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2.
Drug Dev Res ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34859906

RESUMO

Among digestive system cancers, the extremely poor prognosis of pancreatic cancer (PC) is a pressing concern. Nonoperative treatments such as targeted and immunotherapy, have improved the current situation, however, the accompanying side effects of these chemicals should not be ignored. Here, we discovered a novel hydroxycinnamic acid named sinapic acid (SA) derived from fruits, vegetables, cereals, and oil crops as an effective anti-PC molecule. Both the in vitro and in vivo models we designed showed that SA exhibited anticancer activities but not apoptosis induction. Research on the underlying mechanisms illustrated that AKT phosphorylation was blocked by SA, and the downstream Gsk-3ß was downregulated subsequently. Our study revealed the inhibitory activity and underlying mechanisms of SA, providing evidence that SA is a potential strategy for cancer research and can be a promising option of PC chemotherapy.

3.
iScience ; 24(11): 103264, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34761184

RESUMO

Merkel cell carcinoma is an aggressive skin malignancy, mostly caused by Merkel cell polyomavirus (MCPyV). MCPyV T-antigens can induce mature microRNA expressions through the DnaJ domain, but its underlying mechanism is still unknown. Here, we report that the T-antigens induce protein expression and mRNA stability of DICER1, a key factor in microRNA biogenesis, through heat shock cognate 70 (HSC70). HSC70 directly interacts with the AU-rich elements (ARE) of DICER1 mRNA in both coding and 3' untranslated region in the presence of MCPyV T-antigen. The T-antigen/HSC70 interaction could induce luciferase activity of synthetic ARE-containing reporter, as well as the stability of ARE-containing mRNAs, suggesting a broader role of MCPyV T-antigens in regulating multiple mRNAs via HSC70. These findings highlight a new role for the interaction of HSC70 and MCPyV T-antigens in mRNA regulation and an undescribed regulatory mechanism of DICER1 mRNA stability and translation through its direct interaction with HSC70.

4.
Clin Rheumatol ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34757493

RESUMO

OBJECTIVE: To identify clinical characteristics and risk factors related to the progression of interstitial lung disease (ILD) in patients with primary Sjögren's syndrome (pSS). METHODS: In this single-centered, retrospective study, a total of 83 identified pSS-ILD patients with relatively complete clinical data were finally enrolled. Clinical symptoms, laboratory data, high-resolution computed tomography (HRCT), and pulmonary function test (PFT) results were collected. A logistic regression analysis was performed to determine the independent risk factors for ILD progression, and a nomogram was plotted to construct a predictive model. RESULTS: The prevalence of pSS-ILD in our study was 18.89%. Among the 83 enrolled patients, 32 (38.6%) underwent ILD progression. The characteristic features associated with the progression of ILD included male sex, non-sicca onset, reticular pattern on HRCT, higher levels of baseline lactic dehydrogenase (LDH), and low baseline forced vital capacity (FVC). The results of multivariate logistic regression indicated that LDH (OR 1.008, p = 0.030) was an independent risk factor for ILD progression, while sicca onset (OR 0.254, p = 0.044) and FVC (OR 0.952, p = 0.003) were protective factors for ILD progression. A simple predictive model for ILD progression in pSS was developed and validated. CONCLUSION: pSS patients with non-sicca onset, high baseline LDH level, and low baseline FVC were at higher risk of ILD progression.

5.
Ann Transl Med ; 9(18): 1465, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34734017

RESUMO

Background: Non-small cell lung cancer (NSCLC) is a common type of lung cancer with a poor prognosis. N6-methyladenosine (m6A) methylation, which is a reversible ribonucleic acid (RNA) modification, plays an important role in the occurrence and development of NSCLC. However, the potential effect of m6A methylation on immune infiltrates and prognosis remains unclear. Methods: In this study, a weighted gene co-expression network analysis was used to screen out messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) that were co-expressed with m6A regulators. Additionally, 2 molecular subtypes (Clusters 1 and 2) were determined via consensus clustering. Subsequently, a prognostic risk model was constructed using both co-expressed mRNAs and ncRNAs. Based on the risk scores calculated by the prognostic model, the patients were divided into the high-risk group or low-risk group. Finally, the altered patterns of the tumor immune microenvironments (TIMEs) between the 2 stratification methods were thoroughly investigated, and a gene set enrichment analysis was conducted to further examine the potential mechanism. Results: Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival (OS) compared to patients in Cluster 2. A further investigation based on the prognostic model revealed that the PD-L1 expression levels of patients in the high-risk group were significantly upregulated, and the immunoscores were lower than those in the low-risk group. The immune cells with a high infiltration in Cluster 1 showed a significant positive correlation with the risk score; those with low infiltration showed a significant negative correlation. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, the second Gap/Mitosis (G2/M) checkpoint, E2 transcription Factor (E2F) targets, glycolysis, deoxyribonucleic acid (DNA) repair, and unfolded protein response were significantly enriched in Cluster 1, the low-immunoscore group, and the high-risk group. Conclusions: This study revealed that m6A methylation is closely related to the poor prognosis of NSCLC patients via interference with the TIME, which suggests that m6A may play a role in optimizing individualized immunotherapy management and improving prognosis.

