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1.
Zhonghua Nan Ke Xue ; 30(4): 306-314, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-39210416

RESUMEN

OBJECTIVE: To clarify the causal relationship between obesity and male infertility through Mendelian randomization (MR) study. METHODS: We assessed the causal effect of genetically predicted body mass index (BMI) on the risk of male infertility via a two-sample MR analysis, with the BMIs of 99 998 cases and 12 746 controls as the exposure factor and genetic information on male infertility obtained from a genome-wide association study of 73 479 Europeans. In the univariable MR (UVMR) analysis of the causal relationship, we mainly used inverse variance weighting (IVW), with MR-Egger regression and weighted median filtering as the supplementary methods. Sensitivity analyses including the Cochran's Q test, Egger intercept test, MR-PRESSO, leave-one-out analysis and funnel plot were performed to verify the robustness of the MR results. To evaluate the direct causal effects of BMI on MI risk, multivariable MR (MVMR) was performed. RESULTS: UVMR indicated a causal relationship between genetically predicted BMI and an increased risk of male infertility (OR: 1.237, 95% CI: 1.090-1.404, P = 0.001). Sensitivity analysis revealed little evidence of bias in the current study (P> 0.05). With such risk factors as type 2 diabetes, alcohol consumption and smoking adjusted, MVMR confirmed a direct causal effect of genetically predicted BMI on the risk of male infertility (P<0.05). CONCLUSION: Genetically predicted BMI may be associated with an increased risk of male infertility. Further studies are expected to explore the underlying mechanisms of this association and provide some new strategies for the prevention and treatment of BMI-related male infertility.


Asunto(s)
Índice de Masa Corporal , Estudio de Asociación del Genoma Completo , Infertilidad Masculina , Análisis de la Aleatorización Mendeliana , Obesidad , Humanos , Masculino , Infertilidad Masculina/genética , Obesidad/genética , Factores de Riesgo , Polimorfismo de Nucleótido Simple
2.
Transl Androl Urol ; 13(6): 930-939, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38983479

RESUMEN

Background: Benign prostatic hyperplasia (BPH) is one of the most common causes of lower urinary tract symptoms (LUTS) among the aging male population. Recent studies have shown that histological inflammation (HI) plays a significant role in BPH, with prostatic exosomal protein (PSEP) identified as a potential biomarker for prostate diseases. Therefore, this study aimed to explore the effect of HI on LUTS in patients with BPH, and to further explore the clinical value of PSEP as a diagnostic biomarker of BPH complicated with HI and whether PSEP could be used as an index to predict the improvement of LUTS after operation. Methods: This study was an open-label, cohort study. The study enrolled all patients who were clinical diagnosed as BPH with LUTS and prepared to receive operation of the prostate at the Department of Urology of the Second Hospital of Hebei Medical University. International Prostate Symptom Score (IPSS) were used to evaluate the LUTS of the BPH. And the enrolled patients were divided into four groups, including none, mild HI, moderate HI, and severe HI, based on postoperative pathological results. Then the relationships between HI and IPSS, the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), as well as PSEP were analyzed. Simple and multiple linear regression analyses were performed on the preoperative IPSS and the difference of IPSS before and after surgery was examined. SPSS software version 26 was used for statistical analysis and Prism 9.0 was used to make violin plots. Results: A total of 69 patients were enrolled in the study. The violin plot results indicated IPSS and NIH-CPSI scores exhibited significant increases in correlation with the severity levels of HI (P<0.001; P<0.001). Among BPH patients with total prostate-specific antigen (t-PSA) levels higher than 4.0 ng/mL, a significant correlation was observed between PSEP levels and HI (P=0.04). Besides, simple and multiple linear regression analysis showed that HI (P<0.001) or PSEP (P=0.03) was significantly associated with IPSS and improvement of LUTS, assessed by postoperative and preoperative IPSS differences. Conclusions: The study indicated that IPSS and PSEP (when t-PSA >4 ng/mL) were correlated with the severity of HI in patients with BPH. PSEP was linearly correlated with IPSS and the degree of reduction in IPSS after surgery. Consequently, PSEP may serve as a promising predictor for assessing surgical efficacy and diagnosing the severity of HI in patients with BPH.

