Dietary inflammatory potential and the risk of nonfatal cardiovascular diseases in the China Health and Nutrition Survey.

BACKGROUND: To our knowledge, no evidence exists to link dietary inflammatory potential to cardiovascular disease (CVD) in China. Furthermore, the precise mechanisms underlying the link between a pro-inflammatory diet and CVD remain incompletely understood. OBJECTIVE: We aimed to investigate the relationship between dietary inflammatory potential and nonfatal CVD in the Chinese population and to explore the mediating role of insulin resistance. METHODS: A total of 4822 adults who participated in the China Health and Nutrition Survey (CHNS) were included in this analysis. The dietary inflammatory index (DII) was used to assess dietary inflammatory potential. Cox proportional hazards models and restricted cubic spline were applied to assess the longitudinal associations. The triglyceride-glucose (TyG) index was calculated to measure insulin resistance. Mediation analysis using a two-stage regression method for survival data was employed to explore the mediating effects of the TyG index on the association between DII score and nonfatal CVD. RESULTS: During a median follow-up of 18 y, 234 incident cases of nonfatal CVD, including 136 strokes and 114 myocardial infarctions (MIs), were observed. For each standard deviation of the DII score, nonfatal CVD incidence increased by 15% (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.01-1.31), and stroke incidence increased by 22% (HR = 1.22, 95% CI: 1.03-1.45). DII score displayed a linear association with nonfatal CVD and stroke (P for nonlinearity = 0.250 and 0.238, respectively). No significant association was found between the DII score and MI. Mediation analyses showed that the TyG index mediated 5.90% and 9.35% of the total association between DII score and nonfatal CVD and stroke, respectively. CONCLUSIONS: This study provides evidence that dietary inflammatory potential is positively associated with nonfatal CVD and stroke in Chinese adults, and the association was partly mediated by insulin resistance.

Association of dietary calcium intake at dinner versus breakfast with cardiovascular disease in U.S. adults: the national health and nutrition examination survey, 2003-2018.

BACKGROUND: Currently, it is still largely unknown whether the proportion of calcium intake at breakfast and dinner is associated with cardiovascular disease (CVD) in the general population. OBJECTIVES: The aim of this study was to evaluate the association of dietary calcium intake at dinner versus breakfast with CVD in a nationally representative sample of US adults. METHODS: The study population consisted of 36,164 US adults (including 4,040 CVD cases) from the NHANES 2003 to 2018. According to the ratio of dietary calcium intake at dinner and breakfast (Δ = dinner/breakfast), 36,164 participants were divided into five groups. After adjustment for a series of confounder factors, logistic regression analyses were performed to examine the association between Δ and CVD. Dietary substitution models were used to explore the changes in CVD risk when a 5% dietary calcium intake at dinner was substituted with dietary calcium intake at breakfast. RESULTS: Compared with participants in the lowest quintile, participants in the highest quintile were more likely to have CVD, with an adjusted OR of CVD of 1.16 (95% CI, 1.03 to 1.31). When the total calcium intake remained constant, replacing a 5% dietary calcium intake at dinner with dietary calcium intake at breakfast was associated with a 6% lower risk of CVD. CONCLUSIONS: Compared to the lowest quintile of Δ, participants in the highest quintile of Δ were likely to experience CVD in the general population. It is necessary to scientifically allocate dietary calcium intake at breakfast and dinner.

Comprehensive Analysis on Prognostic Signature Based on T Cell-Mediated Tumor Killing Related Genes in Gastric Cancer.

Although immunotherapy is a valuable treatment for gastric cancer (GC), identifying the patients who would benefit most from this approach presents a challenge. In this study, GC patients were divided into two subtypes by consensus clustering according to T cell-mediated tumor killing related genes (TTKRGs), and there were significant differences in tumor-infiltrating immune cells, signaling pathways, and gene expression of immunomodulators and inhibitory immune checkpoints between the two subtypes. Then, we developed an individualized signature based on TTKRGs, and its clinical and predictive value in GC patients for chemotherapeutic and immunotherapeutic responses was assessed. We confirmed the expression levels of signature genes in GC tumor tissue using quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, to improve the accuracy of GC prognosis predictions, we established a nomogram. We further identified some compounds as sensitive drugs targeting GC risk groups. The signature showed significant predictive ability across RNA-seq, microarray, and qRT-PCR cohorts, which could assist in predicting survival, immunotherapeutic and chemotherapeutic outcomes in GC patients.

