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1.
Cell Chem Biol ; 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35316658

RESUMO

Phospholipids are ligands for nuclear hormone receptors (NRs) that regulate transcriptional programs relevant to normal physiology and disease. Here, we demonstrate that mimicking phospholipid-NR interactions is a robust strategy to improve agonists of liver receptor homolog-1 (LRH-1), a therapeutic target for colitis. Conventional LRH-1 modulators only partially occupy the binding pocket, leaving vacant a region important for phospholipid binding and allostery. Therefore, we constructed a set of molecules with elements of natural phospholipids appended to a synthetic LRH-1 agonist. We show that the phospholipid-mimicking groups interact with the targeted residues in crystal structures and improve binding affinity, LRH-1 transcriptional activity, and conformational changes at a key allosteric site. The best phospholipid mimetic markedly improves colonic histopathology and disease-related weight loss in a murine T cell transfer model of colitis. This evidence of in vivo efficacy for an LRH-1 modulator in colitis represents a leap forward in agonist development.

2.
Front Cell Dev Biol ; 10: 862493, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547808

RESUMO

Objective: Gliomas are the most common primary tumors in the central nervous system with a bad prognosis. Pyroptosis, an inflammatory form of regulated cell death, plays a vital role in the progression and occurrence of tumors. However, the value of pyroptosis related genes (PRGs) in glioma remains poorly understood. This study aims to construct a PRGs signature risk model and explore the correlation with clinical characteristics, prognosis, tumor microenviroment (TME), and immune checkpoints. Methods: RNA sequencing profiles and the relevant clinical data were obtained from the Chinese Glioma Genome Atlas (CGGA), the Cancer Genome Atlas (TCGA), the Repository of Molecular Brain Neoplasia Data (REMBRANDT), and the Genotype-Tissue Expression Project (GTEx-Brain). Then, the differentially expressed pyroptosis related genes (PRGs) were identified, and the least absolute shrinkage and selection operator (LASSO) and mutiCox regression model was generated using the TCGA-train dataset. Then the expression of mRNA and protein levels of PRGs signature was detected through qPCR and human protein atlas (HPA). Further, the predictive ability of the PRGs-signature, prognostic analysis, and stratification analysis were utilized and validated using TCGA-test, CGGA, and REMBRANDT datasets. Subsequently, we constructed the nomogram by combining the PRGs signature and other key clinical features. Moreover, we used gene set enrichment analysis (GSEA), GO, KEGG, the tumor immune dysfunction and exclusion (TIDE) single-sample GSEA (ssGSEA), and Immunophenoscore (IPS) to determine the relationship between PRGs and TME, immune infiltration, and predict the response of immune therapy in glioma. Results: A four-gene PRGs signature (CASP4, CASP9, GSDMC, IL1A) was identified and stratified patients into low- or high-risk group. Survival analysis, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group than in the low-risk group. Correlation analysis showed that the risk score was correlated with poor disease features. Furthermore, GSEA and immune infiltrating and IPS analysis showed that the PRGs signature could potentially predict the TME, immune infiltration, and immune response in glioma. Conclusion: The newly identified four-gene PRGs signature is effective in diagnosis and could robustly predict the prognosis of glioma, and its impact on the TME and immune cell infiltrations may provide further guidance for immunotherapy.

3.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35555357

RESUMO

Preeclampsia (PE) is a pregnancy-specific syndrome that affects 5~8% pregnancies and is a leading cause of maternal and neonatal morbidity and mortality, especially in low-income and middle-income countries. Widespread systemic inflammation and endothelial dysfunction are hallmarks of injury in PE, however, the molecular mechanisms linking inflammation and endothelial dysfunction remain largely unknown. We tested the hypothesis that placental IL-1ß impairs endothelial functions by inhibiting VE-cadherin expression in PE. We found that NLRP3 inflammasome was overactivated in preeclamptic placenta, which induced more IL-1ß release. We also observed that IL-1ß significantly increased endothelial permeability of Human Umbilical Vein Endothelial Cells (HUVECs) in a dose-response manner, and inhibition of IL-1ß receptor significantly attenuated the increase of endothelial permeability induced by IL-1ß. We further revealed that both mRNA and protein level of VE-cadherin was reduced by IL-1ß in HUVECs. and overexpression of VE-cadherin in endothelial cells reversed IL-1ß-induced increase in endothelial permeability. Taken together, our preliminary data suggested that excessive placental IL-1ß significantly impaired endothelial functions by inhibiting VE-cadherin expression.

