolomics approach coupled with chemometrics was used to determine the five narrow-geographic origins of Keemun black tea. Thirty-nine differentiated compounds (VIP > 1) were identified, of which eight were quantified. Chemometric analysis revealed that the linear discriminant analysis (LDA) classification accuracy model is 91.7%, with 84.7% cross-validation accuracy. Three machine learning algorithms, namely feedforward neural network (FNN), random forest (RF) and support vector machine (SVM), were introduced to improve the recognition of narrow-geographic origins, the performances of the model were evaluated by confusion matrix, receiver operating characteristic curve (ROC) and area under the curve (AUC). The recognition of RF, SVM and FNN for Keemun black tea from five narrow-geographic origins were 87.5%, 94.44%, and 100%, respectively. Importantly, FNN exhibited an excellent classification effect with 100% accuracy. The results indicate that metabolomics fingerprints coupled with chemometrics can be used to authenticate the narrow-geographic origins of Keemun black teas.


Assuntos
Camellia sinensis , Chá , Algoritmos , Cromatografia Líquida de Alta Pressão , Aprendizado de Máquina , Metabolômica
9.
Front Nutr ; 9: 918777, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845801

RESUMO

Background: Colorectal cancer (CRC) risk is linked to serum and dietary retinol and carotenoids, according to clinical and epidemiological research. However, the findings are not consistent. As a result, we did this meta-analysis to determine the link between them. Methods: From 2000 through 2022, the PubMed, Web of Science, and Embase databases, as well as pertinent article references, were searched and filtered based on inclusion and exclusion criteria and literature quality ratings. High and low intake were used as controls, and OR (odds ratio) or RR (relative risk) and 95% confidence interval were extracted. The extracted data were plotted and analyzed using Stata12.0 software. Results: A total of 22 relevant studies were included, including 18 studies related to diet and 4 studies related to serum. For high and low intake or concentration controls, the pooled OR was as follows: ß-carotene (OR = 0.89, 95% CI: 0.78-1.03), α-carotene (OR = 0.87, 95% CI: 0.72-1.03), lycopene (OR = 0.93, 95% CI: 0.81-1.07), lutein/zeaxanthin (OR = 0.96, 95% CI: 0.87-1.07), ß-cryptoxanthin (OR = 0.70, 95% CI: 0.48-1.01), total carotenoids (OR = 0.97, 95% CI: 0.81-1.15), retinol (OR = 0.99, 95% CI: 0.89-1.10), serum carotenoids (OR = 0.73, 95% CI: 0.58-0.93), serum retinol (OR = 0.62, 95% CI: 0.26-1.49). Subgroup analysis was performed according to tumor type, study type and sex. Conclusion: Total carotenoid intake and Lutein/Zeaxanthin intake were not associated with CRC risk. High ß-carotene, α-carotene, lycopene, and ß-cryptoxanthin all tended to reduce CRC risk. Serum carotenoid concentrations were significantly inversely associated with CRC risk.

10.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(8): 692-698, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-35851082

