Publications by authors named "Hongyan Lin"

59 Publications

Gender-specific prevalence and influencing factors of depression in elderly in rural China: A cross-sectional study.

J Affect Disord 2021 Apr 2;288:99-106. Epub 2021 Apr 2.

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China; Department of Social Medicine and Health Administration, School of Public Health, Tianjin Medical University, Tianjin, China. Electronic address:

Background: With an aging population, late-life depression has been a major health problem in rural China. This study aims to explore the gender-specific prevalence of geriatric depression in rural Tianjin, its influencing factors, and to provide a scientific basis for the prevention and intervention of depression in the elderly.

Methods: A cross-sectional study of 4,933 elderly individuals in rural Tianjin was conducted using the cluster sampling method. The independent samples t-test and chi-squared test were used to assess differences in participants' characteristics by depressive symptoms, while multiple linear regressions and multiple logistic regressions were used to analyze the potential influencing factors of depression.

Results: The prevalence of geriatric depression was found to be 12.2% in the study participants (9.5% in men and 14.5% in women). Gender, education, household income, employment, living alone, social activities, physical exercise and chronic diseases were associated with depression (P<0.05). In addition to the above factors, sleep duration was also related with scores on self-rating depression scale (P<0.05).

Limitations: The study used a cross-sectional approach, so causation cannot be concluded.

Conclusions: Late-life depression is a serious mental health issue in rural China, highlighting the importance of appropriate diagnosis and treatment as a priority to improve the quality of mental health.
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http://dx.doi.org/10.1016/j.jad.2021.03.078DOI Listing
April 2021

Design, synthesis and biological evaluation of anilide (dicarboxylic acid) shikonin esters as antitumor agents through targeting PI3K/Akt/mTOR signaling pathway.

Bioorg Chem 2021 Mar 29;111:104872. Epub 2021 Mar 29.

State Key Laboratory of Pharmaceutical Biotechnology, Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing 210023, China; Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China. Electronic address:

Triple-negative breast cancer (TNBC) has an unfavorable prognosis attribute to its low differentiation, rapid proliferation and high distant metastasis rate. PI3K/Akt/mTOR as an intracellular signaling pathway plays a key role in the cell proliferation, migration, invasion, metabolism and regeneration. In this work, we designed and synthesized a series of anilide (dicarboxylic acid) shikonin esters targeting PI3K/Akt/mTOR signaling pathway, and assessed their antitumor effects. Through three rounds of screening by computer-aided drug design method (CADD), we preliminarily obtained sixteen novel anilide (dicarboxylic acid) shikonin esters and identified them as excellent compounds. CCK-8 assay results demonstrated that compound M9 exhibited better antiproliferative activities against MDA-MB-231, A549 and HeLa cell lines than shikonin (SK), especially for MDA-MB-231 (M9: IC = 4.52 ± 0.28 μM; SK: IC = 7.62 ± 0.26 μM). Moreover, the antiproliferative activity of M9 was better than that of paclitaxel. Further pharmacological studies showed that M9 could induce apoptosis of MDA-MB-231 cells and arrest the cell cycle in G2/M phase. M9 also inhibited the migration of MDA-MB-231 cells by inhibiting Wnt/β-catenin signaling pathway. In addition, western blot results showed that M9 could inhibit cell proliferation and migration by down-regulating PI3K/Akt/mTOR signaling pathway. Finally, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model was also constructed to provide a basis for further development of shikonin derivatives as potential antitumor drugs through structure-activity relationship analysis. To sum up, M9 could be a potential candidate for TNBC therapy.
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http://dx.doi.org/10.1016/j.bioorg.2021.104872DOI Listing
March 2021

Interactions Between Handgrip Strength and Serum Folate and Homocysteine Levels on Cognitive Function in the Elderly Chinese Population.

J Alzheimers Dis 2021 ;80(4):1503-1513

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.

Background: Handgrip strength (HGS) and serum folate and homocysteine (Hcy) levels were associated with cognitive function. However, little was known whether there were interactions between HGS and serum folate and Hcy levels on cognitive function.

Objective: To examine the interactions between HGS and serum folate and Hcy levels on cognitive function.

Methods: This study analyzed the baseline data of the Tianjin Elderly Nutrition and Cognition Cohort study. All participants aged ≥60 years were potential eligible. HGS was measured using a grip strength dynamometer. Serum folate and Hcy levels were assayed using standard laboratory protocol. A Mini-Mental State Examination was used to assess cognitive function. Linear regressions were employed to examine the interactions between HGS and serum folate and Hcy levels on cognitive function.

Results: 4,484 participants were included in this study. There were interactions between HGS and serum folate and Hcy levels on cognitive function. Furthermore, subjects with strong HGS and sufficient folate level had the best cognitive function (β= 2.018), sequentially followed by those with strong HGS and insufficient folate level (β= 1.698) and with poor HGS and sufficient folate level (β= 0.873). Similarly, cognitive function was ranked in the descending order of subjects with strong HGS and normal Hcy level (β= 1.971), strong HGS and high Hcy level (β= 1.467), and poor HGS and normal Hcy level (β= 0.657).

Conclusion: There were interactions between HGS and serum folate and Hcy levels on cognitive function. However, the temporal associations cannot be examined in a cross-sectional study. Further cohort study should be conducted to confirm these associations in the future.
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http://dx.doi.org/10.3233/JAD-201537DOI Listing
January 2021

Differential relieving effects of shikonin and its derivatives on inflammation and mucosal barrier damage caused by ulcerative colitis.

PeerJ 2021 7;9:e10675. Epub 2021 Jan 7.

State Key Laboratory of Pharmaceutical Biotechnology, Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing, China.

Background: Ulcerative colitis (UC) is one of the most challenging human diseases. Natural shikonin (SK) and its derivatives (with have higher accumulation) isolated from the root of have numerous beneficial effects, such as wound healing and anti-inflammatory activities. Some researchers have reported that hydroxynaphthoquinone mixture (HM) and SK attenuate the acute UC induced by dextran sulfate sodium (DSS). However, no existing study has systemically investigated the effectiveness of SK and other hydroxynaphthoquinone natural derivative monomers on UC.

Methods: In this study, mice were treated with SK and its derivatives (25 mg/kg) and mesalazine (200 mg/kg) after DSS administration daily for one week. Disease progression was monitored daily by observing the changes in clinical signs and body weight.

Results: Intragastric administration natural single naphthoquinone attenuated the malignant symptoms induced by DSS. SK or its derivatives remarkably suppressed the serum levels of pro-inflammatory cytokines while increasing the inflammatory cytokine interleukin (IL)-10 . Additionally, both SK and alkanin restrained the activities of cyclooxygenase-2 (COX-2), myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) in serum and colonic tissues. SK and its derivatives inhibited the activation of nucleotide binding oligomerization domain-like receptors (NLRP3) inflammasome and NF-κB signaling pathway, thereby relieving the DSS-induced disruption of epithelial tight junction (TJ) in colonic tissues.