4.
Cell Mol Life Sci ; 79(5): 253, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449370

RESUMO

The crosstalk between macrophages and tubular epithelial cells (TECs) actively regulates the progression of renal fibrosis. In the present study, we revealed the significance of circular RNA ACTR2 (circACTR2) in regulating macrophage inflammation, epithelial-mesenchymal transition (EMT) of TECs, and the development of renal fibrosis. Our results showed UUO-induced renal fibrosis was associated with increased inflammation and EMT, hypertrophy of contralateral kidney, up-regulations of circACTR2 and NLRP3, and the down-regulation of miR-561. CircACTR2 sufficiently and essentially promoted the activation of NLRP3 inflammasome, pyroptosis, and inflammation in macrophages, and through paracrine effect, stimulated EMT and fibrosis of TECs. Mechanistically, circACTR2 sponged miR-561 and up-regulated NLRP3 expression level to induce the secretion of IL-1ß. In TECs, IL-1ß induced renal fibrosis via up-regulating fascin-1. Knocking down circACTR2 or elevating miR-561 potently alleviated renal fibrosis in vivo. In summary, circACTR2, by sponging miR-561, activated NLRP3 inflammasome, promoted macrophage inflammation, and stimulated macrophage-induced EMT and fibrosis of TECs. Knocking down circACTR2 and overexpressing miR-561 may, thus, benefit the treatment of renal fibrosis.


Assuntos
Nefropatias , MicroRNAs , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/genética , Feminino , Fibrose , Humanos , Inflamassomos/genética , Inflamassomos/metabolismo , Inflamação/patologia , Nefropatias/metabolismo , Macrófagos/metabolismo , Masculino , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , RNA Circular/genética
5.
Front Oncol ; 12: 831506, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433476

RESUMO

Objective: The purpose of the study is to explore the mechanism of NRAGE enhancing radioresistance of esophageal squamous cell carcinoma (ESCC) in 2D and 3D levels. Methods: Stably NRAGE-overexpressed ESCC cells and 3D-printing models for ESCC cells were established. Then, cellular malignancy indexes, such as cell morphology, proliferation, radioresistance, motility, apoptosis, cell cycle, and proteins of the Wnt/ß-catenin pathway, were compared between radioresistant and its parental cells in 2D and 3D levels. Additionally, 44 paraffin ESCC specimens with radical radiotherapy were selected to examine NRAGE and ß-catenin protein expression and analyze the clinical correlation. Results: Experiments in 2D culture showed that morphology of the Eca109/NRAGE cells was more irregular, elongated spindle-shaped and disappeared polarity. It obtained faster growth ability, stronger resistance to irradiation, enhanced motility, reduced apoptosis ratio and cell cycle rearrangement. Moreover, Western blot results showed ß-catenin, p-Gsk-3ß and CyclinD1 expressions were induced, while p-ß-catenin and Gsk-3ß expressions decreased in Eca109/NRAGE cells. Experiments in the 3D-printing model showed Eca109/NRAGE cell-laden 3D scaffolds had the advantage on growth and spheroiding according to the brightfield observation, scanning electron microscopy and Ki-67 IHC staining, and higher expression at the ß-catenin protein. Clinical analysis showed that NRAGE expression was higher in tumor tissues than in control tissues of ESCC patients from the Public DataBase. Compared with radiotherapy effective group, both NRAGE total and nuclear and ß-catenin nuclear expressions were significantly upregulated from ESCC specimens in invalid group. Further analysis showed a positive and linear correlation between NRAGE nuclear and ß-catenin nuclear expressions. Additionally, results from univariate and multivariate analyses revealed NRAGE nuclear expression could serve as a risk factor for ESCC patients receiving radical radiotherapy. Conclusion: ESCC cells with NRAGE nuclear accumulation demonstrated greater radioresistance, which may be related to the activation of the Wnt/ß-catenin signaling pathway. It indicated that NRAGE nuclear expression was a potential biomarker for monitoring radiotherapeutic response.