3.
Vaccines (Basel) ; 12(6)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38932417

RESUMEN

Human papillomavirus (HPV) is a prevalent cause of mucosal and cutaneous infections and underlying conditions ranging from benign warts to anogenital and oropharyngeal cancers affecting both males and females, notably cervical cancer. Cervical cancer is the fourth leading cause of cancer deaths among women globally and is the most impactful in low- and middle-income countries (LMICs), where the costs of screening and licensed L1-based HPV vaccines pose significant barriers to comprehensive administration. Additionally, the licensed L1-based HPV vaccines fail to protect against all oncogenic HPV types. This study generated three independent lots of an L2-based target antigen (LBTA), which was engineered from conserved linear L2-protective epitopes (aa11-88) from five human alphapapillomavirus genotypes in E. coli under cGMP conditions and adjuvanted with aluminum phosphate. Vaccination of rabbits with LBTA generated high neutralizing antibody titers against all 17 HPV types tested, surpassing the nine types covered by Gardasil®9. Passive transfer of naïve mice with LBTA antiserum revealed its capacity to confer protection against vaginal challenge with all 17 αHPV types tested. LBTA shows stability at room temperature over >1 month. Standard in vitro and in vivo toxicology studies suggest a promising safety profile. These findings suggest LBTA's promise as a next-generation vaccine with comprehensive coverage aimed at reducing the economic and healthcare burden of cervical and other HPV+ cancers in LMICs, and it has received regulatory approval for a first-in-human clinical study (NCT05672966).

4.
Front Genet ; 15: 1377770, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846962

RESUMEN

Background: Several previous animal and human studies have found a strong association between asthma and spermatozoa quality, but whether these associations are causal or due to bias remains to be elucidated. Methods: We performed a two-sample Mendelian randomization (MR) analysis to assess the causal effect of genetically predicted asthma on the risk of abnormal spermatozoa. Asthma, childhood-onset asthma (COA), and adult-onset asthma (AOA) (sample sizes ranging from 327,670 to 408,442) were included as the exposures. Genetic information for abnormal spermatozoa was obtained from a genome-wide association study (GWAS) comprising 209,921 participants. In univariable MR (UVMR) analysis, the inverse variance weighted (IVW) method was conducted as the primary method, with the MR Egger and weighted median used as supplementary methods for causal inference. Sensitivity analyses, including the Cochran Q test, Egger intercept test, MR-PRESSO, and leave-one-out analysis, were performed to verify the robustness of the MR results. Multivariable MR (MVMR) was conducted to evaluate the direct causal effects of asthma on abnormal spermatozoa risk. Results: UVMR detected causal associations between genetically predicted asthma and an increased risk of abnormal spermatozoa (OR: 1.270, 95% CI: 1.045-1.545, p = 0.017). Moreover, we found that AOA (OR: 1.46, 95% CI: 1.051, 2.018, p = 0.024) has positive causal effects on the risk of abnormal spermatozoa rather than COA (p = 0.558). Sensitivity analysis found little evidence of bias in the current study (p > 0.05). MVMR further confirmed that asthma directly affected the risk of abnormal spermatozoa. Conclusion: Our MR study suggested that genetically predicted asthma could be associated with an increased risk of abnormal spermatozoa, and similar results were obtained in AOA. Further studies are warranted to explain the underlying mechanisms of this association and may provide new avenues for prevention and treatment.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38166515

RESUMEN

To provide a comprehensive account of the association of MMP-9 gene polymorphisms (rs3918242) with susceptibility to cancer. A literature search for eligible candidate gene studies published before May 27, 2022 was conducted in PubMed, Medline, Google Scholar and Web of Science. Potential sources of heterogeneity were sought out across subgroups and sensitivity analysis. Publication bias were also estimated. Overall, a total of 37 articles with 7616 cases and 8165 controls for rs3918242 gene polymorphisms were enrolled. Our meta-analysis suggests that MMP-9 rs3918242 might be associated with breast cancer and gastric cancer susceptibility, and perhaps reduce the risk of lung cancer.