RESUMO

Objective To explore the effect and mechanism of paeoniflorin (PAE) on apoptosis of fibroblast synovial cells derived from rheumatoid arthritis tissues. Methods Rheumatoid arthritis fibroblast-like synovial cells (RA-FLSs) were cultured under different concentrations of PAE (20, 40, 80 µmol/L). Survival rate of cells was determined at different incubation time-points (24, 48, 72 hours) by MTT assay. Flow cytometry was performed to determine apoptosis rate of cells. Cells were transfected with 3 small interfering RNAs(siRNAs) fragments of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1(lncRNA MALAT1) for 48 hours. Real-time quantitative PCR was performed to determine if MALAT1 knockdown was successful. Cells were assigned into control group, PAE group, si-NC group, si-MALAT1 group and PAE combined with si-MALAT1 group. Cell apoptosis rate was determined by flow cytometry after knockdown of MALAT1 expression. mRNA expression levels of Wnt1, ß-catenin, caspase-3, caspase-9, B-cell lymphoma 2(Bcl2) and Bcl2-associated X protein (BAX) were determined using real-time quantitative PCR. Western blot analysis was performed to determine protein expression levels of Wnt1, ß-catenin, caspase-3, caspase-9, Bcl2 and BAX in each group. Results The findings showed that incubation of RA-FLSs with PAE at the tested concentration decreased their viability in a time-dependent manner. Expression level of lncRNA MALAT1 was lower in RA-FLSs group compared with the level in NC-FLSs group. Analysis showed that apoptosis rate was higher in cells treated with PAE. si-MALAT1 group had the lowest apoptosis rate, whereas the PAE combined with si-MALAT1 group showed a significantly higher apoptosis rate compared with si-MALAT1 group. mRNA levels of Bcl2, Wnt1 and ß-catenin were lower in PAE group compared with the level in control group, whereas mRNA expression levels of caspase-3, caspase-9 and BAX were higher in PAE group compared with the levels in control group. Expression level of Bcl2 was significantly higher in si-MALAT1 group compared with the level in the control group. Expression level of BAX, caspase-3 and caspase-9 were higher in PAE combined with si-MALAT1 group compared with the level in the control group. Conclusion PAE promotes apoptosis and inhibits the Wnt1/ß-catenin pathway in RA-FLSs by upregulating expression of lncRNA MALAT1.


Assuntos
Artrite Reumatoide , RNA Longo não Codificante , Sinoviócitos , Apoptose/genética , Artrite Reumatoide/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Proliferação de Células/genética , Células Cultivadas , Fibroblastos/metabolismo , Glucosídeos , Humanos , Monoterpenos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Sinoviócitos/metabolismo , Via de Sinalização Wnt , Proteína Wnt1/metabolismo , Proteína X Associada a bcl-2/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
11.
J Oncol ; 2022: 8903265, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35874631

RESUMO

Background: Although combination therapies have substantially improved the clinical outcomes of cancer patients, the prognosis and early diagnosis remain unsatisfactory. As a result, it is critical to look for novel indicators linked to cancer. Despite a number of recent studies indicating that the lncRNA brain cytoplasmic RNA1(BCYRN1) may be a potential predictive biomarker in cancer patients, BCYRN1's prognostic value is still being debated. Methods: We utilized PubMed, Embase, Web of Science, and the Cochrane Library to search for studies related to BCYRN1 until October 2021. Valid data were extracted after determining the articles according to the inclusion and exclusion criteria, and forest plots were made using Stata software. We used hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals to evaluate the relationship between abnormal BCYRN1 expression and patient prognosis and clinicopathological characteristics. Results: Meta-analysis revealed that increased BCYRN1 expression was associated with both overall tumor survival (OS; HR = 1.84, 95% CI 1.51-2.25, p < 0.0001) and disease-free survival (DFS; HR = 1.65, 95% CI 1.20-2.26, p=0.002). Furthermore, a strong association was discovered between increased BCYRN1 expression and tumor invasion depth (OR = 2.11, 95% CI 1.49-2.99, p=0.000), clinical stage (OR = 2.52, 95% CI 1.18-5.37, p=0.017), and distant tumor metastasis (OR = 4.19, 95% CI 1.45-12.05, p=0.008). Conclusions: We found that high BCYRN1 expression was associated with poor survival prognosis and aggressive clinicopathological characteristics in various cancers, indicating that it is a potential prognostic indicator as well as a therapeutic target. Further research is needed on pan-cancer cohorts to determine the clinical relevance of BCYRN1 in distinct cancer types.