6.
Obes Surg ; 32(6): 1872-1883, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35386040

RESUMO

PURPOSE: Bariatric surgery has been uncovered to relieve nonalcoholic fatty liver disease (NAFLD) in patients with obesity, while current studies have neutral or opposite results. This systematic review and meta-analysis aimed to evaluate the effects of bariatric surgery on NAFLD in patients with obesity. MATERIALS AND METHODS: PubMed, Embase, Cochrane Central, and Web of Science databases were performed to obtain publications containing comparison results of liver biopsy before and after bariatric surgery in obesity. Primary outcomes were biopsy-confirmed remission of NAFLD and NAFLD activity scores. Secondary outcomes were liver function. This study was registered with PROSPERO, CRD42021240346. RESULTS: Thirty-seven studies were included. After bariatric surgery, a biopsy-confirmed resolution of steatosis was improved in 56% of patients, ballooning degeneration in 49%, inflammation in 45%, and fibrosis in 25%. Bariatric surgery significantly decreased mean NAFLD activity scores. RYGB achieved the most obviously improvements in steatosis, and SG attained the most notably ameliorations in fibrosis. The percentage of patients with improved steatosis and hepatic fibrosis in Asian countries was higher than non-Asian countries. The reduction of ALT and AST was 11.95U/L and 6.44 U/L after surgery. CONCLUSION: Our study has revealed that bariatric surgery brought out significantly resolution of NAFLD in individuals with obesity. RYGB and SG have been proved to be of benefit to many hepatic parameters, and the improvement of liver steatosis and fibrosis, particularly in Asian countries. It is strongly suggested that bariatric surgery should be considered as a novel treatment for NAFLD.


Assuntos
Cirurgia Bariátrica , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Cirurgia Bariátrica/métodos , Humanos , Fígado/patologia , Fígado/cirurgia , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade/cirurgia , Obesidade Mórbida/cirurgia
7.
Mol Cancer ; 21(1): 86, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35337361

RESUMO

Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of carcinogenic death. To date, surgical resection is regarded as the gold standard by the operator for clinical decisions. Because conventional tissue biopsy is invasive and only a small sample can sometimes be obtained, it is unable to represent the heterogeneity of tumor or dynamically monitor tumor progression. Therefore, there is an urgent need to find a new minimally invasive or noninvasive diagnostic strategy to detect CRC at an early stage and monitor CRC recurrence. Over the past years, a new diagnostic concept called "liquid biopsy" has gained much attention. Liquid biopsy is noninvasive, allowing repeated analysis and real-time monitoring of tumor recurrence, metastasis or therapeutic responses. With the advanced development of new molecular techniques in CRC, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and tumor-educated platelet (TEP) detection have achieved interesting and inspiring results as the most prominent liquid biopsy markers. In this review, we focused on some clinical applications of CTCs, ctDNA, exosomes and TEPs and discuss promising future applications to solve unmet clinical needs in CRC patients.


Assuntos
DNA Tumoral Circulante , Neoplasias Colorretais , Células Neoplásicas Circulantes , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Biópsia Líquida/métodos , Recidiva Local de Neoplasia , Células Neoplásicas Circulantes/patologia , Prognóstico
8.
Toxicon ; 210: 148-154, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35248587

RESUMO

Microcystin-LR (MC-LR) is an environmental toxin that is synthesized by cyanobacteria and considered a potential human carcinogen. However, the role of MC-LR in prostate cancer progression has not been elucidated. The purpose of this study was to investigate the effect of MC-LR on prostate cancer cell invasion and its underlying mechanisms. Transwell assay was performed, and the result showed that MC-LR increased DU145 cell invasion in a concentration-dependent manner. The result of Western blot showed that MC-LR promoted ERK phosphorylation, while enhancing VASP and ezrin phosphorylation. Moreover, PD0325901 was used to verify the role of the ERK/VASP/ezrin axis in MC-LR-promoted cell invasion. The results revealed that MC-LR promoted microfilament rearrangement and cell invasion by activating the ERK/VASP/ezrin pathway in DU145 cells. Finally, in vivo assay was performed, and the result suggested that MC-LR promoted p-ERK, p-VASP and p-ezrin expression and local invasion in nude mice model. Taken together, our data proved that MC-LR induced microfilament rearrangement and cell invasion by activating the ERK/VASP/ezrin pathway in DU145 cells.


