The association between meat consumption and the metabolic syndrome: a cross-sectional study and meta-analysis.

The findings regarding the associations between red meat, fish and poultry consumption, and the metabolic syndrome (Mets) have been inconclusive, and evidence from Chinese populations is scarce. A cross-sectional study was performed to investigate the associations between red meat, fish and poultry consumption, and the prevalence of the Mets and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 4424 participants were eligible for the analysis. A logistic regression model was used to estimate the OR and 95 % CI for the prevalence of the Mets and its components according to red meat, fish and poultry consumption. In addition, the data of our cross-sectional study were meta-analysed under a random effects model along with those of published observational studies to generate the summary relative risks (RR) of the associations between the highest v. lowest categories of red meat, fish and poultry consumption and the Mets and its components. In the cross-sectional study, the multivariable-adjusted OR for the highest v. lowest quartiles of consumption was 1·23 (95 % CI 1·02, 1·48) for red meat, 0·83 (95 % CI 0·72, 0·97) for fish and 0·93 (95 % CI 0·74, 1·18) for poultry. In the meta-analysis, the pooled RR for the highest v. lowest categories of consumption was 1·20 (95 % CI 1·06, 1·35) for red meat, 0·88 (95 % CI 0·81, 0·96) for fish and 0·97 (95 % CI 0·85, 1·10) for poultry. The findings of both cross-sectional studies and meta-analyses indicated that the association between fish consumption and the Mets may be partly driven by the inverse association of fish consumption with elevated TAG and reduced HDL-cholesterol and, to a lesser extent, fasting plasma glucose. No clear pattern of associations was observed between red meat or poultry consumption and the components of the Mets. The current findings add weight to the evidence that the Mets may be positively associated with red meat consumption, inversely associated with fish consumption and neutrally associated with poultry consumption.

Galectin-2 in Health and Diseases.

Galectin-2 is a prototype member of the galactoside-binding galectin family. It is predominately expressed in the gastrointestinal tract but is also detected in several other tissues such as the placenta and in the cardiovascular system. Galectin-2 expression and secretion by epithelial cells has been reported to contribute to the strength of the mucus layer, protect the integrity of epithelia. A number of studies have also suggested the involvement of galectin-2 in tissue inflammation, immune response and cell apoptosis. Alteration of galectin-2 expression occurs in inflammatory bowel disease, coronary artery diseases, rheumatoid arthritis, cancer, and pregnancy disorders and has been shown to be involved in disease pathogenesis. This review discusses our current understanding of the role and actions of galectin-2 in regulation of these pathophysiological conditions.

Appearance of peanut agglutinin in the blood circulation after peanut ingestion promotes endothelial secretion of metastasis-promoting cytokines.

Peanut agglutinin (PNA) is a carbohydrate-binding protein in peanuts that accounts for ~0.15% peanut weight. PNA is highly resistant to cooking and digestion and is rapidly detectable in the blood after peanut consumption. Our previous studies have shown that circulating PNA mimics the actions of endogenous galactoside-binding protein galectin-3 by interaction with tumour cell-associated MUC1 and promotes circulating tumour cell metastatic spreading. The present study shows that circulating PNA interacts with micro- as well as macro-vascular endothelial cells and induces endothelial secretion of cytokines MCP-1 (CCL2) and IL-6 in vitro and in vivo. The increased secretion of these cytokines autocrinely/paracrinely enhances the expression of endothelial cell surface adhesion molecules including integrins, VCAM and selectin, leading to increased tumour cell-endothelial adhesion and endothelial tubule formation. Binding of PNA to endothelial surface MCAM (CD146), via N-linked glycans, and subsequent activation of PI3K-AKT-PREAS40 signalling is here shown responsible for PNA-induced secretion of MCP-1 and IL-6 by vascular endothelium. Thus, in addition to its influence on promoting tumour cell spreading by interaction with tumour cell-associated MUC1, circulating PNA might also influence metastasis by enhancing the secretion of metastasis-promoting MCP-1 and IL-6 from the vascular endothelium.

