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1.
J Hazard Mater ; 474: 134786, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38824778

ABSTRACT

Volatile organic compounds (VOCs) as environmental pollutants were associated with respiratory diseases. Pulmonary fibrosis (PF) was characterized by an increase of extracellular matrix, leading to deterioration of lung function. The adverse effects on lung and the potential mechanism underlying VOCs induced PF had not been elucidated clearly. In this study, the indoor VOCs exposure mouse model along with an ex vivo biosensor assay was established. Based on scRNA-seq analysis, the adverse effects on lung and potential molecular mechanism were studied. Herein, the results showed that VOCs exposure from indoor decoration contributed to decreased lung function and facilitated pulmonary fibrosis in mice. Then, the whole lung cell atlas after VOCs exposure and the heterogeneity of fibroblasts were revealed. We explored the molecular interactions among various pulmonary cells, suggesting that endothelial cells contributed to fibroblasts activation in response to VOCs exposure. Mechanistically, pulmonary microvascular endothelial cells (MPVECs) secreted Gas6 after VOCs-induced PANoptosis phenotype, bound to the Axl in fibroblasts, and then activated fibroblasts. Moreover, Atf3 as the key gene negatively regulated PANoptosis phenotype to ameliorate fibrosis induced by VOCs exposure. These novel findings provided a new perspective about MPVECs could serve as the initiating factor of PF induced by VOCs exposure.


Subject(s)
Endothelial Cells , Fibroblasts , Lung , Pulmonary Fibrosis , Volatile Organic Compounds , Animals , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Volatile Organic Compounds/toxicity , Lung/drug effects , Lung/pathology , Intercellular Signaling Peptides and Proteins/metabolism , Mice , Axl Receptor Tyrosine Kinase , Mice, Inbred C57BL , Air Pollution, Indoor/adverse effects , Male , Signal Transduction/drug effects
2.
Dokl Biochem Biophys ; 516(1): 58-65, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38722403

ABSTRACT

The objectives of this study were to investigate the anti-fatigue effects of Paris polyphylla polysaccharide component 1 (PPPm-1) and explore its mechanisms. A mouse model of exercise-induced fatigue was established by weight-bearing swimming to observe the effects of different concentrations of PPPm-1 on weight-bearing swimming time. The anti-fatigue effect of PPPm-1 was determined by the effects of contraction amplitude, contraction rate, and diastolic rate of the frog gastrocnemius muscle in vivo before and after infiltration with 5 mg/mL PPPm-1. The effects of PPPm-1 on the contents of blood lactate, serum urea nitrogen, hepatic glycogen, muscle glycogen in the exercise fatigue model of mice, and acetylcholine (ACh) content and acetylcholinesterase (AChE) activity at the junction of the frog sciatic nerve-gastrocnemius under normal physiological, and Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities of the frog gastrocnemius were determined by enzyme-linked immunosorbent assay (ELISA), to investigate the anti-fatigue mechanisms of PPPm-1. The results showed that PPPm-1 could significantly prolong the weight-bearing swimming time in mice (P < 0.01), decrease the contents of blood lactate and serum urea nitrogen, increase the contents of the hepatic glycogen and muscle glycogen of mice after exercise fatigue compared with those of the control group, and there was extremely significant difference in most indicators (P < 0.01). The 5 mg/mL of PPPm-1 could significantly promote the contraction amplitude, contraction rate, and relaxation rate of the gastrocnemius muscle in the frogs, and the content of ACh at the junction of the frog sciatic nerve-gastrocnemius (P < 0.01), but it had obvious inhibitory effetc on the activity of AChE at the junction of the frog sciatic nerve-gastrocnemius (P < 0.01). PPPm-1 could increase the Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities of gastrocnemius in the frogs (for Ca2+-Mg2+-ATPase, P < 0.01). The above results suggested that the PPPm-1 had a good anti-fatigue effect, and its main mechanisms were related to improving endurance and glycogen reserve, reducing glycogen consumption, lactate and serum urea nitrogen accumulation, and promoting Ca2+ influx.


