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1.
Adv Clin Exp Med ; 29(3): 345-353, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32237286

RESUMO

BACKGROUND: The pathogenesis of glucocorticoid (GC)-induced osteonecrosis (ON) of the femoral head remains unclear. Recent research has suggested that it is closely associated with injured bone microvascular endothelial cells (BMECs). However, few studies have used BMECs to perform research pertaining ON of the femoral head. OBJECTIVES: The objective of this study was to investigate the functional changes of BMECs treated with a GC and to detect the changes in related genes using microarrays. MATERIAL AND METHODS: Cells were isolated using an enzymatic method and identified with EC markers, such as von Willebrand factor (vWF), CD31 and vascular endothelial cadherin (VE-cadherin). Bone microvascular endothelial cells were treated with 0.1 mg/mL and 0.3 mg/mL of hydrocortisone to establish a GC-damaged model of BMECs. The mRNA microarrays were used to detect the differential expression profiles between BMECs with and without GC damage. RESULTS: Primary cells appeared as having a cobblestone-like morphology. Immunofluorescence staining revealed that the cells were 100% positive for vWF and CD31, and near 100% positive for VE-cadherin. It also confirmed that the cells were BMECs. Bone microvascular endothelial cells treated with 0.1 mg/mL of hydrocortisone showed shrinkage, and those treated with 0.3 mg/mL of hydrocortisone mostly showed apoptosis. The mRNA microarray showed that genes associated with endothelial cells, such as endothelin 1 (ET-1) receptor, angiotensin II (AII) receptor, intercellular adhesion molecule 1 (ICAM-1), and plasminogen activator inhibitor 1 (PAI-1), were upregulated, and genes associated with endothelial nitric oxide synthase (eNOS), endothelin 1 (ET-1), prostaglandin I2 (PGI2) synthase, PGI2 receptor, vascular endothelial growth factor (VEGF), prostaglandin E (PGE) synthase, and PGE receptor were downregulated. The results of quantitative polymerase chain reaction (qPCR) validation were consistent with the findings of mRNA microarrays. CONCLUSIONS: Glucocorticoids promoted BMECs to express vasoconstrictors and procoagulant factors and related receptors, and decreased the expression of vasodilators and their receptors.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32247616

RESUMO

Spinal cord injury (SCI) is a severe disable symptom and has posed a great health threat to many people. Circ-HIPK3 has been reported to modulate the biological behavior of neuronal cells. Thence, in this study, we explored the mechanism of circ-HIPK3 in affecting functions of neuronal cell in SCI. SCI rat model was constructed to evaluate the apoptosis condition of spinal cord tissue. Meanwhile, 100 µM of CoCl2 was used to treat AGE1.HN and PC12 cells to induce in vitro SCI model. Functional assays were implemented to investigate the apoptosis of AGE1.HN and PC12 cells. RNase R and Act D treatment were both conducted to verify the circular character of circ-HIPK3. In this study, circ-HIPK3 was found lowly expressed in SCI rat models and AGE1.HN and PC12 cells induced by 100uM of CoCl2. Meanwhile, inhibited circ-HIPK3 or overexpressed circ-HIPK3 could separately elevate or reduce the apoptosis of AGE1.HN and PC12 cells. Moreover, circ-HIPK3 was identified as the ceRNA against miR-558 to up-regulate DPYSL5. Circ-HIPK3/miR-558/DPYSL5 axis modulated the apoptosis of AGE1.HN and PC12 cells in SCI. In conclusion, circ-HIPK3 relieves the neuronal cell apoptosis through regulating miR-588/DPYSL5 axis in SCI.

