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1.
Global Spine J ; : 21925682211007116, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33823627

RESUMO

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To evaluate whether pre-existing adjacent spinal canal stenosis (SCS) is associated with short-term outcomes after lumbar fusion surgery. METHODS: We included patients with lumbar spinal stenosis treated surgically between July 2015 and December 2017 at 4 centers. All patients had the same pathology, with L4-S1 as the culprit sections. Patients were divided into 2 groups based on the cerebrospinal fluid occlusion sign on MRI at the adjacent L3/4 level. Patients without SCS (grade 0) and with mild SCS (grade 1) were classified into the non-stenosis (NS) and mild stenosis (MS) groups, respectively. All patients underwent PLIF and completed at least 1-year follow-up. The incidence of adjacent segment degeneration (ASDeg) and clinical outcomes were compared between the 2 groups. RESULTS: A total of 308 patients (NS, 156; MS, 152) met the inclusion criteria. The incidence of ASDeg in the NS group (n = 40, 25.6%) was significantly lower than that in the MS group (n = 74, 48.7%; P < .001). The most frequent type of ASDeg in the 2 groups was the SCS-aggravated type. No significant difference was observed in adjacent segment disease incidence between the 2 groups (P = .243). The NS group had better outcomes according to the clinical function scores (P < .05). CONCLUSIONS: The cerebrospinal fluid occlusion sign on MRI is valuable for evaluating the adjacent segment with pre-existing degeneration. Patients with mild SCS in adjacent segments were more likely to have ASDeg, and the most frequent type of ASDeg was the SCS-aggravated type at early follow-up.

2.
Cell Prolif ; : e13024, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33751722

RESUMO

OBJECTIVES: Guillain-Barré syndrome (GBS) results from autoimmune attack on the peripheral nerves, causing sensory, motor and autonomic abnormalities. Emerging evidence suggests that there might be an association between COVID-19 and GBS. Nevertheless, the underlying pathophysiological mechanism remains unclear. MATERIALS AND METHODS: We performed bioinformatic analyses to delineate the potential genetic crosstalk between COVID-19 and GBS. RESULTS: COVID-19 and GBS were associated with a similar subset of immune/inflammation regulatory genes, including TNF, CSF2, IL2RA, IL1B, IL4, IL6 and IL10. Protein-protein interaction network analysis revealed that the combined gene set showed an increased connectivity as compared to COVID-19 or GBS alone, particularly the potentiated interactions with CD86, IL23A, IL27, ISG20, PTGS2, HLA-DRB1, HLA-DQB1 and ITGAM, and these genes are related to Th17 cell differentiation. Transcriptome analysis of peripheral blood mononuclear cells from patients with COVID-19 and GBS further demonstrated the activation of interleukin-17 signalling in both conditions. CONCLUSIONS: Augmented Th17 cell differentiation and cytokine response was identified in both COVID-19 and GBS. PBMC transcriptome analysis also suggested the pivotal involvement of Th17 signalling pathway. In conclusion, our data suggested aberrant Th17 cell differentiation as a possible mechanism by which COVID-19 can increase the risk of GBS.

3.
Biomed Res Int ; 2021: 6692544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33728339

RESUMO

Objective: The study is aimed at investigating the regulatory relationship between miR-145-5p and ABRACL, and has tried at clarifying the mechanisms underlying the proliferation, migration, and invasion of esophageal carcinoma (EC) cells. Methods: Gene expression data related to EC were accessed from TCGA database, and the "edgeR" package was used to screen differentially expressed genes. TargetScan, miRDB, and miRTarBase databases were used to predict potential targets for the target miRNA miR-145-5p. qRT-PCR and Western blot were performed to assess the expression of miR-145-5p and ABRACL in EC cells. Dual-luciferase reporter assay was performed to validate the targeting relationship between miR-145-5p and ABRACL. Functional experiments including CCK-8 assay, Transwell migration, and invasion assays were used to detect the proliferation, migration, and invasion of EC cells. Results: The expression of miR-145-5p was significantly decreased in EC, while ABRACL was remarkably increased. In addition, there was a negative correlation identified between miR-145-5p and ABRACL mRNA. Overexpressing miR-145-5p was able to suppress cell proliferation, migration, and invasion, whereas silencing miR-145-5p posed an opposite effect. In the meantime, ABRACL was identified as a direct target of miR-145-5p by dual-luciferase reporter assay. Furthermore, miR-145-5p could inhibit the expression of ABRACL, in turn inhibiting the proliferation, migration, and invasion of EC cells. Conclusion: miR-145-5p functions on the proliferation, migration, and invasion of EC cells via targeting ABRACL, and it may be a novel therapeutic target in EC treatment.