Subject(s)
Muscle, Skeletal , Polysaccharides , Animals , Polysaccharides/pharmacology , Polysaccharides/chemistry , Mice , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Muscle Fatigue/drug effects , Male , Sodium-Potassium-Exchanging ATPase/metabolism , Swimming , Glycogen/metabolism , Acetylcholinesterase/metabolism , Fatigue/drug therapy , Blood Urea Nitrogen , Acetylcholine/metabolism , Muscle Contraction/drug effects , Ca(2+) Mg(2+)-ATPase/metabolism
3.
Front Cell Dev Biol ; 11: 1238027, 2023.
Article in English | MEDLINE | ID: mdl-37691829

ABSTRACT

The novel coronavirus disease (COVID-19) continues to endanger human health, and its therapeutic drugs are under intensive research and development. Identifying the efficacy and toxicity of drugs in animal models is helpful for further screening of effective medications, which is also a prerequisite for drugs to enter clinical trials. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invades host cells mainly by the S protein on its surface. After the SARS-CoV-2 RNA genome is injected into the cells, M protein will help assemble and release new viruses. RdRp is crucial for virus replication, assembly, and release of new virus particles. This review analyzes and discusses 26 anti-SARS-CoV-2 drugs based on their mechanism of action, effectiveness and safety in different animal models. We propose five drugs to be the most promising to enter the next stage of clinical trial research, thus providing a reference for future drug development.

4.
Front Pharmacol ; 13: 974107, 2022.
Article in English | MEDLINE | ID: mdl-36249824

ABSTRACT

Background: Glioma as the most frequently discovered tumor affecting the brain shows significant morbidity and fatality rates with unfavorable prognosis. There is an urgent need to find novel therapeutic targets to overcome the low chemotherapeutic efficacy of glioma. This research examined whether the copper-metabolism-domain protein, COMMD4, had predictive and therapeutic significance in glioma. Methods: Using the freely accessible CGGA (The Chinese Glioma Atlas) and TCGA (The Cancer Genome Atlas) databases, we examined the function of COMMD4 in GBM and LGG. CIBERSORT and TIMER were utilized to assess the associations between COMMD4 and immune cells. The Gene Set Enrichment Analysis (GSEA) was employed to examine the functional data. Furthermore, the link between COMMD4 expression and predicted treatment response was evaluated via CellMiner Cross-Database. Meanwhile, qRT-PCR was conducted to examine COMMD4 expression in human glioma. Finally, Migration and invasion of glioma cells (U-87, U-251) were assessed using transwell assays. R was used to analyze the statistical data. Results: According to our findings, COMMD4 expression level was higher in patients having grade-dependent glioma who also showed an unfavorable prognosis. Furthermore, qRT-PCR confirmed the high expression of COMMD4 in glioma tissues and cells. Additionally, using integrated correlation analysis, we acquired significant prognostic findings between isocitrate dehydrogenase 1(IDH1) and COMMD4. Meanwhile, a link between COMMD4 and many tumor-infiltrating immune cells was observed. GSEA and drug response analysis revealed the potential mechanism of COMMD4 in drug resistance of glioma. Conclusion: The current findings validated COMMD4 as a novel biological marker, which might offer insights into the possible drug resistance mechanisms and the impact of the immune microenvironment on glioma. COMMD4 might be used to predict glioma prognosis.

5.
Biomed Pharmacother ; 153: 113358, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35785699

ABSTRACT

The objectives of this study were to investigate the antithrombotic effect and physiological mechanism of okanin, a flavonoid monomer in Coreopsis tinctoria Nutt. The antithrombotic effects of okanin were determined by the anticoagulant activity test in vitro and in vivo, the venous thrombosis and arterial thrombosis test in rats. To study the antithrombotic physiological mechanisms of okanin, UV spectrophotometer and enzyme-linked immunosorbent assay (ELISA) were used to determine the effects of three concentrations of okanin on the contents of 6-keto-prostaglandin F1α (6-Keto-PGF1α), thromboxane B2 (TXB2), endothelin-1 (ET-1), antithrombin III (AT-Ⅲ), protein C (PC) and von willebrand factor (vWF) in the plasma of rats with arterial thrombosis; ELISA was used to detect the effects of okanin on the contents of plasminogen (PLG), tissue plasminogen activator (t-PA) and type-1 plasminogen activator inhibitor (PAI-1) in the plasma of mice and Chinese white rabbits. The results showed that okanin could prolong the coagulation time in vitro and in vivo of animals (P < 0.01 in the high dose group) and the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) of human venous blood (ATPP of medium dose group P < 0.01; PT, TT P < 0.05. P < 0.01 in the high dose group); inhibit the maximum platelet aggregation rate of rabbits (P < 0.05 in the low dose group; P < 0.01 in the medium and high dose groups), decrease the dry and wet weight of venous thrombosis and the wet weight of common carotid artery thrombosis in rats (low dose group, P < 0.05; medium and high dose groups, P < 0.01); increase the levels of 6-Keto-PGF1α, AT-Ⅲ, PLG and t-PA in animal plasma; decrease the levels of TXB2, ET-1, vWF and PAI-1 in animal plasma. It is concluded that okanin can significantly inhibit thrombosis, and its physiological mechanisms were related to affecting the activation of related coagulation factors in endogenous and exogenous coagulation pathways, affecting the physiological characteristics of platelets, repairing damaged vascular endothelial cells and enhancing the activity of the fibrinolytic system.


