ABSTRACT
Jaceosidin (JAC) is a natural flavonoid with anti-oxidant and other pharmacological activities; however, its anti-cancer mechanism remains unclear. We investigated the mechanism of action of JAC in gastric cancer cells. Cytotoxicity and apoptosis assays showed that JAC effectively killed multiple gastric cancer cells and induced apoptosis in human gastric adenocarcinoma AGS cells via the mitochondrial pathway. Network pharmacological analysis suggested that its activity was linked to reactive oxygen species (ROS), AKT, and MAPK signaling pathways. Furthermore, JAC accumulated ROS to up-regulate p-JNK, p-p38, and IκB-α protein expressions and down-regulate the p-ERK, p-STAT3, and NF-κB protein expressions. Cell cycle assay results showed that JAC accumulated ROS to up-regulate p21 and p27 protein expressions and down-regulate p-AKT, CDK2, CDK4, CDK6, Cyclin D1, and Cyclin E protein expressions to induce G0/G1 phase arrest. Cell migration assay results showed JAC accumulated ROS to down-regulate Wnt-3a, p-GSK-3ß, N-cadherin, and ß-catenin protein expressions and up-regulate E-cadherin protein expression to inhibit migration. Furthermore, N-acetyl cysteine pre-treatment prevented the change of these protein expressions. In summary, JAC induced apoptosis and G0/G1 phase arrest and inhibited migration through ROS-mediated signaling pathways in AGS cells.
Subject(s)
Stomach Neoplasms , Humans , Apoptosis , Cell Line, Tumor , Cell Proliferation , Flavonoids/pharmacology , Glycogen Synthase Kinase 3 beta/metabolism , Glycogen Synthase Kinase 3 beta/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathologyABSTRACT
Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay revealed that ISO has a considerable killing effect on HCC cell lines. The apoptosis assay showed that ISO induced mitochondria-dependent apoptosis through the Bad/cyto-c/cleaved (cle)-caspase-3/cleaved (cle)-PARP pathway. The network pharmacological analysis found 13 key target genes, and epidermal growth factor receptor (EGFR), AKT, mitogen-activated protein kinase (MAPK), and reactive oxygen species (ROS) signaling pathways were strongly associated with ISO against HCC. Further verification of the results showed that ISO induced apoptosis by increasing p-p38 and p-JNK expression and decreasing p-EGFR, p-SRC, p-ERK, and p-STAT3 expression. Furthermore, ISO induced G0/G1 phase arrest by downregulating p-AKT, Cyclin D, and CDK 4 expression and upregulating p21 and p27 expression in HepG2 cells. Moreover, ISO inhibited HepG2 cell migration by decreasing p-GSK-3ß, ß-catenin, and N-cadherin expression and increasing E-cadherin expression. Additionally, ISO promoted ROS accumulation in HepG2 cells, and ISO-induced apoptosis, arrest cell cycle, and inhibition of migration were reversed by an ROS scavenger, N-acetyl- l-cysteine. Overall, ISO induced cell apoptosis and cell cycle arrest and inhibited cell migration by ROS-mediated EGFR, AKT, and MAPK signaling pathways in HepG2 cells.