Inactivation of microglia dampens blood-brain barrier permeability and loss of dopaminergic neurons in paraquat-lesioned mice.

Prior studies indicated the involvement of neuroinflammation in the dopaminergic neurodegeneration in mice of paraquat (PQ)-induced Parkinson's disease (PD), but the underlying mechanisms remain to be elucidated. The present study explored whether microglia-mediated inflammation disrupted blood-brain barrier (BBB) and its related mechanism. C57BL/6 mice were injected intraperitoneally with PQ, twice a week for six weeks, following with or without minocycline (intraperitoneal injection, once every two days). The microglial activation, BBB permeability, expression of tight junctions (TJs) proteins and matrix metalloproteinase (MMP), as well as the loss of dopaminergic neurons and neurological deficits assessment, were evaluated. Minocycline efficiently restrained nigral microglial activation induced by PQ in mice. PQ-induced increase of EB content in the brain and excessive expression of zonula occludin-1 (ZO-1), claudin-5 and occludin were significantly dampened by minocycline treatment. Inhibition of microglial activation by minocycline greatly ameliorated the loss of dopaminergic neurons and neurological dysfunctions in PQ-exposed mice. Also, microglial inactivation downregulated the expression of MMP-2/9 in PQ-lesioned mice. These findings suggested the potential protection of suppressing microglia-mediated neuroinflammation against dopaminergic neurodegeneration through attenuating BBB disruption in a mouse of PQ-induced PD, and MMP-2/9 might involve in the contribution, which needs to be verified in future study.

Association Between the Risk of Hyperuricemia and Changes in Branched-Chain Amino Acids Intake Over Twelve Years: A Latent Class Trajectory Analysis From the China Health and Nutrition Survey, 1997-2009.

Objective: This study aims to identify dietary branched-chain amino acids (BCAA) consumption trajectories in Chinese adults and to evaluate their association with the risk of hyperuricemia (HU). Methods: Cohort data from the China Health and Nutrition Survey 1997-2009 were adopted in this research. A total of 6,810 participants aged ≥18 years were included in this study. Participants were designated into four subgroups on basis of the trajectories of dietary BCAA consumption. Cox proportional hazards models were performed to discuss the relationships between varied trajectories and the risk of HU after adjusting potential confounders. The intermediary effect of differential blood indexes between the trajectories and the risk of HU was explored with mediation analysis. Results: Four distinct trajectory groups of dietary BCAA consumption were identified. Compared with the low stable trajectory group, high to low trajectory group was greatly related to an increased risk of HU (HR 1.35 (95% CI 1.03 to 1.79)) with modification for covariates. Total cholesterol (TC), hemoglobin A1c (HbA1c), fasting blood glucose (FBG), and triglyceride (TG) partially regulated trajectories and HU. Conclusion: Gradually decreasing dietary BCAA intake increased the risk of HU, which is, at least, partially mediated by TC, HbA1c, FBG, and TG levels.

Risk and Prognosis of Second Primary Cancers among Ovarian Cancer Patients, Based on SEER Database.

The purposes of the present study were to elucidate the risk and prognostic effect of second primary cancers (SPCs) development, as well as the factors influencing the prognosis of OC patients with SPCs. A statistically significant increase in SPCs risk was observed among OC patients during 2004-2015. The independent factors were used to construct the SPCs-prediction nomogram and the OS-prediction nomogram. Both nomogram were subjected to internal validation and performed well. OC patients with SPCs have a better prognosis than patients without SPCs. Propensity score matching (PSM) was applied to reduce confounding.

Association between risk of type 2 diabetes and changes in energy intake at breakfast and dinner over 14 years: a latent class trajectory analysis from the China health and nutrition Survey, 1997-2011.