Subject(s)
Thrombosis , Tissue Plasminogen Activator , 6-Ketoprostaglandin F1 alpha , Animals , Anticoagulants/pharmacology , Chalcones , Endothelial Cells/metabolism , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/therapeutic use , Humans , Rabbits , Rats , Thrombosis/drug therapy , Thrombosis/prevention & control , Tissue Plasminogen Activator/metabolism , von Willebrand Factor
6.
Digit Health ; 8: 20552076221102772, 2022.
Article in English | MEDLINE | ID: mdl-35651732

ABSTRACT

Objective: To evaluate the effects of intervention by "whole seamless connection of nursing from WeChat interactive platform" on stigma and quality of life of the patients with urinary system cancer. Methods: Overall, 80 patients with urinary cancer were randomly divided (40 cases per group) into control and observation groups. Routine nursing was provided to the control group, whereas positive psychological intervention was provided to the intervention group through a "whole seamless connection of nursing from the WeChat interactive platform" in addition to routine nursing. The Chinese version of social impact and cancer patients' quality of life scales were used to evaluate the effects before and after the intervention. Results: After the intervention, the total score for stigma was significantly lower (p < 0.01), while that of quality of life was higher (p < 0.05) in the observation group relative to the control group. Conclusions: The whole seamless connection of nursing from the WeChat interactive platform could reduce stigma and improve the quality of life of patients with urinary cancer.

7.
Comput Human Behav ; 114: 106568, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32982038

ABSTRACT

During COVID-19, social media has played an important role for public health agencies and government stakeholders (i.e. actors) to disseminate information regarding situations, risks, and personal protective action inhibiting disease spread. However, there have been notable insufficient, incongruent, and inconsistent communications regarding the pandemic and its risks, which was especially salient at the early stages of the outbreak. Sufficiency, congruence and consistency in health risk communication have important implications for effective health safety instruction as well as critical content interpretability and recall. It also impacts individual- and community-level responses to information. This research employs text mining techniques and dynamic network analysis to investigate the actors' risk and crisis communication on Twitter regarding message types, communication sufficiency, timeliness, congruence, consistency and coordination. We studied 13,598 pandemic-relevant tweets posted over January to April from 67 federal and state-level agencies and stakeholders in the U.S. The study annotates 16 categories of message types, analyzes their appearances and evolutions. The research then identifies inconsistencies and incongruencies on four critical topics and examines spatial disparities, timeliness, and sufficiency across actors and message types in communicating COVID-19. The network analysis also reveals increased communication coordination over time. The findings provide unprecedented insight of Twitter COVID-19 information dissemination which may help to inform public health agencies and governmental stakeholders future risk and crisis communication strategies related to global hazards in digital environments.

