Publications by authors named "Li-Hui Zhang"

94 Publications

Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation.

Chin J Nat Med 2022 Jan;20(1):43-53

College of Traditional Chinese Medicine, Hebei University, Baoding 071002, China. Electronic address:

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.
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http://dx.doi.org/10.1016/S1875-5364(22)60144-4DOI Listing
January 2022

Correlation of the detection rate of upper GI cancer with artificial intelligence score: results from a multicenter trial (with video).

Gastrointest Endosc 2022 Jun 30;95(6):1138-1146.e2. Epub 2021 Dec 30.

Department of Endoscopy, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.

Background And Aims: The quality of EGD is a prerequisite for a high detection rate of upper GI lesions, especially early gastric cancer. Our previous study showed that an artificial intelligence system, named intelligent detection endoscopic assistant (IDEA), could help to monitor blind spots and provide an operation score during EGD. Here, we verified the effectiveness of IDEA to help evaluate the quality of EGD in a large-scale multicenter trial.

Methods: Patients undergoing EGD in 12 hospitals were consecutively enrolled. All hospitals were equipped with IDEA developed using deep convolutional neural networks and long short-term memory. Patients were examined by EGD, and the results were recorded by IDEA. The primary outcome was the detection rate of upper GI cancer. Secondary outcomes were part scores, total scores, and endoscopic procedure time, which were analyzed by IDEA.

Results: A total of 17,787 patients were recruited. The total detection rate of cancer-positive cases was 1.50%, ranging from .60% to 3.94% in each hospital. The total detection rate of early cancer-positive cases was .36%, ranging from .00% to 1.58% in each hospital. The average total score analyzed by IDEA ranged from 64.87 ± 16.87 to 83.50 ± 9.57 in each hospital. The cancer detection rate in each hospital was positively correlated with total score (r = .775, P = .003). Similarly, the early cancer detection rate was positively correlated with total score (r = .756, P = .004).

Conclusions: This multicenter trial confirmed that the quality of the EGD result is positively correlated with the detection rate of cancer, which can be monitored by IDEA. (Clinical trial registration number: ChiCTR2000029001.).
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http://dx.doi.org/10.1016/j.gie.2021.12.019DOI Listing
June 2022

Beneficial effects of endoscopic screening on gastric cancer and optimal screening interval: a population-based study.

Endoscopy 2021 Dec 28. Epub 2021 Dec 28.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China.

BACKGROUND : The effectiveness of endoscopic screening on gastric cancer has not been widely investigated in China and the screening interval of repeated screening has not been determined. METHODS : In a population-based prospective study, we included 375,800 individuals, 14,670 of whom underwent endoscopic screening (2012-2018). We assessed the associations between endoscopic screening and risk of incident gastric cancer and gastric cancer-specific mortality, and examined changes in overall survival and disease-specific survival following screening. The optimal screening interval for repeated endoscopy for early detection of gastric cancer was explored. RESULTS : Ever receiving endoscopic screening significantly decreased the risk of invasive gastric cancer (age- and sex-adjusted relative risk [RR] 0.69, 95 % confidence interval [CI] 0.52-0.92) and gastric cancer-specific mortality (RR 0.33, 95 %CI 0.20-0.56), particularly for noncardia gastric cancer. Repeated screening strengthened the beneficial effect on invasive gastric cancer-specific mortality of one-time screening. Among invasive gastric cancers, screening-detected individuals had significantly better overall survival (RR 0.18, 95 %CI 0.13-0.25) and disease-specific survival (RR 0.18, 95 %CI 0.13-0.25) than unscreened individuals, particularly for those receiving repeated endoscopy. For individuals with intestinal metaplasia or low grade intraepithelial neoplasia, repeated endoscopy at an interval of < 2 years, particularly within 1 year, significantly enhanced the detection of early gastric cancer, compared with repeated screening after 2 years (-trend = 0.02). CONCLUSION : Endoscopic screening prevented gastric cancer occurrence and death, and improved its prognosis in a population-based study. Repeated endoscopy enhanced the effectiveness. Screening interval should be based on gastric cancer severity.
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http://dx.doi.org/10.1055/a-1728-5673DOI Listing
December 2021

pH-Responsive Smart Wettability Surface with Dual Bactericidal and Releasing Properties.

ACS Appl Mater Interfaces 2021 Sep 17;13(38):46065-46075. Epub 2021 Sep 17.

School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, Jiangsu, P. R. China.

Biomaterial-associated infections caused by pathogenic bacteria have important implications on human health. This study presents the design and preparation of a smart surface with pH-responsive wettability. The smart surface exhibited synergistic antibacterial function, with high liquid repellency against bacterial adhesion and highly effective bactericidal activity. The wettability of the surface can switch reversibly between superhydrophobicity and hydrophobicity in response to pH; this controls bacterial adhesion and release. Besides, the deposited silver nanoparticles of the surface were also responsible for bacterial inhibition. Benefiting from the excellent liquid repellency, the surface could highly resist bacterial adhesion after immersing in a bacterial suspension for 10 s (85%) and 1 h (71%). Adhered bacteria can be easily eliminated using deposited silver nanoparticles during the subsequent treatment of alkaline bacterial suspension, and the ratio of deactivated bacteria was above 75%. After the pH returned to neutral, the deactivated bacteria can be easily released from the surface. This antibacterial surface showed an improved bacterial removal efficiency of about 99%. The results shed light on future antibacterial applications of the smart surface combining both bactericidal and adhesion-resistant functionalities.
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http://dx.doi.org/10.1021/acsami.1c08263DOI Listing
September 2021

Use of Artificial Intelligence to Improve the Quality Control of Gastrointestinal Endoscopy.

Front Med (Lausanne) 2021 22;8:709347. Epub 2021 Jul 22.

Key Laboratory of Minimally Invasive Techniques and Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, China.

With the rapid development of science and technology, artificial intelligence (AI) systems are becoming ubiquitous, and their utility in gastroenteroscopy is beginning to be recognized. Digestive endoscopy is a conventional and reliable method of examining and diagnosing digestive tract diseases. However, with the increase in the number and types of endoscopy, problems such as a lack of skilled endoscopists and difference in the professional skill of doctors with different degrees of experience have become increasingly apparent. Most studies thus far have focused on using computers to detect and diagnose lesions, but improving the quality of endoscopic examination process itself is the basis for improving the detection rate and correctly diagnosing diseases. In the present study, we mainly reviewed the role of AI in monitoring systems, mainly through the endoscopic examination time, reducing the blind spot rate, improving the success rate for detecting high-risk lesions, evaluating intestinal preparation, increasing the detection rate of polyps, automatically collecting maps and writing reports. AI can even perform quality control evaluations for endoscopists, improve the detection rate of endoscopic lesions and reduce the burden on endoscopists.
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http://dx.doi.org/10.3389/fmed.2021.709347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339701PMC
July 2021

Cancer incidence and mortality in Zhejiang Province, Southeast China, 2016: a population-based study.