Expression of plasma IFN signaling-related miRNAs during acute SARS-CoV-2 infection and its association with RBD-IgG antibody response.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a huge challenge worldwide. Although previous studies have suggested that type I interferon (IFN-I) could inhibit the virus replication, the expression characteristics of IFN-I signaling-related miRNAs (ISR-miRNAs) during acute severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and its relationship with receptor-binding domain (RBD) IgG antibody response at the recovery phase remain unclear. METHODS: Expression profiles of 12 plasma ISR-miRNAs in COVID-19 patients and healthy controls were analyzed using RT-qPCR. The level of RBD-IgG antibody was determined using the competitive ELISA. Spearman correlation was done to measure the associations of plasma ISR-miRNAs with clinical characteristics during acute SARS-CoV-2 infection and RBD-IgG antibody response at the recovery phase. RESULTS: Compared with the healthy controls, COVID-19 patients exhibited higher levels of miR-29b-3p (Z = 3.15, P = 0.002) and miR-1246 (Z = 4.98, P < 0.001). However, the expression of miR-186-5p and miR-15a-5p were significantly decreased. As the results shown, miR-30b-5p was negatively correlated with CD4 + T cell counts (r = - 0.41, P = 0.027) and marginally positively correlated with fasting plasma glucose in COVID-19 patients (r = 0.37, P = 0.052). The competitive ELISA analysis showed the plasma level of miR-497-5p at the acute phase was positively correlated with RBD-IgG antibody response (r = 0.48, P = 0.038). CONCLUSIONS: Our present results suggested that the expression level of ISR-miRNAs was not only associated with acute SARS-CoV-2 infection but also with RBD-IgG antibody response at the recovery phase of COVID-19. Future studies should be performed to explore the biological significance of ISR-miRNAs in SARS-CoV-2 infection.

DHPAC, a novel microtubule depolymerizing agent, suppresses angiogenesis and vasculogenic mimicry formation of human non-small cell lung cancer.

Angiogenesis and vasculogenic mimicry (VM) are the main causes of tumor metastasis and recurrence. In this study, we investigated the antiangiogenesis and anti-VM formation of a novel microtubule depolymerizing agent, DHPAC, as well as combretastatin A4 (CA4, a combretastatin derivate) in non-small-cell lung cancer (NSCLC), subsequently elucidating the underlying mechanisms. In human umbilical vein endothelial cells (HUVECs), DHPAC could enter cells and inhibit proliferation, migration, and angiogenesis in the presence and absence of conditioned medium from H1299 cells. Interestingly, the inhibition was enhanced under the stimulation of the conditioned medium. Under hypoxia or normoxia, DHPAC suppressed signal transducer and activator of transcription 3 phosphorylation and reduced vascular endothelial growth factor (VEGF) expression and secretion from HUVECs, thus impeding the activation of the downstream signal transduction pathway of VEGF/VEGFR2. However, JNK inhibitors reversed the inhibitory effect of DHPAC on the angiogenesis, suggesting that DHPAC regulated angiogenesis through activating JNK. In H1299 cells, DHPAC could inhibit proliferation, migration, invasion, and the formation of VM. In addition, DHPAC inhibited the phosphorylation of FAK and AKT and decreased the expressions of VEGF, matrix metalloproteinase 2 (MMP2), MMP9 and Laminin 5, suggesting that DHPAC inhibited VM formation via the FAK/AKT signaling pathway. In addition, CA4 showed a similar effect as DHPAC against angiogenesis and VM formation. These new findings support the use of microtubule destabilizing agents as a promising strategy for cancer therapy.

Interaction with the heparin-derived binding inhibitors destabilizes galectin-3 protein structure.