8.
Front Oncol ; 10: 1496, 2020.
Article in English | MEDLINE | ID: mdl-32983989

ABSTRACT

Background: Clear cell renal cell carcinoma (ccRCC) is the most frequent and terminal subtype of RCC. Reliable markers associated with the immune response are not available to predict the prognosis of patients with ccRCC. We exploited the extensive number of ccRCC samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repository to perform a comprehensive analysis of immune-related genes (IRGs). Methods: Based on TCGA data, we incorporated IRGs and their expression profiles of 72 normal and 539 ccRCC samples. Univariate Cox analysis was used to evaluate the relationship between overall survival (OS) and IRGs expression. The Lasso Cox regression model identified prognostic genes used to establish a clinical immune prognostic model. The TF-IRG network was used to study the potential molecular mechanisms of action and properties of ccRCC-specific IRGs. Multivariate Cox analysis established a clinical prognostic model of IRGs. Results: We found a significant correlation among 15 differentially expressed IRGs with the OS of patients with ccRCC. Gene function enrichment analysis showed that these IRGs are significantly associated with response to receptor ligand activity. Lasso Cox regression analysis identified 10 genes with the greatest prognostic value. A clinical prognostic model based on six IRGs, which performed well for predicting prognosis, revealed significant associations of patients' survival with age, sex, stage, tumor, node, and metastasis. Moreover, these findings reflect the infiltration of tumors by various immune cells. Conclusion: We identified six clinically significant IRGs and incorporated them into a clinical prognostic model with great significance for monitoring and predicting prognosis of ccRCC.

9.
Int Immunopharmacol ; 87: 106707, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32683297

ABSTRACT

BACKGROUND: Diffuse gliomas are the most prevalent primary brain tumors. The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases provide evidence of the relationships between gliomas and altered molecular pathways. In glioma pathogenesis, the microenvironment has emerged as a potential indicator of tumor progression. METHODS: We investigated and confirmed the role of RELT-like 1 (RELL1) oncogene in glioblastoma and low-grade glioma by data mining large cohorts of TCGA and the CGGA. Correlations between immune cells and RELL1 were verified using the CIBERSORT algorithm. RESULTS: Our analysis revealed that RELL1 expression was much higher in grade-dependent glioma patients with poor prognosis. Comparable prognostic values for isocitrate dehydrogenase 1 (IDH1) and RELL1 were observed during in-depth analyses of the integrated correlations. Moreover, RELL1 was found to be associated with numerous tumor-infiltrating immune cells in glioma-affected patients. CONCLUSION: We conclude that RELL1 might serve as a potential therapeutic target or prognostic marker in glioblastoma and diffuse glioma cases.


Subject(s)
Biomarkers, Tumor , Brain Neoplasms , Carrier Proteins , Glioma , Membrane Proteins , Adult , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Brain Neoplasms/genetics , Brain Neoplasms/immunology , Brain Neoplasms/mortality , Carrier Proteins/genetics , Carrier Proteins/immunology , Disease Progression , Female , Gene Expression Regulation, Neoplastic , Glioma/genetics , Glioma/immunology , Glioma/mortality , Humans , Male , Membrane Proteins/genetics , Membrane Proteins/immunology , Oncogenes , Prognosis , Proportional Hazards Models
10.
Phys Chem Chem Phys ; 22(27): 15649-15657, 2020 Jul 21.
Article in English | MEDLINE | ID: mdl-32618305

ABSTRACT

Hydrogen production from water splitting by sunlight is a promising approach to solve the increasing energy and environmental crises, and the two-dimensional (2D) g-C3N4 monolayer is a red star in this realm. However, it suffers from low quantum efficiency caused by the fast combination of photogenerated electrons and holes. In this work, we investigate the electronic and photocatalytic properties of three newly proposed g-C3N4/SiP-GaS-α, -ß and -γ heterojunctions via first principles predictions. Theoretical results demonstrate that the three g-C3N4/SiP-GaS heterojunctions exhibit direct bandgaps of ∼2.2 eV, and have a type-II band alignment with the valence band maximum (VBM) located at the g-C3N4 layer and the conduction band minimum (CBM) at the SiP-GaS layer. Furthermore, their band edges straddle the redox potential of water in a wide range of biaxial strain. Their absorption coefficients are several times larger than that of most previously discovered 2D heterojunctions. Moreover, the in-built electric field adds a driving force to separate photogenerated electrons and holes. The oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) successfully take place on the g-C3N4 and SiP-GaS layers, respectively. Briefly, separated charge carriers, suitable band edges and strong visible-light absorbance, successful OER and HER enable the three g-C3N4/SiP-GaS heterojunctions to be promising water-splitting photocatalysts.