6.
Cell Death Differ ; 30(12): 2462-2476, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37845385

RESUMEN

Cyclin-dependent kinases (CDKs) regulate cell cycle progression and the transcription of a number of genes, including lipid metabolism-related genes, and aberrant lipid metabolism is involved in prostate carcinogenesis. Previous studies have shown that CDK13 expression is upregulated and fatty acid synthesis is increased in prostate cancer (PCa). However, the molecular mechanisms linking CDK13 upregulation and aberrant lipid metabolism in PCa cells remain largely unknown. Here, we showed that upregulation of CDK13 in PCa cells increases the fatty acyl chains and lipid classes, leading to lipid deposition in the cells, which is positively correlated with the expression of acetyl-CoA carboxylase (ACC1), the first rate-limiting enzyme in fatty acid synthesis. Gain- and loss-of-function studies showed that ACC1 mediates CDK13-induced lipid accumulation and PCa progression by enhancing lipid synthesis. Mechanistically, CDK13 interacts with RNA-methyltransferase NSUN5 to promote its phosphorylation at Ser327. In turn, phosphorylated NSUN5 catalyzes the m5C modification of ACC1 mRNA, and then the m5C-modified ACC1 mRNA binds to ALYREF to enhance its stability and nuclear export, thereby contributing to an increase in ACC1 expression and lipid deposition in PCa cells. Overall, our results disclose a novel function of CDK13 in regulating the ACC1 expression and identify a previously unrecognized CDK13/NSUN5/ACC1 pathway that mediates fatty acid synthesis and lipid accumulation in PCa cells, and targeting this newly identified pathway may be a novel therapeutic option for the treatment of PCa.


Asunto(s)
Acetil-CoA Carboxilasa , Neoplasias de la Próstata , Humanos , Masculino , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/metabolismo , Proteína Quinasa CDC2 , Ácidos Grasos , Lípidos , Metiltransferasas , Proteínas Musculares , Próstata/metabolismo , Neoplasias de la Próstata/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo
7.
Wideochir Inne Tech Maloinwazyjne ; 18(2): 244-253, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37680735

RESUMEN

Introduction: To compare the efficacy and safety of percutaneous nephrolithotomy (PCNL) in the oblique supine position (OSP) and the prone position (PP). Aim: To perform a systematic review and meta-analysis to evaluate the efficacy and safety of OSP versus PP for PCNL. Material and methods: A systematic literature search of PubMed, Ovid, SCOPUS, and citation lists was conducted to identify eligible comparative studies up to November 2022. All studies comparing OSP versus PP for PCNL were included. Statistical analysis was performed with the Collaboration's Review Manager (RevMan) 5.4 software. Results: Overall, eight studies were included involving 1185 patients (OSP = 634; PP = 551). There were no statistically significant differences between OSP and PP in age (WMD = -0.95 years; 95% CI: -2.12 to 0.21; p = 0.83) or proportion of male patients (OR = 0.02; 95% CI: -0.03 to 0.08; p = 0.43). We found that OSP was performed more frequently for smaller stone size and patients with higher BMI (WMD = -0.1 cm, 95% CI: -0.18 to -0.02; p = 0.01) and patients with higher BMI (WMD = 0.66 kg/m2; 95% CI: 0.29 to 1.03; p = 0.0005). The operation time was shorter in OSP than PP (WMD = -14 min; 95% CI: -27.00 to -1.00; p = 0.03). The reduction of hemoglobin was lower in OSP than PP (WMD = -0.39 g/dl; 95% CI: -0.60 to -0.13; p = 0.03). There was no significant difference in stone-free rate and hospitalization between the two groups (OR = 1.32; 95% CI: 0.98 to 1.78; p = 0.07; WMD = -5.99 h; 95% CI: -17.15 to 5.16; p = 0.29). The overall complications were fewer in OSP than in PP (OR = 0.59; 95% CI: 0.43 to 0.81; p = 0.001), but no difference was observed between the positions with regard to the major complications (Clavien-Dindo score ≥ 3) (OR = 0.76; 95% CI: 0.43 to 1.34; p = 0.35). Conclusions: OSP showed non-inferior stone-free rate, blood loss, and hospitalization compared with PP. OSP may be superior in terms of operative time and complications than PP.