12.
Int J Mol Sci ; 23(13)2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35806144

RESUMO

Ferroptosis is a relatively novel form of regulated cell death that was discovered in 2012. With the increasing research related to the mechanisms of ferroptosis, previous studies have demonstrated that the inactive of the intracellular antioxidant system and iron overload can result in the accumulation of reactive oxygen species (ROS), which can ultimately cause lipid peroxidation in the various cell types of the body. ROS accumulation can cause sperm damage by attacking the plasma membrane and damaging DNA. Acute ferroptosis causes oxidative damage to sperm DNA and testicular oxidative stress, thereby causing male reproductive dysfunction. This review aims to discuss the metabolic network of ferroptosis, summarize and analyze the relationship between male reproductive diseases caused by iron overload as well as lipid peroxidation, and provide a novel direction for the research and prevention of various male reproductive diseases.


Assuntos
Ferroptose , Sobrecarga de Ferro , Humanos , Ferro/metabolismo , Peroxidação de Lipídeos , Masculino , Espécies Reativas de Oxigênio/metabolismo , Reprodução , Sêmen/metabolismo
13.
Mol Cancer ; 21(1): 141, 2022 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-35780119

RESUMO

BACKGROUND: Increasing studies suggest that circular RNAs (circRNAs) are critical regulators of cancer development and progression. However, the biological roles and mechanisms of circRNAs in gastric cancer (GC) remain largely unknown. METHODS: We identified the differentially expressed circRNAs in GC by analyzing Gene Expression Omnibus (GEO) datasets. We explored the biological roles of circRNAs in GC by in vitro functional assays and in vivo animal studies. We performed tagged RNA affinity purification (TRAP), RNA immunoprecipitation (RIP), mass spectrometry (MS), RNA sequencing, luciferase reporter assays, and rescue experiments to investigate the mechanism of circRNAs in GC. RESULTS: Downregulated expression of circular RNA EIF4G3 (circEIF4G3; hsa_circ_0007991) was found in GC and was associated with poor clinical outcomes. Overexpression of circEIF4G3 suppressed GC growth and metastasis through the inhibition of ß-catenin signaling, whereas knockdown of circEIF4G3 showed the opposite effects. Mechanistic studies revealed that circEIF4G3 bound to δ-catenin protein to promote its TRIM25-mediated ubiquitin degradation and interacted with miR-4449 to upregulate SIK1 expression. CONCLUSION: Our findings uncovered a tumor suppressor function of circEIF4G3 in GC through the regulation of δ-catenin protein stability and miR-4449/SIK1 axis. CircEIF4G3 may act as a promising prognostic biomarker and therapeutic target for GC.


Assuntos
MicroRNAs , Neoplasias Gástricas , Animais , Cateninas , Linhagem Celular Tumoral , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Neoplasias Gástricas/patologia , Ubiquitina , beta Catenina/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-35793701

RESUMO

BACKGROUND: This study was performed to investigate the association between body mass index (BMI) and gastric cancer (GC) in East and Southeast Asia where most of GC is non-cardia GC. METHODS: Based on 8,997 GC cases among the Asia Cohort Consortium participants from China, Japan, Korea, and Singapore (N=538,835), we assessed GC risk according to BMI by calculating hazard ratios (HRs) and 95% confidence intervals (CIs) using the Cox proportional hazard regression model. RESULTS: A U-shaped associations between BMI and GC risk were observed. GC risks in underweight group (<18.5 kg/m2) and in obesity group (≥27.5 kg/m2) were higher than reference BMI group (23-24.9 kg/m2) (HR=1.15, 95% CI 1.05-1.25 for underweight; HR=1.12, 95% CI 1.03-1.22 for obesity, respectively). The associations of underweight and obesity with GC risk were consistent in the analyses for non-cardia GC, intestinal type GC, and late onset GC. No significant association of underweight and obesity with the risk of cardia GC, diffuse type GC, and early onset GC was observed. Additionally, we found that the U-shaped association between BMI and GC risk remained in non-smokers, while only underweight was related to increased GC risk in smokers. CONCLUSIONS: BMI has a U-shaped association with GC risk in East and Southeast Asian population, especially for the non-cardia GC, intestinal type GC, and late onset GC. IMPACT: Future studies with consideration of anatomical location and histology of GC are needed to establish the association of underweight as well as obesity with GC risk.