The ß-galactoside-binding protein, galectin-3, is extensively involved in cancer development, progression and metastasis through multiple mechanisms. Inhibition of the galectin-3-mediated actions is increasingly considered as a promising therapeutic approach for cancer treatment. Our early studies have identified several novel galectin-3 binding inhibitors from chemical modification of the anticoagulant drug heparin. These heparin-derived galectin-3 binding inhibitors, which show no anticoagulant activity and bind to the galectin-3 canonical carbohydrate-binding site, induce galectin-3 conformational changes and inhibit galectin-3-mediated cancer cell adhesion, invasion and angiogenesis in vitro and reduce metastasis in mice. In this study, we determined the binding affinities of these heparin-derived ligands to galectin-3 using an isothermal titration calorimetry (ITC) ligand displacement approach. Such ITC experiments showed that the 2-de-O-sulphated, N-acetylated (compound E) and 6-de-O-sulphated, N-acetylated (F) heparin-derived ligands and their ultra-low molecular weight sub-fractions (E3 and F3) bind to galectin-3 with KD ranging from 0.96 to 1.32 mM.Differential scanning fluorimetry analysis revealed that, in contrast to the disaccharide ligand, N-acetyl-lactosamine, which binds to the fully folded form of galectin-3 and promotes galectin-3 thermal stability, the heparin-derived ligands preferentially bind to the unfolded state of galectin-3 and cause destabilization of the galectin-3 protein structure. These results provide molecular insights into the interaction of galectin-3 with the heparin-derived ligands and explain the previously demonstrated in vitro and in vivo effects of these binding inhibitors on galectin-3-mediated cancer cell behaviours.

The association between milk consumption and the metabolic syndrome: a cross-sectional study of the residents of Suzhou, China and a meta-analysis.

The association between milk consumption and the metabolic syndrome remains inconclusive, and data from Chinese populations are scarce. We conducted a cross-sectional study to investigate the association between milk consumption and the metabolic syndrome and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 5149 participants were included in the final analysis. A logistic regression model was applied to estimate the OR and 95 % CI for the prevalence of the metabolic syndrome and its components according to milk consumption. In addition, the results of our study were further meta-analysed with other published observational studies to quantify the association between the highest v. lowest categories of milk consumption and the metabolic syndrome and its components. There was no significant difference in the odds of having the metabolic syndrome between milk consumers and non-milk consumers (OR 0·86, 95 % CI 0·73, 1·01). However, milk consumers had lower odds of having elevated waist circumference (OR 0·78, 95 % CI 0·67, 0·92), elevated TAG (OR 0·83, 95 % CI 0·70, 0·99) and elevated blood pressure (OR 0·85, 95 % CI 0·73, 0·99). When the results were pooled together with other published studies, higher milk consumption was inversely associated with the risk of the metabolic syndrome (relative risk 0·80, 95 % CI 0·72, 0·88) and its components (except elevated fasting blood glucose); however, these results should be treated with caution as high heterogeneity was observed. In summary, the currently available evidence from observational studies suggests that higher milk consumption may be inversely associated with the metabolic syndrome.

Investigation of TF-binding lectins from dietary sources and SRL on proliferation and cell cycle progression in human colon HT29 and SW620 cells.

TF antigen binding lectins from dietary sources PNA, ACA, ABL, JAC, and SRL from Sclerotium rolfsii have been reported to induce diverse effects on cancer cell proliferation by different mechanisms. This study aimed to compare effects of these lectins on growth and cell cycle progression in colon cancer HT29 and SW620 cells. As reported SRL, ABL, and JAC inhibited while PNA and ACA increased cell proliferation. ABL and JAC treated HT29 cells showed increased cell population in G0/G1 phase. PNA, ACA, ABL, and JAC increased SW620 cell population in S and decreased in G2/M phase. In contrast, SRL and JAC increased hypodiploid population in both the cells. PNA and ACA reduced whereas SRL and ABL diminished cell cyclin D1 expression. SRL, PNA, and ACA also reduced cellular cyclin D3 level while SRL, ABL, and JAC reduced cyclin E levels. ABL decreased CDK5 levels while SRL and ACA completely abolished CDK5 expression. All the lectins completely abolished cyclin D2 expression. These results not only confirms growth regulatory effects of TF-binding lectins but also indicates different effects of these lectins on cell growth is associated with regulation on expression of cell cycle associated proteins in G1-S phase and on cell cycle progression.

Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells.

The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans. We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model. This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines. Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion. Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells. CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3. Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling. siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells. Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines. We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.

Endogenous and exogenous galectin-3 promote the adhesion of tumor cells with low expression of MUC1 to HUVECs through upregulation of N-cadherin and CD44.