11.
J Safety Res ; 73: 199-209, 2020 06.
Article in English | MEDLINE | ID: mdl-32563395

ABSTRACT

INTRODUCTION: Crashes involving roadway objects and animals can cause severe injuries and property damages and are a major concern for the traveling public, state transportation agencies, and the automotive industry. This project involved an in-depth investigation of such crashes based on the second Strategic Highway Research Program (SHRP 2) Naturalistic Driving Study (NDS) data including detailed information and videos about 2,689 events. METHODS: The research team conducted a variety of logistic regression analyses, complemented by Support Vector Machine (SVM) analyses and detailed case studies. RESULTS: The logistic regression results indicated that driver behavior/errors, involvement of secondary tasks, roadway characteristics, lighting condition, and pavement surface condition are among the factors that contributed significantly to the occurrence and/or increased severity outcomes of crashes involving roadway objects and animals. Among these factors, improper turning movements (odds ratio = 88), avoiding animal or other vehicle (odds ratio = 38), and reaching/moving object in vehicle (odds ratio = 29) particularly increased the odds of crash occurrence. Factors such as open country roadways, sign/signal violation, unfamiliar with roadway, fatigue/drowsiness, and speeding significantly increased the severity outcomes when such crashes occurred. The sensitivity analysis of the three SVM classifiers confirmed that driver behavior/errors, critical speed, struck object type, and reaction time were major factors affecting the occurrence and severity outcomes of events involving roadway objects and animals. Practical Applications: The study provides insights on risk factors influencing safety events involving roadway objects, including their occurrence and the severity outcomes. The findings allow researchers and traffic engineers to better understand the causes of such crashes and therefore develop more effective roadway- and vehicle- based countermeasures.


Subject(s)
Accidents, Traffic/statistics & numerical data , Automobile Driving/statistics & numerical data , Accidents, Traffic/classification , Humans , Lighting , Logistic Models , Risk Factors , United States
12.
PeerJ ; 7: e8205, 2019.
Article in English | MEDLINE | ID: mdl-31875150

ABSTRACT

There has been an increase in the mortality rate and morbidity of kidney cancer (KC) with kidney renal clear cell carcinoma (KIRC) being the most common subtype of KC. GRAMD1C (GRAM Domain Containing 1C) has not been reported to relate to prognosis and immunotherapy in any cancers. Using bioinformatics methods, we judged the prognostic value of GRAMD1C expression in KIRC and investigated the underlying mechanisms of GRAMD1C affecting the overall survival of KIRC based on data downloaded from The Cancer Genome Atlas (TCGA). The outcome revealed that reduced GRAMD1C expression could be a promising predicting factor of poor prognosis in kidney renal clear cell carcinoma. Meanwhile, GRAMDIC expression was significantly correlated to several tumor-infiltrating immune cells (TIICs), particularly the regulatory T cells (Tregs). Furthermore, GRAMD1C was most significantly associated with the mTOR signaling pathway, RNA degradation, WNT signaling pathway, toll pathway and AKT pathway in KIRC. Thus, GRAMD1C has the potential to become a novel predictor to evaluate prognosis and immune infiltration for KIRC patients.

13.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(5): 418-421, 2019 Sep.
Article in Chinese | MEDLINE | ID: mdl-31894673

ABSTRACT

OBJECTIVE: To study the effects of Fomes officinalis Ames. polysaccharides(FOPS) on anti-fatigue and hypoxia tolerance in mice. METHODS: Forty-eight mice were randomly divided into control group, low-dose, middle-dose and high-dose group of FOPS (100, 200, 400 mg/kg). All mice were orally administered by 0.20 ml/10 g, once a day for 21 consecutive days. The effects of different doses of FOPS on the loaded-swimming time, the content of serum urea nitrogen, the blood lactic acid, the hepatic glycogen and the muscle glycogen after exercise, the survival time under hypoxia at normal pressure and the maintenance time after decapitation were observed. RESULTS: FOPS could significantly prolong the loaded-swimming time, decrease the contents of serum urea nitrogen , blood lactic acid and increase the contents of hepatic glycogen and muscle glycogen, significantly prolong the survival time under hypoxia and the maintenance time after decapitation comparing with the control group. Compared with the control group, FOPS could prolong the weight-bearing swimming time, anti-hypoxia survival time and respiratory maintenance time of mice after decapitation in a dose-dependent manner (P<0.05 or 0.01). FOPS could decrease the contents of serum urea nitrogen and blood lactic acid, and increase the contents of hepatic glycogen and muscle glycogen in exercise mice, and most of them were significantly different (P<0.05) or extremely significant (P<0.01). CONCLUSION: FOPS has anti-fatigue effects and can improve hypoxia tolerance.