3.
Analyst ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186558

RESUMO

Colorectal cancer is associated with changed IgG glycosylation, but the alteration in specific subclasses of IgG is unknown. Initially, we optimized five common IgG glycopeptide enrichment methods to acquire a comprehensive profile of IgG glycopeptides. However, an incomplete tryptic digestion of IgG occurred when using an ordinary protease to protein ratio, which significantly impacted the final statistical analysis. Herein, we introduced a two-step enzymatic digestion, enabling the complete digestion of IgG glycopeptides and further improving the detection intensity of the target glycopeptides. In order to rapidly process and automatically integrate the MS data, we developed a simple and effective code using MATLAB. Following statistical analysis, we observed that IgG1_H3N4F1 and IgG1_H3N4 were substantially increased in CRC, while IgG1_H5N5F1, IgG1_H5N4F1S1 and IgG2_H5N4F1 were markedly decreased. A further evaluation of the diagnostic performance showed that they all achieved a fair performance in discriminating the patients from the normal. In terms of the glycan features, it was demonstrated that the CRC progression was associated with increased agalactosylation, and the decreased digalactosylation and galactosylation per antenna on the diantenna glycans of IgG1 and IgG2. Concurrently, the decreased sialylation of IgG1 was strongly correlated with CRC. Moreover, an analysis of tumor-specific glycosylation showed that the alterations of IgG glycosylation were more significant in colon cancer, and no obvious difference was observed between colon and rectal cancer. This study comprehensively optimized the glycopeptide enrichment methods, evaluated the enzymatic digestion effect, and explored the association between CRC progression and subclass-specific glycosylation.

4.
Int J Nanomedicine ; 15: 1421-1435, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184596

RESUMO

Purpose: In this study, we aim to explore the effects of graphene oxide (GO), a derivative of graphene, nanoparticles of four different sizes on the cellular fate of mouse neural stem cells (mNSCs). Methods: GO NPs were characterized with transmission electron microscopy (TEM), scanning electron micrography (SEM), atomic force microscopy (AFM) and Raman Spectra analysis. The cytotoxic effects of the GO NPs of different sizes on the mNSCs were determined using CCK-8 assay, Annexin V-APC/ 7-AAD staining and EdU staining assays. We investigated the biological and the mechanisms of GO NPs on cells using immunofluorescence analysis and quantitative real-time PCR (qPCR). Results: The average hydrodynamic sizes of the GO NPs were 417 nm, 663 nm, 1047 nm, and 4651 nm, with a thickness of approximately 22.5 nm, 17.7 nm, 22.4 nm, and 13.4 nm, respectively. GO NPs of all sizes showed low cytotoxicity at a concentration of 20 µg/mL on the mNSCs. Immunostaining demonstrated that treatment with GO NPs, especially the 663 nm ones, enhanced the self-renewal ability of mNSCs in the absence of EGF and bFGF. Under differentiation medium conditions that are free of mitogenic factors, all the GO NPs, particularly the 4651 nm ones, increased the expression level of Tuj1 and GFAP. With regards to the migration ability, we found that 417 nm GO-NP-treated mNSCs migrated over a longer distance than the control group obviously. In addition, higher expression of Rap1, Vinculin and Paxillin was observed in the GO NP-treated groups compared to the control group. mRNA-Sequence analysis and Western blotting results suggested that the 4651 nm GO NPs triggered positive neuronal differentiation through phosphorylation of ERK1/2 by the downregulating of TRPC2. Conclusion: GO NPs play an important role in the applications of inducing self-renewal and differentiation of mNSC, and are promising in the future for further studies.