4.
Br J Neurosurg ; : 1-6, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245247

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of modified facet joint fusion (MFF) for the treatment of multilevel (three-level or more) lumbar spinal stenosis (LSS). PATIENTS AND METHODS: In this retrospective study, 135 consecutive patients who underwent initial MFF for multilevel LSS were included. Clinical outcomes included fusion rate, change of visual analogue scale pain scores for low back pain (VAS-LBP) and leg pain (VAS-LP), Japanese Orthopedic Association scores (JOA), Oswestry Disability Index (ODI) and MacNab classification before and after MFF. The complications were also analyzed. RESULTS: The fusion rates were 46.7% (63/135) at 6-month and 89.6% (121/135) at 1-year. The mean VAS-LBP, VAS-LP, and ODI significantly decreased from 5.2 ± 0.6, 5.7 ± 0.8 and 65 ± 7.9 to 1.58 ± 0.4, 0.58 ± 0.3 and 20.8 ± 5.8, respectively (all p < 0.001). The mean JOA markedly improved from 10.0 ± 1.3 to 26.1 ± 1.5 (p < 0.001). Excellent/good results of MacNab classification were achieved in 88.9% (120/135) of the patients. The overall rate of complications after MFF was 5.9%, including poor wound healing (2.2%), calf muscular venous thrombosis (0.74%), deep venous thrombosis (0.74%), superficial wound infection (1.48%), transient foot drop (0.74%). All the complications were transient and improved without prolonged hospital stay and sequelae. CONCLUSION: MFF may be safe and efficient for multilevel LSS with high fusion rate and significant symptom relief, which is worthy of further study.

5.
Cell Prolif ; : e12936, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33103338

RESUMO

Osteosarcoma is the most common primary bone malignancy and is a neoplasm thought to be derived from the bone-forming mesenchymal stem cells. Aberrant activation of oncogenes and inactivation of tumour suppressor genes by somatic mutations and epigenetic mechanisms play a pivotal pathogenic role in osteosarcoma. Aside from alterations in these protein-coding genes, it has now been realized that dysregulation of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and the recently discovered circular RNAs (circRNAs), is crucial to the initiation and progression of osteosarcoma. CircRNAs are single-stranded RNAs that form covalently closed loops and function as an important regulatory element of the genome through multiple machineries. Recently, an increasing number of studies suggested that circRNAs also played critical roles in osteosarcoma. This review summarizes recent development and progression in circRNA transcriptome analysis and their functions in the modulation of osteosarcoma progression.

6.
Food Chem ; : 128252, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33067044

RESUMO

This study tries to elucidate the different mechanisms of functional properties among pasteurized egg white (P-EW), spray-dried egg white (SD-EW) and fresh egg white (F-EW) via quantitative N-glycoproteomic analyses. The results showed that spray-drying increased the surface hydrophobicity (181.4%) and zeta potential (25.6%) of egg white, which contributed to the enhancement of emulsifying activity index (20.1%) and foaming capacity (35.2%). Pasteurization caused the disintegration of natural protein aggregates in F-EW and resulted in a "block-like" P-EW gel and higher water holding capacity (6.2%). Spray-drying caused formation of thermal aggregates and led to a "mesh-like" SD-EW gel and better cohesiveness (3.6%). Quantitative N-glycoproteomic analysis showed that the abundance of 32 N-glycosites from 18 N-glycoproteins (such as Mucin 5B) of SD-EW was significantly reduced comparing to F-EW, indicated that the N-glycans of egg white protein are likely to be covalently cross-linked during spray-drying and are involved in thermal aggregation.