Chin Med J (Engl) 2021 07 29;134(16):1959-1966. Epub 2021 Jul 29.

Zhejiang Provincial Office for Cancer Prevention and Control, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.

Backgrounds: Cancer is one of the main causes of death worldwide, seriously threatening human health and life expectancy. We aimed to analyze the cancer incidence and mortality rates during 2016 in Zhejiang Province, Southeast China.

Methods: Data were collected from 14 population-based cancer registries across Zhejiang Province of China. Cancer incidence and mortality rates stratified by sex and region were analyzed. The crude rate, age-standardized rate, age-specific and region-specific rate, and cumulative rate were calculated. The proportions of 10 common cancers in different groups and the incidence and mortality rates of the top five cancers in different age groups were also calculated. The Chinese national census of 2000 and the world Segi population was used for calculating the age-standardized incidence and mortality rates.

Results: The 14 cancer registries covered a population of 14,250,844 individuals, accounting for 29.13% of the population of Zhejiang Province. The total reported cancer cases and deaths were 55,835 and 27,013, respectively. The proportion of morphological verification (MV%) was 78.95% of the population, and percentage of incident cases identified through death certificates only (DCO%) was 1.23% with a mortality-to-incidence ratio (M/I ratio) of 0.48. The crude incidence rate in Zhejiang cancer registration areas was 391.80/105; the age-standardized incidence rate of the Chinese standard population (ASIRC) and the age-standardized incidence rate of the world standard population (ASIRW) were 229.76/105 and 220.96/105, respectively. The incidence rate in men was higher than that in women. The incidence rate increased rapidly after 45 years of age and peaked in individuals aged 80 to 84 years. The top 10 incidence rates of cancers were lung cancer, female breast cancer, thyroid cancer, colorectal cancer, stomach cancer, liver cancer, prostate cancer, cervical cancer, esophageal cancer, and pancreatic cancer (from highest to lowest). The crude mortality rate in Zhejiang cancer registration areas was 189.55/105; the age-standardized mortality rate of the Chinese standard population (ASMRC) and the age-standardized mortality rate of the world standard population (ASMRW) were 94.46/105 and 93.42/105, respectively. The mortality rate in men was higher than that in women, and the male population in rural areas was higher than that in urban areas. The cancer mortality rate increased rapidly after 50 years of age and peaked in individuals aged 85+ years. The top 10 mortality rates of cancers were lung cancer, liver cancer, stomach cancer, colorectal cancer, pancreatic cancer, esophageal cancer, female breast cancer, prostate cancer, lymphoma, and leukemia (from highest to lowest).

Conclusions: Lung cancer, female breast cancer, thyroid cancer, colorectal cancer, prostate cancer, liver cancer, and stomach cancer were the most common cancers in Zhejiang Province. Effective prevention and control measures should be established after considering the different characteristics of cancers in urban and rural areas.
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http://dx.doi.org/10.1097/CM9.0000000000001666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382332PMC
July 2021

Dried sludge reburning blended with calcium magnesium acetate addition in a fluidized bed combustor.

Waste Manag 2021 Mar 11;123:120-130. Epub 2021 Feb 11.

Anhui Province Key Laboratory of Metallurgical Engineering & Resources Recycling (Anhui University of Technology), School of Energy and Environment, Anhui University of Technology, Ma'anshan 243002, Anhui Province, China. Electronic address:

The combustion and pollutant emission characteristics of the dried sludge in a fluidized bed combustor (FBC) were studied. The sludge reburning technology was employed for the first time in FBC. A scheme for using the dried sludge reburning blended with calcium magnesium acetate (CMA) to reduce pollutants simultaneously was also proposed, and the effect of the CMA addition was investigated. Results showed that fluidized bed reburning technology can be used to effectively treat the sewage sludge with lower calorific values. As the secondary fuel mass percentage increases, the unburned carbon content in fly ash and the CO emission increase, resulting in lower combustion efficiency. However, the de-NO ratio increases from 37.1% to 53.7%, and the de-SO ratio only increased from 1.6% to 7.6% as the secondary fuel mass percentage increase from 10% of 25%. For dried sludge blended with CMA, the minimum emissions of SO and NO significantly decrease to 254 mg/Nm and 70.9 mg/Nm at Ca/S ratio of 2, respectively. Results of main gaseous pollutant emissions from the sludge combustion in an FBC using different pollutant removal methods were compared under well-defined conditions. Fuel reburning blended with CMA addition has the smallest SO and NO emissions.
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http://dx.doi.org/10.1016/j.wasman.2021.01.028DOI Listing
March 2021

Double-hit lymphoma (rearrangements of MYC, BCL-2) during pregnancy: A case report.

World J Clin Cases 2021 Jan;9(2):482-488

Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China.

Background: Double-hit lymphoma is a highly aggressive B-cell lymphoma that is genetically characterized by rearrangements of and and/or . Lymphoma is often accompanied by atypical systemic symptoms similar to physiological changes during pregnancy and is often ignored. Herein, we describe a gravid patient with high-grade B-cell lymphoma with a and gene rearrangement involving multiple parts of the body.

Case Summary: A 32-year-old female, gestational age 22 wk, complained of abdominal distension, chest tightness and limb weakness lasting approximately 4 wk, and ovarian tumors were found 14 d ago. Auxiliary examinations and a trimanual gynecologic examination suggested malignant ovarian tumor and frozen pelvis. Coupled with rapid progression, severe compression symptoms of hydrothorax, ascites and moderate anemia, labor was induced. Next, biopsy and imaging examinations showed high-grade B-cell lymphoma with a and gene rearrangement involving multiple parts of the body. She was referred to the Department of Oncology and Hematology for chemotherapy. Because of multiple recurrences after complete remission, chemotherapy plans were continuously adjusted. At present, the patient remains in treatment and follow-up.