Assuntos
Citoesqueleto de Actina , Microcistinas , Animais , Proteínas do Citoesqueleto , Masculino , Toxinas Marinhas , Camundongos , Camundongos Nus , Microcistinas/toxicidade
9.
Arch Virol ; 167(4): 1075-1087, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35246734

RESUMO

Analysis of orthology is important for understanding protein conservation, function, and phylogenomics. In this study, we performed a comprehensive analysis of gene orthology in the family Ascoviridae based on identification of 366 protein homologue groups and phylogenetic analysis of 34 non-single-copy proteins. Our findings revealed 90 newly annotated proteins, five newly identified core proteins for the family Ascoviridae, and 14 core proteins for the genus Ascovirus. A phylogenomic tree of 11 Ascoviridae members was constructed based on a concatenation of 35 of the 45 ortholog groups. In combination with phosphoproteomic results and conservation estimations, 30 conserved phosphorylation sites on 17 phosphoproteins were identified from a total of 176 phosphosites on 57 phosphoproteins from Heliothis virescens ascovirus 3h (HvAV-3h), providing potential research targets for investigating the role of these protein in the regulation of viral infection. This study will facilitate genome annotation and comparison of further Ascoviridae members as well as functional genomic investigations.


Assuntos
Ascoviridae , Mariposas , Animais , Fosforilação , Filogenia , Proteínas/genética
10.
Int J Biol Macromol ; 202: 80-90, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35038467

RESUMO

Developing novel bilayer food packing film having the ability to prevent bacterial infections and capable of inhibiting oxidation is utmost important, since bacterial infections and oxidation can cause food spoilage. Ag-Metal-organic framework loaded p-coumaric acid modified chitosan (P-CS/Ag@MOF) or chitosan nanoparticles (P-CSNPs/Ag@MOF) and polyvinyl alcohol/starch (PVA/ST) were used as the upper film and lower layer film to successfully prepare a bilayer composite film. The microscopic morphology, water resistance, oil resistance, oxidation resistance, optical properties, cytotoxicity and antibacterial properties of the composite films were compared. The results showed that the surface of P-CS/Ag@MOF bilayer was relatively smooth and its tensile strength (TS) was higher (27.67 MPa). Among them, P-CS/Ag@MOF bilayer films had better oil resistance and oxidation resistance activity. In addition, the P-CS/Ag@MOF bilayer film had good UV-blocking properties and transparency. P-CSNPs/Ag@MOF bilayer film had higher antibacterial activity and cytotoxicity.


Assuntos
Quitosana , Nanopartículas , Antibacterianos/farmacologia , Quitosana/farmacologia , Ácidos Cumáricos , Embalagem de Alimentos/métodos , Álcool de Polivinil/farmacologia , Amido , Resistência à Tração
11.
J Environ Radioact ; 243: 106809, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34995997

RESUMO

A method was developed to measure trace noble gas element adsorption to the surfaces of geologic materials in the presence of a background gas that could potentially compete for surface adsorption sites. Adsorption of four noble gas elements (Ne, Ar, Kr, and Xe) at a concentration of 100 ppm in helium and nitrogen were measured on a sample of crushed tuff at 0, 15, 30, and 45 °C. In addition, Ne, Ar, Kr, and Xe at 250 ppm and 500 ppm in nitrogen at 15 °C were measured. Noble gas adsorption was found to increase with increasing atomic mass and decreasing temperature. It was also observed that the relative increase in noble gas element adsorption with decreasing temperature tends to increase with increasing atomic mass. As the noble gas concentrations in nitrogen increased, adsorption increased in a slightly non-linear fashion which could be modeled using a Freundlich isotherm. For noble gas concentrations that were ≤100 ppm Henry's Law constant were calculated.