Tumor cell-endothelial adhesion is one of the key steps in tumor cell haematogenous dissemination in metastasis and was previously shown to be mediated by interaction of galectin-3 with the transmembrane mucin protein MUC1. In this study, the effect of exogenous as well as endogenous galectin-3 on adhesion of two cell lines (low MUC1-expressing human prostate cancer PC-3M cells and non-small-cell lung cancer A549 cells) to monolayer of umbilical vein endothelial cells (HUVECs) was investigated. We found that suppression of endogenous galectin-3 expression reduced tumor cell adhesion to HUVECs and also decreased cell invasion and migration. Exogenous galectin-3 promoted tumor cell adhesion to HUVECs by entering cells. Both exogenous and endogenous galectin-3 upregulated the expression of ß-catenin and increased ß-catenin nuclear accumulation, and subsequently upregulated the expression of N-cadherin and CD44. We deduced that both exogenous as well as endogenous galectin-3 promoted low MUC1-expressing cancer cell adhesion to HUVECs by increasing the expression of N-cadherin and CD44 via an increase of nuclear ß-catenin accumulation. These results were confirmed further by using a ß-catenin/TCF transcriptional activity inhibitor, N-cadherin or CD44 siRNAs. Taken together, our results suggest a new molecular mechanism of galectin-3-mediated cell adhesion in cancer metastasis.

Metformin incombination with curcumin inhibits the growth, metastasis, and angiogenesis of hepatocellular carcinoma in vitro and in vivo.

Hepatocellular carcinoma (HCC) has poor prognosis due to the advanced disease stages by the time it is diagnosed, high recurrence rates and metastasis. In the present study, we investigated the effects of metformin (a safe anti-diabetic drug) and curcumin (a turmeric polyphenol extracted from rhizome of Curcuma longa Linn.) on proliferation, apoptosis, invasion, metastasis, and angiogenesis of HCC in vitro and in vivo. It was found that co-treatment of metformin and curcumin could not only induce tumor cells into apoptosis through activating the mitochondria pathways, but also suppress the invasion, metastasis of HCC cells and angiogenesis of HUVECs. These effects were associated with downregulation of the expression of MMP2/9, VEGF, and VEGFR-2, up-regulation of PTEN, P53 and suppression of PI3K/Akt/mTOR/NF-κB and EGFR/STAT3 signaling. Co-administration of metformin and curcumin significantly inhibited HCC tumor growth than administration with metformin or curcumin alone in a xenograft mouse model. Thus, metformin and curcumin in combination showed a better anti-tumor effects in hepatoma cells than either metformin or curcumin presence alone and might represent an effective therapeutic strategy for HCC treatment.

Atherogenic index of plasma is a novel and better biomarker associated with obesity: a population-based cross-sectional study in China.

BACKGROUND: Atherogenic index of plasma (AIP) has been reported to be associated with cardiovascular diseases. However no study has yet systematically evaluated the association between AIP and obesity and its advantage in obesity prediction compared with conventional lipid components. METHODS: A total of 6465 participants aged over 30 years were included in this study. Blood lipid components including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured, and AIP was calculated as log10(TG/HDL-C). Pearson correlation analyses, multivariable logistic analyses and predictive analyses were used to evaluate the association and discrimination ability between AIP, four conventional lipid profiles and obesity. RESULTS: Subjects in the higher quartiles of AIP all had a significantly increased risk of obesity compared with those in the lowest quartile (P for trend< 0.01). AIP showed a stronger association with obesity than the conventional lipid components as the pearson coefficient reached up to 0.372 and the adjusted odds ratio was 5.55. Using AIP rather than HDL-C and TG significantly improved risk prediction for obesity (AUC improvement = 0.011, P = 0.011; Continuous net reclassification index = 29.55%, P < 0.01; Category net reclassification index = 6.06%; Integrated discrimination improvement = 0.68%, P < 0.01). CONCLUSIONS: Higher AIP level was positively and strongly associated with obesity. AIP is a novel and better biomarker associated with obesity. Controlling the AIP level would be more helpful for the prevention of obesity.

Risk of reduced platelet counts in patients with nonalcoholic fatty liver disease (NAFLD): a prospective cohort study.

