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  • 1
    Online Resource
    Online Resource
    Metformin Reduces the Senescence of Renal Tubular Epithelial Cells in Diabetic Nephropathy via the MBNL1/miR-130a-3p/STAT3 Pathway
    Hindawi Limited ; 2020
    In:  Oxidative Medicine and Cellular Longevity Vol. 2020 ( 2020-02-10), p. 1-22
    Details
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2020 ( 2020-02-10), p. 1-22
    Abstract: Senescence of renal tubular epithelial cells plays an important role in diabetic nephropathy, but the mechanism is unknown. Metformin may alleviate diabetic nephropathy by reducing this senescence. This study is aimed at clarifying the effects and mechanism of metformin on the senescence of renal tubular epithelial cells in diabetic nephropathy. We found that metformin reduced the expression of senescence-associated gene P21 in high-glucose-induced (30 mmol/L) renal tubular epithelial cells and decreased the β -galactosidase positive staining rate (decreased 16%, p 〈 0.01 ). Metformin was able to reduce senescence by upregulating the expression of RNA-binding protein MBNL1 and miR-130a-3p and reducing STAT3 expression. MBNL1 prolonged the half-life of miR-130a-3p, and miR-130a-3p could negatively regulate STAT3 by binding to its mRNA 3 ′ UTR. In db/db diabetic mice, we found an enhanced senescence level combined with low expression of MBNL1 and miR-130a-3p and high expression of STAT3 compared with db/m control mice during nephropathy development. Meanwhile, metformin (200 mg/kg/day) could increase the expression of MBNL1 and miR-130a-3p and decreased STAT3 expression, thus reducing this senescence in db/db mice. Our results suggest that metformin reduces the senescence of renal tubular epithelial cells in diabetic nephropathy via the MBNL1/miR-130a-3p/STAT3 pathway, which provided new ideas for the therapy of this disease.
    Type of Medium: Online Resource
    ISSN: 1942-0900 , 1942-0994
    URL: Article
    DOI: 10.1155/2020/8708236
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2455981-7
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  • 2
    Online Resource
    Online Resource
    Differential Regulatory Analysis Based on Coexpression Network in Cancer Research
    Hindawi Limited ; 2016
    In:  BioMed Research International Vol. 2016 ( 2016), p. 1-8
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2016 ( 2016), p. 1-8
    Abstract: With rapid development of high-throughput techniques and accumulation of big transcriptomic data, plenty of computational methods and algorithms such as differential analysis and network analysis have been proposed to explore genome-wide gene expression characteristics. These efforts are aiming to transform underlying genomic information into valuable knowledges in biological and medical research fields. Recently, tremendous integrative research methods are dedicated to interpret the development and progress of neoplastic diseases, whereas differential regulatory analysis (DRA) based on gene coexpression network (GCN) increasingly plays a robust complement to regular differential expression analysis in revealing regulatory functions of cancer related genes such as evading growth suppressors and resisting cell death. Differential regulatory analysis based on GCN is prospective and shows its essential role in discovering the system properties of carcinogenesis features. Here we briefly review the paradigm of differential regulatory analysis based on GCN. We also focus on the applications of differential regulatory analysis based on GCN in cancer research and point out that DRA is necessary and extraordinary to reveal underlying molecular mechanism in large-scale carcinogenesis studies.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2016/4241293
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2016
    detail.hit.zdb_id: 2698540-8
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  • 3
    Online Resource
    Online Resource
    Ligustilide Improves Cognitive Impairment via Regulating the SIRT1/IRE1α/XBP1s/CHOP Pathway in Vascular Dementia Rats
    Hindawi Limited ; 2022
    In:  Oxidative Medicine and Cellular Longevity Vol. 2022 ( 2022-8-16), p. 1-15
    Details
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2022 ( 2022-8-16), p. 1-15
    Abstract: Vascular dementia (VaD), the second cause of dementia, is caused by chronic cerebral hypoperfusion, producing progressive damage to cerebral cortex, hippocampus, and white matter. Ligustilide (LIG), one of the main active ingredients of Angelica sinensis, exerts the neuroprotective effect on neurodegenerative diseases. However, the mechanism remains unclear. An in vivo model of bilateral common carotid artery occlusion and in vitro model of oxygen glucose deprivation (OGD) were employed in this study. LIG (20 or 40 mg/kg/day) was intragastrically administered to the VaD rats for four weeks. The results of the Morris water maze test demonstrated that LIG effectively ameliorated learning and memory deficiency in VaD rats. LIG obviously relieved neuronal oxidative stress damage by increasing the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) and decreasing the level of malondialdehyde (MDA) in VaD rats. Nissl staining showed that LIG increased the number of the Nissl body in VaD rats. After LIG administration, the apoptotic-related protein, Bax, was decreased and Bcl-2 was increased in the hippocampus of VaD rats. Moreover, the expressions of sirtuin 1 (SIRT1) and protein disulfide isomerase (PDI) were decreased, binding immunoglobulin protein (BIP) and phospho-inositol-requiring enzyme-1α (P-IRE1α), X-box binding protein 1 (XBP1s), and C/EBP-homologous protein (CHOP) were increased in VaD rats. After LIG treatment, these changes were reversed. The immunofluorescence results further showed that LIG upregulated the expression of SIRT1 and downregulated the expression of P-IRE1α in VaD rats. In addition, in vitro experiment showed that EX-527 (SIRT1 inhibitor) partly abolished the inhibitory effect of LIG on the IRE1α/XBP1s/CHOP pathway. In conclusion, these studies indicated that LIG could improve cognitive impairment by regulating the SIRT1/IRE1α/XBP1s/CHOP pathway in VaD rats.