6.
Reprod Biomed Online ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34740515

RESUMO

RESEARCH QUESTION: Is there any difference in live birth rate between the natural cycle and hormone replacement therapy (HRT) endometrial preparation protocols for women with regular menstrual cycles undergoing their first single vitrified-warmed euploid blastocyst transfer? DESIGN: This was a retrospective cohort study that enrolled 722 women who underwent vitrified-warmed euploid blastocyst transfer at assisted reproductive technology (ART) centre of The First Affiliated Hospital of Zhengzhou University, from January 2013 to December 2019. Univariate and multivariate logistic regression models were used to analyse the relationship between the endometrial preparation protocols and live birth rates. Stratified analyses and sensitivity analyses were performed to ensure the reliability and stability of the results. RESULTS: A total of 722 single vitrified-warmed euploid blastocyst transfer cycles were included. Overall, the live birth rates were 50.00% (110/220) in the natural cycle group and 47.61% (239/502) in the HRT group. Multiple logistic regression analyses showed that there was no significant association (adjusted odds ratio 0.82; 95% confidence interval 0.56-1.20; P = 0.313) between natural cycle and HRT protocols and the live birth rate. Interaction analysis showed that there was no significant difference in live birth rates between the two groups for any subgroup after adjusting for confounding factors. CONCLUSIONS: For single vitrified-warmed euploid blastocyst transfer, natural cycle and HRT endometrial preparation protocols result in similar live birth rates among women with regular menstrual cycles. Further studies are needed into the effects of endometrial preparation protocols on pregnancy outcomes.

7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(11): 1068-1072, 2021 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-34729745

RESUMO

OBJECTIVE: To carry out preimplantation genetic testing (PGT) for a couple where the husband was affected by osteogenesis imperfecta combined with balanced translocation using the karyomapping technique. METHODS: Blastocysts were detected using karyomapping, the carrier status of COL1A1 c.760G>A (p.Gly254Arg) variant and the carrier status of the translocated chromosome were analyzed simultaneously. RESULTS: For a total of 10 blastocysts, two euploid blastocysts were found to not carry the COL1A1 c.760G>A (p.Gly254Arg) variant but a balanced translocation. After transplanting one of the blastocysts, clinical pregnancy was achieved. Amniocentesis at 18th gestational week and prenatal genetic testing was in keeping with the result of PGT.A healthy female was born at 40+4 weeks gestation. CONCLUSION: For patients simultaneously carrying genetic variant and balanced chromosomal translocation, PGT can be performed with efficiency by the use of karyomapping method.


Assuntos
Osteogênese Imperfeita , Diagnóstico Pré-Implantação , Blastocisto , Feminino , Fertilização In Vitro , Testes Genéticos , Humanos , Osteogênese Imperfeita/genética , Gravidez , Cônjuges , Translocação Genética
8.
Appl Environ Microbiol ; : AEM0172921, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34818101