Conclusion: The early detection and accurate diagnosis of lymphoma during pregnancy can help expedite proper multidisciplinary treatment to delay disease progression and decrease the mortality rate.
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http://dx.doi.org/10.12998/wjcc.v9.i2.482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812893PMC
January 2021

Long non-coding RNA MEG3 inhibits M2 macrophage polarization by activating TRAF6 via microRNA-223 down-regulation in viral myocarditis.

J Cell Mol Med 2020 11 13;24(21):12341-12354. Epub 2020 Oct 13.

Department of Cardiovascular Medicine, Shanxi Dayi Hospital Affiliated to Shanxi Medical University, Taiyuan, China.

Viral myocarditis (VMC) commonly triggers heart failure, for which no specific treatments are available. This study aims to explore the specific role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) in VMC. A VMC mouse model was induced by Coxsackievirus B3 (CVB3). Then, MEG3 and TNF receptor-associated factor 6 (TRAF6) were silenced and microRNA-223 (miR-223) was over-expressed in the VMC mice, followed by determination of ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). Dual-luciferase reporter assay was introduced to test the interaction among MEG3, TRAF6 and miR-223. Macrophages were isolated from cardiac tissues and bone marrow, and polarization of M1 or M2 macrophages was induced. Then, the expressions of components of NLRP3 inflammatory body (NLRP3, ASC, Caspase-1), M1 markers (CD86, iNOS and TNF-α) and M2 markers (CD206, Arginase-1 and Fizz-1) were measured following MEG3 silencing. In the VMC mouse model, MEG3 and TRAF6 levels were obviously increased, while miR-223 expression was significantly reduced. Down-regulation of MEG3 resulted in the inhibition of TRAF6 by promoting miR-223. TRAF6 was negatively correlated with miR-223, but positively correlated with MEG3 expression. Down-regulations of MEG3 or TRAF6 or up-regulation of miR-223 was observed to increase mouse weight, survival rate, LVEF and LVFS, while inhibiting myocarditis and inflammation via the NF-κB pathway inactivation in VMC mice. Down-regulation of MEG3 decreased M1 macrophage polarization and elevated M2 macrophage polarization by up-regulating miR-223. Collectively, down-regulation of MEG3 leads to the inhibition of inflammation and induces M2 macrophage polarization via miR-223/TRAF6/NF-κB axis, thus alleviating VMC.
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http://dx.doi.org/10.1111/jcmm.15720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686963PMC
November 2020

Glucagon-like peptide 1 treatment reverses vascular remodelling by downregulating matrix metalloproteinase 1 expression through inhibition of the ERK1/2/NF-κB signalling pathway.

Mol Cell Endocrinol 2020 12 30;518:111005. Epub 2020 Aug 30.

Key Laboratory of Chemical Biology and Molecular Engineering, Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, 030006, Shanxi province, China. Electronic address:

In addition to serving as an incretin-based treatment of type 2 diabetes mellitus (T2DM), glucagon-like peptide 1 (GLP-1) can also reverse cardiovascular diseases caused by vascular remodelling. However, a detailed mechanism underlying how GLP-1 reverses vascular remodelling remains unclear. Here, Spontaneous hypertension rats (SHR) were used as an in vivo model of vascular remodelling. Treatment with a GLP-1 receptor (GLP-1R) agonist Liraglutide or dipeptidyl peptidase 4 (DPP4) inhibitor Alogliptin decreased systolic blood pressure (SBP), diastolic blood pressure (DBP), thickness of vascular wall, and overall collagen levels in SHR. In vitro vascular remodelling can be induced by exposing rat aortic smooth muscle cells (RASMC) to angiotensin II (Ang II); GLP-1 treatment attenuated AngII induction of RASMC proliferation, migration, and excessive extracellular matrix (ECM) degradation. Downregulation of matrix metalloproteinase 1 (MMP1) enhanced the inhibitory effects of GLP-1, and extracellular regulated protein kinase 1/2 (ERK1/2) and nuclear factor kappa-B (NF-κB) signalling participated in these processes. These results provide a new mechanistic understanding of key therapeutic strategies for the treatment of vascular remodelling-related diseases.
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http://dx.doi.org/10.1016/j.mce.2020.111005DOI Listing
December 2020

Role of shear wave elastography in the evaluation of the treatment and prognosis of supraspinatus tendinitis.

World J Clin Cases 2020 Jul;8(14):2977-2987

Department of Ultrasonic Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai 201800, China.

Background: Supraspinatus tendinitis recurs easily after treatment. One of the main reasons is the lack of objective tools for the efficacy evaluation. Shear wave elastography (SWE) can quantitatively analyze the tissue elasticity of region of interest by measuring the Young's modulus (YM) value.

Aim: To explore the role of SWE in the efficacy and prognostic evaluation of supraspinatus tendinitis.

Methods: Eighty-seven patients with supraspinatus tendinitis treated in Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences were recruited. Another 30 healthy volunteers were enrolled as the control group. The visual analogue scale (VAS) and Constant-Murley Score (CMS) were recorded before treatment. All participants were scanned by SWE scan, and the YM value of the region of interest were recorded. Spearman correlation analysis was performed on YM values with VAS and CMS. Univariate repeated measures analysis of variance was used to calculate the changing trend of VAS, CMS and SWE under different treatment courses. After treatment, the patients were further grouped based on who achieved significantly effective and curative treatment. The patients in the continued treatment group continued to receive treatment according to the YM value, and the remaining patients who stopped receiving treatment were included in the stopped treatment group. All patients were followed up for 1 year, and the difference in recurrence rates between the continued treatment group and the stopped treatment group were compared.

Results: The SWE images of supraspinatus muscle in healthy volunteers were mainly blue, while those of patients with supraspinatus tendinitis showed regional red and green areas. The average YM value of the supraspinatus muscle in healthy volunteers was 26.12 ± 4.03 kPa. The average YM value of patients with supraspinatus muscle was greater than that of healthy volunteers (average YM = 60.61 ± 11.53 kPa, = 26.344, < 0.001). The YM value was positively correlated with VAS ( = 0.564, < 0.001) and negatively correlated with CMS ( = -0.411, < 0.001). The changes of VAS and CMS were the most obvious in course 1 and then decreased gradually. The degree of change in YM values was similar in different courses. After a 1-year follow-up, the cumulative relapse-free rate in the continued treatment group was 91.43%, which was significantly higher than that in the stopped treatment group (64.71%, = 7.379, = 0.007).