    Type of Medium: Online Resource
    ISSN: 1942-0994 , 1942-0900
    URL: Article
    DOI: 10.1155/2022/6664990
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
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  • 4
    Online Resource
    Online Resource
    Molecular Dynamics Studies on the Conformational Transitions of Adenylate Kinase: A Computational Evidence for the Conformational Selection Mechanism
    Hindawi Limited ; 2013
    In:  BioMed Research International Vol. 2013 ( 2013), p. 1-7
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2013 ( 2013), p. 1-7
    Abstract: Escherichia coli adenylate kinase (ADK) is a monomeric phosphotransferase enzyme that catalyzes reversible transfer of phosphoryl group from ATP to AMP with a large-scale domain motion. The detailed mechanism for this conformational transition remains unknown. In the current study, we performed long time-scale molecular dynamics simulations on both open and closed states of ADK. Based on the structural analyses of the simulation trajectories, we detected over 20 times conformational transitions between the open and closed states of ADK and identified two novel conformations as intermediate states in the catalytic processes. With these findings, we proposed a possible mechanism for the large-scale domain motion of Escherichia coli ADK and its catalytic process: (1) the substrate free ADK adopted an open conformation; (2) ATP bound with LID domain closure; (3) AMP bound with NMP domain closure; (4) phosphoryl transfer occurred with ATP, and AMP converted into two ADPs, and no conformational transition was detected in the enzyme; (5) LID domain opened with one ADP released; (6) another ADP released with NMP domain open. As both open and closed states sampled a wide range of conformation transitions, our simulation strongly supported the conformational selection mechanism for Escherichia coli ADK.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2013/628536
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2013
    detail.hit.zdb_id: 2698540-8
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  • 5
    Online Resource
    Online Resource
    Effects of a Preconditioning Oral Nutritional Supplement on Pig Livers after Warm Ischemia
    Hindawi Limited ; 2012
    In:  HPB Surgery Vol. 2012 ( 2012-06-25), p. 1-8
    Details
    In: HPB Surgery, Hindawi Limited, Vol. 2012 ( 2012-06-25), p. 1-8
    Abstract: Background . Several approaches have been proposed to pharmacologically ameliorate hepatic ischemia/reperfusion injury (IRI). This study was designed to evaluate the effects of a preconditioning oral nutritional supplement (pONS) containing glutamine, antioxidants, and green tea extract on hepatic warm IRI in pigs. Methods . pONS (70 g per serving, Fresenius Kabi, Germany) was dissolved in 250 mL tap water and given to pigs 24, 12, and 2 hrs before warm ischemia of the liver. A fourth dose was given 3 hrs after reperfusion. Controls were given the same amount of cellulose with the same volume of water. Two hours after the third dose of pONS, both the portal vein and the hepatic artery were clamped for 40 min. 0.5, 3, 6, and 8 hrs after reperfusion, heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), portal venous flow (PVF), hepatic arterial flow (HAF), bile flow, and transaminases were measured. Liver tissue was taken 8 hrs after reperfusion for histology and immunohistochemistry. Results . HR, MAP, CVP, HAF, and PVF were comparable between the two groups. pONS significantly increased bile flow 8 hrs after reperfusion. ALT and AST were significantly lower after pONS. Histology showed significantly more severe necrosis and neutrophil infiltration in controls. pONS significantly decreased the index of immunohistochemical expression for TNF- α , MPO, and cleaved caspase-3 (). Conclusion . Administration of pONS before and after tissue damage protects the liver from warm IRI via mechanisms including decreasing oxidative stress, lipid peroxidation, apoptosis, and necrosis.