Subject(s)
Carcinoma, Hepatocellular , Flavones , Liver Neoplasms , Humans , Hep G2 Cells , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Glycogen Synthase Kinase 3 beta , Network Pharmacology , ErbB ReceptorsABSTRACT
BACKGROUND: Clinical diagnosis of cirrhotic cardiomyopathy (CCM) often encounters challenges of lack of timeliness and disease severity, with the commonly positive indicator usually associated with advanced heart failure. AIM: To explore suitable biomarkers for early CCM prediction. METHODS: A total of 505 eligible patients were enrolled in this study and divided into four groups according to Child-Pugh classification: Group I, Class A without CCM (105 cases); Group II, Class A with CCM (175 cases); Group III, Class B with CCM (139 cases); and Group IV, Class C with CCM (86 cases). Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine whether red blood cell distribution width (RDW) was an independent risk factor for CCM risk. The relationships between RDW and Child-Pugh scores, Model for End-Stage Liver Disease (MELD) scores, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analyzed by Pearson correlation analysis. RESULTS: A constant RDW increase was evident from Group I to Group IV (12.54 ± 0.85, 13.29 ± 1.19, 14.30 ± 1.96, and 16.25 ± 2.13, respectively). Pearson correlation analysis showed that RDW was positively correlated with Child-Pugh scores (r = 0.642, P < 0.001), MELD scores (r = 0.592, P < 0.001), and NT-proBNP (r = 0.715, P < 0.001). Furthermore, between Group I and Group II, RDW was the only significant index (odds ratio: 2.175, 95% confidence interval [CI]: 1.549-3.054, P < 0.001), and it reached statistical significance when examined by ROC curve analysis (area under the curve: 0.686, 95%CI: 0.624-0.748, P < 0.001). CONCLUSION: RDW can serve as an effective and accessible clinical indicator for the prediction of diastolic dysfunction in CCM, in which a numerical value of more than 13.05% may indicate an increasing CCM risk.
Subject(s)
Cardiomyopathies , End Stage Liver Disease , Humans , End Stage Liver Disease/complications , Severity of Illness Index , Erythrocyte Indices , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Cardiomyopathies/etiology , Cardiomyopathies/complications , Erythrocytes , Prognosis , Retrospective Studies , ROC CurveABSTRACT
Protein modifications such as post-translational modifications (PTMs) and sequence variants (SVs) occur frequently during protein biosynthesis and have received great attention by biopharma industry and regulatory agencies. In this study, an aberrant peak near light chain (LC) was observed in the non-reduced capillary electrophoresis sodium dodecyl sulfate (nrCE-SDS) electrophoretogram during cell line development of one bispecific antibody (BsAb) product, and the detected mass was about 944 Da higher than LC. The corresponding peak was then enriched by denaturing size-exclusion chromatography (SEC-HPLC) and further characterized by nrCE-SDS and peptide mapping analyses. De novo mass spectra/mass spectra (MS/MS) analysis revealed that the aberrant peak was LC related sequence variant, with the truncated C-terminal sequence "SFNR" ("GEC"deleted) linked with downstream SV40 promotor sequence "EAEAASASELFQ". The unusual sequence was further confirmed by comparing with the direct synthetic peptide "SFNREAEAASASELFQ". It was demonstrated by mRNA sequencing of the cell pool that the sequence variant was caused by aberrant splicing at the transcription step. The prepared product containing this extension variant maintained well-folded structure and good functional properties though the LC/Heavy chain (HC) inter-chain disulfide was not formed. Several control strategies to mitigate the risk of this LC related sequence variant were also proposed.
ABSTRACT
Atractylodin (ATR) has anticancer effects on some tumor cells by inducing apoptosis, but its mechanism in lung cancer remains unclear. This study investigates the inhibitory effect of ATR on A549 lung cancer cells. Cell viability was detected by the Cell Counting Kit-8 assay, and results showed that ATR could significantly inhibit the proliferation of A549 cells. Apoptosis was detected by Annexin V-FITC/PI staining, and apoptosis rate and mitochondrial membrane potential were detected by flow cytometry. Results showed that the effect of ATR on the apoptosis of A549 cells was negatively correlated with the change in mitochondrial membrane potential. Western blot analysis showed that ATR regulated apoptosis induced by mitogen-activated protein kinase, signal transducer and activator of transcription 3, and nuclear factor kappa B signaling pathways. Analyses of reactive oxygen species (ROS), cell cycle, and cell migration showed that ATR induced intracellular ROS accumulation as an initiation signal to induce cell cycle arrest regulated by the AKT signaling pathway and cell migration inhibition regulated by the Wnt signaling pathway. Results showed that ATR can inhibit cell proliferation, induce cell apoptosis, induce cell cycle arrest, and inhibit the migration of A549 cells (p < 0.05 was considered statistically significant, * p < 0.05, ** p < 0.01 and *** p < 0.001).