15.
Gastric Cancer ; 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35715658

RESUMO

BACKGROUND: CENPK is a novel oncogene which is aberrantly expression in some malignant tumors. However, the role and mechanisms of CENPK in gastric cancer have not been explored. METHODS: In this study, we use RT-PCR and IHC to study CENPK expression in gastric cancer cells and tissues. In addition, we constructed the two kinds of CENPK siRNA lentivirus to knock down CENPK. Then, we use High content living cell imaging System, Cell Counting Kit-8, colony formation, wound healing and Transwell assays to demonstrate the function of CENPK on gastric cancer cells AGS and MKN45. Meanwhile, we use flow cytometry assay to study CENPK function on gastric cancer cell apoptosis and cell cycle arrest. Subcutaneous tumorigenesis in nude mice was also performed to confirm CENPK function on gastric cancer. Finally, we use Co-IP, LC-MS and function rescue assay to study the downstream interaction molecular of CENPK. RESULTS: We demonstrated that CENPK expression were up-regulated in GC cell lines. Poor differentiation and III-IV stage had more percentages of high CENPK expression. Knocking down CENPK could significantly suppress GC cells proliferation, migration and invasion, and induce GC cells apoptosis and G1/S phase transition arrest. Subcutaneous tumorigenesis confirmed the tumor-promoting effects of CENPK in vivo. Remarkably, we found for the first time that XRCC5 might be interacted with CENPK through Co-IP, LC-MS and rescue study. CONCLUSION: CENPK promotes GC cell proliferation and migration via interacting with XRCC5 and may be a novel prognostic factor or therapeutic target for CENPK.

16.
Int J Biol Markers ; : 3936155221106217, 2022 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-35722719

RESUMO

BACKGROUND: A whole-exome or targeted cancer genes panel by next-generation sequencing has been used widely in assisting individualized treatment decisions. Currently, multiple algorithms are developed to estimate DNA copy numbers based on sequencing data, which makes a comprehensive global glance at chromosomal integrity possible. We aim to classify gastric cancers based on chromosomal integrity to guide personalized therapy. METHODS: We investigated copy number variations (CNV) across the entire genome of 124 gastric carcinomas via exome or targeted sequencing. Chromosomal integrity was classified as chromosomal stability (CS), chromosomal instability (CIN) and intermediate state (CIN/CS) based on CNV results. Chromosomal integrity was correlated to molecular features and clinical characteristics. RESULTS: According the states of chromosomal integrity, gastric carcinomas can be stratified into two cohorts: CS and CIN. Our results showed a significant relationship between CIN status and TP53 mutation, but not RB1, phosphatase and tensin homolog (PTEN), or other reported DNA damage repair genes. The mutation frequency of the TP53 gene had great relevance. Our study initially revealed clinical significance of chromosomal integrity that CIN patients were prone to HER2-positive and mucinous adenocarcinoma, while CS patients were a diffuse subtype and poorly differentiated but had longer overall survival. CONCLUSIONS: We classified gastric carcinomas into two states of chromosomal integrity with clinical implications. The dichotomy is applicable to clinical transformation. We proposed that classifying gastric cancers based on chromosomal integrity would enable us to achieve personalized therapy for patients and may be beneficial to patient stratification in future clinical trials.

17.
Biomed Environ Sci ; 35(5): 419-436, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35676813

RESUMO

Objective: To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM). Methods: GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay. Results: Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation. Conclusion: Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , DNA/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Radiação Ionizante , Temozolomida/farmacologia , Temozolomida/uso terapêutico
18.
Front Oncol ; 12: 799265, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719909