5.
World Neurosurg ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32201290

RESUMO

OBJECTIVE: To assess and compare clinical outcomes and sagittal balance following unstable hangman's fracture between anterior C2-C3 discectomy and fusion (ACDF) and posterior C2-C3 short-segment fixation and fusion. METHODS: A total of 45 patients performed ACDF (20 cases) and posterior C2-C3 short-segment fixation and fusion (25 cases) between March 2005 and June 2013. Visual Analogue Scale (VAS), Neck Disability Index (NDI), Odom's grading system, American Spinal Injury Association Impairment Scale (AIS), C2-C3 angle, displacement of C2-C3 (DC2-C3), occiput-C2 angel (O-C2 angle), cervical lordosis (CL), C2-C7 sagittal vertical axis (cSVA) were assessed at the pre-operation and final follow-up. RESULTS: The follow-up duration was 20.0 (18.0, 21.0) months in the anterior group and 19.0 (18.0, 20.0) months in the posterior group. Satisfactory bony fusions were achieved in two groups. The VAS score and NDI score were significantly lower than their respective preoperative score in each group (P < 0.001), whereas no difference between two groups (P = 0.78; P = 0.85). A statistically significant decrease of O-C2 angle and cSVA between pre- and postoperative data was found in each group (P < 0.001), and CL increased statistically (P < 0.001). For O-C2 angle, CL and cSVA, the changes of parameters after posterior approach were more significant than that of anterior approach (P < 0.05). CONCLUSIONS: Both anterior and posterior surgical techniques are effective for unstable hangman's fracture, and both can restore sagittal balance of cervical spine. Furthermore, posterior approach has an advantage over anterior in promoting recovery of cervical sagittal balance.

6.
J Orthop Surg Res ; 15(1): 92, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138759

RESUMO

BACKGROUND: The mobile Oxford unicompartmental knee arthroplasty (UKA) implant has been widely used with an intramedullary guide for femoral preparation. We modified the femoral guide technique based on the tibial cut first and spacer block technique. This study was performed to determine the radiographic accuracy and early clinical outcomes of the extramedullary method. METHODS: We retrospectively evaluated 50 consecutive patients who underwent UKA using the extramedullary technique. An equal number of patients who underwent UKA with the conventional technique were matched as the control group. Clinical outcomes were evaluated in terms of the operating time, blood loss, range of motion, and Hospital for Special Surgery score. Radiographic accuracy was evaluated by the implant position and alignment in the coronal and sagittal planes. RESULTS: The mean follow-up period was 39.76 ± 5.77 months. There were no differences in the postoperative Hospital for Special Surgery score, range of motion, or hip-knee-ankle angle between the two groups. The operating time in the extramedullary group was shorter than that in the conventional group (54.78 ± 7.95 vs. 59.14 ± 10.91 min, respectively; p = 0.025). The drop in hemoglobin after 3 days was only 12.34 ± 4.98 g/L in the extramedullary group which was less than that in the conventional group (p = 0.001). No significant differences were found in the postoperative coronal and sagittal angles between the two groups. Acceptable radiographic accuracy of the implant alignment and position was achieved in 92% of patients in the extramedullary group and 96% of patients in the conventional group. CONCLUSIONS: The radiographic and clinical results of the extramedullary technique were comparable with those of the conventional technique with the advantage of no intramedullary interruption, less blood loss, a shorter operating time, and more rapid recovery. As the technique depends on the accurate tibial cut and overall alignment, we do not recommend it to surgeons without high volume experiences. TRIAL REGISTRATION: Retrospectively registered LEVEL OF EVIDENCE: IV, retrospective study.

7.
Chem Commun (Camb) ; 56(23): 3457-3460, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32101229

RESUMO

Amide bioconjugation and interfacial enzyme polymerization are designed to provide a general strategy for regulating the mechanical strength (storage modulus from 3 kPa to 100 kPa) of printable hydrogel inks.