RESUMO

The acyl-CoA dehydrogenase family enzyme DmdC catalyzes the third step in the dimethylsulfoniopropionate (DMSP) demethylation pathway, the oxidation of 3-methylmercaptopropionyl-CoA (MMPA-CoA) to 3-methylthioacryloyl-CoA (MTA-CoA). To study its substrate specificity, the recombinant DmdC1 from Ruegeria pomeroyi was characterized. In addition to MMPA-CoA, the enzyme was highly active with short chain acyl-CoAs, with Km values for MMPA-CoA, butyryl-CoA, valeryl-CoA, caproyl-CoA, heptanoyl-CoA, caprylyl-CoA and isobutyryl-CoA of 36, 19, 7, 11, 14, 10, and 149 µM, respectively, and kcat values of 1.48, 0.40, 0.48, 0.73, 0.46, 0.23 and 0.01 sec-1, respectively. Among these compounds, MMPA-CoA was the best substrate. The high affinity of DmdC1 for its substrate supports the model for kinetic regulation of the demethylation pathway. In contrast to DmdB, which catalyzes the formation of MMPA-CoA from MMPA, CoA and ATP, DmdC1 was not affected by physiological concentrations of potential effectors, such as DMSP, MMPA, ATP and ADP. Thus, compared to the other enzymes of the DMSP demethylation pathway, DmdC1 has only minimal adaptations for DMSP metabolism compared to other enzymes in the same family with similar substrates, supporting the hypothesis that it evolved relatively recently from a short chain acyl-CoA dehydrogenase involved in fatty acid oxidation. Importance We report the kinetic properties of DmdC1 from the model organism R. pomeroyi and close an important gap in the literature. While the crystal structure of this enzyme was recently solved and its mechanism of action described (X. Shao, H. Y. Cao, F. Zhao, M. Peng, et al., Mol Microbiol 111:1057-1073, 2019, https://doi.org/10.1111/mmi.14211), its substrate specificity and sensitivity to potential effectors was never examined. We show that DmdC1 has a high affinity for other short chain acyl-CoAs in addition to MMPA-CoA, which is the natural substrate in DMSP metabolism and is not affected by the potential effectors tested. This evidence supports the hypothesis that DmdC1 possesses few adaptations to DMSP metabolism and likely evolved relatively recently from a short chain acyl-CoA dehydrogenase involved in fatty acid oxidation. This work is important because it expands our understanding about the adaptation of marine bacteria to the increased availability of DMSP about 250 million years ago.

9.
Nature ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795452

RESUMO

Nutrients are emerging regulators of adaptive immunity1. Selective nutrients interplay with immunological signals to activate mechanistic target of rapamycin complex 1 (mTORC1), a key driver of cell metabolism2-4, but how these environmental signals are integrated for immune regulation remains unclear. Here we use genome-wide CRISPR screening combined with protein-protein interaction networks to identify regulatory modules that mediate immune receptor- and nutrient-dependent signalling to mTORC1 in mouse regulatory T (Treg) cells. SEC31A is identified to promote mTORC1 activation by interacting with the GATOR2 component SEC13 to protect it from SKP1-dependent proteasomal degradation. Accordingly, loss of SEC31A impairs T cell priming and Treg suppressive function in mice. In addition, the SWI/SNF complex restricts expression of the amino acid sensor CASTOR1, thereby enhancing mTORC1 activation. Moreover, we reveal that the CCDC101-associated SAGA complex is a potent inhibitor of mTORC1, which limits the expression of glucose and amino acid transporters and maintains T cell quiescence in vivo. Specific deletion of Ccdc101 in mouse Treg cells results in uncontrolled inflammation but improved antitumour immunity. Collectively, our results establish epigenetic and post-translational mechanisms that underpin how nutrient transporters, sensors and transducers interplay with immune signals for three-tiered regulation of mTORC1 activity and identify their pivotal roles in licensing T cell immunity and immune tolerance.

10.
Front Endocrinol (Lausanne) ; 12: 735783, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603211

RESUMO

Objectives: To evaluate the combined impact of male and female BMI on cumulative pregnancy outcomes after the first ovarian stimulation. Design: Retrospective cohort study. Setting: University-affiliated reproductive medicine center. Patients: A total of 15,972 couples undergoing their first ovarian stimulations from June 2009 to June 2016 were included. During the follow-up period between June 2009 and June 2018, 14,182 couples underwent a complete ART cycle involving fresh embryo transfer and subsequent frozen embryo transfers (FETs) after their first ovarian stimulations. Patients with a BMI <24 kg/m2 served as the reference group. Patients with a BMI ≥ 24 kg/m2 were considered to be overweight, and those with a BMI ≥28 kg/m2 were considered to be obese. Interventions: None. Primary Outcome Measure: The primary outcome was the cumulative live birth rate (CLBR), which defined as the delivery of at least one live birth in the fresh or in the subsequent FET cycles after the first ovarian stimulation. Results: In the analyses of females and males separately, compared with the reference group, overweight and obese females had a reduced CLBR (aOR 0.83, 95% CI 0.7.92 and aOR 0.76, 95% CI 0.64-0.90). Similarly, overweight males had a reduced CLBR (aOR 0.91, 95% CI 0.83-0.99) compared with that of the reference group. In the analyses of couples, those in which the male was in the reference or overweight group and the female was overweight or obese had a significantly lower CLBR than those in which both the male and female had a BMI <24 kg/m2. Conclusions: The CLBR is negatively impacted by increased BMI in the female and overweight status in the male, both individually and together.