Subject(s)
Coriolaceae , Hypoxia , Polysaccharides , Animals , Blood Urea Nitrogen , Coriolaceae/chemistry , Fatigue/drug therapy , Glycogen/metabolism , Hypoxia/drug therapy , Lactic Acid/blood , Liver/drug effects , Liver/metabolism , Mice , Plant Extracts/pharmacology , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Swimming
14.
Am J Reprod Immunol ; 79(1)2018 Jan.
Article in English | MEDLINE | ID: mdl-29083087

ABSTRACT

PROBLEM: To understand the mechanisms of action of Tim-3 at the maternal-fetal interface and explore how Tim-3 might be involved in the pathogenesis of abortion by constructing an in vitro trophoblast-lymphocyte system. METHODS OF STUDY: Female CBA/J × male DBA/2 matings were used as the abortion-prone model and CBA/J × male BALB/c matings as control. The expression of Tim-3 at the maternal-fetal interface and in the peripheral blood lymphocytes was measured by immunohistochemistry and Western blotting. The proliferation index of lymphocytes and levels of Th1/Th2-derived cytokines in peripheral blood and in the co-culture system were determined using CCK-8 assay and ELISA, respectively. RESULTS: The expression level of Tim-3 was higher in abortion-prone matings than that of control (P < .05). A preponderance of Th1 was observed in the co-culture system in the abortion-prone mating group. Recombinant Tim-3 Ig reversed the imbalance of Th1/Th2 immunity of abortion-prone matings by suppressing the secretion of IFN-γ and IL-2 but had no direct effect on the generation of IL-4. CONCLUSION: Tim-3 might contribute to successful pregnancy by restraining Th1 bias, and the maternal immune system might develop a strategy including upregulation of Tim-3 at the maternal-fetal interface and in peripheral blood so as to maintain moderate inflammatory responses against miscarriage.


Subject(s)
Abortion, Habitual/immunology , Hepatitis A Virus Cellular Receptor 2/metabolism , Maternal-Fetal Exchange/immunology , Th1 Cells/immunology , Th2 Cells/immunology , Animals , Cytokines/metabolism , Disease Models, Animal , Embryo, Mammalian , Female , Hepatitis A Virus Cellular Receptor 2/genetics , Humans , Male , Mice , Mice, Inbred CBA , Mice, Inbred DBA , Pregnancy , Th1-Th2 Balance , Up-Regulation
15.
Oxid Med Cell Longev ; 2017: 7180943, 2017.
Article in English | MEDLINE | ID: mdl-29057033

ABSTRACT

Methylglyoxal (MGO), an active metabolite of glucose, has been reported to induce vascular cell apoptosis in diabetic complication. Polydatin (PD), a small natural compound from Polygonum cuspidatum, has a number of biological functions, such as antioxidative, anti-inflammatory, and nephroprotective properties. However, the protective effects of PD on MGO-induced apoptosis in endothelial cells remain to be elucidated. In this study, human umbilical vein endothelial cells (HUVECs) were used to explore the effects of PD on MGO-induced cell apoptosis and the possible mechanism involved. HUVECs were pretreated with PD for 2 h, followed by stimulation with MGO. Then cell apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) impairment, mitochondrial morphology alterations, and Akt phosphorylation were assessed. The results demonstrated that PD significantly prevented MGO-induced HUVEC apoptosis. PD pretreatment also significantly inhibited MGO-induced ROS production, MMP impairment, mitochondrial morphology changes, and Akt dephosphorylation. These results and the experiments involving N-acetyl cysteine (antioxidant), Cyclosporin A (mitochondrial protector), and LY294002 (Akt inhibitor) suggest that PD prevents MGO-induced HUVEC apoptosis, at least in part, through inhibiting oxidative stress, maintaining mitochondrial function, and activating Akt pathway. All of these data indicate the potential application of PD for the treatment of diabetic vascular complication.