8.
Cancer Epidemiol Biomarkers Prev ; 29(3): 565-573, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32041895

RESUMO

BACKGROUND: Epidemiologic studies have investigated the association between nut intake and risk for multiple cancers. However, current findings are inconsistent and no definite conclusion has been drawn from prospective studies. We therefore conducted this meta-analysis to evaluate the relationship between nut consumption and risk of cancer. METHODS: Prospective studies reporting associations between nut intake and risk for all types of cancer were identified by searching Web of Science and PubMed databases up to June 2019. Risk ratios (RR) and 95% confidence intervals (CI) were extracted and then pooled across the studies using a random-effect model. A dose-response analysis was modeled by performing restricted cubic splines when data were available. RESULTS: Thirty-three studies that included more than 50,000 cancer cases were eligible for the analysis. When comparing the highest with the lowest category of nut intake, high consumption of nuts was significantly associated with decreased risk of overall cancer (RR = 0.90; 95% CI, 0.85-0.95). The protective effect of nut consumption was especially apparent against cancers from the digestive system (RR = 0.83; 95% CI, 0.77-0.89). Among different nut classes, significant association was only obtained for intake of tree nuts. We also observed a linear dose-response relationship between nut consumption and cancer: Per 20 g/day increase in nut consumption was related to a 10% (RR = 0.90; 95% CI, 0.82-0.99) decrease in cancer risk. CONCLUSIONS: Our analysis demonstrated an inverse association of dietary nut consumption with cancer risk, especially for cancers from the digestive system. IMPACT: This study highlights the protective effect of nuts against cancer.

9.
Mol Psychiatry ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32086435

RESUMO

Parkinson's disease (PD) is characterized by dopaminergic neuronal loss and the presence of intra-neuronal Lewy body (LB) inclusions with aggregated α-synuclein (α-Syn) as the major component. MAOB, a crucial monoamine oxidase for dopamine metabolism, triggers oxidative stress in dopaminergic neurons and α-Syn aggregation. However, the key molecular mechanism that mediates PD pathogenesis remains elusive. Here we show that C/EBPß acts as an age-dependent transcription factor for both α-Syn and MAOB, and initiates the PD pathologies by upregulating these two pivotal players, in addition to escalating δ-secretase activity to cleave α-Syn and promotes its neurotoxicity. Overexpression of C/EBPß in human wild-type α-Syn transgenic mice facilitates PD pathologies and elicits motor disorders associated with augmentation of δ-secretase, α-Syn, and MAOB. In contrast, depletion of C/EBPß from human α-Syn Tg mice abolishes rotenone-elicited PD pathologies and motor impairments via downregulating the expression of these key factors. Hence, our study supports that C/EBPß/δ-secretase signaling mediates PD pathogenesis via regulating the expression and cleavage of α-Syn and MAOB.

10.
Environ Pollut ; 259: 113820, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31918130

RESUMO

Environmental exposure to 2,3,7,8-tetrachlorodibenzofuran (TCDF), one of typical persistent organic pollutants (POPs) produced from municipal waste combustion, exerts toxic effects on human healthy. In the current study, we mainly used targeted metabolomics combined with untargeted 1H NMR-based metabolomics to investigate the effects of TCDF exposure on lipid homeostasis in mice. We found that TCDF exposure induced hepatic lipogenesis, the early-stage of non-alcoholic fatty liver disease, manifested by excessive lipids including triglycerides, fatty acids and lipotoxic ceramides accumulated in the liver together with elevated serum very low-density lipoprotein by activating the aryl hydrocarbon receptor (AHR) and its target genes such as Cyp1a1 and Cd36. We also found that TCDF exposure induced alteration of phospholipids and choline metabolites and endoplasmic reticulum (ER) markers in the liver of mice, indicating that disruption of host cell membrane structural integrity and ER stress leading to hepatic steatosis. In addition, complementary information was also obtained from histopathologic assessments and biological assays, strongly supporting toxic effects of TCDF. These results provide new evidence of TCDF toxicity associated with fatty liver disease and further our understanding of health effects of environmental pollutants exposure.