Assuntos
Monitoramento de Radiação , Adsorção , Geologia , Nitrogênio
12.
J Hazard Mater ; 425: 127779, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-34823954

RESUMO

This study investigates the impacts of Ni doping on technetium-99 (Tc) sequestration in aqueous solutions through transformation of Fe(OH)2(s) to iron spinel (magnetite) under alkaline conditions. Extensive solid characterization was performed for the mineral phases produced, as well as the Tc/Ni speciation and distribution within these phases. X-ray diffraction results show that iron spinel was the dominant mineral product without detectable Ni incorporation. The doped Ni ions mainly precipitated as fine Fe/Ni oxide/hydroxide particles, including strongly reduced nanometer-sized spheroidal Ni-rich and metallic Ni phases. High-resolution analytical scanning transmission electron microscopy using energy dispersive X-ray spectroscopy and electron energy loss spectroscopy on the produced solid samples (focused ion beam-prepared specimens) revealed three Tc distribution domains dominated by nanocrystals and, especially, a Tc-rich metallic phase. Instances of metallic Tc were specifically found in spheroidal, Ni-rich and metallic nanoparticles exhibiting a core/shell microstructure that suggests strong reduction and sequential precipitation of Ni-Tc-Ni. Mass balance analysis showed nearly 100% Tc removal from the 4.8 × 10-4 M Tc solutions. The finding of the metallic Tc encapsulation indicates that Tc sequestration through Ni-doped Fe(OH)2(s)-to-iron spinel transformation process likely provides an alternative treatment pathway for Tc removal and could be combined into further waste treatment approaches.

13.
Biomed Pharmacother ; 145: 112472, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34861634

RESUMO

Myopia has become one of the most critical health problems in the world with the increasing time spent indoors and increasing close work. Pathological myopia may have multiple complications, such as myopic macular degeneration, retinal detachment, cataracts, open-angle glaucoma, and severe cases that can cause blindness. Mounting evidence suggests that the cause of myopia can be attributed to the complex interaction of environmental exposure and genetic susceptibility. An increasing number of researchers have focused on the genetic pathogenesis of myopia in recent years. Scleral remodeling and excessive axial elongating induced retina thinning and even retinal detachment are myopia's most important pathological manifestations. The related signaling pathways are indispensable in myopia occurrence and development, such as dopamine, nitric oxide, TGF-ß, HIF-1α, etc. We review the current major and recent progress of biomedicine on myopia-related signaling pathways and mechanisms.


Assuntos
Miopia , Transdução de Sinais , Pesquisa Biomédica/métodos , Pesquisa Biomédica/tendências , Humanos , Miopia/genética , Miopia/metabolismo
14.
Pain Res Manag ; 2021: 8609921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900072

RESUMO

BACKGROUND: High tibial osteotomy (HTO) is used to treat medial degeneration of the osteoarthritis (OA) knee. However, shortcomings still exist in the current procedure, like unprecise creation, inability to correct knee rotation, and internal fixed failure. Here, we reported a novel procedure: patient-specific 3D-printed plates for opening wedge high tibial osteotomy (OWHTO) combined with Taylor spatial frame (TSF). The detailed technique was described, and the clinical outcomes were evaluated. METHODS: We prospectively evaluate outcomes of patient-specific 3D-printed plates for OWHTO with use of TSF in 25 patients with knee OA and varus alignment. Postoperative efficacy was evaluated using the HSS knee score, pain visual simulation score (VAS), and knee joint motion (ROM), and lower limb alignment was evaluated by measuring femorotibial angle (FTA) and hip-knee-ankle (HKA). Results and Conclusion. All patients did not experience complications such as wound infection, nerve damage, or bone amputation. 25 patients were followed up for 6-18 months. The bony union at bone amputation was achieved in 3 months after surgery, and the pain symptoms were significantly alleviated or disappeared. The VAS score was significantly reduced in 6 months after surgery compared with preoperative; the HSSS score was significantly added in 6 months after surgery compared with preoperative. The ROM of knee joint increased significantly 6 months after operation compared with that before operation, and the difference was statically significant (P < 0.05). The FTA and HKA after operation were significantly superior to that before operation, and the difference was statically significant (P < 0.01). CONCLUSIONS: Our study showed that patient-specific 3D-printed plates for HTO with the use of TSF have the advantages of small trauma, few complications, simple operation, and fast recovery in treating knee OA and varus alignment.