Conclusions: Our findings shed more lights on the pharmacological efficacy of SK and its derivatives in UC against inflammation and mucosal barrier damage.
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http://dx.doi.org/10.7717/peerj.10675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797173PMC
January 2021

Association between methionine cycle metabolite-related diets and mild cognitive impairment in older Chinese adults: a population-based observational study.

Nutr Neurosci 2021 Jan 25:1-14. Epub 2021 Jan 25.

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China.

Background: Homocysteine (Hcy) and folate, involved in a common metabolic pathway supplying essential methyl groups for DNA and protein synthesis, have been found to be associated with cognitive function. Moreover, diet may influence methionine cycle metabolites (MCM) as well as mild cognitive impairment (MCI), but MCM-related dietary patterns are unclear in an older population.

Objective: The study aimed to identify MCM-related dietary patterns of older Chinese adults, and examine their association with the prevalence of MCI in a large population-based study.

Methods: This study included 4457 participants ≥ 60 years of age from the Tianjin Elderly Nutrition and Cognition Cohort study. Dietary data were collected using a valid self-administered food frequency questionnaire, and factor analysis was used to identify major dietary patterns in the population. MCM-based dietary patterns were derived using reduced rank regression (RRR) based on serum folate and Hcy as response variables.

Results: Compared with the participants in the lowest quartile of vegetarian pattern and processed foods pattern, the odds ratios (ORs) of MCI in the highest quartile were 0.72 (95% CI 0.53-0.98) and 1.39 (95% CI 1.03-1.88), respectively. In the MCM-based dietary patterns derived using RRR, the ORs for MCI for the highest quartile of MCM patterns I and II were 0.58 (95% CI 0.44-0.78) and 1.38 (95% CI 1.04-1.83), respectively, compared with participants in the lower quartile.

Conclusions: Findings from this large population-based study suggested that adopting an MCM-related dietary pattern, especially avoiding processed foods, can decrease the occurrence of MCI.
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http://dx.doi.org/10.1080/1028415X.2021.1872959DOI Listing
January 2021

TP53-induced glycolysis and apoptosis regulator (TIGAR) ameliorates lysosomal damage in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-mediated mouse model of Parkinson's disease.

Toxicol Lett 2021 Mar 24;339:60-69. Epub 2020 Dec 24.

Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, Jiangsu, China. Electronic address:

The progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) correlates with rupture of lysosome in Parkinson's disease (PD). It has been found that TP53-induced glycolysis and apoptosis regulator (TIGAR) has been attributed to the regulation of metabolic pathways and neuroprotective effect. In the present study, we showed in a mouse model that 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) caused lysosomal damage and DA neurons loss in the SNpc. MPTP only induced SP1-mediated TIGAR upregulation in the early stage of neurotoxin-induced pathology, and this compensatory mechanism was not enough to maintain normal lysosomal function. MPTP significantly decreased the levels of NADPH and GSH, and the effects were ameliorated by the expression of exogenous TIGAR but execerbated by knockdown of TIAGR. TIGAR or NADPH alleviated oxidative stress, rescued lysosomal dysfunction and attenuated DA neurons degeneration. Overexpression of TIGAR or NADPH supplement inhibited MPP-mediated reactive oxygen species (ROS), lysosomal membrane permeabilization (LMP) and autophagic flux impairment in PC12 cells. Together, these findings suggest that TIGAR reduces MPTP-mediated oxidative stress, lysosomal depletion and DA neuron damage.
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http://dx.doi.org/10.1016/j.toxlet.2020.12.011DOI Listing
March 2021

Age- and Sex-Specific Prevalence and Modifiable Risk Factors of Mild Cognitive Impairment Among Older Adults in China: A Population-Based Observational Study.

Front Aging Neurosci 2020 30;12:578742. Epub 2020 Oct 30.

Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.

Background: Minimal data are available on the prevalence of mild cognitive impairment (MCI) in older Chinese adults. Moreover, the current information on MCI shows important geographical variations.

Objective: We aimed to assess the prevalence and risk factors for MCI by age and sex among older adults in a North Chinese population.

Methods: In this population-based cross-sectional study, we enrolled a random sample of 4,943 adults aged ≥ 60 years between March 2018 and June 2019 in Tianjin, China. Of these, 312 individuals were excluded due to a lack of data (e.g., fasting blood test). As a result, 4,631 subjects were assessed. Individuals with MCI were identified using neuropsychological assessments, including the Mini-Mental State Examination and Activities of Daily Living scale, based on a modified version of the Petersen's criteria.

Results: The mean (SD) age of the 4,631 participants was 67.6 (4.89) years, and 2,579 (55.7%) were female. The overall age- and sex-standardized prevalence of MCI in our study population was 10.7%. There were significant associations of MCI with age [65-69 vs. 60-64 years, OR = 0.74; 95% confidence interval (CI): 0.58, 0.96], physical activity (≥23.0 vs. <23.0 MET-hours/week, OR = 0.79; 95% CI: 0.64, 0.96), body mass index (BMI) (OR = 0.92; 95% CI: 0.89, 0.95), grip strength (OR = 0.50; 95% CI: 0.38, 0.67), hypertension (yes vs. no, OR = 1.44; 95% CI: 1.18, 1.77), higher levels of sleepiness (OR = 1.80; 95% CI: 1.36, 2.37), and longer sleep duration (OR = 1.40; 95% CI: 1.14, 1.72). The inverse association between BMI and MCI was stronger in older age groups ( for heterogeneity = 0.003). Moreover, the magnitude of association between triglycerides and MCI was different between the sexes ( for heterogeneity = 0.029).

Conclusion: The age- and sex-standardized prevalence of MCI was 10.7% in the study sample. Physical activity, BMI, grip strength, sleepiness, sleep duration, and hypertension were associated with the prevalence of MCI. Additionally, triglycerides and BMI might be differently associated with the presence of MCI for different sexes and age stages, respectively.
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http://dx.doi.org/10.3389/fnagi.2020.578742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662098PMC
October 2020

Influence of Inclination of Welding Torch on Weld Bead during Pulsed-GMAW Process.

Materials (Basel) 2020 Jun 10;13(11). Epub 2020 Jun 10.

School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China.

This work is about the influence rule of inclination of welding torch on the formation and characteristics of weld bead during the pulsed-gas metal arc welding (GMAW) process based on the robotic operation. The inclination of welding torch was an important operation condition during the pulsed-GMAW process, because it can affect the formation and quality of weld bead, which was the output of the process. In this work, the different inclination modes and values were employed to conduct actual welding experiments, and some influence rules can be obtained according to examine the surface topography and cross section. Then, to obtain further rules, serious measurements for the geometry characteristic parameters were conducted and corresponding curve fitting equations between inclination angles and the bead width, penetration and bead height were obtained, and the largest error of these curve fitting equations was 0.117 mm, whose corresponding mean squared error (MSE) was 0.0103. Corresponding verification experiments validated the effectiveness of the curve fittings and showed the second order polynomials were proper, and the largest errors between measurements and curve fitting equations for inclination angle under backward mode were larger than those under forward mode, and were 0.10 mm and 0.15 mm, respectively, which corresponded to the penetration and were below 10%, therefore the equations can be used to predict the geometry of the weld bead. This work can benefit the process and operation optimization of the pulsed-GMAW process, both in the academic researches and actual industrial production.
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http://dx.doi.org/10.3390/ma13112652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321599PMC
June 2020

Associations of Plasma BACE1 Level and BACE1 C786G Gene Polymorphism with Cognitive Functions in Patients with Type 2 Diabetes: A Cross- Sectional Study.