Subject(s)
Lung Neoplasms , A549 Cells , Apoptosis , Cell Cycle Checkpoints , Cell Line, Tumor , Cell Proliferation , Furans , Humans , Lung Neoplasms/metabolism , Reactive Oxygen Species/metabolism , Signal TransductionABSTRACT
1,4-naphthoquinone and its derivatives have attracted widespread attention due to their multiple biological activities, such as induction of cancer cell apoptosis; however, most of these compounds have high cytotoxicity. In this study, in order to reduce their toxicity and increase their potential anti-tumor effects, we synthesized a novel 1,4-naphthoquinone derivative named 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ), and investigated its apoptotic effects and underlying mechanism. Our results showed that NTDMNQ inhibited the viability of HepG2, Hep3B, and Huh7 human hepatocellular carcinoma (HCC) cells. It also increased the accumulation of cells in the G0/G1 phase of the cell cycle by increasing the expression levels of p-p53, p21 and p27, while decreasing the levels of Cyclin D1, Cyclin E, Cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. Inhibition of reactive oxygen species (ROS) by the ROS scavenger N-acetyl-L-cysteine (NAC) decreased apoptosis in NTDMNQ-treated cells. Western blot analysis showed that NTDMNQ increased the phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), AKT, and signal transducer and activator of transcription-3 (STAT3); these effects were blocked by NAC. Both the JNK inhibitor (SP600125) and p38 inhibitor (SB203580) reversed the phosphorylation of STAT3, and the ERK inhibitor (FR180204) and AKT inhibitor (LY294002) reduced the expression of STAT3. Taken together, these findings suggest that NTDMNQ induces apoptosis via ROS-mediated MAPK, AKT and STAT3 signaling pathways in HepG2 cells, and may be a potent anticancer agent.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Apoptosis , Carcinoma, Hepatocellular/drug therapy , Hep G2 Cells , Humans , Liver Neoplasms/drug therapy , Naphthalenes , Naphthoquinones , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , STAT3 Transcription Factor , Signal TransductionABSTRACT
Challenges remain for clinicians over balancing the efficacy of active antithrombotic therapy and simultaneous bleeding reduction in patients. The clinical data of 347 patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) were retrospectively analyzed. On the basis of the given tirofiban, the patients were assigned into three different dose groups: high dose group (group H), medium dose group (group M), and low dose group (group L). The tirofiban efficacy was evaluated in terms of major adverse cardiovascular event (MACE) parameters and lab endpoints, including platelet count and function. The tirofiban safety was assessed by the occurrence of bleeding events. The patients were followed up for 1 month after the PCI. No significant difference in MACE events was evident among these groups (p > 0.05). Groups H and M reported an obvious reduction in platelet count (p < 0.05 for both) and an increased platelet inhibition rate (p < 0.05 for both). Group H showed a higher rate of total bleeding events than the other groups (Group H vs. Group M: 34.4% vs. 16.5%; Group H vs. Group L: 34.4% vs. 10.3%; p < 0.05 for both). A proper administration of a low dose of tirofiban may be a superior alternative in treating ACS patients, which can produce a similar favorable clinical outcome and a decrease in bleeding complication.