Assuntos
Osteoartrite do Joelho , Humanos , Articulação do Joelho , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/cirurgia , Osteotomia , Impressão Tridimensional , Estudos Retrospectivos , Tíbia/cirurgia
15.
Biomed Res Int ; 2021: 7479326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34961841

RESUMO

METHODS: MCM4 expression difference in HCC were analyzed from TCGA and GEO data and verified by real-time PCR and western blot. ROC curve was used to analyze the diagnostic value of MCM4 and AFP. Additionally, the relationship between MCM4 and stage or nodal metastasis status or grade or age in TCGA cohort with HCC was observed from the UALCAN website. The univariate and multivariate Cox and functional analyses were done to explore the prognostic value of MCM4 in TCGA cohort. RESULTS: It was found that MCM4 was significantly highly expressed in HCC tissues from TCGA, GEO, and experimental data. Furthermore, ROC curve analysis showed that MCM4 was superior to be a diagnostic biomarker than AFP from TCGA (AUCMCM4 = 0.9461, AUCAFP = 0.7056) and GEO (GSE19665: AUCMCM4 = 0.8800, AUCAFP = 0.5100; GSE64041 AUCMCM4 = 0.8038, AUCAFP = 0.6304). AUC of MCM4 from real-time PCR result in 60 pairs of HCC and adjacent tissues was 0.7172, demonstrating the prediction value of MCM4. Besides, different expression tendencies of MCM4 among different stages or nodal metastasis status or grade or age were observed from the UALCAN website. In addition, multiROC analysis showed the advantage of MCM4 as a survival prediction at 1, 3, and 5 years with the higher AUC at 0.69 of 1 year, 0.65 of 3 years, and 0.61 of 5 years. It was shown that MCM4 was independently associated with OS in univariate and multivariate Cox analysis. And GSEA displayed that MCM4 was highly enriched in KEGG_CELL_CYCLE signaling pathway following higher correlation positively with CDC6, PLK1, CRC1, and BUB1B in HCC. CONCLUSION: MCM4 might be a potential biomarker in guiding the prognostic status of HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Componente 4 do Complexo de Manutenção de Minicromossomo/genética , Adulto , Biomarcadores Tumorais/genética , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Transdução de Sinais/genética
16.
Front Physiol ; 12: 772577, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34819878

RESUMO

Background: Insulin resistance (IR) is closely associated with the pathogenesis of type 2 diabetes mellitus (T2DM). However, remission of insulin sensitivity after bariatric surgery in patients with T2DM and a body mass index (BMI) of 27.5-32.5 kg/m2 has not been fully elucidated. Methods: Thirty-six T2DM patients with a BMI of 27.5-32.5 kg/m2 were prospectively consecutively recruited for laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG). Hyperinsulinemic euglycemic clamp, oral glucose tolerance test (OGTT), and other indicators were tested at baseline and 6 months postoperative. Glucose disposal rate (GDR), time to reach euglycemia, homeostatic model assessment of IR, quantitative insulin sensitivity check index (QUICKI), triglyceride glucose (TyG) index, 30-min insulinogenic index (IGI30), and disposition index (DI) were calculated at baseline and 6 months after surgery. The criterion for remission in T2DM patients was the achievement of the triple composite endpoint. Results: Anthropometric and glucolipid metabolism parameters significantly improved following surgery. The GDR increased significantly from baseline to 6 months after LRYGB (from 4.28 ± 1.70 mg/kg/min to 8.47 ± 1.89 mg/kg/min, p < 0.0001) and LSG (from 3.18 ± 1.36 mg/kg/min to 7.09 ± 1.69 mg/kg/min, p < 0.001). The TyG index decreased after surgery (RYGB group, from 9.93 ± 1.03 to 8.60 ± 0.43, p < 0.0001; LSG group, from 10.04 ± 0.79 to 8.72 ± 0.65, p = 0.0002). There was a significant reduction in the IGI30 (RYGB group, from 2.04 ± 2.12 to 0.83 ± 0.47, p = 0.005; LSG group, from 2.12 ± 1.73 to 0.92 ± 0.66, p = 0.001). The mean DI significantly increased from 1.14 ± 1.35 to 7.11 ± 4.93 in the RYGB group (p = 0.0001) and from 1.25 ± 1.78 to 5.60 ± 4.58 in the LSG group (p = 0.003). Compared with baseline, HOMR-IR, QUICKI, area under the curve-C-peptide release test (AUC-CRT), and AUC-OGTT were significantly changed at 6 months postoperative. Overall, 52.63% of patients in the LRYGB group versus 29.41% of patients in the LSG group achieved the triple composite endpoint. Conclusion: Both LRYGB and LSG effectively induced remission of IR in patients with T2DM and a BMI of 27.5-32.5 kg/m2.