OBJECTIVE: This study aimed to investigate the association between the trajectories of energy consumption at dinner versus breakfast and the risk of type 2 diabetes (T2D). DESIGN: Cohort study. SETTING: The study was conducted in China. PARTICIPANTS: A total of 10 727 adults, including 5239 men and 5488 women, with a mean age of 42.7±11.2 years and a mean follow-up time of 9.1 years, met the study criteria and completed a questionnaire about energy intake and diabetes status from the China Health and Nutrition Survey in 1997-2011. PRIMARY OUTCOME MEASURES: Participants were divided into subgroups based on the trajectories of the ratio of energy consumption at dinner versus breakfast. Cox multivariate regression models were used to explore the associations between different trajectories and the risk of T2D after adjustment for confounders and their risk factors. Mediation analysis was performed to explore the intermediary effect of triacylglycerol (TG), total cholesterol (TC), uric acid (UA) and apolipoprotein B (ApoB) between the trajectories and the risk of T2D. RESULTS: For energy consumption at dinner versus breakfast, compared with a low-stable trajectory, the adjusted HR of T2D in low-increasing from early-stage trajectory was 1.29 (95% CI 1.04 to 1.60). TG, TC, UA and ApoB were significantly higher in low-increasing from early-stage trajectory than other trajectories and play partial regulation roles between trajectories and T2D. CONCLUSIONS: This study emphasised the harmful effect of a gradual increase in the ratio of energy consumption at dinner versus breakfast from early stage on the development of T2D and partially mediated by TG, TC, UA and ApoB, highlighting that it is necessary to intake more energy at breakfast compared with dinner to prevent T2D in adults.

The association of energy and macronutrient intake at dinner vs breakfast with the incidence of type 2 diabetes mellitus in a cohort study: The China Health and Nutrition Survey, 1997-2011.

BACKGROUND: This study aims to investigate the association of energy and macronutrient intake at dinner vs breakfast with the incidence of type 2 diabetes mellitus (T2DM). METHODS: A total of 11 153 adults, including 811 with T2DM, completed a questionnaire about energy and macronutrient intake in the China Health and Nutrition Survey (1997-2011). The differences (Δ) in energy and macronutrient intake between dinner and breakfast (Δ = dinner - breakfast) were categorized into quintiles. Cox proportional hazards regression models were performed to explore the association between Δ and the risk of T2DM and to investigate the change of the risk when 5% total energy or energy provided by macronutrients at dinner was substituted with total energy or energy provided by macronutrients at breakfast by isocaloric substitution models. RESULTS: After adjustment for potential confounders, compared with participants in the lowest quintile, participants in the highest quintile were more likely to develop T2DM (hazard ratio [HR]Δenergy 1.46, 95% CI 1.13-1.87; HRΔfat 1.85, 95% CI 1.43-2.41; HRΔprotein 1.37, 95% CI 1.06-1.78). Isocalorically replacing 5% energy at dinner with energy at breakfast was associated with a 7% lower T2DM risk. Replacing 5% energy provided by fat at dinner with energy provided by carbohydrate, protein, and fat at breakfast was associated with a 9%, 5%, and 7% lower T2DM risk, respectively. Replacing 5% energy provided by protein at dinner with energy provided by carbohydrate or protein at breakfast was associated with a 5% lower T2DM risk. CONCLUSIONS: Higher intake of energy, protein, and fat at dinner than at breakfast increased the risk of T2DM.

Construction of few-layered black phosphorus/graphite-like carbon nitride binary hybrid nanostructure for reducing the fire hazards of epoxy resin.

Black phosphorus (BP) and graphite-like carbon nitride (g-C3N4) were combined to prepare BP-CN hybrid nanostructure through a simple self-assembly method assisted by ultra-sonication, and as-obtained materials were further used as fire retardants introduced into epoxy resin to fabricate EP/BP-CNx nanocomposites. It was found that the introduction of 2 wt% BP-CNx into EP contributed to considerable decrements in peak heat release rate (up to 47.72%) and total heat release (utmost to 49.60%) of composites, and LOI value increased from 25% to 31%. SSTF results revealed that the introducing of BP-CN can distinctly reduce the production of smoke. TG-IR results demonstrated that the addition of BP-CN0.5 and BP-CN2.0 into EP matrix exert different influences on the decomposition of resin. Analyses of residual chars further validated through adjusting the proportion of BP and CN can achieve different fire performances of matrix. This work illustrates that BP can reduce the fire hazards of EP, and the hybridization of CN can achieve better flame retarded efficiency, which provides a new strategy for black phosphorus to be used as a flame retardant.