BACKGROUND: The production of peripheral platelet is mainly regulated by thrombopoietin, which is a glycoprotein hormone predominantly synthesized in the liver. Previously, many studies have reported that there was an inverse correlation between the degree of chronic viral hepatitis and the peripheral platelet count. However, the effect of nonalcoholic fatty liver disease (NAFLD) on the peripheral platelet counts remains unclear. METHODS: With 1303 participants from "The prevention of MS and multi-metabolic disorders in Jiangsu province of China (PMMJS)" cohort study, we investigated the associations between NAFLD and the risk of platelet counts reduction in Chinese adults. The paired-samples T test was used to explore the platelet counts changes between baseline and follow-up. Multivariate logistic regression was used to examine the association between presence of NAFLD and the risk of platelet reduction by calculating the odds ratios (ORs) and 95% confidence interval (CI). RESULTS: After five years of follow-up, platelet counts were markedly reduced from 220.6 ± 42.22 (109/L) at baseline to 208.41 ± 40.70 (109/L) at follow-up in NAFLD group (P < 0.0001). However, platelet counts were slightly lowered from 213.2 ± 43.26(109/L) at baseline to 211.8 ± 41.65 (109/L) at follow-up in non-NAFLD people (P = 0.2349). Meanwhile, there was a significant association between NAFLD and the risks of platelet count reduction, even after adjustment for confounding variables (OR: 1.68, 95% CI: 1.06-2.67). Additionally, among the participants with BMI ≤ 23 kg/m2 and SUA ≤ 344.3 µmol/L, the NAFLD participants have an increased risk of platelet count reduction compared to the persons in non-NAFLD group. CONCLUSIONS: Our present results suggested that NAFLD individuals have an increased risk of platelet counts reduction.

[Relationship between abdominal obesity and dyslipidemia in postmenopausal women in a community of Suzhou City in 2014].

OBJECTIVE: To explore the relationship between abdominal obesity and dyslipidemia in postmenopausal women. METHODS: Based on the project of 2014 community comprehensive intervention for prevention of chronic diseases in Suzhou Industrial Park, 2 000 residents in a community were randomly selected. Among them, a total of 323 women with natural menopause for more than 12 months were observed. Height, body weight, waist circumference, blood pressure, and plasma levels of triglycerides( TG) level, total cholesterol( TC) level, high-density lipoprotein cholesterol( HDL-C) level and low-density lipoprotein cholesterol( LDL-C) were measured. Abdominal obesity was diagnosed by waist circumference( ≥85 cm) according to Criteria of Weight for Adults. Hyperglycemia was diagnosed by TG, TC, HDL-C and LDL-C in Guidelines for Prevention and Treatment of Dyslipidemia in Chinese Adults( 2007). Relationship between abdominal obesity and dyslipidemia was analyzed by Logistic regressionmethod. RESULTS: The incidences of abdominal obesity and dyslipidemia were13. 6%( 44/323) and 29. 7%( 96/323), respectively. The rate of dyslipidemia was significantly higher in abdominal obesity group than in the control group( 43. 2% vs27. 6%, P = 0. 036). Waist circumference was positively correlated with TG( r = 0. 28, P < 0. 01) and LDL-C( r = 0. 20, P < 0. 01), and negatively correlated with HDL-C( r =-0. 26, P < 0. 01). The multivariate Logistic regression analysis showed that abdominal obesity had significantly increased risk of dyslipidemia( OR = 2. 07, 95% CI 1. 04-4. 13, P = 0. 039). The OR for TG and HDL-C were 3. 81( 95% CI 1. 69-8. 60, P =0. 001) and 3. 19( 95% CI 1. 36-7. 52, P = 0. 008), respectively. CONCLUSION: Abdominal obesity is likely to be a risk factor for dyslipidemia in postmenopausal women.

[Relationship between abdominal obesity/pre-obesity and hyperglycemia in postmenopausal women].