17.
Front Oncol ; 11: 758856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760705

RESUMO

OBJECTIVE: Gliomas are the most aggressive intracranial tumors accounting for the vast majority of brain tumors with very poor prognosis and overall survival (OS). Cancer-derived immunoglobulin G (cancer-IgG) has been found to be widely expressed in several malignancies such as breast cancer, colorectal cancer, and lung cancer. Cancer-IgG could promote tumorigenesis and progression. However, its role in glioma has not been revealed yet. METHODS: We mined open databases including the Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) to study the role of IGHG1, which encodes cancer-IgG in glioma. Examination of the differential expression of IGHG1 was carried out in the GEO and TCGA databases. Furthermore, its expression in different molecular subtypes was analyzed. Stratified analysis was performed with clinical features. Subsequently, immune infiltration analysis was conducted using single-sample gene set enrichment analysis (ssGSEA). GSEA was performed to reveal the mechanisms of IGHG1. Lastly, immunohistochemistry was processed to validate our findings. RESULTS: In this study, we found that the expression of IGHG1 was higher in glioma and molecular subtypes with poor prognosis. The overall survival of patients with a high expression of IGHG1 was worse in the stratified analysis. Immune infiltration analysis indicated that the expression level of IGHG1 was positively correlated with the stromal score, ESTIMATE score, and immune score and negatively correlated with tumor purity. Results from the GSEA and DAVID demonstrated that IGHG1 may function in phagosome, antigen processing and presentation, extracellular matrix structural constituent, antigen binding, and collagen-containing extracellular matrix. Finally, immunohistochemistry assay validated our findings that patients with a high expression of cancer-IgG had poor OS and disease-free survival (DFS). CONCLUSION: Cancer-IgG is a promising biomarker of diagnosis and treatment for patients with glioma.

18.
Front Oncol ; 11: 698278, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631528

RESUMO

BACKGROUND: Glioma is the most frequent brain malignancy presenting very poor prognosis and high recurrence rate. Focal adhesion complexes play pivotal roles in cell migration and act as hubs of several signaling pathways. METHODS: We used bioinformatic databases (CGGA, TCGA, and GEO) and identified a focal adhesion-related differential gene expression (FADG) signature by uniCox and LASSO regression analysis. We calculated the risk score of every patient using the regression coefficient value and expression of each gene. Survival analysis, receiver operating characteristic curve (ROC), principal component analysis (PCA), and stratified analysis were used to validate the FADG signature. Then, we conducted GSEA to identify the signaling pathways related to the FADG signature. Correlation analysis of risk scores between the immune checkpoint was performed. In addition, the correlation of risk scores and genes related with DNA repair was performed. CIBERSORT and ssGSEA were used to explore the tumor microenvironment (TME). A nomogram that involved our FADG signature was also constructed. RESULTS: In total, 1,726 (528 patients diagnosed with WHO II, 591 WHO III, and 603 WHO IV) cases and 23 normal samples were included in our study. We identified 29 prognosis-related genes in the LASSO analysis and constructed an eight FADG signature. The results from the survival analysis, stratified analysis, ROC curve, and univariate and multivariate regression analysis revealed that the prognosis of the high-risk group was significantly worse than the low-risk group. Correlation analysis between risk score and genes that related with DNA repair showed that the risk score was positively related with BRCA1, BRCA2, RAD51, TGFB1, and TP53. Besides, we found that the signature could predict the prognosis of patients who received radiation therapy. SsGSEA indicated that the high-risk score was positively correlated with the ESTIMATE, immune, and stromal scores but negatively correlated with tumor purity. Notably, patients in the high-risk group had a high infiltration of immunocytes. The correlation analysis revealed that the risk score was positively correlated with B7-H3, CTLA4, LAG3, PD-L1, and TIM3 but inversely correlated with PD-1. CONCLUSION: The FADG signature we constructed could provide a sensitive prognostic model for patients with glioma and contribute to improve immunotherapy management guidelines.