Connectivity between visual brain regions and whole brain among children diagnosed with autism spectrum disorder / 中国学校卫生

Objective@#To explore the functional connectivity between the visual brain regions and whole brain in children with autism spectrum disorder (ASD) at resting state, and to further analyze the correlation with their clinical manifestations.@*Methods@#The functional magnetic resonance imaging (fMRI) data of 34 boys with ASD enrolled from ASD designated rehabilitation institutions and 29 healthy boys enrolled from several kindergartens in Heilongjiang were collected. Based on the resting-state functional connectivity magnetic resonance imaging (rs-fc MRI) analysis, the BA17 of the primary visual brain region and the BA18/19 of the higher visual brain region were taken as the regions of interest (ROI) to calculate the functional connectivity level between the visual brain regions and whole brain, and the differences between the two groups were compared. Multiple developmental scales were used to evaluate the behavior of ASD children, and Pearson correlation analysis was used to explore the relationship between functional connection strength and autistic behavior.@*Results@#The ASD group had decreased positive connectivity between BA17 and the right fusiform gyrus (FFG), and was negatively correlated with social interaction of ADI-R and the total scores of CARS (r=-0.41, -0.48, P<0.05); ASD group had decreased positive connectivity between BA17 and the left FFG, there was a negative correlation with social motivation of SRS (r=-0.43, P<0.05); ASD group had decreased positive connectivity between BA17 and the left posterior cingulate gyrus (PCG). Children with ASD had decreased positive connectivity between BA18/19 and left calcarine fissure and surrounding cortex (CAL), which was positively correlated with attention conversion of AQ, total scores of CARS (r=0.43, 0.40, P<0.05), and the children with ASD had deceased positive connectivity between BA18/19 and right precuneus (PCUN).@*Conclusion@#In resting state, the functional connectivity of primary and higher visual brain regions and whole brain of ASD children is different from that in healthy children, and there is a significant correlation between abnormal level and autistic behaviors.

Nacre-Inspired Black Phosphorus/Nanofibrillar Cellulose Composite Film with Enhanced Mechanical Properties and Superior Fire Resistance.

Natural nacre offers an optimized guiding principle for the assembly of lightweight and high-strength nanocomposites with excellent mechanical properties. Inspired by the "brick-and-mortar" layered structure of natural nacre, we present a cohort of bioinspired nanocomposites consisting of nanofibrillar cellulose (NFC) and few-layer hydroxyl functionalized black phosphorus (BP-OH) via a vacuum-assisted filtration self-assembly procedure. Owing to the well dispersed two-dimensional (2D) BP-OH in one-dimensional (1D) NFC and strong interfacial hydrogen bonding between them, these novel nacre-like BP-OHx/NFC composite films show excellent mechanical performance with tensile strength up to 214.0 MPa, 300% increase compared to pure NFC and tensile fracture strain up to 23.8%, 1.8 times higher than that of pure NFC. Moreover, these nacre-like composite films bare good fire resistance and high thermal stability. This nacre-inspired approach demonstrates a promising strategy for designing high-performance BP-OHx/NFC composite film, and the obtained bioinspired material could be a potential candidate in the application of flexible construction materials and flame retarded insulation materials.

Combination of black phosphorus nanosheets and MCNTs via phosphoruscarbon bonds for reducing the flammability of air stable epoxy resin nanocomposites.

As a rising star of two-dimensional material, black phosphorus (BP) has attracted tremendous attention in applications of photovoltaics, transistors and batteries due to its unique characteristics. Inspiring, we developed a simple strategy to fabricate BP-MCNTs as highly promising inorganic phosphorus-based flame retardant. After incorporation 2 wt% BP-MCNTs11(the mass ratio of BP:MCNTs=1:1) nanohybrid, the peak of heat release rate and total heat release of EP nanocomposites reduced by 55.81% and 41.17% at a phosphorus content of only 1 wt%, and the comprehensive index FGI for evaluating the flame retardant of materials decreased from 17.35 to 6.97. In addition, the typical flammable volatile are suppressed significantly, and the first stage of carbon monoxide release is disappeared. The improvement of fire safety and inhibition of smoke toxicity could be attributed to the the synergistic effects of nano-barrier, catalytic charring and radicals trapping of BP-MCNTs nanohybrid. More importantly, BP hybrid with MCNTs and wrapped in EP matrix which formed effective isolation protection against the ambient degradation. Raman spectra and SEM results confirmed that EP/BP-MCNTs performed enhanced ambient stability than EP/BP-BS nanocomposites after three months. This study demonstrates its great potential for preparation of air-stable BP based nanocomposites with enhanced fire safety.

Nonreceptor tyrosine phosphatase 14 promotes proliferation and migration through regulating phosphorylation of YAP of Hippo signaling pathway in gastric cancer cells.