11.
ACS Nano ; 14(1): 927-936, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31927974

RESUMO

Image-guided surgery plays a crucial role in realizing complete tumor removal, reducing postoperative recurrence and increasing patient survival. However, imaging of tumor lesion in the typical metabolic organs, e.g., kidney and liver, still has great challenges due to the intrinsic nonspecific accumulation of imaging probes in those organs. Herein, we report an in situ self-assembled near-infrared (NIR) peptide probe with tumor-specific excretion-retarded (TER) effect in tumor lesions, enabling high-performance imaging of human renal cell carcinoma (RCC) and achieving complete tumor removal, ultimately reducing postoperative recurrence. The NIR peptide probe first specifically recognizes αvß3 integrin overexpressed in renal cancer cells, then is cleaved by MMP-2/9, which is up-regulated in the tumor microenvironment. The probe residue spontaneously self-assembles into nanofibers that exhibit an excretion-retarded effect in the kidney, which contributes to a high signal-to-noise (S/N) ratio in orthotopic RCC mice. Intriguingly, the TER effect also enables precisely identifying eye-invisible tiny lesions (<1 mm), which contributes to complete tumor removal and significantly reduces the postoperative recurrence compared with traditional surgery. Finally, the TER strategy is successfully employed in high-performance identification of human RCC in an ex vivo kidney perfusion model. Taken together, this NIR peptide probe based on the TER strategy is a promising method for detecting tumors in metabolic organs in diverse biomedical applications.

12.
Gene ; 731: 144357, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31935503

RESUMO

BACKGROUND: Genome-wide association studies (GWAS) have identified 5p15.33 as a susceptible locus for lung cancer. However, for non-small cell lung cancer (NSCLC), low-frequency risk variants in this region have not been systematically studied. We intended to explore the associations between low-frequency variants on 5p15.33 and NSCLC using a next-generation sequencing based approach in this study. METHODS: We have acquisited the variation spectrum of 400 NSCLC patients on 5p15.33 by sequencing the targeted region before. Candidate variants were primarily selected by restricting the minor allele frequency (MAF 1-5%) and then by comparing their frequency in 400 NSCLC patients with 1008 East Asians from The genome Aggregation Database (gnomAD). The associations between candidate variants and NSCLC were discovered and replicated in two case-control sets: discovery stage with 960 cases and 916 controls, and replication stage with 1596 cases and 1614 controls in total. RESULTS: Five low-frequency variants were selected as our candidates and subsequent association analyses showed that 2 polymorphisms were significantly associated with risk of NSCLC, including rs33963617 (OR = 0.63, 95% CI: 0.53-0.76, P = 3.80 × 10-7) in TERT and rs77518573 (OR = 0.73, 95% CI: 0.63-0.84, P = 2.00 × 10-5) in upstream of CLPTM1L. When stratified by histologic subtype, a significant association was only investigated in adenocarcinoma for rs77518573. We also observed an obvious cumulative effect of the two significant variants. CONCLUSIONS: We newly identified two NSCLC related variants on chromosome 5p15.33. Both TERT-rs33963617 and CLPTM1L-rs77518573 conferred reduced risk for NSCLC in Chinese Han population.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Telomerase/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
13.
J Cell Physiol ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31989652

RESUMO

Activation of cannabinoid receptor type II (CB2R) by AM1241 has been demonstrated to protect dopaminergic neurons in Parkinson's disease (PD) animals. However, the specific mechanisms of the action of the CB2R agonist AM1241 for PD treatment have not been characterized. Wild-type (WT), CB1R knockout (CB1-KO), and CB2R knockout (CB2-KO) mice were exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 1 week to obtain a PD mouse model. The therapeutic effects of AM1241 were evaluated in each group. Behavioral tests, analysis of neurotransmitters, and immunofluorescence results demonstrated that AM1241 ameliorated PD in WT animals and CB1-KO animals. However, AM1241 did not ameliorate PD symptoms in CB2-KO mice. RNA-seq analysis identified the lncRNA Xist as an important regulator of the protective actions of AM1241. Specifically, AM1241 allowed WT and CB1-KO animals treated with MPTP to maintain normal expression of Xist, which affected the expression of miR-133b-3p and Pitx3. In vitro, overexpression of Xist or AM1241 protected neuronal cells from death induced by 6-hydroxydopamine and increased Pitx3 expression. The CB2 receptor agonist AM1241 alleviated PD via regulation of the Xist/miR-133b-3p/Pitx3 axis, and revealed a new approach for PD treatment.