8.
Wideochir Inne Tech Maloinwazyjne ; 18(2): 313-327, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37680736

RESUMEN

Introduction: Prediction models are increasingly being used to predict outcomes after surgery, and such a model would be a precious tool for patients with clear cell renal cell carcinoma (ccRCC) after surgery. Aim: To develop a comprehensive model for predicting disease-free survival (DFS) in patients with localized ccRCC. Material and methods: In a retrospective analysis of 612 patients, least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to identify significant predictors, and then risk factors were used to construct a prognostic model. Harrell's concordance index (C-index) was used to assess the accuracy of the model. Results: The lymphocyte-to-monocyte ratio (LMR), Mayo Clinic stage, size, grade, necrosis score (SSIGN), and Mayo adhesive probability score (MAPS) were the significant risk factors screened by LASSO Cox regression and reconfirmed by multivariate Cox regression analysis in 44 variables. Then a model was constructed by combining the LMR, SSIGN, and MAPS. The C-index of the LMR-SSIGN-MAPS model was greater than the SSIGN score alone. Kaplan-Meier survival analysis demonstrated a significant association between higher LMR-SSIGN-MAPS score and poorer DFS. Conclusions: The LMR-SSIGN-MAPS model, which consists of preoperative inflammation biomarkers, a perinephric adipose tissue image-based scoring system, and pathological features, showed the strengths of easy-to-use and high predictability and might also be used as a promising prognosis model in predicting DFS for patients with localized ccRCC.

9.
BMC Cancer ; 23(1): 804, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37641032

RESUMEN

BACKGROUND: Cuproptosis is a newly discovered programmed cell death dependent on mitochondrial respiratory disorder induced by copper overload. Pyruvate dehydrogenase E1 subunit beta (PDHB) is one of the cuproptosis genesand is a nuclear-encoded pyruvate dehydrogenase, which catalyzes the conversion of pyruvate to acetyl coenzyme A. However, the mechanism of PDHB in clear cell renal cell carcinoma (ccRCC) remains unclear. METHODS: We used data from TCGA and GEO to assess the expression of PDHB in normal and tumor tissues. We further analyzed the relationship between PDHB and somatic mutations and immune infiltration. Finally, we preliminarily explored the impact of PDHB on ccRCC. RESULTS: The expression level of PDHB was lower in tumor tissue compared with normal tissue. Meanwhile, the expression level of PDHB was also lower in high-grade tumors than low-grade tumors. PDHB is positively correlated with prognosis in ccRCC. Furthermore, PDHB may be associated with decreased risk of VHL, PBRM1 and KDM5C mutations. In 786-O cells, copper chloride could promote the expression of cuproptosis genes (DLAT, PDHB and FDX1) and inhibit cell growth. Last but not least, we found that PDHB could inhibit the proliferation and migration of ccRCC cells. CONCLUSION: Our results demonstrated that PDHB could inhibit the proliferation, migration and invasion in ccRCC cells, which might be a prognostic predictor of ccRCC. Targeting this molecular might provide a new therapeutic strategy for patients with advanced ccRCC.


Asunto(s)
Apoptosis , Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Humanos , Biomarcadores , Carcinoma de Células Renales/genética , Cobre , Neoplasias Renales/genética
10.
Nucleosides Nucleotides Nucleic Acids ; 42(12): 1004-1018, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37345793

RESUMEN

Some studies have suggested that MNS16A polymorphism in telomerase reverse transcriptase (TERT) gene is associated with cancer risk in various populations and types of cancer. However, the results of previous studies exploring this link have been inconclusive. To be able to accurately assess the association between TERT MNS16A polymorphism and cancer risk, we performed a meta-analysis based on 17 studies described in 12 articles, including 13,764 controls and 7,132 cases. Combined odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to assess the strength of the association in either a fixed-effects model or, if applicable, a random-effects model. Heterogeneity between articles and their publication bias were also tested. Overall, pooled results showed that no significant association between this polymorphism and cancer was found in the five gene models tested.Considering that there may be too many negative studies in the included studies, diluting the results of the total sample size, we stratified these studies according to ethnicity, source of controls and cancer type. In the stratified analysis, a statistically significant association was observed between Asians and population-based studies. We also analyzed by cancer type and found a significantly increased risk of brain cancer in five genetic models. Our results suggest that TERT MNS16A polymorphism is likely to contribute to increased cancer risk.