7.
Food Sci Biotechnol ; 29(9): 1201-1211, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32802559

RESUMO

This study examined the effects of different doses of irradiation treatments on protein structure and digestion characteristic of seed-watermelon seed kernel protein. The results showed that, the molecular structure of seed-watermelon kernel protein was unfolded after the irradiation treatment, the content of ß-sheet structure in the secondary structure was decreased, while the content of random coil structure increased. The average particle size of the protein increased, and the hydrophobic group buried in the ß-sheet structure was exposed hence the surface hydrophobicity increased. Besides, the surface morphology of seed-watermelon protein changed from smooth and flat to coarse and concave, the specific surface area in contact with the aqueous medium increased and its solubility increased, the distribution of peptides in the digesta became wider, and the small molecular weight peptides gradually increased.

8.
Biomed Res Int ; 2020: 9414196, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802886

RESUMO

Background: Arsenic is a toxic metalloid widely present in nature, and arsenic poisoning in drinking water is a serious global public problem. Glutathione is an important reducing agent that inhibits arsenic-induced oxidative stress and participates in arsenic methylation metabolism. Therefore, glutathione plays an important role in regulating arsenic toxicity. In recent years, a large number of studies have shown that arsenic can regulate glutathione synthesis in many ways, but there are many contradictions in the research results. At present, the mechanism of the effect of arsenic on glutathione synthesis has not been elucidated. Objective: We will conduct a meta-analysis to illustrate the effects of arsenic on GSH synthesis precursors Glu, Cys, Gly, and rate-limiting enzyme γ-GCS in mammalian models, as well as the regulation of p38/Nrf2 of γ-GCS subunit GCLC, and further explore the molecular mechanism of arsenic affecting glutathione synthesis. Results: This meta-analysis included 30 studies in vivo and 58 studies in vitro, among which in vivo studies showed that arsenic exposure could reduce the contents of GSH (SMD = -2.86, 95% CI (-4.45, -1.27)), Glu (SMD = -1.11, 95% CI (-2.20,-0.02)), and Cys (SMD = -1.48, 95% CI (-2.63, -0.33)), with no statistically significant difference in p38/Nrf2, GCLC, and GCLM. In vitro studies showed that arsenic exposure increased intracellular GSH content (SMD = 1.87, 95% CI (0.18, 3.56)) and promoted the expression of p-p38 (SMD = 4.19, 95% CI (2.34, 6.05)), Nrf2 (SMD = 4.60, 95% CI (2.34, 6.86)), and GCLC (SMD = 1.32, 95% CI (0.23, 2.41)); the p38 inhibitor inhibited the expression of Nrf2 (SMD = -1.27, 95% CI (-2.46, -0.09)) and GCLC (SMD = -5.37, 95% CI (-5.37, -2.20)); siNrf2 inhibited the expression of GCLC, and BSO inhibited the synthesis of GSH. There is a dose-dependent relationship between the effects of exposure on GSH in vitro. Conclusions. These indicate the difference between in vivo and in vitro studies of the effect of arsenic on glutathione synthesis. In vivo studies have shown that arsenic exposure can reduce glutamate and cysteine levels and inhibit glutathione synthesis, while in vitro studies have shown that chronic low-dose arsenic exposure can activate the p38/Nrf2 pathway, upregulate GCLC expression, and promote glutathione synthesis.

9.
Int J Biol Macromol ; 164: 3125-3132, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32860793

RESUMO

The chicken egg vitelline membrane (CEVM) is an important structure for the transmembrane transport of egg yolk components, protection of the blastodisc, and separation of egg white and egg yolk. In this study, the N-glycoproteome of the CEVM was mapped and analyzed in depth. Total protein of the CEVM was digested, and the glycopeptides were enriched by a hydrophilic interaction liquid chromatography microcolumn and identified by nano liquid chromatography/tandem mass spectrometry. A total of 435 N-glycosylation sites on 208 N-glycoproteins were identified in CEVM. Gene Ontology enrichment analysis showed that CEVM N-glycoproteins are mainly involved in the regulation of proteinases/inhibitors and transmembrane transport of lipids. Mucin-5B is the primary N-glycoprotein in the CEVM. Comparison of the main N-glycoproteins between the CEVM and other egg parts revealed the tissue specificity of N-glycosylation of egg proteins. The results provide insights into protein N-glycosylation in the chicken egg, CEVM functions and underlying mechanisms.