Conclusion: SWE can objectively indicate the severity of supraspinatus tendinitis. Using the YM value as a criterion for curative effect may reduce the recurrence rate.
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http://dx.doi.org/10.12998/wjcc.v8.i14.2977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385596PMC
July 2020

Hypoglycemic agents for non-alcoholic fatty liver disease with type 2 diabetes mellitus: A protocol for systematic review and network meta-analysis.

Medicine (Baltimore) 2020 Aug;99(32):e21568

Henan University of Chinese Medicine.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries, and strongly associated with type 2 diabetes mellitus (T2DM). Several studies have shown that hypoglycemic agents are effective for NAFLD combined with T2DM. However, there is still controversy over which hypoglycemic agent is the best for NAFLD combined with T2DM patients.

Objective: To systematically evaluate the efficacy and safety of hypoglycemic agents in NAFLD combined with T2DM patients.

Methods: A comprehensive electronic search will be conducted by searching Web of Science, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Clinical Trials and Chinese Biomedical Medicine. All randomized controlled trials of hypoglycemic agents interventions for NAFLD combined with T2DM will be identified. Two reviewers independently screened and evaluated each included study and extracted the outcome indexes. ADDIS 1.16.8 software will be used for the network meta-analysis and STATA 14 software will be used for drawing network evidence plots and funnel plots.

Conclusion: This network meta-analysis will provide stronger evidence for the efficacy and safety of hypoglycemic agents in the treatment of NAFLD combined with T2DM, and provide a reference for clinical application.

Protocol Registration Number: INPLASY202070016.
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http://dx.doi.org/10.1097/MD.0000000000021568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593046PMC
August 2020

Measuring Self-Efficacy and Readiness for Advance Care Planning in Chinese Older Adults.

J Pain Symptom Manage 2020 09 20;60(3):622-629. Epub 2020 Jun 20.

Faculty of Medicine, The Nethersole School of Nursing, The Chinese University of Hong Kong, Hong Kong SAR, China.

Context: Self-efficacy and readiness for advance care planning (ACP) is underresearched in the Chinese population given that these are novel concepts in the culture.

Objectives: To translate the self-efficacy and readiness subscales of the ACP Engagement Scale into Chinese using the Brislin's Model and test its psychometric properties in Chinese older adults.

Methods: Content validity and face validity were established based on the views of a group of experts and older adults. Then, a survey was conducted with a convenience sample of 204 community-dwelling older adults. Convergent validity was evaluated using Pearson's correlation coefficients with the SURE test, a decisional conflict scale. The scores between older adults who had hospitalization experience in the previous year and those who did not have were compared to examine discriminant validity.

Results: The findings showed that the Chinese subscales had good internal consistency (Cronbach's α 0.94-0.97) and acceptable one-week test-retest reliability (intraclass correlation coefficient 0.66-0.70). There was a significantly high correlation between the self-efficacy and the readiness subscales (r = 0.809; P < 0.01) and moderate correlation between the two subscales and the SURE test (r = 0.509-0.587; P < 0.01). Discriminant validity was supported by significant differences between older adults who had hospitalization experience in the last year and those who did not have (P < 0.05).

Conclusion: The Chinese readiness and self-efficacy subscales of the ACP Engagement Survey are valid and reliable tools for assessing the preparedness of the Chinese older adults for ACP.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.06.013DOI Listing
September 2020

A network pharmacology approach to investigate the mechanism of Shuxuening injection in the treatment of ischemic stroke.

J Ethnopharmacol 2020 Jul 18;257:112891. Epub 2020 Apr 18.

Shenzhen TCM Hospital, Shenzhen, Guangdong, 518000, China. Electronic address:

Ethnopharmacological Relevance: Shuxuening injection (SXNI), a popular herbal medicine, is an extract of Ginkgo biloba leaves (GBE), and is used to treat ischemic stroke (IS) in China. However, its specific active ingredients and molecular mechanisms in IS remain unclear.

Aim Of The Study: The purpose of the research is to identify the main active ingredients in GBE and explore its molecular mechanisms in the treatment of IS.

Materials And Methods: The main active components of GBE were discerned through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, and absorption, distribution, metabolism and excretion (ADME) analysis. The targets related to IS were obtained using Genecards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and Disgenet. We discovered an intersection of genes. Subsequently, protein-protein interaction (PPI) networks were constructed with Cytoscape 3.7.1 and the String database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to analyze the intersection of targets via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8. Built on the above analysis, we made a Compound-Target-Pathway (C-T-P) network. Autodock Vina was used for molecular docking analysis. Maestro 11.9 was used to calculate the root-mean-square deviation (RMSD). Animal experiments were performed to verify the core targets. Triphenyl tetrazolium chloride (TTC) staining was used to calculate the infarct volume in rats. Hematoxylin-eosin (HE) staining was employed to observe the morphology of hippocampal neuron cells. RT-qPCR was applied to detect relative mRNA levels, and protein expression was determined using Western blotting.

Results: Molecular docking showed that PTGS2, NOS3 and CASP3 docked with small molecule compounds. According to RT-qPCR and Western blotting, mRNA and protein expression of PTGS2 and CASP3 were up-regulated (P < 0.05), and mRNA and protein levels of NOS3 were down-regulated (P < 0.05).

Conclusions: SXNI can treat IS through multiple targets and routes, and reduce the apoptosis of neuron cells in brain tissue by inhibiting inflammation and regulating the level of oxidative stress, thereby protecting rats brain tissue.
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http://dx.doi.org/10.1016/j.jep.2020.112891DOI Listing
July 2020

Efficacy and Safety of Dulaglutide Monotherapy Compared to Glimepiride in Oral Antihyperglycemic Medication-Naïve Chinese patients with Type 2 Diabetes: A Post Hoc Analysis of AWARD-CHN1.

Diabetes Ther 2020 May 26;11(5):1077-1090. Epub 2020 Mar 26.

Division of Endocrinology and Metabolism, West China Hospital of Sichuan University, Sichuan, 610041, China.

Introduction: Glucagon-like peptide (GLP)-1 receptor agonists are glucose-lowering agents associated with weight loss, cardiovascular benefits, and low hypoglycemic risk and are recommended by recent guidelines as first-line therapy for some patients with type 2 diabetes (T2D). This post hoc analysis of the AWARD-CHN1 study compared the efficacy and safety of once-weekly dulaglutide with glimepiride in oral antihyperglycemic medication (OAM)-naïve Chinese patients with T2D.