Asunto(s)
Neoplasias , Telomerasa , Humanos , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Neoplasias/genética , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Telomerasa/genética
11.
Medicine (Baltimore) ; 102(24): e33993, 2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37327284

RESUMEN

BACKGROUND: This meta-analysis was performed to examine the association of 3 endothelial nitric oxide synthase (eNOS) gene polymorphisms with male infertility. METHODS: The literature on the relation between the mutant of eNOS and male infertility before July 1, 2022, was conducted in Pubmed, Medline, and Web of Science. The search strategy is as follows: (eNOS OR ECNOS OR nitric oxide synthase 3 OR NOS3) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (male infertility). Statistical analysis was performed with the web of MetaGenyo, Stata 12, trial sequential analysis 0.9Beta, and the web of GTEx. RESULTS: Overall, 13 studies (26 case-controls) were included involving 6518 cases and 5461 controls for 3 polymorphisms (rs2070744, rs1799983, rs61722009) of eNOS. We found that eNOS rs2070744 was correlated with an increased risk of male infertility (C vs. T: odds ratio [OR], 1.48; 95% confidence interval [CI], [1.19-1.85]; CC vs. TT: OR, 2.59; 95% CI, [1.40-4.80]; CT vs. TT: OR, 1.17; 95% CI, [1.00-1.38]; CC vs. CT + TT: OR, 2.50; 95% CI, [1.35-4.62]; CC + CT vs. TT: OR, 1.41; 95% CI, [1.21-1.64]). And eNOS rs1799983 was correlated with an increased risk of male infertility (allele contrast T vs. G: OR, 1.41; 95% CI, [1.01-1.96]; P = .043; recessive model TT vs. TG + GG: OR, 2.00; 95% CI, [1.03-3.90]; P = .042). In the stratified analysis of rs61722009, we found Asians might be correlated with an increased risk of male infertility (4a vs. 4b: OR, 1.50; 95% CI, [0.94-2.38]; 4a4a vs. 4b4b: OR, 2.56; 95% CI, [0.70-9.38]; 4a4b vs. 4b4b: OR, 1.36; 95% CI, [0.87-2.13]; 4a4a vs. 4a4b + 4b4b: OR, 2.57; 95% CI, [0.91-7.30]; 4a4a + 4a4b vs. 4b4b: OR, 1.44; 95% CI, [0.87-2.40]). CONCLUSION: The eNOS rs2070744 polymorphism and rs1799983 are associated with the risk of male infertility, and rs61722009 might be a risk factor for Asians.


Asunto(s)
Predisposición Genética a la Enfermedad , Infertilidad Masculina , Humanos , Masculino , Estudios de Casos y Controles , Genotipo , Infertilidad Masculina/genética , Óxido Nítrico Sintasa de Tipo III/genética , Polimorfismo de Nucleótido Simple
12.
Medicine (Baltimore) ; 102(23): e33937, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37335680

RESUMEN

BACKGROUND: This meta-analysis was performed to address the association of 2 ESR2 gene polymorphisms (rs1256049 and rs4986938) with susceptibility to cancer. METHODS: An extensive literature search for eligible candidate gene studies published before May 10, 2022, was conducted in PubMed, Medline, and Web of Science. The search strategy was as follows: (ESR2 OR ERß OR ER beta OR estrogen receptor beta) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (PCa OR PC OR prostate cancer). Potential sources of heterogeneity were sought out via trial sequential analysis, subgroup, and sensitivity analysis. RESULTS: Overall, a total of 10 articles involving 18,064 cases and 19,556 controls for 2 polymorphisms of the ESR2 gene were enrolled. In the stratified analysis of rs1256049, we found that Caucasians might be correlated with an increased risk of prostate cancer (PCa), while less susceptibility was found in Asians. We observed that rs4986938 was not associated with PCa risk. CONCLUSION: ESR2 rs1256049 polymorphism is associated with a higher risk of PCa in the Caucasian population and a lower risk of PCa in the Asian population.