10.
Environ Sci Pollut Res Int ; 27(26): 32467-32473, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32556990

RESUMO

Emerging evidence suggested that long non-coding RNAs (lncRNAs) play pivotal roles in tumorigenesis. LINC01133 is a newly identified lncRNA first discovered as an oncogene in lung squamous cell carcinoma. Subsequent studies further demonstrated this lncRNA was deregulated in a wide spectrum of tumors, including colorectal, gastric, lung, and pancreatic ductal adenocarcinoma as well as osteosarcoma and hepatocellular carcinoma. Intriguingly, this lncRNA exerted oncogenic or tumor-suppressive action in a tissue-dependent manner. This review sought to summarize our current understanding concerning the deregulation of LINC01133 in human tumors in relation to its molecular mechanisms and cellular functions. The clinical utilization of LINC01133 as a potential prognostic biomarker and a treatment target is also discussed.


Assuntos
Neoplasias Ósseas , Neoplasias Pulmonares/genética , Osteossarcoma , RNA Longo não Codificante , Regulação Neoplásica da Expressão Gênica , Humanos
11.
Food Chem ; 330: 127167, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32531632

RESUMO

Eggshell matrix (EM) proteins play an important biological role in eggshell mineralization and embryo development. Many studies have demonstrated that some matrix proteins undergo posttranslational modifications, including phosphorylation and glycosylation, which have important regulatory effects on the functional properties of the proteins. Systematic analysis of the proteome, the phosphorylated modified proteome and the glycosylated modified proteome of the chicken EM was performed using a proteomics strategy. A total of 112 phosphorylation sites from 69 phosphoproteins and 297 N-glycosylation sites from 182 N-glycoproteins were identified in the chicken EM. Among all these identified modified proteins, 129 were not identified in the proteome (547 proteins). Therefore, a total of 676 EM proteins were identified in this study. Gene ontology (GO) enrichment analysis indicated that EM proteins and phosphoproteins were mainly enriched in regulation of enzyme activity, while EM N-glycoproteins were enriched in immune response regulation.


Assuntos
Galinhas/metabolismo , Proteínas do Ovo/metabolismo , Casca de Ovo/metabolismo , Glicoproteínas/metabolismo , Fosfoproteínas/metabolismo , Proteoma/metabolismo , Animais , Glicosilação , Fosforilação , Processamento de Proteína Pós-Traducional , Proteômica
12.
Oper Neurosurg (Hagerstown) ; 19(3): 255-263, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32469075

RESUMO

BACKGROUND: Controversy still exists regarding the optimal fusion technique for the treatment of unstable lumbar spondylolisthesis. OBJECTIVE: To evaluate the safety and efficacy of modified facet joint fusion (MFF). METHODS: A total of 491 patients with unstable lumbar spondylolisthesis who underwent MFF were retrospectively reviewed. Computed tomography was used to evaluate the fusion rate of MFF at 6- and 12-mo follow-up postoperatively. Clinical outcomes included visual analog scale pain scores for low back pain (VAS-LBP) and leg pain (VAS-LP), Japanese Orthopedic Association scores (JOA), and Oswestry Disability Index (ODI), all of which were obtained preoperatively and postoperatively at 1-, 3-, 6-, and 12-mo follow-up times. The clinical outcomes were determined to be excellent, good, fair, or poor according to the MacNab classification at the last follow-up time. RESULTS: Of the 491 patients, the fusion rates at the 6-mo and 1-yr follow-up were 56.8% and 96.1%, respectively. Between baseline and 1-yr follow-up time, VAS-LP and VAS-LBP improved from 5.6 ± 0.9 to 0.4 ± 0.5 and 5.1 ± 1.2 to 1.5 ± 0.9, respectively (P < .001). JOA improved from 9.0 ± 2.0 to 27.7 ± 1.0, and ODI decreased from 64.0 ± 2.0 to 19 ± 1.0 (P < .001). At the final evaluation, 93.6% patients showed excellent or good results, and 3.2% showed fair results. There were no MFF technique-related complications. CONCLUSION: MFF technique achieved satisfactory clinical outcomes and fusion rate and appears to be a promising alternative fusion technique for the treatment of unstable lumbar spondylolisthesis.