RESUMO

Background: Cancer is one of the leading causes of death worldwide. Early diagnosis can significantly lower cancer-related mortality. Studies have shown that the lncRNA Forkhead box P4 antisense RNA 1 (FOXP4-AS1) is aberrantly expressed in various solid tumors. A meta-analysis was performed to evaluate the correlation of FOXP4-AS1 with the prognosis of cancer patients and determine the clinical value of FOXP4-AS1 as a potential diagnostic marker. Methods: Correlational studies from the Web of Science, Embase, OVID, Cochrane and PubMed databases were screened (up to April 1, 2021). Meta-analysis was performed using Stata SE12.0 software. Results: Eleven original studies with 1,332 patients who were diagnosed with a solid cancer (nasopharyngeal carcinoma, hepatocellular carcinoma, colorectal cancer, gastric cancer, osteosarcoma, mantle cell lymphoma, prostate cancer, and pancreatic ductal adenocarcinoma) were included in the meta-analysis. High expression of FOXP4-AS1 was correlated with poor overall survival (OS) (HR = 1.77, 95% CI 1.29-2.44, P < 0.001) and shorter disease-free survival (DFS) (HR = 1.66, 95% CI 1.01-2.72, P = 0.044). Subgroup analysis based on sample size, follow-up time and Newcastle-Ottawa Scale (NOS) score revealed significant differences between FOXP4-AS1 levels and OS (P < 0.05). However, the expression level of FOXP4-AS1 was not significantly correlated with the OS of gastric cancer patients (P = 0.381). High expression of FOXP4-AS1 was predictive of a larger tumor size (OR = 3.82, 95% CI 2.3-6.3, P < 0.001). Conclusions: Overexpression of FOXP4-AS1 correlates with poor prognosis of cancer patients, and is a potential prognostic biomarker and therapeutic target. Systematic Review Registration: PROSPERO, identifier CRD42021245267.

19.
Front Chem ; 10: 880128, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720985

RESUMO

Glycosylation is one of the major forms of protein post-translational modification. N-glycans attached to proteins by covalent bonds play an indispensable role in intercellular interaction and immune function. In human bodies, most of the cell surface glycoproteins and secreted glycopeptides are modified with complex-type N-glycans. Thus, for analytical or medicinal purposes, efficient and universal methods to provide homogeneous complex-type N-glycans have been an urgent need. Despite the extremely complicated structures, tremendous progress in the synthesis of N-glycans has been achieved. On one hand, chemical strategies are shown to be effective to prepare core oligosaccharides of N-glycans by focusing on stereoselective glycosylations such as ß-mannosylation and α-sialylation, as well as the methodology of the N-glycan assembly. On the other hand, chemoenzymatic strategies have also become increasingly powerful in recent years. This review attempts to highlight the very recent advancements in chemical and chemoenzymatic strategies for eukaryotic complex-type N-glycans.

20.
Am J Cancer Res ; 12(5): 2132-2145, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693070

RESUMO

Natural killer (NK) cells are lymphocytes and play a pivotal role in innate and adaptive immune responses against infections and malignancies. Longitudinal studies have indicated the feasibility of perinatal blood for large-scale NK cell generation, yet the systematic and detailed comparations of the signatures of resident and expanded NK cells (rNKs, eNKs) are largely obscure. Herein, we harvested rNKs from umbilical cord blood (rUC-NKs) and placental blood (rP-NKs) as well as the corresponding eNKs (eUC-NKs, eP-NKs). Furthermore, the biological properties and transcriptomic signatures including cellular subpopulations, cytotoxicity, gene expression profiling, genetic characteristics, signaling pathways and gene set-related biological process were investigated. The enriched rNKs and eNKs exhibited diversity in biomarker expression pattern, and eNKs with higher percentages of NKG2D+, NKG2A+, NKp44+ and NKp46+ subsets. rNKs or eNKs with different origins showed more similarities in transcriptomic signatures than those with the same origin. Our data revealed multifaceted similarities and differences of the indicated rNKs and pNKs both at the cellular and molecular levels. Our findings provide new references for further dissecting the efficacy and molecular mechanisms of rNKs and eNKs, which will collectively benefit the fundamental and translational studies of NK cell-based immunotherapy.

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