19.
PeerJ ; 9: e12146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616614

RESUMO

BACKGROUND: Aberrant DNA methylation of tumor suppressor genes is a common event in the development and progression of gastric cancer (GC). Our previous study showed NDRG1, which could suppress cell invasion and migration, was frequently down-regulated by DNA methylation of its promoter in GC. PURPOSE AND METHODS: To analyze the relationship between the expression and DNA methylation of NDRG1 and DNA methyltransferase (DNMT) family. We performed a comprehensive comparison analysis using 407 patients including sequencing analysis data of GC from TCGA. RESULTS: NDRG1 was down-regulated in GC, and was negatively correlative to DNMT1 (r = -0.11, p = 0.03), DNMT3A (r = -0.10, p = 0.01), DNMT3B (r = -0.01, p = 0.88), respectively, whereas the DNA methylation of NDRG1 was positively correlative to DNMT family (DNMT1 r = 0.20, p < 0.01; DNMT3A r = 0.26, p < 0.001; DNMT3B r = 0.03, p = 0.57, respectively). NDRG1 expression was significantly inverse correlated with invasion depth (p = 0.023), but DNMT1 was significantly positive correlated with invasion depth (p = 0.049). DNMT3B was significantly correlated with the degree of tumor cell differentiation (p = 0.030). However, there was no association between the expression of DNMT3A and clinicopathological features. The KM plotter showed that NDRG1 (HR = 0.95, 95% CI [0.8-1.12], p = 0.53) and DNMT1 (HR = 1.04, 95% CI [0.88-1.23], p = 0.67) had no association with prognosis of GC patients, while, DNMT3A (p = 0.0064) and DNMT3B (p = 0.00025) displayed significantly association. But the overall survival of high expression of NDRG1 tended to be prolonged. CONCLUSION: These data suggest that down-regulation of NDRG1expression in GC may be due to its promoter DNA methylation via DNMT family. The demethylating agent maybe a potential target drug for GC patients.

20.
Polymers (Basel) ; 13(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34578053

RESUMO

In this paper, polyvinyl alcohol/Ag-Metal-organic framework (PVA/Ag@MOF) and polyvinyl alcohol/chitosan (PVA/CS) were used as the inner and outer layers to successfully prepare a bilayer composite hydrogel for tissue engineering scaffold. The performance of bilayer hydrogels was evaluated. The outer layer (PVA/CS) has a uniform pore size distribution, good water retention, biocompatibility and cell adhesion ability. The inner layer (PVA/Ag@MOF) has good antibacterial activity and poor biocompatibility. PVA, PVA/0.1%Ag@MOF, PVA/0.5%Ag@MOF, and PVA/1.0%Ag@MOF show anti-microbial activity in ascending order. However, its use as an inner layer avoids direct contact with cells and prevents infection. The cell viability of all samples was above 90%, indicating that the bilayer hydrogel was non-toxic to A549 cells. The bilayer hydrogel scaffold combines the advantages of the inner and outer layers. In summary, this new bilayer composite is an ideal lung scaffold for tissue engineering.

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