13.
Food Chem ; 326: 126983, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32413763

RESUMO

Confirmed to be a new type of food resource, quail egg can provide humans with high-quality protein and offer various nutrients that can promote growth and development. Post-translational modification of proteins can regulate their molecular structures and physiological functions. However, the understanding and related research of quail egg holoproteins and post-translationally modified proteins is not yet sufficient. This study provides an in-depth analysis of quail egg proteins using an omics strategy. A total of 175 proteins, 109 N-glycoproteins (293 N-glycosylation sites) and 23 phosphoproteins (84 phosphorylation sites) were identified. Motif analysis showed that N-glycosylation sites of quail eggs were classical sites. The main characteristic sequence of the phosphorylation site is "S-X-E" (77%). Functional analysis indicated that quail egg proteins, modified proteins were enriched in the regulation of enzyme activity. These results have significant reference value for understanding the structure, function of quail eggs, explaining the physicochemical reaction during the storage.


Assuntos
Proteínas do Ovo/metabolismo , Ovos/análise , Codorniz/metabolismo , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Glicoproteínas/metabolismo , Glicosilação , Humanos , Fosfoproteínas/metabolismo , Fosforilação , Proteoma/análise
14.
J Med Genet ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381727

RESUMO

BACKGROUND: Early-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening. METHODS: In this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited. RESULTS: After ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis. CONCLUSION: ES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.

15.
J Gene Med ; 22(10): e3231, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32436632

RESUMO

BACKGROUND: Growing evidence indicates that Long noncoding RNAs contribute to cell differentiation, invasion, metabolism, proliferation and metastasis. However, the potential role of LINC01121 in progression of intervertebral disc degeneration (IDD) remains unclear. METHODS: LINC01121, matrix metalloprotease (MMP)-16 and miR-150-5p expression was determined by a quantitative-reverse transcriptase-polymerase chain reaction assay. Inflammatory cytokines level was measured by an enzyme-linked immunosorbent assay and cell counting kit-8 analysis was used to assess cell proliferation. MMP-16-specific binding with miR-150-5p was verified with a luciferase reporter assay. RESULTS: We noted that interleukin (IL)-1ß and tumor necrosis factor (TNF)-α treatment enhanced LINC01121 and MMP-16 expression in nucleus pulposus (NP) cells. LINC01121 was higher in IDD specimens compared to that in control specimens. Higher expression of LINC01121 was correlated with disc degeneration degree. Ectopic expression of LINC01121 enhanced cell proliferation and promoted ki-67, MMP-3 and ADAMTS5 expression and also suppressed collagen II expression in NP cells. We observed that overexpression of LINC01121 increased the secretion of three inflammatory cytokines, including IL-6, TNF-α and IL-1ß. We found that ectopic expression of LINC01121 decreased the miR-150-5p level in NP cells. Luciferase reporter data confirmed that MMP-16 was one direct target of miR-150-5p. Overexpression of miR-150-5p inhibited MMP-16 level and elevated the expression of LINC01121 enhanced MMP-16 level. We also found that MMP-16 was up-regulated in IDD specimens compared to that in control specimens. Higher expression of MMP-16 was correlated with disc degeneration degree. Interestingly, MMP-16 expression was positively related to LINC01121 in IDD specimens. Finally, overexpression of LINC01121 regulated cell growth, extracellular matrix degradation and inflammatory cytokine secretion via modulating MMP-16. CONCLUSIONS: our data suggested LINC01121 may be a new therapeutic target for IDD.