Subject(s)
Myocardial Infarction/drug therapy , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/administration & dosage , Tirofiban/administration & dosage , Adult , Aged , Female , Humans , Male , Middle Aged , Myocardial Infarction/surgery , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Tirofiban/adverse effects , Tirofiban/therapeutic useABSTRACT
Liquiritin (LIQ), a major constituent of Glycyrrhiza Radix, exhibits various pharmacological activities. In this study, to explore the potential anti-cancer effects and its underlying molecular mechanisms of LIQ in hepatocellular carcinoma (HCC) cells. LIQ significantly decreased viability and induced apoptosis in HepG2 cells by decreasing mitochondrial membrane potential and regulating Bcl-2 family proteins, cytochrome c, cle-caspase-3, and cle-PARP. The cell cycle analysis and western blot analysis revealed that LIQ induced G2/M phase arrest through increased expression of p21 and decreased levels of p27, cyclin B, and CDK1/2. The flow cytometry and western blot analysis also suggested that LIQ promoted the accumulation of ROS in HepG2 cells and up-regulated the phosphorylation expression levels of p38 kinase, c-Jun N-terminal kinase (JNK), and inhibitor of NF-κB (IκB-α); the phosphorylation levels of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), signal transducer activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) were down-regulated. However, these effects were reversed by N-acetyl-L-cysteine (NAC), MAPK, and AKT inhibitors. The findings demonstrated that LIQ induced cell cycle arrest and apoptosis via the ROS-mediated MAPK/AKT/NF-κB signaling pathway in HepG2 cells, and the LIQ may serve as a potential therapeutic agent for the treatment of human HCC.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cell Proliferation/drug effects , Flavanones/pharmacology , Glucosides/pharmacology , MAP Kinase Signaling System/drug effects , NF-kappa B/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Reactive Oxygen Species/antagonists & inhibitors , Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis/drug effects , Apoptosis/physiology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Cell Proliferation/physiology , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Flavanones/therapeutic use , Glucosides/therapeutic use , Glycyrrhiza , Hep G2 Cells , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , MAP Kinase Signaling System/physiology , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolismABSTRACT
Cytisine is a natural product isolated from plants and is a member of the quinolizidine alkaloid family. This study aims to investigate the effect of cytisine in human lung cancer. Cell viability was determined using the CCK-8 assay, and the results showed that cytisine inhibited the growth of lung cancer cell lines. The apoptotic effects were evaluated using flow cytometry, and the results showed that cytisine induced mitochondrial-dependent apoptosis through loss of the mitochondrial membrane potential; increased expression of BAD, cleaved caspase-3, and cleaved-PARP; and decreased expression levels of Bcl-2, pro-caspase-3, and pro-PARP. In addition, cytisine caused G2/M phase cell cycle arrest that was associated with inhibiting the AKT signalling pathway. During apoptosis, cytisine increased the phosphorylation levels of JNK, p38, and I-κB, and decreased the phosphorylation levels of ERK, STAT3, and NF-κB. Furthermore, cytisine treatment led to the generation of ROS, and the NAC attenuated cytisine-induced apoptosis. In vivo, cytisine administration significantly inhibited the lung cancer cell xenograft tumorigenesis. In conclusion, cytisine plays a critical role in suppressing the carcinogenesis of lung cancer cells through cell cycle arrest and induction of mitochondria-mediated apoptosis, suggesting that it may be a promising candidate for the treatment of human lung cancer.
Subject(s)
Alkaloids/pharmacology , Antineoplastic Agents/pharmacology , Lung Neoplasms/pathology , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Animals , Apoptosis/drug effects , Azocines/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , M Phase Cell Cycle Checkpoints/drug effects , Male , Membrane Potential, Mitochondrial/drug effects , Mice , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Quinolizines/pharmacology , STAT3 Transcription Factor/metabolism , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: Hepatitis E virus (HEV) superinfection is a suspected promoting factor for hepatocellular carcinoma (HCC) in patients with chronic hepatitis and cirrhosis. However, to date, very few cases of HEV-related HCC have been reported. Nevertheless, the role of HEV re-infection in cirrhotic liver without other chronic hepatitis infections has rarely been explored. CASE SUMMARY: A 53-year-old male farmer was diagnosed with liver cirrhosis and splenomegaly in August 2016, accompanied with negative HEV-IgM and positive HEV-IgG. No evidence of hepatitis B virus or hepatitis C virus infection was found. Since then the patient was evaluated for liver function and viral parameters every 3 mo. In June 2017, the patient presented severe fatigue with whole body itching and was diagnosed with HCC. Afterwards this patient experienced quick HCC development, progression, relapse, and metastasis in the following 8 mo, and presented persistent dual positivity of HEV-IgM and HEV-IgG. This patient had a long history of smoking and alcohol consumption. CONCLUSION: This unique case invokes the importance of HEV surveillance and treatment among cirrhotic patients, HCC cases, and blood donors.