Asunto(s)
Receptor beta de Estrógeno , Predisposición Genética a la Enfermedad , Neoplasias de la Próstata , Humanos , Masculino , Estudios de Casos y Controles , Receptor beta de Estrógeno/genética , Genotipo , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética
13.
Wideochir Inne Tech Maloinwazyjne ; 18(1): 42-51, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37064569

RESUMEN

Introduction: Both percutaneous nephrolithotomy (PCNL) and laparoscopic ureterolithotomy (LU) are effective treatment options for large proximal ureteral stones. Aim: To perform a meta-analysis on this topic to assess the efficacy, safety, and potential complications of the two procedures. Material and methods: A systematic literature search was performed using PubMed, Ovid and Scopus to identify eligible suitable studies until May 2022. All studies comparing LU vs PCNL in large proximal ureteral stones were included. The Cochrane Collaboration's Review Manager (RevMan) 5.4 software was used to analyze statistical significance. Results: A total of nine publications involving 933 patients (LU 465; PCNL 468) were included, of which 4 were randomized control trails (RCTs) and 5 were non-RCTs. The meta-analysis of available data showed that compared with PCNL, LU had a higher initial stone-free rate (OR = 3.26; p = 0.004), but longer operative time (WMD = 35.08 min; p = 0.0003). However, the final stone-free rate (OR = 2.08; p = 0.07) and length of hospital stay (WMD = 0.32 d; p = 0.48) were comparable between the two groups. Meanwhile, LU had a lower transfusion rate (OR = 0.13; p = 0.007) than PCNL. There was no significant difference in terms of complications (OR = 0.97; p = 0.84), Clavien-Dindo score ≥ 3 complications (OR = 1.03; p = 0.93), auxiliary procedures (OR = 0.44; p = 0.08), or ureteral stenosis (OR = 0.24; p = 0.13) between LU and PCNL. Conclusions: Our meta-analysis revealed that LU is a safe and feasible option for large proximal ureteral stones with a higher initial stone-free rate and lower transfusion rate compared with PCNL.

14.
Front Immunol ; 14: 1135753, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37033952

RESUMEN

Sertoli cell -only syndrome (SCOS) is a type of testicular pathological failure that causes male infertility and no effective treatment strategy, is available for this condition. Moreover, the molecular mechanism underlying its development remains unknown. We identified DExD/H-Box helicase 58 (DDX58) as a key gene in SCOS based on four datasets of testicular tissue samples obtained from the Gene Expression Synthesis database. DDX58 was significantly upregulated in SCOS testicular Sertoli cells. Moreover, high expression of DDX58 was positively correlated with the expression of several testicular inflammatory factors, such as IL -1ß, IL-18, and IL-6. Interestingly, DDX58 could be induced in the D-galactose (D-gal)-stimulated TM4 cell injury model. Whereas silencing of DDX58 inhibited D-gal -mediated p65 expression, inflammatory cytokine release, and growth arrest. Mechanistically, we found that DDX58 acts as an RNA-binding protein, which enhances p65 expression by promoting mRNA stability. Furthermore, p65 gene silencing decreased the expression of inflammatory cytokines and inhibition of cell growth in D-gal-induced cells. In conclusion, our findings demonstrate that DDX58 promotes inflammatory responses and growth arrest in SCOS Sertoli cells by stabilizing p65 mRNA. Accordingly, the DDX58/p65 regulatory axis might be a therapeutic target for SCOS.


Asunto(s)
Síndrome de Sólo Células de Sertoli , Células de Sertoli , Humanos , Masculino , Células de Sertoli/metabolismo , Síndrome de Sólo Células de Sertoli/genética , Síndrome de Sólo Células de Sertoli/metabolismo , Síndrome de Sólo Células de Sertoli/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Testículo/metabolismo , Inflamación/metabolismo , Citocinas/metabolismo , Proteína 58 DEAD Box/metabolismo , Receptores Inmunológicos/metabolismo
15.
Talanta ; 257: 124329, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-36801553

RESUMEN

Nuclease, such as RNase H and DNase I, plays key roles in plenty of cellular processes and could be potential therapeutic target for drug development. It is necessary to establish rapid and simple-to-use methods to detect nuclease activity. Herein, we develop a Cas12a-based fluorescence assay without any nucleic acid amplification steps for ultrasensitive detection of RNase H or DNase I activity. By our design, the pre-assembled crRNA/ssDNA duplex triggered the cleavage of fluorescent probes in the presence of Cas12a enzymes. However, the crRNA/ssDNA duplex was selectively digested with the addition of RNase H or DNase I, which leaded to fluorescence intensity changes. Under optimized conditions, the method exhibited good analytical performance, achieving a limit of detection (LOD) as low as 0.0082 U/mL for RNase H and 0.13 U/mL for DNase I, respectively. The method was feasible for analysis of RNase H in human serum and cell lysates, as well as for screening of enzyme inhibitors. Moreover, it can be adopted to image RNase H activity in living cells. Together, this study provides a facile platform for nuclease detection and could be expanded for other biomedical research and clinical diagnostics.