14.
Prog Neurobiol ; 185: 101730, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31778772

RESUMO

Traumatic brain injury (TBI) is associated in some studies with clinical dementia, and neuropathological features, including amyloid plaque deposition and Tau neurofibrillary degeneration commonly identified in Alzheimer's disease (AD). However, the molecular mechanisms linking TBI to AD remain unclear. Here we show that TBI activates transcription factor CCAAT/Enhancer Binding Protein Beta (C/EBPß), increasing delta-secretase (AEP) expression. Activated AEP cleaves both APP and Tau at APP N585 and Tau N368 sites, respectively, which mediate AD pathogenesis by promoting Aß production and Tau hyperphosphorylation and inducing neuroinflammation and neurotoxicity. Knockout of AEP or C/EBPß diminishes TBI-induced AD-like pathology and cognitive impairment in the 3xTg AD mouse model. Remarkably, viral expression of AEP-resistant Tau N368A in the hippocampus of 3xTg mice also ameliorates the pathological and cognitive consequences of TBI. Finally, clinical TBI activates C/EBPß and escalates AEP expression, leading to APP N585 and Tau N368 proteolytic cleavage in TBI patient brains. Hence, our findings support a potential role for AEP in linking TBI exposure with AD pathogenesis.

15.
FEBS J ; 287(4): 783-799, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31482685

RESUMO

Non-small cell lung cancer (NSCLC) is the main type of lung cancer, with a low 5-year survival rate because of the absence of effective clinical biomarkers for early diagnosis. Based on the immunosurveillance theory, we proposed that changes in the immune system are more pronounced than tumour-associated antigens during the early stage of cancer. Therefore, a new strategy was designed to screen early diagnostic biomarkers from peripheral leukocytes in early-stage NSCLCs with transcriptome sequencing. A total of 358 immune-related differentially expressed genes were identified between early-NSCLC patients and healthy individuals. Orosomucoid-1 (ORM1, a acute phase protein), the total ORM and chitotriosidase-1 (involved in degradation of chitobiose) were selected for further verification in 210 serum samples by western blotting, ELISA and nephelometry immunoassay (based on immuno-scatter turbidmetry). Receiver operating characteristic curve analysis show that ORM1 and total ORM have excellent diagnostic efficacies, with area under the curve of 0.862 and 0.920, respectively, which significantly distinguished very early-NSCLC (IA) from healthy samples. Flow cytometry results showed that CD15+ neutrophils made up 73% of ORM1+ peripheral leukocytes. In mouse lung cancer model, serum ORM1, but not liver ORM1, changed significantly in the early stage of NSCLC. ORM1 expression in peripheral leukocytes was regulated by TGF-ß and mediated by the TGF-ß/Smad signalling pathway. Our results indicated that combined ORM and TGF-ß could be a promising clinical biomarker in the diagnosis of early NSCLC.

16.
Biol Chem ; 401(3): 349-360, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31408432

RESUMO

Angiogenesis is believed to protect against hypoxia/reoxygenation (H/R)-induced cell injury. MALAT1 and microRNA-320a (miR-320a) are involved in cancer angiogenesis. To investigate the function of the MALAT1/miR-320a axis in H/R-induced cell injury, human umbilical vein endothelial cell (HUVEC) angiogenesis was detected using the Cell Counting Kit-8 (CCK-8), Transwell migration, cell adhesion and tube formation assays. The expression of MALAT1 and miR-320a was revealed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The direct binding relationship between miR-320a and MALAT1 was detected by RNA immunoprecipitation (RIP) and dual luciferase reporter assays. The data indicated that H/R induces angiogenesis injury and that the expression of MALAT1 was augmented in H/R-stimulated HUVECs. Overexpression of MALAT1 alleviated H/R-stimulated HUVEC dysfunction, whereas silencing of MALAT1 exerted the opposite effects. MALAT1 also reduced miR-320a levels in HUVECs. Overexpression of miR-320a repressed the function of MALAT1 on H/R-stimulated HUVECs, whereas inhibition of miR-320a exerted the opposite effect. Additionally, miR-320a inhibition alleviated H/R-stimulated HUVEC injury via RAC1. Taken together, this investigation concluded that MALAT1 represses H/R-stimulated HUVEC injury by targeting the miR-320a/RAC1 axis.