ABSTRACT
BACKGROUND: Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) may be a potential biomarker of coronary artery disease (CAD) and stroke. OBJECTIVE: We aimed to investigate the association and prognostic value of elevated sLOX-1 concentrations with regard to long-term major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with CAD undergoing primary percutaneous coronary intervention (PCI). METHODS: A total of 1011 patients were enrolled. Serum sLOX-1 concentrations were detected by the enzyme-linked immunosorbent assay (ELISA). Patients were followed for 2 years. Multivariate Cox regression and Kaplan-Meier survival curve were explored to assess the association between sLOX-1 and MACCEs. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of sLOX-1. RESULTS: Two-year MACCEs were associated with serum sLOX-1 concentrations (HR 1.278, 95% CI 1.019-1.604, P = 0.034), left main disease (HR 2.938, 95% CI 1.246-6.925, P = 0.014), small-caliber stents used (HR 2.207, 95% CI 1.189-4.095, P = 0.012), and total stent length (HR 1.057, 95% CI 1.005-1.112, P = 0.030). Serum sLOX-1 concentration ≥ 1.10 ng/ml had maximum sensitivity and specificity in predicting the occurrence of 2-year MACCEs (P < 0.001). Patients with higher serum sLOX-1 concentrations showed a significantly higher incidence of MACCEs in the Kaplan-Meier curve (P < 0.001). The combination of any of the risk factors identified in multiple Cox regression was associated with a stepwise increase in MACCE rate (P < 0.001). CONCLUSIONS: High baseline serum sLOX-1 concentration predicts 2-year MACCEs and shows an additional prognostic value to conventional risk factors in patients after primary PCI. sLOX-1 determination might play a complementary role in the risk stratification of patients with CAD treated with PCI.
Subject(s)
Biomarkers/blood , Cardiovascular Diseases/etiology , Cerebrovascular Disorders/etiology , Coronary Artery Disease/surgery , Percutaneous Coronary Intervention/adverse effects , Scavenger Receptors, Class E/blood , Aged , Cardiovascular Diseases/blood , Cerebrovascular Disorders/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cohort Studies , Coronary Artery Disease/blood , Coronary Artery Disease/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , ROC Curve , Sensitivity and SpecificityABSTRACT
INTRODUCTION: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in the pathophysiology of atherosclerosis and acute coronary syndromes (ACS). Circulating soluble LOX-1 (sLOX-1) has been linked to the risk of coronary artery disease (CAD). Our aim was to test if baseline serum sLOX-1 was associated with major adverse cardiovascular events (MACE) in patients with stable CAD. MATERIALS AND METHODS: This multicentre pilot study enrolled 833 stable CAD patients. All patients were followed for two years. Serum sLOX-1 concentrations were detected by enzyme-linked immunosorbent assay (ELISA). The association between sLOX-1 concentrations and MACE was assessed by logistic regression, Kaplan-Meier survival curves and Cox proportional hazards analyses. Logistic regression analysis was employed to assess the predictors of complex lesion. RESULTS: Multivariate logistic regression analysis revealed that sLOX-1 concentration was an independent predictor of MACE (OR 2.07, 95%CI 1.52 - 2.82; P < 0.001). Kaplan-Meier cumulative survival curves showed that the incidence of MACE in patients with a high sLOX-1 concentration was significantly higher than in patients with an intermediate or low sLOX-1 concentration (P < 0.001). Soluble LOX-1 concentrations were independently correlated with coronary complex lesions (OR 2.32, 95%CI 1.81 - 2.97; P < 0.001). CONCLUSIONS: Baseline sLOX-1 concentrations were correlated with 2-year MACE in stable CAD patients. Furthermore, patients with high serum sLOX-1 concentrations had higher cumulative incidence of MACE compared to those with low serum sLOX-1 concentrations.