Methods: AWARD-CHN1 was a phase 3, double-blind study with 737 patients randomized 1:1:1 to once-weekly dulaglutide (1.5 or 0.75 mg) or glimepiride (1-3 mg/day). This is a post hoc analysis of AWARD-CHN1 based on mixed-model repeated measures using a modified intent-to-treat analysis set with only the OAM-naïve Chinese population.

Results: There were 264 OAM-naïve Chinese patients included in this analysis (dulaglutide 1.5 mg, n = 87; dulaglutide 0.75 mg, n = 90; glimepiride, n = 87). A greater glycated hemoglobin (HbA1c) reduction from baseline was observed with dulaglutide 1.5 mg and 0.75 mg compared to glimepiride (- 2.02% and - 1.84% vs - 1.37%, respectively; both P < 0.001). Significantly more patients in dulaglutide 1.5 mg and 0.75 mg groups achieved HbA1c targets < 7.0% compared to glimepiride (86.2% and 81.1% vs 65.5%; P = 0.002 and P = 0.026, respectively). Beta cell function was significantly increased for dulaglutide groups compared to glimepiride. Mean body weight was significantly reduced for dulaglutide 1.5 mg and 0.75 mg compared to glimepiride (- 1.40 kg and - 0.96 kg vs + 0.73 kg, respectively; both P < 0.001). Through 26 weeks, 7.9%, 4.2%, and 18.2% of patients reported hypoglycemia, and 40.4%, 23.2%, and 8.0% of patients reported at least one gastrointestinal treatment emergent adverse event, in dulaglutide 1.5 mg, 0.75 mg, and glimepiride groups, respectively.

Conclusions: In this post hoc analysis, dulaglutide was effective in reducing both HbA1c and weight with favorable tolerability and safety profile, which is consistent with results seen in larger international dulaglutide monotherapy studies.

Trial Registration: ClinicalTrials.gov NCT01644500.
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http://dx.doi.org/10.1007/s13300-020-00799-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192982PMC
May 2020

MFAP2 is overexpressed in gastric cancer and promotes motility via the MFAP2/integrin α5β1/FAK/ERK pathway.

Oncogenesis 2020 Feb 13;9(2):17. Epub 2020 Feb 13.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P.R. China.

Gastric cancer (GC) is one of the most common malignancies and its prognosis is extremely poor. This study identifies a novel oncogene, microfibrillar-associated protein 2 (MFAP2) in GC. With integrative reanalysis of transcriptomic data, we found MFAP2 as a GC prognosis-related gene. And the aberrant expression of MFAP2 was explored in GC samples. Subsequent experiments indicated that silencing and exogenous MFAP2 could affect motility of cancer cells. The inhibition of silencing MFAP2 could be rescued by another FAK activator, fibronectin. This process is probably through affecting the activation of focal adhesion process via modulating ITGB1 and ITGA5. MFAP2 regulated integrin expression through ERK1/2 activation. Silencing MFAP2 by shRNA inhibited tumorigenicity and metastasis in nude mice. We also revealed that MFAP2 is a novel target of microRNA-29, and miR-29/MFAP2/integrin α5β1/FAK/ERK1/2 could be an important oncogenic pathway in GC progression. In conclusion, our data identified MFAP2 as a novel oncogene in GC and revealed that miR-29/MFAP2/integrin α5β1/FAK/ERK1/2 could be an important oncogenic pathway in GC progression.
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http://dx.doi.org/10.1038/s41389-020-0198-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018958PMC
February 2020

Significant improvement of the enantioselectivity of a halohydrin dehalogenase for asymmetric epoxide ring opening reactions by protein engineering.

Appl Microbiol Biotechnol 2020 Mar 14;104(5):2067-2077. Epub 2020 Jan 14.

School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, No. 1, Wenyuan Road, Nanjing, 210023, People's Republic of China.

Halohydrin dehalogenases (HHDHs) have attracted much attention due to their ability to synthesize enantiomerically enriched epoxides and β-haloalcohols. However, most of the HHDHs exhibit low enantioselectivity. Here, a HHDH from the alphaproteobacteria isolate 46_93_T64 (AbHHDH), which shows only poor enantioselectivity in the catalytic resolution of rac-PGE (E = 9.9), has been subjected to protein engineering to enhance its enantioselectivity. Eight mutants (R89K, R89Y, V137I, P178A, N179Q, N179L, F187L, F187A) showed better enantioselectivity than the wild type. The best single mutant N179L (E = 93.0) showed a remarkable 9.4-fold increase in the enantioselectivity. Then, the single mutations were combined to produce the double, triple, quadruple, and quintuple mutants. Among the combinational mutants, the best variant (R89Y/N179L) showed an increased E value of up to 48. The E values of the variants N179L and R89Y/N179L for other epoxides 2-7 were 12.2 to > 200, which showed great improvement compared to 1.2 to 10.5 for the wild type. Using the variant N179L, enantiopure (R)-PGE with > 99% ee could be readily prepared, affording a high yield and a high concentration.
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http://dx.doi.org/10.1007/s00253-020-10356-xDOI Listing
March 2020

Correction to: Functional exploration of co-expression networks identifies a nexus for modulating protein and citric acid titres in submerged culture.

Fungal Biol Biotechnol 2019;6:26. Epub 2019 Dec 17.

1Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308 People's Republic of China.

[This corrects the article DOI: 10.1186/s40694-019-0081-x.].
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http://dx.doi.org/10.1186/s40694-019-0087-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918661PMC
December 2019

Conservation of glucagon like peptide-1 level with liraglutide and linagilptin protects the kidney against angiotensin II-induced tissue fibrosis in rats.

Eur J Pharmacol 2020 Jan 4;867:172844. Epub 2019 Dec 4.