11.
Food Funct ; 12(19): 9391-9404, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606557

RESUMO

Cisplatin is one of the most effective chemotherapeutic agents used for the treatment of a wide variety of cancers. However, cisplatin has been associated with nephrotoxicity, which limits its application in clinical treatment. Various studies have indicated the protective effect of phospholipids against acute kidney injury. However, no study has focused on the different effects of phospholipids with different fatty acids on cisplatin-induced nephrotoxicity and on the combined effects of phospholipids and cisplatin in tumour-bearing mice. In the present study, the potential renoprotective effects of phospholipids with different fatty acids against cisplatin-induced nephrotoxicity were investigated by determining the serum biochemical index, renal histopathological changes, protein expression level and oxidative stress. The results showed that docosahexaenoic acid-enriched phospholipids (DHA-PL) and eicosapentaenoic acid-enriched phospholipids (EPA-PL) could alleviate cisplatin-induced nephrotoxicity by regulating the caspase signaling pathway, the SIRT1/PGC1α pathway, and the MAPK (mitogen-activated protein kinase) signaling pathway and by inhibiting oxidative stress. In particular, DHA-PL exhibited a better inhibitory effect on oxidative stress and apoptosis compared to EPA-PL. Furthermore, DHA-PL exhibited an additional effect with cisplatin on the survival of ascitic tumor-bearing mice. These findings suggested that DHA-PL are one kind of promising supplement for the alleviation of cisplatin-induced nephrotoxicity without compromising its antitumor activity.

12.
EMBO Rep ; : e52124, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647680

RESUMO

This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues and tumor-associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2-polarized macrophage-derived exosomes (M2-exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2-exo reverses the promotional effect of M2-exo on cell proliferation in CDDP-treated GC cells and homograft tumor growth in CDDP-treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4-1 (NEDD4-1)-mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2-exo enhances the CDDP sensitivity of GC cells treated with M2-exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM-derived exosomes.

13.
Bioinformatics ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34718416

RESUMO

MOTIVATION: Coiled-coil is composed of two or more helices that are wound around each other. It widely exists in proteins and has been discovered to play a variety of critical roles in biology processes. Generally, there are three types of structural features in coiled-coil: coiled-coil domain (CCD), oligomeric state, and register. However, most of the existing computational tools only focus on one of them. RESULTS: Here, we describe a new deep learning model, CoCoPRED, which is based on convolutional layers, bidirectional long short-term memory, and attention mechanism. It has three networks, i.e., CCD network, oligomeric state network, and register network, corresponding to the three types of structural features in coiled-coil. This means CoCoPRED has the ability of fulfilling comprehensive prediction for coiled-coil proteins. Through the 5-fold cross-validation experiment, we demonstrate that CoCoPRED can achieve better performance than the state-of-the-art models on both CCD prediction and oligomeric state prediction. Further analysis suggests the CCD prediction may be a performance indicator of the oligomeric state prediction in CoCoPRED. The attention heads in CoCoPRED indicate that registers a, b, and e are more crucial for the oligomeric state prediction. AVAILABILITY: CoCoPRED is available at http://www.csbio.sjtu.edu.cn/bioinf/CoCoPRED. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