Subject(s)
Cardiovascular System/physiopathology , Coronary Artery Disease/blood , Scavenger Receptors, Class E/blood , Adult , Aged , Aged, 80 and over , Enzyme-Linked Immunosorbent Assay , Female , Humans , Logistic Models , Male , Middle Aged , Pilot ProjectsABSTRACT
The long-term survival benefit of treating unresectable hepatocellular carcinoma (HCC) patients with transarterial chemoembolization (TACE) rather than conservative treatment remains controversial. This retrospective case-control study evaluated the survival of patients with unresectable HCC treated with TACE, relative to that of patients who received best supportive care.From January 2002 to December 2010, 522 of 2386 consecutive patients with unresectable HCC were enrolled. Patients were treated with TACE (nâ=â347) or best supportive care (non-TACE; nâ=â175). A survival analysis compared the survival of the 2 groups, as well as only those at Barcelona Clinic Liver Cancer Classification (BCLC)-C and Child-Pugh-B (39 TACE, 61 non-TACE).The median follow-up was 5 months (0.15-106 months).The overall median survival of the TACE group (8.0 months) was significantly longer than that of the non-TACE (2.0 months; P ≤ .01). Of the patients at BCLC-C and Child-Pugh-B, the overall median survivals of the TACE and non-TACE patients were 6.0 and 2.0 months, respectively (P ≤ .01); and the 1, 2, 3, 5, and 8-year overall survival rates were significantly superior in the TACE group (P ≤ .01). For all the patients, the independent predictors of survival were treatment modalities, portal vein tumor thrombosis, alpha-fetoprotein, and BCLC stage. Regarding the TACE patients, contributors to prognosis were portal vein tumor thrombosis, alpha-fetoprotein level, and the number of TACE procedures.TACE for unresectable HCC was associated with longer survival compared with best supportive care, especially for patients at BCLC-C and Child-Pugh-B.
Subject(s)
Carcinoma, Hepatocellular/mortality , Chemoembolization, Therapeutic/mortality , Liver Neoplasms/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/therapy , Case-Control Studies , Chemoembolization, Therapeutic/methods , Female , Humans , Liver Neoplasms/therapy , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis , Survival Rate , Time Factors , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Malaria control and elimination are challenged by diversity and complexity of the determinants on the international border in the Great Mekong Sub-region. Hekou, a Chinese county on the China-Vietnam border, was used to document Chinese experiences and lessons for malaria control and elimination. METHODS: The design was an ecological study. Malaria burden before 1951 and procedures of 64 years (1952-2015) from malaria hyperendemicity to elimination are described. Single and bilinear regression analysis was utilized to analyse the relationship between the annual malaria incidence (AMI) and gross domestic product (GDP), urbanization rate, and banana planting area (BPA). RESULTS: There was a huge malaria burden before 1951. AMI was reduced from 358.62 per 1000 person-years in 1953 to 5.69 per 1000 person-years in 1960. A system of primary health services, comprising three levels of county township hospitals and village health stations maintained malaria control and surveillance activities in changing political and social-economic settings. However, potential under-reported of malaria and market-oriented healthcare led to a malaria epidemic in 1987. Strong political commitment reoriented malaria from a control to an elimination programme. High coverage of malaria intervention and population access to intervention was crucial for malaria control and elimination; meanwhile, AMI was closely associated with socio-economic development, correlation coefficients (R) -0.6845 (95% CI -0.7978, -0.6845) for national GDP, -0.7014 (-0.8093, -0.7014) for national urbanization rate and -0.5563 (-0.7147, -0.3437) for BPA. CONCLUSIONS: Multifactor, including political commitment, effective interventions, social and economic development and changing ecological environment, and the complicated interactions between these factors contribute to malaria elimination in Hekou County.
Subject(s)
Disease Eradication , Endemic Diseases , Malaria/epidemiology , Malaria/prevention & control , China/epidemiology , Economic Development , Environment , Humans , IncidenceABSTRACT
BACKGROUND: Long-term outcome of drug-eluting stents (DES) for ST-elevation myocardial infarction (STEMI) versus non-ST-elevation acute coronary syndrome (NSTE-ACS) remains unclear. This study sought to compare the long-term outcomes of biodegradable polymer-coated DES in patients with STEMI versus NSTE-ACS. METHODS: We explored a post hoc analysis of the 5-year outcome of the CREATE trial in the subgroup of patients with STEMI (n=318) versus NSTE-ACS (n=1223) who were implanted with biodegradable polymer-coated DES. The primary outcome was the rate of major adverse cardiac events (MACE) at 5 years. Clopidogrel and aspirin for 6 months followed by chronic aspirin therapy were recommended. RESULTS: STEMI patients showed a trend of increase in MACE (8.7% vs. 6.8%, log rank p=0.289) compared to NSTE-ACS patients at 5 years, and a greater risk of cardiac death (5.4% vs. 2.1%, log rank p=0.003), mainly driven by the higher cardiac death rate within the first month after stent placement (log rank p=0.003) and the last year of follow-up (log rank p=0.001). No significant difference in stent thrombosis was found between them (3.1% vs. 2.5%, log rank p=0.653). Prolonged clopidogrel therapy (>6 months) showed no effect on risk of MACE or stent thrombosis between the two groups (both p for interaction >0.1). CONCLUSIONS: STEMI patients have a higher risk of cardiac mortality compared with NSTE-ACS patients after biodegradable polymer-coated DES placement, primarily attribute to more cardiac deaths that happened within the first month after the event and the last year of follow-up.