16.
Chem Res Toxicol ; 33(6): 1458-1467, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32307979

RESUMO

We aimed to systematically evaluate the regulatory effect of arsenic on wnt/ß-catenin signaling pathway and to provide theoretical basis for revealing the mechanism of the relationship between arsenic and cell proliferation. The meta-analysis was carried out using Revman5.2 and Stata13.0 to describe the differences between groups with standard mean difference. We found in normal cells that the levels of wnt3a, ß-catenin, glycogen synthase kinase-3ß phosphorylated at serine 9 (p-GSK-3ß(Ser9)), cyclinD1, proto-oncogene c-myc, and vascular endothelial growth factor (VEGF) in the arsenic intervention group were higher than those in the control group, and the level of glycogen synthase kinase-3ß (GSK-3ß) was lower than that in the control group (P < 0.05, respectively). Subgroup analysis showed that for a long time period (>24 h), the level of ß-catenin in the arsenic intervention group was higher than that in the control group, and the level of GSK-3ß of the same long-time period (>24 h) with low-dose (≤5 µM) intervention was lower than those in the control group (P < 0.05, respectively). In cancer cells, the levels of ß-catenin, cyclinD1, c-myc, and VEGF in the arsenic intervention group were lower than those in the control group, while the level of GSK-3ß in the arsenic intervention group was higher than that in the control group (P < 0.05, respectively). Subgroup analysis showed that the levels of ß-catenin, cyclinD1, and c-myc in the high-dose (>5 µM) arsenic intervention group were lower than those in the control group, and the levels of ß-catenin and cyclinD1 in the high-dose (>5 µM) arsenic intervention group were lower than those in the low-dose (≤5 µM) arsenic intervention group (P < 0.05, respectively). In addition, the regulation of arsenic on ß-catenin was dose-dependent in the range of arsenic concentration from 0 to 7.5 µM. This study revealed that arsenic could upregulate wnt/ß-catenin signaling pathway in normal cells and downregulate it in cancer cells, and its effect was affected by time and dose.

17.
Life Sci ; 251: 117607, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32240679

RESUMO

BACKGROUND: Arsenic trioxide (ATO) can bind directly to the human promyelocytic leukemia (PML) protein, leading to modification of PML by SUMOs. UBC9 is the only known E2-conjugating enzyme involved in SUMOylation. PML degradation via RNF4, an E3 ubiquitin ligases family member. PML is key organizer of nuclear bodies (NBs) that regulate many biological processes such as senescence, and DNA damage. ATO can activate the TGFß/Smad signaling pathway, causing liver fibrosis. However, the roles of PML Sumoylation in ATO-induced liver fibrosis remain unclear. OBJECTIVE: This study aimed to investigate the role of PML Sumoylation in the ATO-induced HSCs activation and to improve the mechanism of ATO-induced liver fibrosis. METHODS: Hepatic stellate cells (HSCs) were treated with 2 µmol/L ATO. Cell viability was detected by CCK-8 analysis. Immunoblot analysis and real-time quantitative PCR were used to detect the expression of IL-1ß, TNF-α, TGF-ß1, p-Smad2/3, α-SMA, Collagen I and PML SUMOylation after silencing PML, UBC9, and RNF4, respectively. The formation of PML-NBs was observed by immunofluorescence staining. RESULTS: 2 and 5 µmol/L ATO intervention increased HSCs cell viability. ATO was able to significantly trigger PML SUMOylation and the formation of PML-NBs. Inhibition of SUMOylated PML by silencing UBC9, subsequently preventing the downregulation of HSCs activation indicators induced by ATO (P < 0.05). Conversely, enhancing SUMOylated PML accumulation by silencing RNF4, activating TGFß/Smad signaling pathway, eventually promoting the induction of liver fibrosis. CONCLUSION: These results indicated that PML SUMOylation plays a critical role in the development of liver fibrosis induced by ATO.


Assuntos
Trióxido de Arsênio/toxicidade , Células Estreladas do Fígado/patologia , Cirrose Hepática/patologia , Proteína da Leucemia Promielocítica/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Inativação Gênica , Humanos , Proteínas Nucleares/genética , Sumoilação , Fatores de Transcrição/genética , Enzimas de Conjugação de Ubiquitina/genética
18.
Biol Trace Elem Res ; 198(2): 449-463, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32124230

RESUMO

The purpose of our study was to investigate the role of hypoxia-inducible factor-1α (HIF-1α) in arsenic-induced carcinogenesis. We included 39 articles for meta-analysis. The results showed that low-dose exposure to arsenic (≤ 10 µmol/L) could promote the expression of phosphatidylinositol 3-kinase (PI3K) and phosphorylation-protein kinase B (p-AKT). High-dose arsenic exposure (> 10 µmol/L) promoted the expression of PI3K, HIF-1α, vascular endothelial growth factor (VEGF), and p38MAPK (P38). Acute arsenic exposure (< 24 h) promoted the expression of PI3K, HIF-1α, and VEGF. Chronic arsenic exposure (≥ 24 h) promoted the expression of PI3K, p-AKT, and P38. Moreover, for normal tissue-derived cells, arsenic could induce the increased expression of PI3K, p-AKT, HIF-1α, and VEGF. For tumor tissue-derived cells, arsenic could induce the expression of PI3K, p-AKT, and P38. We found that arsenic exposure could activate the PI3K/AKT pathway, further induce the high expression of HIF-1α, and then upregulate the levels of miRNA-21 and VEGF, promote the expression of proliferating cell nuclear antigen (PCNA), and ultimately lead to malignant cell proliferation. Our findings indicated that arsenic could increase the expression of HIF-1α by activating the PI3K/AKT pathway and eventually induce malignant cell proliferation.