Asunto(s)
Bioensayo , Sistemas CRISPR-Cas , Humanos , ADN de Cadena Simple , Desoxirribonucleasa I , Endonucleasas , ARN Guía de Sistemas CRISPR-Cas , Ribonucleasa H
16.
Cell Death Dis ; 14(1): 26, 2023 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-36639679

RESUMEN

Splicing factor 3B subunit 4 (SF3B4) plays important functional roles not only in pre-mRNA splicing, but also in the regulation of transcription, translation, and cell signaling, and its dysregulation contributes to various diseases including Nager syndrome and tumorigenesis. However, the role of SF3B4 and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) remain obscure. In the present study, we found that the expression of SF3B4 was significantly elevated in ccRCC tissues and negatively correlated with the overall survival of ccRCC patients. Upregulation of SF3B4 promotes migration and invasion of ccRCC cells in vitro and in vivo. The promoting effect of SF3B4 on cell migration and invasion is mediated by Twist1, a key transcription factor to mediate EMT. Interestingly, SF3B4, a component of the pre-mRNA spliceosome, is able to promote KLF16 expression by facilitating the transport of KLF16 mRNA into the cytoplasm. Mechanistically, SF3B4 promotes the export of KLF16 mRNA from the nucleus to the cytoplasm and thus enhances KLF16 expression, and in turn elevated KLF16 directly binds to the Twist1 promoter to activate its transcription, leading to EMT and ccRCC progression. Our findings provide evidence that the SF3B4-KLF16-Twist1 axis plays important functional roles in the development and progression of ccRCC, and manipulating this pathway may be a novel therapeutic target for the treatment of ccRCC.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/metabolismo , Precursores del ARN/metabolismo , ARN Mensajero/genética , Citoplasma/metabolismo , Línea Celular Tumoral , Neoplasias Renales/metabolismo , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteína 1 Relacionada con Twist/genética , Proteína 1 Relacionada con Twist/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismo
17.
Cancers (Basel) ; 16(1)2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38201567

RESUMEN

Downregulated RNA-binding motif protein 5 (RBM5) promotes the development and progression of various tumors, including bladder cancer (BC). Alternative splicing (AS) plays a crucial role in the progression of cancer by producing protein isomers with different functions or by promoting nonsense-mediated mRNA decay (NMD). However, whether RBM5 modulates the progression of BC through AS-NMD remains unexplored. In this study, we revealed that the downregulation of RBM5 expression promoted the expression of coactivator-associated arginine methyltransferase 1 (CARM1) in BC cells and tissues. Increased expression of CARM1 facilitated the activation of the Wnt/ß-catenin axis and cell proliferation, which then contributed to the poor prognosis of patients with BC. Interestingly, RBM5 bound directly to CARM1 mRNA and participated in AS-NMD, downregulating the expression of CARM1. In addition, we revealed that protein kinase catalytic subunit alpha (PRKACA) functioned as a phosphorylated kinase of GSK3ß, was regulated by CARM1 at the transcription level, and promoted the growth and progression of BC cells. Furthermore, in this study, we demonstrated a regulatory mechanism of Wnt/ß-catenin activation through the RBM5/CARM1/PRKACA axis and identified a novel potential target for treating BC.