17.
Biochim Biophys Acta Gen Subj ; 1864(3): 129510, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31887339

RESUMO

BACKGROUD: Given the increasing morbidity and mortality of colorectal cancer (CRC), it is urgent to develop a noninvasive screening strategy for early diagnosis of CRC. Altered IgG glycosylation is associated with CRC progression, whereas the association of IgG isomeric glycosylation with CRC were not investigated. METHODS: Methylamidation of IgG N-glycans was conducted prior to PGC-based nanoLC-ESI-MS/MS analysis. Data processing was operated by a self-developed application based on MATLAB solution. Statistical analysis including K-S test, t-test, ROC curve and OPLS-DA were successively performed. Additionally, an independent set was utilized to validate the results. RESULTS: Total 28 IgG glycans and 79 compositional isomers were identified, over half of which are firstly identified so far. Statistical analysis showed that CRC associates with increase in IgG agalactosylation, decrease in IgG sialylation and fucosylation of sialylated glycans. Additionally, it was found that three compositional isomers (H3N4F1-a, H3N4F1-b and H4N3S1F1-e) could distinguish CRC and early stages from controls with an accurate area under the receiver operating characteristic curve. Significantly, these results were validated in an independent set by multivariate statistical analysis. CONCLUSIONS: This is the first comprehensively profiling of isomer-specific IgG N-glycosylation, which could differentiate normal controls from colorectal disease patients. The candidate IgG glyco-biomarkers provide important screening indicators for early diagnosis of CRC. GENERAL SIGNIFICANCE: Colorectal cancer progression is strongly associated with isomer-specific IgG N-glycosylation.

18.
Ann Transl Med ; 7(20): 551, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807532

RESUMO

Background: Heat shock cognate protein 70 (HSC70) is a constitutively expressed molecular chaperone protein which can maintain the structure and function of the protein. HSC70 is engaged in a variety of physiological processes, yet its role during skeletal muscle differentiation is still unclear. Methods: C2C12 cells were obtained and cultured. During differentiation, the expression of HSC70 was evaluated by RT-PCR. To determine the function of HSC70 during C2C12 myoblast differentiation, myotube transfection of siR-HSC70 was performed with Lipofectamine 2000 Reagent. Western blot was used to measure the expression of Yin Yang 1 (YY1) after down-regulating HSC70. To further assess if YY1 mediates the pro-differentiation effect of HSC70, a plasmid of YY1 overexpression was used to increase the expression of YY1 in the presence of siR-HSC70-2. The formation of myotubes was visualized by immunofluorescent staining, while the expression levels of MyoD and MyoG were evaluated by RT-PCR. Results: In this study, we found that HSC70 was up-regulated during C2C12 myoblast differentiation. Knockdown of HSC70 not only inhibited the C2C12 myoblast differentiation but also reduced the expression of MyoD and MyoG. When YY1 protein was over-expressed, it could restore the differentiation in cells with HSC70 knockdown or inhibition. Conclusions: Collectively, this study demonstrates that HSC70 is involved in the regulation of C2C12 myoblast differentiation via YY1 and may serve as a potential target for a therapeutic strategy to prevent muscle atrophy.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31681747