    Type of Medium: Online Resource
    ISSN: 0894-8569 , 1607-8462
    URL: Article
    DOI: 10.1155/2012/783479
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2031561-2
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  • 6
    Online Resource
    Online Resource
    To Explore the Mechanism and Equivalent Molecular Group of Radix Astragali and Semen Lepidii in Treating Heart Failure Based on Network Pharmacology
    Hindawi Limited ; 2021
    In:  Evidence-Based Complementary and Alternative Medicine Vol. 2021 ( 2021-7-3), p. 1-9
    Details
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2021 ( 2021-7-3), p. 1-9
    Abstract: Radix Astragali and Semen Lepidii (HQ-TLZ) is a commonly used herbal medicine combination for treatment of heart failure, which has a good clinical effect. However, its active components and mechanism of action are not clear, which limits its clinical application and development. In this study, we explored the mechanism of action of HQ-TLZ in the treatment of heart failure based on network pharmacology. We obtained 11 active ingredients and 109 targets from the TCMSP database and SwissTargetPrediction database. Next, we constructed the action network and carried out enrichment analysis. The results showed that HQ-TLZ treatment of heart failure is primarily achieved by regulating the insulin resistance, erbB signaling pathway, PI3K-Akt signaling pathway, and VEGF signaling pathway. After inverse targeting, molecular docking, and literature search, we determined that the equivalent molecular groups of HQ-TLZ in the treatment of heart failure were quercetin and kaempferol. Based on network pharmacology, we reveal the mechanism of action of HQ-TLZ in the treatment of heart failure to a certain extent. At the same time, we determined the composition of the equivalent molecular group. This provides a bridge for the consistency evaluation of natural herbs and molecular compounds, which is beneficial to the development of novel drugs and further research.
    Type of Medium: Online Resource
    ISSN: 1741-4288 , 1741-427X
    URL: Article
    DOI: 10.1155/2021/5518192
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2148302-4
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  • 7
    Online Resource
    Online Resource
    Blood Pressure Variability during Angiography in Patients with Ischemic Stroke and Intracranial Artery Stenosis
    Hindawi Limited ; 2020
    In:  International Journal of Hypertension Vol. 2020 ( 2020-09-01), p. 1-8
    Details
    In: International Journal of Hypertension, Hindawi Limited, Vol. 2020 ( 2020-09-01), p. 1-8
    Abstract: Our aim was to investigate factors predicting blood pressure (BP) variability during diagnostic cerebral angiography and associations between BP variability and clinical outcomes in patients with acute and subacute ischemic stroke and intracranial artery stenosis. 114 patients with ischemic stroke and intracranial artery stenosis (stenosis rate 〉 50%) were recruited. Patients who underwent cerebral angiography within 3 days and 3–14 days of disease onset are referred to be Group A and Group S, respectively. BP variability in Group A was defined as the coefficient of variance (CV) of BP. Univariate and multivariate regression analyses were used to identify predictors of CV of BP and associations between CV of BP and clinical outcomes at discharge. In Group A patients, advanced age was associated with increased CV of SBP and diastolic blood pressure (DBP), and antihypertensive use was associated with lower CV of SBP. Male was associated with lower CV of DBP. In Group S, higher CV of SBP was associated with hypertension and antihypertensive use. Males had lower CV of SBP than females. The calcium channel blocker was associated with lower CV of DBP. Higher scores of the Stroke Scale at admission were significantly associated with poor clinical outcomes for both groups, while BP variability was not. Factors associated with BP variability are significantly different between stroke patients undergoing angiography within 3 days vs. 3–14 days after disease onset. BP variability is not significantly associated with clinical outcomes at discharge.