19.
Medicine (Baltimore) ; 99(11): e19552, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176112

RESUMO

BACKGROUND: Posterior lumbar interbody fusion (PLIF) surgery is associated with significant blood loss; however, few studies have focused on hidden blood loss (HBL) in PLIF or its regulatory factors. The purpose of this study was to explore the HBL in PLIF surgery as well as the influence of tranexamic acid (TXA) on blood loss in PLIF. METHODS: We performed a randomized controlled trial (RCT) and recruited patients undergoing PLIF into the study from November 2013 to April 2017. All participants were assigned to one of 2 groups according to a simple equal probability randomization scheme. At the end of PLIF surgery, for patients in the TXA group, the surgical field was immersed in TXA (1 g in 100 mL of saline solution) for 5 min before stitching the wound. For the control group, the surgical field was immersed in the same volume of normal saline. RESULTS: In our study, the drainage volume during the first 24 h and the total postoperative drainage volume were significantly lower in patients in the TXA group than in the control group (P = .001). The hematocrit (Hct) of the drainage and calculation of blood contained in the drainage showed similar results. The mean length of hospital stay and rate of blood transfusion in the TXA group were less than those in the control group (P < .05). HBL was responsible for 45.6% of the total blood loss in PLIF, and both of the indicators in the TXA group were much lower than those in the control group. CONCLUSIONS: PLIF is associated with massive perioperative HBL, but the application of topical TXA leads to less postoperative blood loss including less HBL, a lower blood product transfusion rate, and a shorter hospital stay for PLIF.


Assuntos
Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Vértebras Lombares/cirurgia , Ácido Tranexâmico/uso terapêutico , Antifibrinolíticos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fusão Vertebral , Ácido Tranexâmico/administração & dosagem , Resultado do Tratamento
20.
Biomed Res Int ; 2020: 1852070, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190653

RESUMO

Background: Percutaneous endoscopic transforaminal discectomy (PETD) is regarded as a viable alternative option for upper lumbar disc herniation (LDH). However, few studies have evaluated PETD for upper LDH, and no study has compared the advantages of endoscopic procedures versus conventional surgery. The present study was aimed at comparing the surgical outcome and safety of PETD versus conventional open lumbar discectomy in the treatment of upper LDH. Methods: Data from 42 patients treated for upper LDH from July 2015 to July 2018 were retrospectively analyzed, including 21 patients treated with PETD (PETD group) and 21 patients treated with conventional posterior lumbar discectomy (open group). The two groups were compared regarding demographic information, physical examination, radiological evaluations, and perioperative indicators. The clinical outcomes were assessed in accordance with the Oswestry Disability Index (ODI), visual analog scale (VAS), and modified MacNab criteria. Results: The postoperative ODI and VAS scores were significantly improved in both groups compared with the preoperative baseline values (P < 0.001), and the satisfactory rate was 90.5% in both groups in accordance with the modified MacNab criteria. There were no significant differences between the two groups in the clinical outcomes and complication rate (P < 0.001), and the satisfactory rate was 90.5% in both groups in accordance with the modified MacNab criteria. There were no significant differences between the two groups in the clinical outcomes and complication rate (P < 0.001), and the satisfactory rate was 90.5% in both groups in accordance with the modified MacNab criteria. There were no significant differences between the two groups in the clinical outcomes and complication rate (. Conclusions: PETD has a similar outcome to the conventional surgical method for the treatment of upper LDH but provides the typical advantages of minimally invasive procedures such as reduced iatrogenic injury, minimal activity restrictions, and accelerated ambulation recovery postoperatively.

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