Curr Alzheimer Res 2020 ;17(4):355-364

Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No.87 DingJiaQiao Road, Nanjing, China.

Background: β-Site APP-cleaving enzyme 1 (BACE1) is a key enzyme involved in the pathophysiology of Type 2 Diabetes Mellitus (T2DM) and Mild Cognitive Impairment (MCI). We aimed to investigate the potential associations of plasma BACE1 levels and BACE1 gene polymorphism with different cognitive performances in T2DM patients with MCI.

Methods: The recruited 186 T2DM subjects were divided into 92 MCI group and 94 healthy-cognition controls, according to the Montreal Cognitive Assessment (MoCA) scores. Sociodemographic characteristics, clinical parameters and neuropsychological tests were assessed. BACE1 C786G gene polymorphism and plasma BACE1 level were determined.

Results: Compared to controls, MCI patients exhibited higher plasma BACE1 levels. Plasma BACE1 levels were negatively associated with MoCA, Clock Drawing Test and Logical Memory Test scores, whereas positively associated with Trail Making Test-B time in the MCI group (all p<0.05), after adjusting fasting blood glucose, glycosylated hemoglobin, and homeostasis model assessment of insulin resistance by C-peptide. Multivariable logistic regression analysis showed a significant trend towards increased MCI risk with high plasma BACE1 level in T2DM patients (OR = 1.492, p = 0.027). The plasma BACE1 levels of GG and GC genotypes were obviously higher than that of CC genotype in T2DM-MCI patients (p = 0.035; p = 0.026, respectively).

Conclusion: Increased plasma BACE1 levels were associated with poor overall cognition functions, especially visuospatial abilities, visual/logical memory and executive functions in T2DM-MCI patients. Additionally, elevated plasma BACE1 level was a risk factor for MCI in T2DM patients, and might be influenced by BACE1 C786G gene mutations.
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http://dx.doi.org/10.2174/1567205017666200522210957DOI Listing
January 2020

Cx43 and AKAP95 regulate G1/S conversion by competitively binding to cyclin E1/E2 in lung cancer cells.

Thorac Cancer 2020 06 27;11(6):1594-1602. Epub 2020 Apr 27.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.

Background: This study aimed to overexpress or silence connexin 43 (Cx43) and A-kinase anchoring protein 95 (AKAP95) in human A549 cells to explore their effects on cyclins and on G1/S conversion when the interrelationship of Cx43, AKAP95, and cyclin E1/E2 changes.

Methods: The study mainly used Western blot analysis and Co-immuno precipitation to detect the target protein in Cx43/AKAP95 over expressed human A549 cells, and the relationship of proteins Cx43, AKAP95 and Cyclin E during G1-S phase was explored with qualitative and quantitative analysis.

Results: The overexpression of Cx43 inhibited the expression of cyclin D1 and E1 by accelerating their degradation and reduced the Cdk2 activity that blocked the DNA transcription activity. However, the overexpression of AKAP95 increased the expression of cyclin D1 and E1 and inhibited their degradation, and enhanced the Cdk2 activity that promoted the DNA transcription activity. Cx43 and AKAP95 competitively bound to cyclin E1/E2, and the competitive binding affected the Cdk2 activity, Rb phosphorylation, DNA transcription activity, and G1/S conversion.

Conclusions: This study showed that the expression of ERK1/2, PKA, and PKB increased when BEAS-2B cells were treated with PDGF-BB, suggesting that ERK1/2, PKA, and PKB might be involved in the binding of AKAP95 with cyclin E, or the separation of AKAP95 from Cx43 from cyclin E1/E2. The specific mechanism underlying this process still needs further exploration.
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http://dx.doi.org/10.1111/1759-7714.13435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262948PMC
June 2020

High Plasma Resistin Levels Portend the Insulin Resistance-Associated Susceptibility to Early Cognitive Decline in Patients with Type 2 Diabetes Mellitus.

J Alzheimers Dis 2020 ;75(3):807-815

Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, China.

Background: Metabolic disorders, including insulin resistance, obesity, and hyperlipidemia occur frequently prior to hyperglycemia in patients with type 2 diabetes mellitus (T2DM) and cause mild cognitive impairment (MCI).

Objective: We investigated the involvement of resistin in these metabolic abnormalities contributes to MCI in patients with T2DM.

Methods: A total of 138 hospitalized patients with T2DM were enrolled and categorized into MCI and non-MCI groups according to the Montreal Cognitive Assessment (MoCA) score. Metabolic indicators and cognitive state were assessed, and plasma resistin levels were determined by ELISA.

Results: The resistin levels and homeostasis model assessment of insulin resistance (HOMA-IR) scores of MCI and gender-stratified subgroups were significantly higher than those of controls without MCI (all p < 0.01). Correlation analysis showed that the resistin level was negatively associated with majority of cognitive domains, e.g., MoCA (r = -0.693, p < 0.001) and Mini-Mental State Examination (r = -0.571, p < 0.001), and was related to HOMA-IR (r = 0.667, p < 0.001) but not to obesity and lipid indices. Multivariable regression analysis indicated that resistin (β= -0.675, p < 0.001) and educational level (β= 0.177, p = 0.003) were independent risk factors of MoCA in patients with T2DM.

Conclusions: High plasma resistin levels portend the insulin resistance-related susceptibility to early cognitive decline in Chinese patients with T2DM. The involvement of this adipokine in other metabolic disorders leading to diabetic MCI and its clinical value for early disease screening must be further studied.
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http://dx.doi.org/10.3233/JAD-200074DOI Listing
May 2021

SNP rs17079281 decreases lung cancer risk through creating an YY1-binding site to suppress DCBLD1 expression.

Oncogene 2020 05 30;39(20):4092-4102. Epub 2020 Mar 30.