RESUMO

Background: Kidney renal clear cell carcinoma (KIRC) is the malignancy originated from the renal epithelium, with a high rate of distant metastasis. Aberrant alternative splicing (AS) of pre-mRNA are widely reported to be involved in the tumorigenesis and metastasis of multiple cancers. The aim of this study is to explore the mechanism of alternative splicing events (ASEs) underlying tumorigenesis and metastasis of KIRC. Methods: RNA-seq of 537 KIRC samples downloaded from the TCGA database and ASEs data from the TCGASpliceSeq database were used to identify ASEs in patients with KIRC. The univariate and Lasso regression analysis were used to screen the most significant overall survival-related ASEs (OS-SEs). Based on those, the OS-SEs model was proposed. The interaction network of OS-SEs and splicing factors (SFs) with absolute value of correlation coefficient value >0.750 was constructed by Pearson correlation analysis. The OS-SEs significantly related to distant metastasis and clinical stage were identified by non-parametric test, and those were also integrated into co-expression analysis with prognosis-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways identified by Gene Set Variation Analysis (GSVA). ASEs with significance were selected for multiple online database validation. Results: A total of prognostic 6,081 overall survival-related ASEs (OS-SEs) were identified by univariate Cox regression analysis and a prediction model was constructed based on 5 OS-SEs screened by Lasso regression with the Area Under Curve of 0.788. Its risk score was also illustrated to be an independent predictor, which the good reliability of the model. Among 390 identified candidate SFs, DExD-Box Helicase 39B (DDX39B) was significantly correlated with OS and metastasis. After external database validation, Retained Intron of Ras Homolog Family Member T2 (RHOT2) and T-Cell Immune Regulator 1 (TCIRG1) were identified. In the co-expression analysis, overlapped co-expression signal pathways for RHOT2 and TCIRG1 were sphingolipid metabolism and N-glycan biosynthesis. Conclusions: Based on the results of comprehensive bioinformatic analysis, we proposed that aberrant DDX39B regulated RHOT2-32938-RI and TCIRG1-17288-RI might be associated with the tumorigenesis, metastasis, and poor prognosis of KIRC via sphingolipid metabolism or N-glycan biosynthesis pathway.

20.
Chin Med J (Engl) ; 132(22): 2690-2697, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31765355

RESUMO

BACKGROUND: Previously, the authors modified the surgical technique to preserve tibial bone mass for Oxford unicompartmental knee arthroplasty (UKA). The purpose of this study was to determine the clinical outcomes and values of this modified technique. METHODS: Clinical data of 34 consecutive patients who underwent the unilateral modified UKA technique (modified group, 34 knees) were retrospectively analyzed. To compare the outcome, a match-paired control group (conventional group, 34 knees) of an equal number of patients using the conventional technique system in the same period were selected and matched with respect to diagnosis, age, pre-operative range of motion (ROM), and radiological grade of knee arthrosis. Clinical outcomes including knee Hospital for Special Surgery (HSS) score, ROM, and complications were compared between the two groups. Post-operative radiographic assessments included hip-knee-ankle angle (HKA), joint line change, implant position, and alignment. RESULTS: The mean follow-up time was 38.2 ±â€Š6.3 months. There was no difference in baseline between the two groups. The amount of proximal tibial bone cut in the modified group was significantly less than that of the conventional group (4.7 ±â€Š1.1 mm vs. 6.7 ±â€Š1.3 mm, t = 6.45, P < 0.001). Joint line was elevated by 2.1 ±â€Š1.0 mm in the modified group compared with -0.5 ±â€Š1.7 mm in the conventional group (t = -7.46, P < 0.001). No significant differences were observed between the two groups after UKA with respect to HSS score, VAS score, ROM, and HKA. Additionally, the accuracy of the post-operative implant position and alignment was similar in both groups. As for implant size, the tibial implant size in the modified group was larger than that in the conventional group (χ = 4.95, P = 0.035). CONCLUSIONS: The modified technique for tibial bone sparing was comparable with the conventional technique in terms of clinical outcomes and radiographic assessments. It can preserve tibial bone mass and achieve a larger cement surface on the tibial side.

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