14.
Int J Gen Med ; 14: 6863-6873, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703291

RESUMO

Background: Long non-coding RNAs (lncRNAs) can act as a competitive endogenous RNA (ceRNA) to regulate gene expression by sequestering the microRNA (miRNA). However, the lncRNA-miRNA-mRNA ceRNA network in thoracic aortic dissection (TAD) has been rarely documented. Methods: Three Gene Expression Omnibus (GEO) datasets were used to detect differentially expressed mRNAs, miRNAs, and lncRNAs in TAD. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for the differentially expressed mRNAs. A protein-protein interaction network for differentially expressed mRNAs was also constructed, and hub genes were identified. We established a ceRNA network of TAD based on the differentially expressed miRNAs, mRNAs and lncRNAs, and verified our results using an independent dataset and quantitative real-time PCR (qRT-PCR). Results: In TAD, 267 lncRNAs, 81 miRNAs, and 346 mRNAs were identified as differentially expressed. The established ceRNA network consisted of seven lncRNA nodes, three mRNA nodes, and three miRNA nodes, and the expression of miRNAs in TAD was opposite to that of lncRNAs and mRNAs. Subsequently, an independent GEO dataset and qRT-PCR were used to validate the expression of three mRNAs. In addition, the expression differences in SLC7A5, associated miRNA and lncRNA were verified. According to gene set enrichment analysis of SLC7A5, the most significant KEGG pathway was considerably enriched in spliceosome and pentose phosphate pathway. Conclusion: We established a novel ceRNA regulatory network in TAD, which provides valuable information for further research in the molecular mechanisms of TAD.

15.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638938

RESUMO

Metabolic adaptation to increased oxidative phosphorylation (OXPHOS) has been found in gastrointestinal stromal tumor (GIST) upon imatinib treatment. However, the underlying mechanism of imatinib-induced OXPHOS is unknown. Discovering molecules that mediate imatinib-induced OXPHOS may lead to the development of therapeutic strategies synergizing the efficacy of imatinib. In this study, we explored the role of microRNAs in regulating OXPHOS in GIST upon imatinib treatment. Using a microarray approach, we found that miR-483-3p was one of the most downregulated miRNAs in imatinib-treated tumors compared to untreated tumors. Using an extended series of GIST samples, we further validated the downregulation of miR-483-3p in imatinib-treated GIST samples by RT-qPCR. Using both gain- and loss-of-function experiments, we showed that miR-483-3p could regulate mitochondrial respiratory Complex II expression, suggesting its role in OXPHOS regulation. Functionally, miR-483-3p overexpression could rescue imatinib-induced cell death. These findings provide the molecular link for imatinib-induced OXPHOS expression and the biological role of miR-483-3p in regulating cell viability upon imatinib treatment.


Assuntos
Antineoplásicos/farmacologia , Complexo II de Transporte de Elétrons/metabolismo , Neoplasias Gastrointestinais/metabolismo , Tumores do Estroma Gastrointestinal/metabolismo , Mesilato de Imatinib/farmacologia , MicroRNAs/metabolismo , Mitocôndrias/enzimologia , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Regulação para Baixo/efeitos dos fármacos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mesilato de Imatinib/uso terapêutico , MicroRNAs/genética , Mitocôndrias/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos , RNA Mensageiro/genética , Transdução de Sinais/genética , Transfecção
16.
Reprod Biol Endocrinol ; 19(1): 154, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627292

RESUMO

BACKGROUND: To investigate whether the endometrial thickness change ratio from the progesterone administration day to the blastocyst transfer day is associated with pregnancy outcomes in a single frozen-thawed euploid blastocyst transfer cycle. METHODS: All patients used natural cycles with luteal support for endometrial preparation and selected a single euploid blastocyst for transfer after a biopsy for preimplantation genetic testing. The endometrial thickness was measured by transvaginal ultrasound on the progesterone administration day and the transfer day, the change in endometrial thickness was measured, and the endometrial thickness change ratio was calculated. According to the change rate of endometrial thickness, the patients were divided into three groups: the endometrial thickness compaction group, endometrial thickness non-change group and endometrial thickness expansion group. Among them, the endometrial thickness non-change and expansion groups were combined into the endometrial thickness noncompaction group. RESULTS: Ultrasound images of the endometrium in 219 frozen-thawed euploid blastocyst transfer cycles were evaluated. The clinical pregnancy rate increased with the increase in endometrial thickness change ratio, while the miscarriage rate and live birth rate were comparable among the groups. The multiple logistic regression results showed that in the fully adjusted model a higher endometrial thickness change ratio (per 10%) was associated with a higher clinical pregnancy rate (adjusted odds ratio [aOR] 1.29; 95% confidence interval [CI], 1.01-1.64; P = .040). Similarly, when the patients were divided into three groups according to the change rate of endometrial thickness, the endometrial thickness noncompaction group had a significant positive effect on the clinical pregnancy rate compared with the endometrial thickness compaction group after adjusting for all covariates. CONCLUSIONS: In frozen-thawed euploid blastocyst transfer cycles in which the endometrium was prepared by natural cycles with luteal support, the clinical pregnancy rate was higher in cycles without endometrial compaction after progesterone administration.