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Genome-wide association studies (GWAS) have identified numerous genetic variants that are associated with lung cancer risk, but the biological mechanisms underlying these associations remain largely unknown. Here we investigated the functional relevance of a genetic region in 6q22.2 which was identified to be associated with lung cancer risk in our previous GWAS. We performed linkage disequilibrium (LD) analysis and bioinformatic prediction to screen functional SNPs linked to a tagSNP in 6q22.2 loci, followed by two case-control studies and a meta-analysis with 4403 cases and 5336 controls to identify if these functional SNPs were associated with lung cancer risk. A novel SNP rs17079281 in the DCBLD1 promoter was identified to be associated with lung cancer risk in Chinese populations. Compared with those with C allele, patients with T allele had lower risk of adenocarcinoma (adjusted OR = 0.86; 95% CI: 0.80-0.92), but not squamous cell carcinoma (adjusted OR = 0.99; 95% CI: 0.91-1.10), and patients with the C/T or T/T genotype had lower levels of DCBLD1 expression than those with C/C genotype in lung adenocarcinoma tissues. We performed functional assays to characterize its biological relevance. The results showed that the T allele of rs17079281 had higher binding affinity to transcription factor YY1 than the C allele, which suppressed DCBLD1 expression. DCBLD1 behaved like an oncogene, promoting tumor growth by influencing cell cycle progression. These findings suggest that the functional variant rs17079281C>T decreased lung adenocarcinoma risk by creating an YY1-binding site to suppress DCBLD1 expression, which may serve as a biomarker for assessing lung cancer susceptibility.
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http://dx.doi.org/10.1038/s41388-020-1278-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220863PMC
May 2020

Poloxamer 188-mediated anti-inflammatory effect rescues cognitive deficits in paraquat and maneb-induced mouse model of Parkinson's disease.

Toxicology 2020 04 10;436:152437. Epub 2020 Mar 10.

Department of Pharmacology, School of Pharmacy, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu, China. Electronic address:

Mild cognitive impairment in Parkinson's disease (PD-MCI) is considered as a nonmotor clinical symptom in Parkinson's disease (PD). Microglia-mediated inflammation contributes to cognitive function impairment. Poloxamer 188 (P188) is an amphipathic polymer which has cytoprotective effect in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced dopaminergic (DA) neurons degeneration in PD. But whether P188 could ameliorate cognitive impairment in PD is still illusive. In the present study, we showed in a mouse model that paraquat (10 mg/kg) and maneb (30 mg/kg) (P + M) treatment intraperitoneally twice a week for 6 consecutive weeks resulted in cognitive deficits and synapse loss in hippocampus, together with DA neuron damage in the substantia nigra pars compacta (SNpc). P188 (0.8 g/kg) injection via tail vein 30 min after P + M administration significantly restored DA neuron numbers in SNpc and synapse density in hippocampus, and alleviated P + M-mediated cognitive function impairment in novel object recognition task and morris water maze task (MWM). Pathological synapse loss might be attributed to increased microglial phagocytic activity and cell density, and P188 prevented P + M-induced phagocytic state changes of microglia, such as increase in cell body size and decrease in process length, and upregulated microglia abundance in hippocampus. Consistently, P188 attenuated P + M-mediated increased mRNA levels of microglia proliferation related CSF1r and CSF2ra, microglial engulfment associated CD68, ICAM1, and ICAM2, and pro-inflammatory IL-6, IL-1β, CD11b, and TNF-α in hippocampus. Together, these findings suggest that the biocompatible polymer P188 blunts microglia activation which may promote synaptic loss and exacerbate cognitive function in a mouse model of PD-MCI.
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http://dx.doi.org/10.1016/j.tox.2020.152437DOI Listing
April 2020

Various Cd(ii) coordination polymers induced by carboxylates: multi-functional detection of Fe, anions, aspartic acids and bovine serum albumin.

Dalton Trans 2020 Jan;49(3):737-749

College of Chemistry and Chemical Engineering, Professional Technology Innovation Center of Liaoning Province for Conversion Materials of Solar Cell, Bohai University, Jinzhou 121013, P. R. China.

By adjusting carboxylates, six Cd(ii) coordination polymers based on a naphthalene-methylene mixed-bridged-amide ligand, [Cd(L)(DNBA)2] (1), [Cd2(L)2(BDC)2(H2O)2]·2H2O (2), [Cd(L)(1,4-CHDA)] (3), [Cd(L)(HIPA)(H2O)]·H2O (4), [Cd(L)(MIP)]·H2O (5), and [Cd(L)(PMA)0.5(H2O)]·H2O (6) [L = N,N'-bis(4-methylenepyridin-4-yl)-1,4-naphthalene dicarboxamide, HDNBA = 3,5-dinitrobenzoic acid, H2BDC = 1,4-benzenedicarboxylic acid, 1,4-H2CHDA = 1,4-cyclohexanedicarboxylic acid, H2HIPA = 5-hydroxyisophthalic acid, H2MIP = 5-methylisophthalic acid and H4PMA = pyromellitic acid] have been synthesized under hydrothermal conditions. 1 shows a 4-c sql coplanar structure. 2 exhibits a 2-fold vertical interpenetrating structure based on wave-like 4-c sql layers. 3 shows a (3,5)-c pnh network containing a unique μ3-L. 4 features a 4-c sql wave-like network. 5 and 6 exhibit 3D structures with 6-c pcu and 4-c mog topologies. The number of carboxyl groups and functional group positions of the carboxylates have an important influence on the structures of the title complexes. The fluorescent responses of 1-6 towards Fe3+, anions, aspartic acid and bovine serum albumin were investigated. Among them, 4 shows sensitivity and selectivity (KSV = 1.16 × 104 L mol-1 for Fe3+, 1.03 × 104 L mol-1 for CrO42-, 1.08 × 104 L mol-1 for Cr2O72-, 1.17 × 104 L mol-1 for MnO4- and 1.05 × 104 L mol-1 for aspartic acid).
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http://dx.doi.org/10.1039/c9dt04103fDOI Listing
January 2020

Exploration of Weld Bead Forming Rule during Double-Pulsed GMAW Process Based on Grey Relational Analysis.

Materials (Basel) 2019 Nov 7;12(22). Epub 2019 Nov 7.

School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China.

Weld bead forming rule is very important during double-pulsed gas metal arc welding (DP-GMAW) process, and this process has more advantages than that of conventional arc welding process. This work employed grey rational analysis to explore the weld bead forming rule. Since the latest XT DP control process was employed, the parameters adjustment was easier than that of conventional operation. The grey relational analyses between five main process parameters, which were average welding current, welding speed, twin pulse relation, twin pulse frequency together with twin pulse current change in percent, and three key characteristic parameters, which were bead width, bead height and penetration, were conducted to explore the weld bead forming rule. To accurately calculate the grey relational degree, the negative relevancies were transformed to positive ones. According to calculations and corresponding analyses, it can be concluded that the effects of average welding current and welding speed on the weld bead forming and key characteristic parameters of the weld bead were higher than that of other process parameters. Moreover, the relevancies between key characteristic parameters of the weld bead, and process parameters which included twin pulse relation, average welding current and twin pulse current change in percent were positive, while the relevancies between key characteristic parameters and other two process parameters were negative. The work can supply a new method to evaluate the effects of process parameters during the DP-GMAW process on the weld bead forming or other process characteristics, and references for parameters selection and process optimization.
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http://dx.doi.org/10.3390/ma12223662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888504PMC
November 2019

Association between plasma adipsin level and mild cognitive impairment in Chinese patients with type 2 diabetes: a cross-sectional study.