Subject(s)
Acute Coronary Syndrome/surgery , Anti-Bacterial Agents/administration & dosage , Drug-Eluting Stents/statistics & numerical data , ST Elevation Myocardial Infarction/surgery , Sirolimus/administration & dosage , Absorbable Implants/statistics & numerical data , Acute Coronary Syndrome/drug therapy , Aged , Female , Humans , Male , Middle Aged , Polymers , ST Elevation Myocardial Infarction/drug therapy , Time Factors , Treatment OutcomeABSTRACT
Novel hollow porous VOx/C nanoscrolls are synthesized by an annealing process with the VOx/octadecylamine (ODA) nanoscrolls as both vanadium and carbon sources. In the preparation, the VOx/ODA nanoscrolls are first achieved by a two-phase solvothermal method using ammonium metavanadat as the precursor. Upon subsequent heating, the intercalated amines between the vanadate layers in the VOx/ODA nanoscrolls decompose into gases, which escape from inside the nanoscrolls and leave sufficient pores in the walls. As the anodes of lithium-ion batteries (LIBs), such hollow porous VOx/C nanoscrolls possess exceedingly high capacity and rate capability (904 mAh g-1 at 1 A g-1) and long cyclic stability (872 mAh g-1 after 210 cycles at 1 A g-1). The good performance is derived from the unique structural features of the hollow hierarchical porous nanoscrolls with low crystallinity, which could significantly suppress irreversible Li+ trapping as well as improve Li+ diffusion kinetics. This universal method of annealing amine-intercalated oxide could be widely applied to the fabrication of a variety of porous electrode materials for high-performance LIBs and supercapacitors.
ABSTRACT
A new class of mesoporous single crystalline (MSC) material, Co(OH)2 nanoplates, is synthesized by a soft template method, and it is topotactically converted to dual-pore MSC Co3O4. Most mesoporous materials derived from the soft template method are reported to be amorphous or polycrystallined; however, in our synthesis, Co(OH)2 seeds grow to form single crystals, with amphiphilic block copolymer F127 colloids as the pore producer. The single-crystalline nature of material can be kept during the conversion from Co(OH)2 to Co3O4, and special dual-pore MSC Co3O4 nanoplates can be obtained. As the anode of lithium-ion batteries, such dual-pore MSC Co3O4 nanoplates possess exceedingly high capacity as well as long cyclic performance (730 mAh g(-1) at 1 A g(-1) after the 350th cycle). The superior performance is because of the unique hierarchical mesoporous structure, which could significantly improve Li(+) diffusion kinetics, and the exposed highly active (111) crystal planes are in favor of the conversion reaction in the charge/discharge cycles.
ABSTRACT
4-coumaric acid: coenzyme A ligase (4CL) gene is one of the key genes involved in the regulation of lignin metabolism and the synthesis of flavonoid and other secondary metabolites in plant, while the synthesized and polymerized lignin is deposited in cell walls and leads to thickening of secondary walls in some parenchyma cells and formation of stone cells. To better understand the variety and quantity of 4CL genes in Pyrus bretschneideri Rehd., we used the amino acid and cDNA databases of Pyrus bretschneideri Rehd. genome to screen 4CL gene family, and analyzed their classification, evolutionary relationships, physical location, gene structure and conserved motif. Our results showed that 29 4CL genes were identified and preliminarily characterized, and these 4CL genes were distributed in all chromosomes except chromosomes 4, 8, 11, 12 and clustered on chromosomes 9 and 17 through gene location analysis. The relationship between 4CL gene structure and evolution was further determined by comparing gene structure and phylogenetic tree. These findings provide a basis for further analysis of 4CL gene function in Pyrus bretschneideri Rehd.