18.
Light Sci Appl ; 11(1): 329, 2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36414615

RESUMEN

The solar X-ray and Extreme Ultraviolet Imager (X-EUVI), developed by the Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences (CIOMP), is the first space-based solar X-ray and Extreme ultraviolet (EUV) imager of China loaded on the Fengyun-3E (FY-3E) satellite supported by the China Meteorological Administration (CMA) for solar observation. Since started work on July 11, 2021, X-EUVI has obtained many solar images. The instrument employs an innovative dual-band design to monitor a much larger temperature range on the Sun, which covers 0.6-8.0 nm in the X-ray region with six channels and 19.5 nm in the EUV region. X-EUVI has a field of view of 42', an angular resolution of 2.5″ per pixel in the EUV band and an angular resolution of 4.1″ per pixel in the X-ray band. The instrument also includes an X-ray and EUV irradiance sensor (X-EUVS) with the same bands as its imaging optics, which measures the solar irradiance and regularly calibrates the solar images. The radiometric calibration of X-EUVS on the ground has been completed, with a calibration accuracy of 12%. X-EUVI is loaded on the FY-3E satellite and rotates relative to the Sun at a uniform rate. Flat-field calibration is conducted by utilizing successive rotation solar images. The agreement between preliminarily processed X-EUVI images and SDO/AIA and Hinode/XRT images indicates that X-EUVI and the data processing algorithm operate properly and that the data from X-EUVI can be applied to the space weather forecast system of CMA and scientific investigations on solar activity.

19.
Cancers (Basel) ; 14(19)2022 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-36230507

RESUMEN

Background: TCIRG1, also known as V-ATPase-a3, is critical for cellular life activities through its dependent acidification. Prior to the present research, its relationship with prognostic and tumor immunity in clear cell renal cell carcinoma (ccRCC) had not yet been investigated. Methods: We assessed TCIRG1 expression in normal and tumor tissues using data from TCGA, GEO, GTEX, and IHC. We also analyzed the relationship between TCIRG1 and somatic mutations, TMB, DNA methylation, cancer stemness, and immune infiltration. We evaluated the relevance of TCIRG1 to immunotherapy and potential drugs. Finally, we explored the effect of TCIRG1 knockdown on tumor cells. Results: TCIRG1 was overexpressed in tumor tissue and predicted a significantly unfavorable clinical outcome. High TCIRG1 expression may be associated with fewer PBRM1 and more BAP1 mutations and may reduce DNA methylation, thus leading to a poor prognosis. TCIRG1 was strongly associated with CD8+ T-cell, Treg, and CD4+ T-cell infiltration. Moreover, TCIRG1 was positively correlated with TIDE scores and many drug sensitivities. Finally, experiments showed that the knockdown of TCIRG1 inhibited the migration of ccRCC cells. Conclusions: TCIRG1 may have great potential in identifying prognostic and immunomodulatory mechanisms in tumor patients and may provide a new therapeutic strategy for ccRCC.

20.
Nucleosides Nucleotides Nucleic Acids ; 41(11): 1205-1223, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35797106

RESUMEN

To provide a comprehensive account of the association of ACYP2 gene polymorphisms with susceptibility to cancer. A literature search for eligible candidate gene studies published before April 20, 2022 was conducted in the PubMed, Medline and Web of Science. The following combinations of main keywords were used: (ACYP2 OR acylphosphatase 2) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (cancer OR tumor OR neoplasm OR malignancy OR carcinoma OR adenocarcinoma). Potential sources of heterogeneity were sought out via subgroup and sensitivity analysis. Publication bias were also estimated. Overall, a total of 10 articles with 5,230 cases and 5,086 controls for thirteen polymorphisms of ACYP2 gene were enrolled. We found that ACYP2 rs11125529, rs11896604, rs12615793, rs17045754, rs6713088, rs843645, rs843706, rs843711 and rs843752 were correlated with an increased risk of cancer. However, we found that ACYP2 rs12621038 might have less susceptibility to cancer. While for other polymorphisms, the results showed no significant association with cancer risk. ACYP2 rs11125529, rs11896604, rs12615793, rs17045754, rs6713088, rs843645, rs843706, rs843711 and rs843752 are associated with cancer risk. ACYP2 rs12621038 polymorphism is inversely associated with cancer risk.


Asunto(s)
Predisposición Genética a la Enfermedad , Neoplasias , Humanos , Polimorfismo de Nucleótido Simple , Haplotipos , Pueblo Asiatico , Ácido Anhídrido Hidrolasas/genética , Estudios de Casos y Controles , Neoplasias/genética
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