BMC Endocr Disord 2019 Oct 24;19(1):108. Epub 2019 Oct 24.

Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No. 87 DingJiaQiao Road, Nanjing, 210009, People's Republic of China.

Background: The adipokine adipsin contributes to insulin resistance (IR), inflammation, and obesity, which are all regarded as high-risk factors for mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus. This research aimed to uncover the role of adipsin in Chinese type 2 diabetes mellitus (T2DM) population with early cognitive dysfunction and determine whether adipsin contributes to diabetic MCI caused by IR.

Methods: In our study, 126 patients with T2DM were enrolled. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive impairment. Demographic data and neuropsychological test results were evaluated. Plasma adipsin level was measured by enzyme-linked immunosorbent assay.

Results: The MCI group (n = 57) presented higher plasma adipsin levels compared with the healthy controls (p = 0.018). After adjustment for educational attainment, and age, begative correlations were found between plasma adipsin levels and MoCA, Mini Mental State Exam, and Verbal Fluency Test scores(r = - 0.640, p < 0.001; r = - 0.612, p < 0.001; r = - 0.288, p = 0.035; respectively). Correlation analysis demonstrated that adipsin levels were significantly positively correlated with fasting C-peptide; homeostasis model of assessment for insulin resistance (HOMA-IR) (r = 0.368, p < 0.001; r = 0.494, p < 0.001; respectively). Multivariable regression analysis further indicated that high plasma adipsin level was a significant independent determinant of MCI in the Chinese population withT2DM (p = 0.017).

Conclusions: Elevated plasma adipsin level was associated with MCI in Chinese T2DM patients. Further large-scale studies should be designed to determine whether adipsin is linked to IR-associated susceptibility to early cognitive decline in T2DM patients.
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http://dx.doi.org/10.1186/s12902-019-0431-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814099PMC
October 2019

In Addition to Poor Glycemic Control, a High Level of Irisin in the Plasma Portends Early Cognitive Deficits Clinically in Chinese Patients With Type 2 Diabetes Mellitus.

Front Endocrinol (Lausanne) 2019 13;10:634. Epub 2019 Sep 13.

Department of Endocrinology, Affiliated Zhongda Hospital, Southeast University, Nanjing, China.

Irisin plays an important role in the metabolism and homeostasis of energy balance, which is involved in cognitive impairment. This study aimed to investigate the role of irisin in mild cognitive impairment (MCI) among Chinese patients with type 2 diabetes mellitus (T2DM). We recruited 133 Chinese patients with T2DM, and divided them according to the Montreal Cognitive Assessment score. Demographic data were collected and the level of irisin in the plasma was determined. In addition, the results of neuropsychological testing were examined. The concentration of irisin in the plasma was measured using an enzyme immunoassay. A total of 59 patients were diagnosed with MCI and 74 patients were included as healthy-cognition controls. The level of irisin in the plasma ( = 0.043) and homeostasis model of assessment for insulin resistance ( = 0.032) in diabetic patients with MCI were higher than those observed in the healthy controls. A higher level of irisin in the plasma was associated with impaired overall cognition, specifically executive function. Linear regression analysis suggested that irisin ( = 0.017) and glycosylated hemoglobin ( = 0.036) were independent factors of diabetic MCI. The level of irisin in the plasma correlated with cognitive impairment in T2DM patients, particularly with executive function. These results further suggest that, in addition to poor glycemic control, a high level of irisin in the plasma portends early cognitive deficits clinically in Chinese patients with T2DM.
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http://dx.doi.org/10.3389/fendo.2019.00634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753617PMC
September 2019

Statins significantly reduce mortality in patients receiving clopidogrel without affecting platelet activation and aggregation: a systematic review and meta-analysis.

Lipids Health Dis 2019 May 24;18(1):121. Epub 2019 May 24.

Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No. 87 DingJiaQiao Road, Nanjing, 210009, People's Republic of China.

Background: Combination of statins and clopidogrel is frequently administered in patients with coronary artery disease (CAD). They are mainly activated and eliminated in the liver by cytochrome P450 isoenzyme 3A4 (CYP3A4). The aim was to clarify whether the coadministration of clopidogrel and statins attenuate respective efficacy.

Methods: PubMed, Embase, the Cochrane Library, Web of Science and Clinical Trials. gov were searched for until August 2018. Randomized controlled trials (RCTs) and cohort studies were taken into quality evaluation. Data were pooled using random effect models to estimate standard mean difference (SMD) or risk ratio (RR) with 95% confidence interval (CI).

Results: In total, 28 studies representing 25,267 participants were included. Statins reduce the mortality of patients administered clopidogrel (RR 0.54; 95% CI 0.40,0.74; p = 0.000), no differences were found in platelet aggregation (PA) (SMD 0.02; 95% CI -0.38,0.42; p = 0.920) and the expressions of P-selectin (SMD -0.04; 95% CI -0.14,0.05; p = 0.346), CD40L (SMD 0.09; 95% CI -0.29,0.48; p = 0.633), CD63 (SMD 0.09; 95% CI -0.01,0.19; p = 0.079) and PAC-1 (SMD 0.03; 95% CI -0.08,0.13; p = 0.633). Furthermore, CYP3A4 metabolized or non-CYP3A4 metabolized statins have no discrepancies in PA (SMD 0.13; 95% CI -0.31,0.58; p = 0.556), P-selectin (SMD 0.17; 95% CI -0.16,0.51; p = 0310), death (RR 0.89; 95% CI 0.38,2.07; p = 0.791), except for triglyceride (TG) (SMD -0.19; 95% CI -0.33,-0.06; p = 0.005).

Conclusions: This meta-analysis confirmed that statins reduce mortality in patients undergoing clopidogrel treatment without affecting platelet activation and aggregation.
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http://dx.doi.org/10.1186/s12944-019-1053-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533696PMC
May 2019

U-Shaped Association Between Serum Uric Acid Levels and Cognitive Functions in Patients with Type 2 Diabetes: A Cross-Sectional Study.

J Alzheimers Dis 2019 ;69(1):135-144

Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, Nanjing, PR China.

Background: Serum uric acid (SUA) is a natural antioxidant that may exert neuroprotective effects against neurodegenerative diseases. The relationship between uric acid and cognitive functions has been extensively studied, but results remain conflicting.

Objective: To investigate potential associations between SUA level and mild cognitive impairment (MCI), and different domains of cognitive performances in patients with type 2 diabetes mellitus (T2DM).

Methods: A total of 352 T2DM subjects (208 males and 144 females) were enrolled. SUA level was determined by using the uricase method. Cognitive performances were assessed using a validated neuropsychological test battery. Generalized additive models and binary logistic regression analysis were fitted to determine the association between SUA and cognitive functions.