Subject(s)
Apoptosis/drug effects , Drugs, Chinese Herbal/therapeutic use , Endothelial Cells/metabolism , Glucosides/therapeutic use , Human Umbilical Vein Endothelial Cells/drug effects , Mitochondria/metabolism , Stilbenes/therapeutic use , Drugs, Chinese Herbal/pharmacology , Glucosides/pharmacology , Humans , Oxidative Stress , Stilbenes/pharmacology
16.
J Am Heart Assoc ; 6(7)2017 Jul 03.
Article in English | MEDLINE | ID: mdl-28673898

ABSTRACT

BACKGROUND: Coagulation factor V (FV) plays a key role in hemostasis, is present in plasma and platelets, and has both pro- and anticoagulant properties; however, the contribution of platelet-derived FV to arterial thrombosis remains undetermined. METHODS AND RESULTS: Using transgenic mice with various levels of FV gene expression that was restricted to the plasma or platelets, the roles of platelet FV were evaluated in the regulation of arterial thrombosis and platelet activation. Mice with higher levels of platelet FV exhibited faster thrombotic occlusion of the carotid artery after injury compared with mice with lower platelet FV levels. Infusion of platelets with higher levels of FV into transgenic mice with undetectable levels of platelet FV reduced the time to carotid artery occlusion. In contrast, infusion of purified recombinant plasma FV into mice with undetectable platelet FV levels failed to reduce the carotid occlusion times following injury. Evaluation of isolated platelets revealed that platelet-derived FV was critical for the regulation of platelet activation. These effects were associated with an increased level of expression of P-selectin and increased cGMP in platelets. CONCLUSIONS: We established that platelet-derived FV is a critical mediator of arterial thrombosis that involves platelet activation.


Subject(s)
Blood Coagulation , Blood Platelets/metabolism , Carotid Artery Diseases/blood , Factor V/metabolism , Platelet Activation , Thrombosis/blood , Animals , Blood Coagulation/drug effects , Blood Coagulation/genetics , Blood Platelets/drug effects , Carotid Artery Diseases/genetics , Cyclic GMP/blood , Disease Models, Animal , Factor V/administration & dosage , Factor V/genetics , Genetic Predisposition to Disease , Infusions, Intravenous , Male , Mice, Knockout , Phenotype , Platelet Activation/drug effects , Platelet Activation/genetics , Recombinant Proteins/administration & dosage , Selenoprotein P/blood , Thrombosis/genetics , Time Factors , Transforming Growth Factor beta
17.
Article in Chinese | MEDLINE | ID: mdl-26653224

ABSTRACT

OBJECTIVE: To describe the incidence, development and death of pneumoconiosis reported in Hebei from 2001 to 2012 and investigate the epidemiological trends and characteristics of pneumoconiosis to provide basic data for formulating the guidelines and policies for control of pneumoconiosis. METHODS: The Hebei database of new cases of pneumoconiosis reposed from 2001 to 2012 were subjected to systematic arrangement. Clean data and descriptive analysis using SPSS 17.0. The statistical indices included number of new and death pneumoconiosis cases in each year. RESULTS: From 2001 to 2012 a total of 4558 new cases of pneumoconiosis were reported. The situation was same to coal-workers' pneumoconiosis and silicosis. (2) The pneumoconiosis cases were distributed mainly in the city of Tang Shan, Cheng De, Zhang Jia Kou and Han Dan (88.24%). (3) Most cases were centerred in coal industry, metallurgical industry, nonferrous metals industry, architectural material industry and light industry. (4) The mean age of onset in new cases was shorted each year for silicosis, coal-workers' pneumoconiosis, potter pneumoconiosis and electric welder pneumoconiosis, especially for 2010 to 2012 (9 years). (5) The work types of these cases mainly included drilling (26.72%), mining as the main work (6.67%), hybrid coal mine work (6.95%), molding worker (5.24%) and berterring worker (4.82%). (6) The new cases of pneumoconiosis reposed from 2001 to 2012 were diagnosissed I (3415, 74.92%), II (782, 17.16%), III (361, 7.92%). (7) The death cases of pneumoconiosis reposed from 2001 to 2012 were 1182, most of them were distributed mainly in the city of Tang Shan, Cheng De, Zhang Jia Kou and Han Dan (88.24%). CONCLUSION: The incidence of pneumoconiosis is still high: the new cases of pneumoconiosis is still rising. The mean age of onset in new cases was shorted each year. The new cases of pneumoconiosis reposed from 2001 to 2012 were diagnosed II was above 25%. The prevention and control of pneumoconiosis should be enhanced in key industries and for people engaging in key regions, industries, types of work according to the epidemiological characteristics of pneumoconiosis. Most cases were centerred in coal-workers' pneumoconiosis and silicosis.