OBJECTIVE: To explore the relationship between abdominal obesity/pre-obesity and hyperglycemia in postmenopausal women. METHODS: A total of 323 women aged than 35 years or older and with natural menopause more than 12 months were selected from Suzhou Industrial Park in 2014 community comprehensive intervention for prevention and control of chronic diseases. Blood pressure, height, body weight, waist circumference, fasting plasma glucose (FPG) level, glycated hemoglobin (HbA1c) and blood lipids were measured. Abdominal obesity and pre-obesity was diagnosed by waist circumference. Hyperglycemia was diagnosed by FPG and HbA1c. RESULTS: The incidence of abdominal obesity was 31.0% in this population. The level of waist circumference was positively correlated with FPG (r = 0.18, P < 0.01) and HbA1c (r = 0.20, P < 0.01). The incidence of hyperglycemia was 34.4% and 83.9%, respectively, according to diagnostic criteria of FPG and HbA1c. When FPG was used as diagnosis, there were no significant difference on hyperglycemia incidence and risk between abdominal obesity/pre-obesity and non-obesity populations (31.8% vs 40.0%, P = 0.076). When HbA1c was used as diagnosis, hyperglycemic incidence was significantly higher in abdominal obesity/pre-obesity population than in non-obesity population (91.0% vs 80.7%, P = 0.020). The multivariate logistic regression analysis showed that abdominal obesity/ pre-obesity had significantly increased risk of hyperglycemia, with OR of 2.46 (95% CI 1.07 - 5.62, P = 0.034). CONCLUSION: Abdominal obesity is likely to be a risk factor for hyperglycemia.

Molecular mechanism of anticancer effect of Sclerotium rolfsii lectin in HT29 cells involves differential expression of genes associated with multiple signaling pathways: A microarray analysis.

Sclerotium rolfsii lectin (SRL) is a lectin isolated from fungus S. rolfsii and has high binding specificity toward the oncofetal Thomsen-Friedenreich carbohydrate antigen (Galß1-3GalNAc-α-O-Ser/Thr, T or TF), which is expressed in more than 90% of human cancers. Our previous studies have shown that binding of SRL to human colon, breast and ovarian cancer cells induces cell apoptosis in vitro and suppresses tumor growth in vivo. This study investigated the SRL-mediated cell signaling in human colon cancer HT29 cells by mRNA and miRNA microarrays. It was found that SRL treatment results in altered expression of several hundred molecules including mitogen-activated protein kinase (MAPK) and c-JUN-associated, apoptosis-associated and cell cycle and DNA replication-associated signaling molecules. Pathway analysis using GeneSpring 12.6.1 revealed that SRL treatment induces changes of MAPK and c-JUN-associated signaling pathways as early as 2 h while changes of cell cycle, DNA replication and apoptosis pathways were significantly affected only after 24 h. A significant change of cell miRNA expression was also observed after 12 h treatment of the cells with SRL. These changes were further validated by quantitative real time polymerase chain reaction and immunoblotting. This study thus suggests that the presence of SRL affects multiple signaling pathways in cancer cells with early effects on cell proliferation pathways associated with MAPK and c-JUN, followed by miRNA-associated cell activity and apoptosis. This provides insight information into the molecular mechanism of the anticancer activity of this fungal lectin.

Peanut agglutinin appearance in the blood circulation after peanut ingestion mimics the action of endogenous galectin-3 to promote metastasis by interaction with cancer-associated MUC1.

Peanut agglutinin (PNA), which accounts for ~0.15% of the weight of the common peanut, is a carbohydrate-binding protein that binds the oncofoetal Thomsen-Friedenreich (TF) disaccharide (galactoseß1,3N-acetylgalactosamineα-) that is overexpressed by ~90% of human cancers. Previous studies have shown that PNA is highly resistant to cooking and digestion and rapidly enters the human blood circulation after peanut ingestion. This study investigates the hypothesis that PNA appearance in the circulation after peanut ingestion may mimic the actions of endogenous TF-binding human galectin-3 in metastasis promotion. It shows that PNA at concentrations similar to those found in blood circulation after peanut ingestion increases cancer cell heterotypic adhesion to the blood vascular endothelium and enhances the formation of tumour cell homotypic aggregates, two important steps in the metastasis cascade, and enhances metastasis in a mouse metastasis model. These effects of PNA are shown to result from its interaction with the cancer-associated TF disaccharide on the transmembrane mucin protein MUC1, causing MUC1 cell surface polarization that reveals underlying cell surface adhesion molecules. Thus, PNA appearance in the blood circulation after peanut ingestion mimics the actions of endogenous galectin-3 and promotes cancer cell metastatic spread by interaction with cancer-associated TF/MUC1. As metastasis accounts for the majority of cancer-associated fatality, regular consumption of peanuts by cancer patients would therefore be expected to have an adverse effect on cancer survival.