Subject(s)
Coenzyme A Ligases/genetics , Genome, Plant , Pyrus/genetics , Amino Acid Sequence , Molecular Sequence Data , Physical Chromosome MappingABSTRACT
OBJECTIVES: To investigate plasma total ghrelin and obestatin levels and the ghrelin/obestatin ratio prospectively, in hypertensive obese patients. METHODS: Height, weight, and waist and hip circumferences were measured in hypertensive and normotensive obese patients and matched healthy controls; the body mass index and waist to hip ratio were calculated. Fasting glucose and insulin levels were measured and the homeostasis model assessment of insulin resistance (HOMA-IR) was determined. Fasting ghrelin and obestatin concentrations were measured by radioimmunoassay and the ghrelin/obestatin ratio was calculated. RESULTS: A total of 38 hypertensive obese patients, 40 normotensive obese patients and 38 controls were enrolled. Hypertensive obese patients had lower plasma levels of ghrelin and obestatin than normotensive obese patients or controls. In addition, normotensive obese patients had lower plasma ghrelin and obestatin levels than controls. In hypertensive obese patients, ghrelin and obestatin levels were negatively associated with systolic and diastolic blood pressure, fasting insulin and HOMA-IR. In normotensive obese patients, ghrelin, obestatin and the ghrelin/obestatin ratio were negatively associated with fasting insulin and HOMA-IR. In both patient groups, fasting obestatin and ghrelin concentrations were significantly and positively correlated with each other. CONCLUSION: Changes in the levels of ghrelin and obestatin may play a role in the pathophysiology of obesity and hypertension.
Subject(s)
Ghrelin/blood , Hypertension/blood , Insulin/blood , Obesity/blood , Blood Glucose/analysis , Body Height , Body Mass Index , Body Weight , Fasting/blood , Female , Humans , Male , Middle Aged , Waist Circumference , Waist-Hip RatioABSTRACT
OBJECTIVE: To evaluate the effect of integrated control measures on soil-transmitted nematodiasis so as to provide the evidence for formulating the appropriate control strategies and measures in Jinhu County, Jiangsu Province. METHODS: Since 1995, the comprehensive control measures were carried out for soil-transmitted nematodiasis, and the measures included deworming, health education, safe water, sanitation and environmental remediation. The effects of the comprehensive control measures were evaluated by the investigations of the prevalence of soil-transmitted nematodiasis, awareness of health knowledge, and behaviors of residents. RESULTS: From 1995 to 2012, 646,437 person--times were administrated in deworming medication with 2.48 times per capita; the benefit rate of safe water was 97.90%; the popularity rate of harmless toilets was 86.89%. The awareness rate of health knowledge increased from 54.05% in 1996 to 95.60% in 2012, the difference between them were statistically significant (chi2 = 230.92, P < 0.01); the rate of correct health behaviors increased from 59.07% in 1996 to 96.40% in 2012, the difference between them had statistical significance (chi2 = 202.69, P < 0.01). The prevalence of soil-transmitted nematodiasis decreased from 62.57% in 1989 to 1.21% in 2012, the difference had statistical significance (chi2 = 1016.92, P < 0.01). The infection rates of Ascaris lumbricodes, hookworm and Trichuris trichiura were 0.58%, 1.12% and 0, respectively in 2012, and compared with the rates of those infections in 1989, the decline rates were 94.96%, 97.28% and 100% respectively, the differences between them were statistically significant (chi2 Ascaris = 129.50, chi2 hookworm = 544.62, chi2 Trichurisch = 254.19, all P < 0.01). CONCLUSION: The comprehensive control strategies and measures are effective and soil-transmitted nematodiasis has been controlled in Jinhu County.