Subject(s)
Pneumoconiosis/epidemiology , Anthracosis/epidemiology , China/epidemiology , Coal Industry , Humans , Incidence , Metallurgy , Mining , Silicosis/epidemiology
18.
Eur J Obstet Gynecol Reprod Biol ; 194: 85-91, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26342682

ABSTRACT

OBJECTIVE: It is well documented that an imbalance in immune tolerance at the maternal-fetal interface is likely to play an essential role in the etiology of preeclampsia. However, the mechanisms underlying immune tolerance during preeclampsia are still poorly understood. Tim-3, a Th1-specific cell surface molecule, is a relatively newly described molecule with important immunological functions. It can regulate Th1 responses with its ligand galectin-9 (Gal-9), and has become an attractive candidate for exploring the pathogenesis of preeclampsia. STUDY DESIGN: Twenty normal pregnancies and 20 preeclamptic pregnancies were enrolled in the present study. We examined the expression and function of Tim-3/Gal-9 in decidual tissue at the RNA and protein levels. In order to analyze their correlation with the development of preeclampsia, we measured the expression of Tim-3 on peripheral blood leukocytes using flow cytometry. IFN-γ, IL-10, and IL-17 in the peripheral blood plasma were measured by ELISA. RESULTS: Tim-3/Gal-9 was upregulated in decidual tissue of preeclamptic vs. normotensive pregnancies. There was a significantly increased Th1 and Th17 response in PE as demonstrated by the upregulated levels of IFN-γ/IL-17, whereas IL-10 secreted by Th2 cells was sharply reduced. CONCLUSIONS: The present study showed that an abnormal Tim-3/Gal-9 pathway was able to facilitate the development of preeclampsia. Our data uncovered a novel mechanism by which the Tim-3/Gal-9 pathway regulates immune responses, and we now identify this pathway as a potential therapeutic target in preeclampsia.


Subject(s)
Galectins/physiology , Membrane Proteins/physiology , Pre-Eclampsia/etiology , Female , Galectins/blood , Hepatitis A Virus Cellular Receptor 2 , Humans , Membrane Proteins/blood , Pre-Eclampsia/immunology , Pregnancy , Th1 Cells/immunology , Th17 Cells/immunology , Up-Regulation
19.
J Phys Chem A ; 119(14): 3384-92, 2015 Apr 09.
Article in English | MEDLINE | ID: mdl-25781354

ABSTRACT

Understanding the structure and properties of cyclohexoxy radical and its substitutes is important because of their presence in combustion processes, in atmospheric chemistry, and as intermediates in the hydrocarbon reactions. In this work, jet-cooled laser-induced fluorescence (LIF) spectra of five dimethyl substituted cyclohexoxy radicals are obtained for the first time. The correlation between the spectral variations and the radical structural changes is studied with the assistance of theoretical calculations at the B3LYP/6-31+G(d) and CASSCF/6-31+G(d) levels. The results show that the spectral characters of the dimethylcyclohexoxy radicals and their dissociation kinetics are predominantly affected by the methyl substitution position related to the C-O group. The spectral effect of the two methyl groups will add up if they locate on asymmetric carbons of the cyclohexoxy ring. Methyl substitution on ß carbon weakens the six-member ring of cyclohexoxy and results in unimolecular dissociation via ß C-C bond cleavage on the methyl group side and forms vinoxy variants. This study clearly shows that the LIF spectra can be used to identify cyclohexoxy and the isomers of its methyl substitutes. The results will help to understand the photochemistry of cyclic hydrocarbons in the atmospheric and combustion processes.

20.
J Huazhong Univ Sci Technolog Med Sci ; 34(4): 586-590, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25135732

ABSTRACT

The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.


Subject(s)
Abortion, Spontaneous/metabolism , Chorionic Villi/metabolism , Galectins/biosynthesis , Membrane Proteins/biosynthesis , Pregnancy Proteins/biosynthesis , Up-Regulation , Abortion, Spontaneous/pathology , Adolescent , Adult , Chorionic Villi/pathology , Female , Hepatitis A Virus Cellular Receptor 2 , Humans , Interleukin-12/blood , Interleukin-4/blood , Pregnancy
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