A tetramethylpyrazine piperazine derivate CXC137 prevents cell injury in SH-SY5Y cells and improves memory dysfunction of rats with vascular Dementia.

We investigated the effects of CXC137, a tetramethylpyrazine piperazine derivate, on cell damage induced by N-methyl-D-aspartate (NMDA) in human derived neuroblastoma cells (SH-SY5Y) and its effect on memory dysfunction of rats with vascular dementia. It was found that the presence of CXC137 increased SH-SY5Y cells viability by inhibition of cell apoptosis induced by NMDA. These effects of CXC137 were accompanied by increases of the antioxidant superoxide dismutase activity and the level of reduced glutathione, and a decrease of lipid peroxidation product, malondialdehyde. The presence of CXC137 also showed to produce strong inhibition of cellular lactate dehydrogenase leakage, cell apoptosis and intracellular calcium overload. In a vascular dementia rat model established by bilateral common carotid arteries occlusion, treatment with CXC137 from 2 to 35 day of post-operation significantly improves the motor performance, spatial learning and memory capability of rats in both the prehensile traction test and Morris water maze test, an effect that was companied by reductions of the animal glutamic acid levels and the degree of brain mitochondrial swelling. These results suggest that CXC137 can improve the memory dysfunction in dementia and thus has important therapeutic potential for the treatment of dementia.

Factors influencing contractors' low-carbon construction behaviors in China: a LDA-DEMATEL-ISM approach.

Contractors' low-carbon construction behaviors (CLCB) are pivotal in advancing decarbonization during the construction phase. However, there exists a notable gap in the comprehensive exploration of the multifaceted factors and mechanisms influencing CLCB. Therefore, this study aims to systematically identify the factors influencing CLCB in China, examine the interrelationships among these factors, and pinpoint the key determinants. Based on topic modeling of Latent Dirichlet Allocation (LDA), influencing factors are identified firstly from the pertinent literature. Subsequently, the causality degree and centrality degree between these factors are assessed by the Decision-Making Trial and Evaluation Laboratory (DEMATEL), followed by the establishment of a hierarchical structure using the Interpretive Structural Modeling (ISM) method, culminating in the identification of pivotal factors. Findings reveal that (1) 21 influential factors influencing CLCB are identified. (2) "Incentive policies for relevant stakeholders" and "Low-carbon regulation and supervision" emerge as key influences. (3) CLCB should be guided by policy and subjective awareness, fortified by market and management support, underpinned by technology, and directly driven by economic considerations. This research furnishes valuable insights for promoting low-carbon development during the construction phase, thereby assisting the construction sector in achieving carbon peak and carbon neutrality.

Inhibition of PTEN expression and activity by angiotensin II induces proliferation and migration of vascular smooth muscle cells.

PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor and has been suggested recently to be involved in the regulation of cardiovascular diseases. The molecular mechanisms of this regulation are however poorly understood. This study shows that down regulation of PTEN expression and activity by angiotensin II (Ang II) increased proliferation and migration of vascular smooth muscle cells (VSMCs). The presence of Ang II induced rapid PTEN phosphorylation and oxidation in accordance with increased AKT and FAK phosphorylation. The Ang II-mediated VSMC proliferation and migration was inhibited when cellular PTEN expression was increased by AT1 inhibitor losartan, PPARγ agonist rosiglitazone, NF-κB inhibitor BAY 11-7082. Over expression of PTEN in VSMCs by adenovirus transduction also resulted in inhibition of cell proliferation and migration in response to Ang II. These results suggest that PTEN down-regulation is involved in proliferation and migration of VSMCs induced by Ang II. This provides insight into the molecular regulation of PTEN in vascular smooth muscle cells and suggests that targeting the action of PTEN may represent an effective therapeutic approach for the treatment of cardiovascular diseases.