Results: A total of 157 T2DM patients had MCI, and 195 displayed normal cognition. Compared with the controls, MCI patients exhibited lower SUA level (p = 0.009). Generalized additive models revealed a U-shaped curve relationship among SUA with Montreal Cognitive Assessment, Auditory Verbal Learning Test-immediate recall and Trail Making Test-B scores (all p < 0.05). Further logistic regression analysis showed a significant trend toward decreased MCI risk with increased SUA level among the subjects whose SUA level was below the cut-point (388.63 μmol/L); each unit increment in SUA level reduced the MCI risk by 0.7% (p = 0.003).

Conclusion: A U-shaped association between SUA level and global cognitive function, especially executive and memory function, existed in T2DM patients. Our findings will provide additional suggestions that an increase of SUA to a certain level may be a novel method to reduce the burden of T2DM-associated cognitive impairment.
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http://dx.doi.org/10.3233/JAD-181126DOI Listing
September 2020

Elevated Plasma Level of D-dimer Predicts the High Risk of Early Cognitive Impairment in Type 2 Diabetic Patients as Carotid Artery Plaques become Vulnerable or Get Aggravated.

Curr Alzheimer Res 2019 ;16(5):396-404

Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No.87 DingJiaQiao Road, Nanjing 210009, China.

Background And Objective: D-dimer prompts fibrinolysis system, which is involved in Alzheimer's disease and the complications of type 2 diabetic patients, especially among those with carotid artery plaques. Hence, this study aims to investigate the role of D-dimer in early cognitive impairment among type 2 diabetic patients with carotid artery plaques.

Methods: A total of 175 Chinese patients with type 2 diabetes were recruited and divided into two groups according to the Montreal Cognitive Assessment score. Demographic data were collected, plasma D-dimer was tested through VIDAS D-dimer New, neuropsychological tests were examined, and carotid artery plaques were detected by ultrasound and further stratified by vulnerability and level.

Results: A total of 67 types 2 diabetic patients with Mild Cognitive Impairment (MCI) displayed significantly increased plasma D-dimer levels compared with their health-cognition controls (p = 0.011). Plasma D-dimer concentration was negatively related with Digit Span Test scores in diabetic patients with vulnerable plaques (r=-0.471, p=0.023) and Stroop Color Word Test C (number) in diabetic patients with stable plaques (r=-0.482, p<0.001). Multivariable regression analysis further showed that D-dimer concentration was an independent factor of diabetic MCI with carotid artery plaque (p=0.005), and D-dimer concentration especially contributed to the high risk of MCI with vulnerable plaques (p=0.028) or high levels of carotid plaque (p=0.023).

Conclusion: Elevated D-dimer level predicts the high risk of early cognitive impairment in type 2 diabetic patients with carotid artery plaques, especially vulnerable plaques or high levels of carotid plaques.
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http://dx.doi.org/10.2174/1567205016666190321164741DOI Listing
August 2020

Increased Ratio of Global -GlcNAcylation to Tau Phosphorylation at Thr212 Site Is Associated With Better Memory Function in Patients With Type 2 Diabetes.

Front Physiol 2019 14;10:110. Epub 2019 Feb 14.

Department of Endocrinology, Affiliated Zhongda Hospital, Southeast University, Nanjing, China.

Aberrant -GlcNAc modification has been implicated in type 2 diabetes mellitus (T2DM) and the pathogenesis of neurodegenerative diseases via competition with tau phosphorylation. We aimed to investigate the association between global -GlcNAcylation, tau phosphorylation levels and mild cognitive impairment (MCI) in the whole blood of patients with T2DM. Sociodemographic, clinical characteristics and cognitive performances of the enrolled T2DM subjects were extensively assessed. Global -GlcNAcylation and tau phosphorylation levels in the whole blood were also determined using Western blot. Forty-eight T2DM subjects, including 24 with MCI and 24 with normal cognition, were enrolled in this study. Compared with cognitively normal controls, T2DM with MCI subjects displayed decreased global -GlcNAcylation level, but increased tau phosphorylation levels (all < 0.05). To reflect the combined effect, the ratios of global -GlcNAcylation to tau phosphorylation levels, including specific sites, such as Ser396, Ser404, Thr212, and Thr231, were all significantly decreased in MCI subjects (all < 0.05). Further multivariable logistic regression analysis revealed that high glycated hemoglobin A1c was an independent risk factor, whereas increased -GlcNAc/p-T212 was an independent protective factor for MCI in patients with T2DM (odds ratio [OR] = 2.452, 95% confidence interval [CI] 1.061-5.668, = 0.036; OR = 0.028, 95%CI 0.002-0.388, = 0.008, respectively). With regard to each cognitive domain, -GlcNAc/p-T212 was positively correlated with the score of Auditory Verbal Learning Test-delayed recall ( = 0.377, = 0.010). Our study suggests that increased ratio of global -GlcNAcylation to tau phosphorylation at Thr212 site in the whole blood is associated with decreased risk of MCI, especially with better memory function in T2DM subjects. www.ClinicalTrials.gov, identifier ChiCTR-OCC-15006060.
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http://dx.doi.org/10.3389/fphys.2019.00110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382671PMC
February 2019

ERα upregulates the expression of long non-coding RNA LINC00472 which suppresses the phosphorylation of NF-κB in breast cancer.

Breast Cancer Res Treat 2019 Jun 4;175(2):353-368. Epub 2019 Mar 4.

University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA.

Purpose: Low expression of long intergenic non-coding RNA LINC00472 in breast cancer is associated with aggressive tumors and unfavorable disease outcomes in multiple clinical datasets, but the reasons for these associations were unknown.

Methods: To study the mechanisms underlying the lncRNA's connection to breast cancer, we investigated the molecular targets and regulation of LINC00472 in breast cancer cells, and analyzed relevant molecular features in relation to patient survival. Gene expression profiles of breast cancer cells overexpressing LINC00472 were analyzed for its regulatory pathways and downstream targets. Effects of LINC00472 overexpression on cell behaviors were evaluated in vitro and in vivo. Meta-analysis was performed using online datasets and our own study.

Results: Analysis of LINC00472 transcriptome revealed ERα upregulation of LINC00472 expression, and an ERα-binding site in the LINC00472 promoter was identified. Evaluation of LINC00472 overexpression also indicated a possible link between LINC00472 and NF-κB. Cell experiments confirmed that LINC00472 suppressed the phosphorylation of p65 and IκBα through binding to IKKβ, inhibiting its phosphorylation. High LINC00472 expression inhibited tumor growth both in vitro and in vivo and suppressed aggressive tumor cell behaviors in vitro. Suppressing LINC00472 expression in ER-positive tumor cells increased cell aggressive behaviors. Tamoxifen treatment of ER-positive cells inhibited ERα and LINC00472 expression and increased p65 and IκBα phosphorylation. Meta-analysis showed that LINC00472 expression were higher in ER-positive than ER-negative tumors and that high expression was associated with better disease outcomes in ER-positive patients.