Cardiovascular Research Laboratory, Mercer University School Medicine, Savannah, GA, USA. Electronic address:

This study tested the hypothesis that the enhancement of glucagon-like peptide-1 (GLP-1) level through either exogenous supply of GLP-1 agonist, liraglutide or prevention of endogenous GLP-1 degradation with dipeptidyl peptidease-4 inhibitor, lingaliptin ameliorates angiotensin II (Ang II)-induced renal fibrosis. Sprague-Dawley rats were randomly divided into four groups: 0.9% saline or Ang II (500 ng/kg/min) was infused with osmotic minipumps for 4 weeks, defined as sham and Ang II groups. In drug treated groups, liraglutide (0.3 mg/kg) was injected subcutaneously twice daily or linagliptin (8 mg/kg) was administered daily via oral gavage during Ang II infusion. Compared with Ang II stimulation, liraglutide or linagliptin comparatively down-regulated the protein level of the AT receptor, and up-regulated the AT receptor, as identified by a reduced AT/AT ratio (all p < 0.05), consistent with less locally-expressed AT receptor and enhanced AT receptor in the glomerular capillaries and proximal tubules of the renal cortex. Furthermore, both drugs significantly increased the expression of GLP-1 receptor and attenuated the protein levels of TLR4, NOX4 and IL-6. The populations of macrophages and α-SMA expressing myofibroblasts decreased with treatment of liraglutide and linagliptin, in coincidence with the reduced expression of phosphor-Smad2/3, Smad4, TGFβ1, and up-regulated Smad7. Along with these modulations, renal morphology was preserved and synthesis of fibronectin/collagen I was down-regulated, as identified by small collagen-rich area in the renal cortex. These results suggest that the preservation of GLP-1 level using liraglutide or linagliptin might be considered as an add-on therapeutic option for inhibiting Ang II induced renal fibrosis and failure.
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http://dx.doi.org/10.1016/j.ejphar.2019.172844DOI Listing
January 2020

GLP-1 Relaxes Rat Coronary Arteries by Enhancing ATP-Sensitive Potassium Channel Currents.

Cardiol Res Pract 2019 23;2019:1968785. Epub 2019 Oct 23.

Department of Geriatrics, Shanxi Dayi Hospital Affiliated to Shanxi Medical University, Taiyuan 030024, Shanxi, China.

GLP-1 is a new type of antidiabetic agent that possesses many beneficial effects. Although its cardiovascular actions have been widely examined, little is known about GLP-1's effects on the rat coronary artery (RCA) or about the mechanisms underpinning these effects. Here, we report that GLP-1 inhibits depolarization- or thromboxane receptor agonist (U46619)-induced RCA contraction in a dosage-dependent manner. Vasorelaxation was attenuated by denuding the endothelium, L-NAME (nitric oxide synthase inhibitor), and glyburide (K channel blocker) but was not affected by indomethacin (cyclooxygenase inhibitor), iberiotoxin [Ca-activated K channel (K) blocker], or 4-aminopyridine (K channel blocker). Furthermore, GLP-1 increased outward K currents by enhancing the K channel in rat coronary arterial smooth muscle cells (RCASMCs). These results show that GLP-1 is an endothelial-dependent vasospasmolytic agent in the RCA and imply that the relaxant effect is regulated by enhancing K rather than K or K currents in RCASMCs.
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http://dx.doi.org/10.1155/2019/1968785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854269PMC
October 2019

Functional exploration of co-expression networks identifies a nexus for modulating protein and citric acid titres in submerged culture.

Fungal Biol Biotechnol 2019 9;6:18. Epub 2019 Nov 9.

1Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308 People's Republic of China.

Background: Filamentous fungal cell factories are used to produce numerous proteins, enzymes, and organic acids. Protein secretion and filamentous growth are tightly coupled at the hyphal tip. Additionally, both these processes require ATP and amino acid precursors derived from the citric acid cycle. Despite this interconnection of organic acid production and protein secretion/filamentous growth, few studies in fungi have identified genes which may concomitantly impact all three processes.

Results: We applied a novel screen of a global co-expression network in the cell factory to identify candidate genes which may concomitantly impact macromorphology, and protein/organic acid fermentation. This identified genes predicted to encode the Golgi localized ArfA GTPase activating protein (GAP, AgeB), and ArfA guanine nucleotide exchange factors (GEFs SecG and GeaB) to be co-expressed with citric acid cycle genes. Consequently, we used CRISPR-based genome editing to place the titratable Tet-on expression system upstream of , , and in . Functional analysis revealed that and are essential whereas was dispensable for early filamentous growth. Next, gene expression was titrated during submerged cultivations under conditions for either protein or organic acid production. ArfA regulators played varied and culture-dependent roles on pellet formation. Notably, or expression levels had major impacts on protein secretion, whereas was dispensable. In contrast, reduced expression of each predicted ArfA regulator resulted in an absence of citric acid in growth media. Finally, titrated expression of either GEFs resulted in an increase in oxaloacetic acid concentrations in supernatants.

Conclusion: Our data suggest that the Golgi may play an underappreciated role in modulating organic acid titres during industrial applications, and that this is SecG, GeaB and AgeB dependent in . These data may lead to novel avenues for strain optimization in filamentous fungi for improved protein and organic acid titres.
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http://dx.doi.org/10.1186/s40694-019-0081-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842248PMC
November 2019

Application of chemicals for enhancing lipid production in microalgae-a short review.

Bioresour Technol 2019 Dec 7;293:122135. Epub 2019 Sep 7.

School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, 2 Xuelin Road, Qixia District, Nanjing, Jiangsu Province, China; Jiangsu National Synergetic Innovation Center for Advanced Materials, State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, School of Pharmacy, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing 211816, China.

Microalgae have attracted great attention as a promising sustainable resource for biofuel production. In studies aiming to improve lipid accumulation, many key enzymes involved in lipid biosynthesis were identified and confirmed, but genetic engineering remains a challenge in most species of microalgae. In an alternative approach, various chemical modulators can be used to directly regulate the lipid biosynthesis pathway, with similar effects to gene overexpression and interference approaches, including improving the precursor supply and blocking competing pathways. The produced lipid can be protected from being converted into other metabolites by the chemicals such as lipase inhibitors. In addition, a few chemicals were also demonstrated to greatly influence cell growth and lipid accumulation by indirect regulation of the lipid biosynthesis pathway, such as increasing cell permeability or regulating oxidative stress. Thus, adding chemical modulators can be a useful alternative strategy for improving lipid accumulation in large-scale cultivation of microalgae.
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http://dx.doi.org/10.1016/j.biortech.2019.122135DOI Listing
December 2019

Silencing of STAT4 Protects Against Autoimmune Myocarditis by Regulating Th1/Th2 Immune Response via Inactivation of the NF-κB Pathway in Rats.

Inflammation 2019 Aug;42(4):1179-1189

Department of Cardiovascular Medicine, Shanxi Dayi Hospital Affiliated to Shanxi Medical University, No. 99, Longcheng Street, Taiyuan, 030032, Shanxi Province, People's Republic of China.