    Type of Medium: Online Resource
    ISSN: 2090-0384 , 2090-0392
    URL: Article
    DOI: 10.1155/2020/6214581
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2573167-1
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  • 8
    Online Resource
    Online Resource
    Impact of Obesity on Long-Term Urinary Incontinence after Radical Prostatectomy: A Meta-Analysis
    Hindawi Limited ; 2018
    In:  BioMed Research International Vol. 2018 ( 2018), p. 1-9
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2018 ( 2018), p. 1-9
    Abstract: Obesity is a known risk factor for prostate cancer progression and may contribute to poor treatment outcomes. However, little is known concerning the relationship between obesity (body mass index [BMI] ⩾ 30) and the urinary incontinence (UI) of patients after radical prostatectomy (RP). The goal of this study was to focus on the prevalence and duration of UI after RP with specific attention to the BMI. Subsequently, trials were identified in a literature search of PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar using appropriate search terms. All comparative studies reporting BMI, study characteristics, and outcome data including the relationship between BMI and urinary incontinence data were included. Finally, four studies comprising 6 trials with 2890 participants were included. The results showed that obesity increased UI risk at 12 months in patients who underwent robotic-assisted laparoscopic radical prostatectomy (RLRP) (odds ratio [OR] 2.43, 95% confidence interval [CI] [1.21, 4.88], P = 0.01 ). When stratified by the surgical methods, the pooled results showed that obesity increased UI risk at 24 months in patients who underwent RLRP (OR 2.00, 95% CI [1.57, 2.56], P 〈 0.001 ). However, in patients who underwent laparoscopic radical prostatectomy (LRP), the pooled results showed that obesity does not increase UI risk at 24 months (OR 1.13, 95% CI [0.74, 1.72], P = 0.58 ). This is the first study to include obesity as the primary independent variable. Outcomes indicate that obesity (BMI ≥ 30) may increase the UI risk at 12 and 24 months after RLRP. Well-designed randomized controlled trials with strict control of confounders are needed to make results comparable.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2018/8279523
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
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  • 9
    Online Resource
    Online Resource
    Comparisons of Treatment for HER2-Positive Breast Cancer between Chinese and International Practice: A Nationwide Multicenter Epidemiological Study from China
    Hindawi Limited ; 2021
    In:  Journal of Oncology Vol. 2021 ( 2021-9-15), p. 1-8
    Details
    In: Journal of Oncology, Hindawi Limited, Vol. 2021 ( 2021-9-15), p. 1-8
    Abstract: Objective. To better understand the status of medical treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the differences between the Chinese and the international clinical practice. Methods. This was a retrospective, nationwide, multicenter, epidemiological study of advanced breast cancer patients from China. Between January 01, 2012, and December 31, 2014, a total of 3649 patients, covering 7 geographic regions and 21 institutions, participated in this series of studies. HER2-positive breast cancer was selected among the group and adopted into this study. In comparison, we summarized the demographics and clinical characteristics of HER2-positive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database. Results. A total of 918 patients diagnosed as HER2-positive breast cancer patients were included. The median age at diagnosis was 46 years (ranging, 23 to 78) with a single-peak incidence. The proportions of stages II–IV at diagnosis and distance metastasis in viscera were more than half of the participants. In comparison, the prevalence of estrogen or progesterone receptor-positive expression and luminalB subtype was relatively lower than that of the United States. The receipt of chemotherapy was fairly higher, while the usage of targeted therapy was seriously insufficient. Tumor size was in significantly positive associations with the duration of targeted therapy (Kendall’s correlation coefficient = 0.3, P 〈 0.0001 ), while no prohibitive variables among clinical characteristics were detected. Conclusion. Our study suggested that HER2-positive breast cancer patients were characterized as a younger trend, a lower prevalence of hormonal receptor (HR)-positive expression, and less accessible to anti-HER2 targeted therapy with insufficient duration over the past few years in China. Concerted efforts should be exerted for promising survival benefits in the future. The trial registration number is https://clinicaltrials.gov/ct2/show/NCT03047889.
    Type of Medium: Online Resource
    ISSN: 1687-8469 , 1687-8450
    URL: Article
    DOI: 10.1155/2021/6621722
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2461349-6
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  • 10
    Online Resource
    Online Resource
    OC-STAMP Overexpression Drives Lung Alveolar Epithelial Cell Type II Senescence in Silicosis
    Hindawi Limited ; 2021
    In:  Oxidative Medicine and Cellular Longevity Vol. 2021 ( 2021-8-14), p. 1-11
    Details
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2021 ( 2021-8-14), p. 1-11
    Abstract: Cellular senescence has been considered an important driver of many chronic lung diseases. However, the specific mechanism of cellular senescence in silicosis is still unknown. In the present study, silicotic rats and osteoclast stimulatory transmembrane protein (Ocstamp) overexpression of MLE-12 cells were used to explore the mechanism of OC-STAMP in cellular senescence in alveolar epithelial cell type II (AEC2). We found an increasing level of OC-STAMP in AEC2 of silicotic rats. Overexpression of Ocstamp in MLE-12 cells promoted epithelial-mesenchymal transition (EMT), endoplasmic reticulum (ER) stress, and cellular senescence. Myosin heavy chain 9 (MYH9) was a potential interacting protein of OC-STAMP. Knockdown of Ocstamp or Myh9 inhibited cellular senescence in MLE-12 cells transfected with pcmv6-Ocstamp. Treatment with 4-phenylbutyrate (4-PBA) to inhibit ER stress also attenuated cellular senescence in vitro or in vivo. In conclusion, OC-STAMP promotes cellular senescence in AEC2 in silicosis.
    Type of Medium: Online Resource
    ISSN: 1942-0994 , 1942-0900
    URL: Article
    DOI: 10.1155/2021/4158495
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2455981-7
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