Conclusions: The study demonstrates that ERα upregulates LINC00472 which suppresses the phosphorylation of NF-κB, and suggests that endocrine treatment may lower LINC00472 and increase NF-κB activities, leading to tumor progression and disease recurrence.
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http://dx.doi.org/10.1007/s10549-018-05108-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534447PMC
June 2019

LncRNA LCPAT1 is involved in DNA damage induced by CSE.

Biochem Biophys Res Commun 2019 01 30;508(2):512-515. Epub 2018 Nov 30.

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address:

Cigarette smoking plays an important role in the process of lung cancer, during which DNA damage is proved to be involved. Non-coding RNAs are found to be involved in the DNA damage and repair processes induced by cigarette smoke. In the present study, we investigated the role of lncRNA LCPAT1 in DNA damage caused by CSE in Beas-2B cells. Our results indicate that LCPAT1, through RCC2 is involved in the CSE-induced DNA damage providing new insight into the lung carcinogenesis related to cigarette smoking.
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http://dx.doi.org/10.1016/j.bbrc.2018.11.171DOI Listing
January 2019

Knockdown of long non-coding RNA inhibits autophagy in lung cancer.

Cancer Biol Med 2018 Aug;15(3):228-237

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Objective: Long non-coding RNAs (lncRNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lncRNA, , which is highly expressed in lung carcinomas, and termed it lung cancer progression-associated transcript 1 (). To characterize the role of in lung cancer, we conducted the current study.

Methods: Expression of and autophagy-associated markers in tumor tissues and lung cancer cell lines was determined by real-time quantitative polymerase chain reaction (qPCR). Hematoxylin and eosin (HE) staining, qPCR, Western blot, and immunohistochemistry were performed to evaluate xenografted tumor tissues. Autophagy induced by rapamycin was detected by Western blot and immunofluorescence in lung cancer cell lines.

Results: Expression of and microtubule-associated protein 1 light chain 3 beta () was positively correlated in lung cancer. Knockdown of inhibited tumor growth and suppressed cell autophagy . Moreover, knockdown in lung cancer cell lines resulted in decreased autophagy-associated gene expression and alleviated the cell autophagy induced by rapamycin.

Conclusions: We speculate that plays a crucial role in regulating autophagy in lung cancer.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2017.0150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121053PMC
August 2018

Low expression of LINC00982 and PRDM16 is associated with altered gene expression, damaged pathways and poor survival in lung adenocarcinoma.

Oncol Rep 2018 Nov 14;40(5):2698-2709. Epub 2018 Aug 14.

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.

Recently, long non‑coding RNAs (lncRNAs) have been shown to play critical roles in lung adenocarcinoma (LUAD). The present study aimed to explore the effect of LINC00982 and PRDM16 on clinical features and survival in LUAD. We found that LUAD patients demonstrated lower expression and copy number variation but higher methylation of long intergenic non‑protein coding RNA 982 (LINC00982) and PR domain containing 16 (PRDM16) compared with controls. Thus, we divided the LUAD patients into two groups according to the median expression of LINC00982 and PRDM16. Through differential expression, KEGG pathway enrichment and Ingenuity® Pathway Analysis (IPA), we found that patients with low expression of both LINC00982 and PRDM16 presented with more deregulated genes, as well as more significant pathways, than patients with high expression of these two genes. In addition, Kaplan‑Meier curves and Cox proportional hazards models revealed that patients with low expression of LINC00982, PRDM16 or both, showed poorer survival than the groups with high expression of LINC00982, PRDM16. We further used multivariate survival models to verify these results. Furthermore, we confirmed that the expression of LINC00982 and PRDM16 was significantly decreased in LUAD cell lines compared to normal cell lines in vitro. In conclusion, the present study revealed that LINC00982 and PRDM16 may serve as biomarkers or potential drug targets for the diagnosis and therapy of LUAD.
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http://dx.doi.org/10.3892/or.2018.6645DOI Listing
November 2018

Polycarboxylate-directed semi-rigid pyridyl-amide-based various Ni complexes: electrochemical properties and enhancements of photocatalytic activities by calcination.

Dalton Trans 2018 Jul;47(29):9903-9911

Department of Chemistry, Bohai University, Jinzhou, 121000, P. R. China.

In this work, four new NiII coordination polymers (CPs) based on a bi-methylene-bridged semi-rigid bis-pyridyl-bis-amide ligand and various polycarboxylates, namely, [Ni(4-bmbpd)(H2O)4]·(TPD) (1), [Ni2(4-bmbpd)2(1,3-BDC)2(H2O)4]·5H2O (2), [Ni2(4-bmbpd)2(MIP)2(H2O)2]·3H2O (3) and [Ni3(4-bmbpd)3(BTC)2(H2O)4]·4H2O (4) [4-bmbpd = N,N'-bis(4-methylenepyridin-4-yl)-1,4-benzenedicarboxamide, H2TPD = 2,5-thiophenedicarboxylic acid, 1,3-H2BDC = 1,3-benzenedicarboxylic acid, H2MIP = 5-methylisophthalic acid and 1,3,5-H3BTC = 1,3,5-benzenetricarboxylic acid] have been hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction analyses, thermal gravimetric (TG) analyses, IR spectroscopy and powder X-ray diffraction (PXRD). In complex 1, the μ2-bridging 4-bmbpd ligands connect adjacent NiII ions leading to a 1D [Ni-4-bmbpd]n wave-like chain, while the TPD anions act as discrete counter ions. Complexes 2 and 3 are similar 2D 4-connected grid networks derived from [Ni-4-bmbpd]n chains and [Ni-L]n (L = BDC or MIP) chains. 4 shows a 3D (2,3,4,4)-connected framework, which contains [Ni-1,3,5-BTC]n 1D double chains, [Ni-(4-bmbpd)]n linear chains and [Ni2(4-bmbpd)2] rings. The 1D chains for 1 and the 2D networks for 2 and 3 are finally extended into 3D supramolecular architectures by hydrogen bonding interactions. The role of polycarboxylates in the assembly and structures of the target compounds was discussed. Moreover, photoluminescence properties, electrochemical properties of complexes 1-4 and the photocatalytic activities of calcination products of 1 and 4 (Ni@NC1 and Ni@NC4) were investigated. More importantly, the photocatalytic performances of Ni@NC1 and Ni@NC4 are enhanced compared with the title complexes 1 and 4.
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http://dx.doi.org/10.1039/c8dt00836aDOI Listing
July 2018

Increased plasma Interleukin-1β level is associated with memory deficits in type 2 diabetic patients with mild cognitive impairment.

Psychoneuroendocrinology 2018 10 22;96:148-154. Epub 2018 Jun 22.

Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, Nanjing, PR China. Electronic address:

Type 2 diabetes mellitus (T2DM) and mild cognitive impairment (MCI) are both chronic inflammatory diseases. We aimed to investigate the association of plasma Interleukin-1β (IL-1β) levels with the risk of MCI in T2DM patients. We divided recruited T2DM patients into two groups, MCI group and healthy-cognition controls, according to Montreal Cognitive Assessment (MoCA) scores. Demographic characteristics, clinical parameters and neuropsychological tests were examined. We recruited 202 T2DM patients in this study, including 94 MCI and 108 healthy-cognition controls. T2DM patients with MCI exhibited increased plasma IL-1β and decreased amyloid-β 42 (Aβ42) levels compared to the controls (all p < 0.05). After adjusting fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR) and Aβ42, plasma IL-1β levels were negatively correlated with MoCA and AVLT delayed recall scores, which represented memory function. Multivariable logistic regression model showed that high plasma IL-1β level and low plasma Aβ42 level were correlated with increased risk for MCI in T2DM patients. Increased plasma IL-1β level was significantly associated with MCI in T2DM patients, especially memory deficits. Our findings will provide additional insights into the inflammation pathogenesis of cognitive impairments in T2DM.
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http://dx.doi.org/10.1016/j.psyneuen.2018.06.014DOI Listing
October 2018

LncRNA LCPAT1 Mediates Smoking/ Particulate Matter 2.5-Induced Cell Autophagy and Epithelial-Mesenchymal Transition in Lung Cancer Cells via RCC2.

Cell Physiol Biochem 2018 15;47(3):1244-1258. Epub 2018 Jun 15.

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background/aims: Ecological studies have shown that air pollution and prevalence of cigarette smoking are positively correlated. Evidence also suggests a synergistic effect of cigarette smoking and PM2.5 exposure (Environmental Particulate Matter ≤ 2.5 µm in diameter) on lung cancer risk. We aimed to evaluate the interaction between smoking prevalence and PM2.5 pollution in relation to lung cancer mortality and determine its underlying mechanisms in vitro.

Methods: "MOVER" method was used to analyze the interaction between smoking prevalence and PM2.5 pollution in relation to lung cancer mortality. Cell autophagy and malignant behaviors induced by cigarette smoke extract (CSE) and PM2.5 exposure were examined in vitro. Gene expression was examined by qRT-PCR and western blot. RNA and protein interaction was determined using a RNA binding protein immunoprecipitation assay.

Results: An increased risk for lung cancer death (RERI (the relative excess risk) =0.28) was observed with a synergistic interaction between cigarette smoking and PM2.5 pollution. Cell migration, invasion, EMT (epithelial-mesenchymal transition) and autophagy were elevated when lung cancer cells were treated with CSE and PM2.5 in combination. A lncRNA, named lung cancer progression-association transcript 1 (LCPAT1), was up-regulated after the treatment of CSE and PM2.5, and knocking down the lncRNA impaired the effect of CSE and PM2.5 on lung cancer cells. In addition, LCPAT1 was shown to bind to RCC2, and RCC2 mediated the effect of LCPAT1 on cell autophagy, migration, invasion and EMT in lung cancer.

Conclusions: Our results suggest that combined exposure to CSE and PM2.5 induces LCPAT1 expression, which up-regulates autophagy, and promotes lung cancer progression via RCC2.
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http://dx.doi.org/10.1159/000490220DOI Listing
August 2018

Low Plasma Leptin and High Soluble Leptin Receptor Levels Are Associated With Mild Cognitive Impairment in Type 2 Diabetic Patients.

Front Aging Neurosci 2018 15;10:132. Epub 2018 May 15.

Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, China.

Metabolic disturbances, such as hyperglycemia, hyperlipidemia, and obesity, are thought to be risk factors for Alzheimer's disease. This study aimed to investigate whether adipokine leptin and soluble leptin receptor (sOBR) levels are correlated with mild cognitive impairment (MCI) and metabolic status of the patients of type 2 diabetes mellitus (T2DM). Total of 169 T2DM patients were recruited and divided according to the Montreal Cognitive Assessment (MoCA) score. Their cognition and metabolic parameters were extensively assessed. Plasma leptin and sOBR levels were determined by RIA and ELISA, respectively. Free leptin index (FLI) was calculated. Of 124 enrolled T2DM patients, 61 were diagnosed with MCI (MoCA < 26). In MCI group and female subgroup, leptin levels and FLI were significantly lower and sOBR concentrations were higher when compared with their respective health cognition controls (all < 0.05). Leptin levels and FLI were positively associated with the most cognitive domains and their Waist-to-Hip Ratio (WHR), a traditional index of central obesity. Leptin, sOBR, and WHR were independent variables of MCI in all individuals (all < 0.05). For the females, MoCA was also positively correlated with leptin (β = 0.893, < 0.001) and negatively correlated with WHR (β = -0.363, = 0.014). Leptin was positively correlated only with WHR (β = 0.441, = 0.025). This study showed that a high level of leptin and low level of sOBR are associated with the improved cognitive function in T2DM patients and more significantly in female individuals, while WHR, as an indicator of the visceral obesity, contributes to cognitive deficits. Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060; http://www.chictr.org.cn/showproj.aspx?proj=10536.
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http://dx.doi.org/10.3389/fnagi.2018.00132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962657PMC
May 2018

Association between Plasma Levels of PAI-1, tPA/PAI-1 Molar Ratio, and Mild Cognitive Impairment in Chinese Patients with Type 2 Diabetes Mellitus.

J Alzheimers Dis 2018 ;63(2):835-845

Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China.

Background: Plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (tPA) are involved in the complications of type 2 diabetes mellitus (T2DM) and early pathology of Alzheimer's disease.

Objective: This study aimed to investigate the association between plasma PAI-1, tPA/PAI-1 molar ratio, and mild cognitive impairment (MCI) in Chinese T2DM patients.

Methods: A total of 162 Chinese T2DM patients were recruited and divided into two groups according to the Montreal Cognitive Assessment score. Demographic data were collected, plasma PAI-1 and tPA levels were measured through enzyme-linked immunosorbent assay, tPA/PAI-1 molar ratio was calculated, and neuropsychological test results were examined. The association between PAI-1, tPA/PAI-1 molar ratio, and cognition was analyzed.

Results: There were 66 diabetic MCI patients and 96 healthy cognition participants (controls). T2DM patients with MCI displayed significantly increased plasma PAI-1 levels (p = 0.016) and decreased tPA/PAI-1 molar ratio (p = 0.021) compared with the controls. High PAI-1 levels and low tPA/PAI-1 molar ratio were associated with MCI in T2DM patients, e.g., plasma level of PAI-1 were negatively correlated (r = -0.343, p = 0.007) with logic memory in T2DM patients with MCI. Linear regression analysis further revealed that PAI-1 concentration was an independent factor of diabetic MCI (p = 0.001).

Conclusions: High PAI-1 levels and low tPA/PAI-1 molar ratio were significantly correlated with T2DM-associated cognitive impairment, especially memory function, in Chinese patients.
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http://dx.doi.org/10.3233/JAD-171038DOI Listing
June 2019