Signal transducer and activator of transcription 4 (STAT4) has been implicated in the progression of myocarditis. The aim of the current study was to investigate the role by which STAT4 influences autoimmune myocarditis in an attempt to identify a theoretical therapeutic perspective for the condition. After successful establishment of an autoimmune myocarditis rat model, the expression patterns of STAT4, NF-κB pathway-related genes, Th1 inflammatory cytokines (IFN-γ and IL-2), and Th2 inflammatory cytokines (IL-6 and IL-10) were subsequently determined. The rats with autoimmune myocarditis were treated with oe-STAT4 or sh-STAT4 lentiviral vectors to evaluate the role of STAT4 in autoimmune myocarditis, or administrated with 1 mL 10 μmol/L of BAY11-7082 (the NF-κB pathway inhibitor) via tail vein to investigate the effect of the NF-κB pathway on autoimmune myocarditis. Finally, cell apoptosis was evaluated. The serum levels of IFN-γ and IL-2, extent of IκBα and P65 phosphorylation, and the expression of STAT4 were elevated, while the serum levels of IL-6 and IL-10 as well as the expression of IκBα were reduced among the rats with autoimmune myocarditis, which was accompanied by an increase in the apoptotic cells. More importantly, the silencing of STAT4 or the inhibition of the NF-κB pathway was detected to result in a decrease in the serum levels of IFN-γ and IL-2 and an elevation of the serum levels of IL-6 and IL-10, and inhibited myocardial cell apoptosis in rats with autoimmune myocarditis. Moreover, STAT4 silencing was also observed to decrease the extent of IκBα and P65 phosphorylation while acting to elevate the expression of IκBα. Taken together, silencing of STAT4 could hinder the progression of autoimmune myocarditis by balancing the expression of Th1/Th2 inflammatory cytokines via the NF-κB pathway, which may provide a novel target for experimental autoimmune myocarditis (EAM) treatment.
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http://dx.doi.org/10.1007/s10753-019-00978-3DOI Listing
August 2019

Cancer cell membrane-cloaked mesoporous silica nanoparticles with a pH-sensitive gatekeeper for cancer treatment.

Colloids Surf B Biointerfaces 2019 Mar 13;175:477-486. Epub 2018 Dec 13.

Department of Urology, Mindong Hospital Affiliated to Fujian Medical University, Fu'an, 355000, People's Republic of China.

Nanoparticular drug delivery system (NDDS) has great potential for enhancing the efficacy of traditional chemotherapeutic drugs. However, it is still a great challenge to fabricate a biocompatible NDDS with simple structure capable of optimizing therapeutic efficacy, such as high tumor accumulation, suitable drug release profile (e.g. no premature drug leakage in normal physiological conditions while having a rapid release in cancer cells), low immunogenicity, as well as good biocompatibility. In this work, a simple core/shell structured nanoparticle was fabricated for prostate cancer treatment, in which a mesoporous silica nanoparticle core was applied as a container to high-efficiently encapsulate drugs (doxorubicin, DOX), CaCO interlayer was designed to act as sheddable pH-sensitive gatekeepers for controlling drug release, and cancer cell membrane wrapped outlayer could improve the colloid stability and tumor accumulation capacity. In vitro cell experiments demonstrated that the as-prepared nanovehicles (denoted as DOX/[email protected]@CM) could be efficiently uptaken by LNCaP-AI prostate cancer cells and even exhibited a better anti-tumor efficiency than free DOX. In addition, Live/Dead cell detection and apoptosis experiment demonstrated that MSN/[email protected]@CM could effectively induce apoptosis-related death in prostate cancer cells. In vivo antitumor results demonstrated that DOX/[email protected]@CM administration could remarkably suppress the tumor growth. Compared with other tedious approaches to optimize the therapeutic efficacy, this study provides an effective drug targeting system only using naturally biomaterials for the treatment of prostate cancer, which might have great potential in clinic usage.
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http://dx.doi.org/10.1016/j.colsurfb.2018.12.038DOI Listing
March 2019

GLP-1 attenuates Ang II-induced proliferation and migration in rat aorta smooth muscle cells inhibition of the RhoA/ROCK2 signaling pathway.

Pharmazie 2018 12;73(12):692-699

Glucagon-like peptide 1 (GLP-1), a neuroendocrine hormone produced by the gastrointestinal tract, plays a significant role in blood glucose regulation; drugs derived from GLP-1 are currently used for the treatment of type 2 diabetes. In addition to regulating glucose homeostasis, the protective effects of GLP-1 on the cardiovascular system are also of interest. However, the vascular protective mechanisms of GLP-1 remain unclear. The present study was designed to evaluate the role of GLP-1 in the proliferation and migration of vascular smooth muscle cells, and the underlying mechanisms. In this study, proliferation, migration, cyclin D1 expression, and phosphorylation of MLC, as well as RhoA and Rho-associated coiled-coil forming protein kinase 2 (ROCK2) expression, were increased in rat aorta smooth muscle cells (RASMCs) following incubation with angiotensin II (Ang II). These effects were significantly attenuated by GLP-1, forskolin (a cAMP activator) and Y-27632 (a ROCK2 inhibitor). However, H89 (a PKA inhibitor) inhibited the action of GLP-1, both in terms of inhibition of RASMC proliferation and migration, and RHOA/ROCK2 expression. These results indicate that GLP-1 inhibits Ang II-induced RASMC proliferation and migration via the cAMP/PKA/RhoA/ROCK2 signaling pathway. Our data suggest that GLP-1 should be considered for use in the clinical treatment of cardiovascular diseases, in addition to its current use in the treatment of diabetes mellitus.
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http://dx.doi.org/10.1691/ph.2018.8693DOI Listing
December 2018

L-3-n-butylphthalide attenuates cognitive deficits in db/db diabetic mice.

Metab Brain Dis 2019 02 1;34(1):309-318. Epub 2018 Dec 1.

Department of Endocrinology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road Xinhua District, Shijiazhuang, 050000, People's Republic of China.