17.
Genomics ; 113(6): 4075-4087, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34688795

RESUMO

Transcription factors (TFs) play an important role in tumors. We integrated and analyzed 13 GPL570 platform gastric cancer (GC) microarrays, identified 10 independent prognostic TFs, and constructed a GC prognostic model. Using GSE26942 as the verification set, the Kaplan-Meier curve showed that the signature distinguish the survival rate of GC patients (P < 0.01), and the AUC values are 0.746 and 0.630, respectively. Compared with the clinicopathological characteristics, the signature is an independent prognostic factor (P < 0.05). A nomogram was established based on the model, and the five-year calibration curve verified that the prediction of the nomogram was almost consistent with the actual survival rate, C-index of 0.747 indicated a moderate prognostic ability. The analysis of target genes of 10 TFs showed that they are closely related to the progression of GC. External database and rt-PCR showed that the RNA and protein expression of TFs are consistent with our analysis.

18.
Future Oncol ; 17(36): 5077-5091, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34704816

RESUMO

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

19.
Mar Drugs ; 19(9)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34564161

RESUMO

Prevention of acute kidney injury caused by drugs is still a clinical problem to be solved urgently. Astaxanthin (AST) and docosahexaenoic acid (DHA) are important marine-derived active ingredients, and they are reported to exhibit renal protective activity. It is noteworthy that the existing forms of AST in nature are mainly fatty acid-acylated AST monoesters and diesters, as well as unesterified AST, in which DHA is an esterified fatty acid. However, no reports focus on the different bioactivities of unesterified AST, monoesters and diesters, as well as the recombination of DHA and unesterified AST on nephrotoxicity. In the present study, vancomycin-treated mice were used to evaluate the effects of DHA-acylated AST monoesters, DHA-acylated AST diesters, unesterified AST, and the recombination of AST and DHA in alleviating nephrotoxicity by determining serum biochemical index, histopathological changes, and the enzyme activity related to oxidative stress. Results found that the intervention of DHA-acylated AST diesters significantly ameliorated kidney dysfunction by decreasing the levels of urea nitrogen and creatinine, alleviating pathological damage and oxidative stress compared to AST monoester, unesterified AST, and the recombination of AST and DHA. Further studies revealed that dietary DHA-acylated AST esters could inhibit the activation of the caspase cascade and MAPKs signaling pathway, and reduce the levels of pro-inflammatory cytokines. These findings indicated that the administration of DHA-acylated AST esters could alleviate vancomycin-induced nephrotoxicity, which represented a potentially novel candidate or therapeutic adjuvant for alleviating acute kidney injury.

20.
Aging (Albany NY) ; 13(17): 21497-21512, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491904

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a highly malignant gastrointestinal cancer with a high recurrence rate and poor prognosis. Although N6-methyladenosine (m6A), the most abundant epitranscriptomic modification of mRNAs, has been implicated in several cancers, little is known about its participation in ESCC progression. We found reduced expression of ALKBH5, an m6A demethylase, in ESCC tissue specimens with a more pronounced effect in T3-T4, N1-N3, clinical stages III-IV, and histological grade III tumors, suggesting its involvement in advanced stages of ESCC. Exogenous expression of ALKBH5 inhibited the in vitro proliferation of ESCC cells, whereas depletion of endogenous ALKBH5 markedly enhanced ESCC cell proliferation in vitro. This suggests ALKBH5 exerts anti-proliferative effects on ESCC growth. Furthermore, ALKBH5 overexpression suppressed tumor growth of Eca-109 cells in nude mice; conversely, depletion of endogenous ALKBH5 accelerated tumor growth of TE-13 cells in vivo. The growth-inhibitory effects of ALKBH5 overexpression are partly attributed to a G1-phase arrest. In addition, ALKBH5 overexpression reduced the in vitro migration and invasion of ESCC cells. Altogether, our findings demonstrate that the loss of ALKBH5 expression contributes to ESCC malignancy.

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