Numerous epidemiological studies have shown that diabetes mellitus (DM) is associated with dementia and cognition decline. However, there is currently no effective treatment for diabetes-induced cognitive dysfunction. The neuroprotective effect of L-3-n-butylphthalide (L-NBP) has been demonstrated in vascular dementia animal models. The purpose of this study was to determine whether L-NBP can ameliorate cognitive deficits in db/db mice, a model of obesity and type 2 diabetes. The mice were administered with vehicle or L-NBP (120 mg/kg) by gavage daily for 6 weeks. Then, Morris water maze tasks were performed, and hippocampal LTP was recorded in vivo. Next, the synaptic structure of the CA1 hippocampus region was investigated via electron microscopy. Finally, the expression levels of MDA, SOD, 8-OHdG, and NADPH oxidase subunits gp91 and p67, as well as the expression of NF-κB p65, TNF-α, IL-1β and caspase-3 were measured by Western blot, RT-PCR and ELISA. Treatment with L-NBP significantly attenuated the learning and memory deficits in db/db mice. Concomitantly, L-NBP also increased hippocampus synaptic plasticity, characterized by an enhanced in vivo LTP, and suppressed oxidative stress, as indicated by increased SOD activity and decreased MDA, 8-OHdG, and NADPH oxidase subunits p67 and gp91. L-NBP also significantly decreased NF-κB p65, TNF-α, IL-1βand caspase-3 levels in the hippocampus. L-NBP significantly ameliorated cognitive decline in type 2 diabetic mice, and this effect was accompanied by an improvement in hippocampal plasticity and an amelioration of oxidative stress, inflammation and apoptosis cascades. Thus, L-NBP may be a promising therapeutic agent against DM-mediated cognitive dysfunction.
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http://dx.doi.org/10.1007/s11011-018-0356-6DOI Listing
February 2019

Association of white matter hyperintensities with migraine features and prognosis.

BMC Neurol 2018 Jul 2;18(1):93. Epub 2018 Jul 2.

Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, 710061, Shaanxi, China.

Background: White matter hyperintensities (WMHs) are frequently detected in migraine patients. However, their significance and correlation to migraine disease burden remain unclear. This study aims to examine the correlation of WMHs with migraine features and explore the relationship between WMHs and migraine prognosis.

Methods: A total of 69 migraineurs underwent MRI scans to evaluate WMHs. Migraine features were compared between patients with and without WMHs. After an average follow-up period of 3 years, these patients were divided into two groups, according to the reduction of headache frequency: improved and non-improved groups. The percentage and degree of WMHs were compared between these two groups.

Results: A total of 24 patients (34.8%) had WMHs. Patients with WMHs were significantly older (39.0 ± 7.9 vs. 30.6 ± 10.4 years, P < 0.001) and had a longer disease duration (median: 180.0 vs. 84.0 months, P = 0.013). Furthermore, 33 patients completed the follow up period (15 patients improved and 18 patients did not improve). Patients in the non-improved group had a higher frequency of WMHs (55.6% vs. 13.3%, P = 0.027) and median WMHs score (1.0 vs. 0.0, P = 0.030).

Conclusions: WMHs can predict unfavorable migraine prognosis. Furthermore, WMHs may have a closer association with age than migraine features.
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http://dx.doi.org/10.1186/s12883-018-1096-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027560PMC
July 2018

Effects of congestion on drivers' speed choice: Assessing the mediating role of state aggressiveness based on taxi floating car data.

Accid Anal Prev 2018 Aug 10;117:318-327. Epub 2018 May 10.

Institute of Transportation Engineering, Zhejiang University, Hangzhou, 310058, China. Electronic address:

Inappropriate cruising speed, such as speeding, is one of the major contributors to the road safety, which increases both the quantitative number and severity of traffic accidents. Previous studies have indicated that traffic congestion is one of the primary causes of drivers' frustration and aggression, which may lead to inappropriate speed choice. In this study, the large taxi floating car data (FCD) was used to empirically evaluate how traffic congestion-related negative moods, defined as state aggressiveness, affected drivers' speed choice. The indirect effect of traffic delay on the cruising speed adjustment through the state aggressiveness was assessed through the mediation analysis. Furthermore, the moderated mediation analysis was performed to explore the effect of driver type, value of time, and working duration on the mediation role of state aggressiveness. The results proved that the state aggressiveness was the mediator of the relationship between travel delays and driving speed adjustment, and the mediation role was different across various driver types. As compared to the aggressive drivers, the normal drivers and the steady drivers tended to behave more aggressively after experiencing non-recurrent congestion during the early stage of the trips. When the value of time was high, steady drivers were more likely to adjust their speed choice although the effect was not statistically significant for other driver types. The validation results indicated that the speed model incorporating state aggressiveness could better predict the travel time than the traditional speed model that only considering the specific expected speed distribution. The prediction results for the manifest indicators of state aggressiveness, such as the maximum speed and the speed deviation, also demonstrated a reasonable reflection of the field data.
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http://dx.doi.org/10.1016/j.aap.2018.04.030DOI Listing
August 2018

The cytoplasmic nuclear shuttling of Beclin 1 in neurons with Alzheimer's disease-like injury.

Neurosci Lett 2017 Nov 28;661:63-70. Epub 2017 Sep 28.

Department of Pharmacology, Hangzhou Key Laboratory of Medical Neurobiology, School of Medicine, Hangzhou Normal University, Hangzhou 310036, China. Electronic address:

The abnormal expression of the autophagy-related protein Beclin 1 has been implicated in Alzheimer's disease (AD) brains, whereas the precise involvement of Caspase-mediated Beclin 1 cleavage in AD neurons has not yet been fully clarified. In this study, we investigated the distribution of Beclin 1 fragments in neurons with AD-like injury. Our results demonstrated that Beclin 1 was expressed in neurons but not in astrocytes in both neuron-glia co-cultures and in cortical tissue slices. The full length and C-terminal fragments of human Beclin 1 was mainly expressed in cytoplasm, while the N-terminal fragment of Beclin 1 was predominantly localized in nucleus. Compared to amyloid-β (Aβ) treatment control, exposure of PC12 cells or cortical neurons to Aβ resulted in cell injury, with the appearance of neuritic shortening, reduced nuclear diameter in PC12 cells, beading formation and fragmentation in cortical neurons. A partial nuclear translocation of Beclin 1 was detected in cells incubated with Aβ, which could be inhibited by the administration of pan-Caspase inhibitor or Caspase 3 specific inhibitor. Moreover, Beclin 1 mutation at 146/149 sites was resistant to Aβ-induced nuclear translocation. The nuclear translocation of Beclin 1 could also been detected in the brains of 12-month-old APP/PS1 transgenic mice. Our findings suggest that after Caspase 3-mediated Beclin 1 cleavage at 146/149 sites, the N-terminal fragments of Beclin 1 may partially translocate into nuclei in neurons subjected to AD-like injury.
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http://dx.doi.org/10.1016/j.neulet.2017.09.055DOI Listing
November 2017
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