BACKGROUND: The Hippo signaling pathway is associated with cell proliferation and organ size, and its transcriptional coactivator Yes-associated protein (YAP), emerges as a crucial oncoprotein in multiple cancers. It was increasingly recognized that nonreceptor tyrosine phosphatase 14 (PTPN14) was relevant to the cell membrane and cytoskeleton, and had a critical effect on cell adhesion, growth, and actin cytoskeleton organization. Furthermore, PTPN14 was also certified to operate the translocation and phosphorylation of YAP. The present experiment was aimed to explore the impact of PTPN14 on gastric cancer (GC) cell proliferation and migration through regulating the phosphorylation of YAP. METHODS: The pEGFP-N1-PTPN14 recombinant plasmid was stably transfected into three differentiation degrees GC cell lines, including MKN-28, SGC-7901, and BGC-823. Quantitative reverse transcription-polymerase chain reaction and Western blot assay were performed to analyze the messenger RNA (mRNA) and protein levels. The proliferative and migratory capacity of cells was appraised by Cell Counting Kit-8 assay and transwell chamber. RESULTS: Compared with the normal control and vector transfection group, the capacity of these three cell lines, which transfected with the pEGFP-N1-PTPN14 to proliferate and migrate in vitro was increased obviously (P < .05). There was no YAP mRNA detected in MKN-28 cell line. Meanwhile, after transfecting the pEGFP-N1-PTPN14 plasmid, the mRNA level of YAP in SGC-7901 was reduced (P < .05), and it was increased in BGC-823 (P < .05). The YAP protein level in SGC-7901 and BGC-823 has no apparent transformation by transfecting, but the protein level of phospho-Ser127 YAP and phospho-Ser397 YAP is upregulated (P < .05). CONCLUSION: PTPN14 could enhance the proliferative and migratory ability of GC cells by promoting the YAP phosphorylation in the Hippo signaling pathway. Taken together, PTPN14 might be involved in the occurrence and development of GC and become a molecular regulator to treat GC.

Aberrant methylation of FAT4 and SOX11 in peripheral blood leukocytes and their association with gastric cancer risk.

Background: Aberrant DNA methylation, especially tumor suppressor gene hypermethylation, is a well-recognized biomarker of initial tumorogenesis stages. FAT4 and SOX11 are putative tumor suppressor genes and can be down-regulated by hypermethylation in various cancers tissues. However, in peripheral blood leukocytes, the association between these two genes methylation status, as well as the effects of gene-environment interactions, and gastric cancer (GC) risk remain unclear. Methods: A hospital-based case-control study including 375 cases and 394 controls was conducted. Peripheral blood leukocytes DNA methylation status were detected by methylation-sensitive high-resolution melting (MS-HRM) assay. Logistic regression was adopted to analyze the relationship of FAT4 and SOX11 methylation with GC susceptibility. Results: Positive methylation (Pm) and total positive methylation (Tpm) of FAT4 were significantly increased the risk of GC (OR = 2.204, 95% CI: 1.168-4.159, P = 0.015; OR = 1.583, 95% CI: 1.031-2.430, P = 0.036, respectively). Compared with controls, cases exhibited higher SOX11 Pm frequencies with OR of 2.530 (95% CI: 1.289-4.969, P = 0.007). Nonetheless, no statistically significant association between SOX11 Tpm and GC risk was observed. Additionally, interactions between FAT4 Tpm and increased consumption of freshwater fish (≥1 times/week) displayed an antagonistic effect on GC (OR = 0.328, 95% CI: 0.142-0.762, P = 0.009), and high salt intake interacted with SOX11 Tpm also showed statistically significant (OR = 0.490, 95% CI: 0.242-0.995, P = 0.048). Conclusions:FAT4 aberrant methylation in peripheral blood leukocytes and gene-environment interactions were associated with the risk of GC, while SOX11 was controversial and needed to be more investigated.

Association of peripheral blood leukocyte KIBRA methylation with gastric cancer risk: a case-control study.

KIBRA was reported to be involved in various types of cancer and can be detected in blood. The purpose of this study was to investigate the relationship between the status of KIBRA methylation in peripheral blood leukocytes and gastric cancer (GC) risk. A case-control study was carried out to evaluate the association of blood cell-derived KIBRA methylation with the risk of GC using methylation-sensitive high-resolution melting analysis. A total of 393 cases and 393 controls were detected, respectively. Compared with the subjects in the KIBRA negative methylation (NM) group, positive methylation (PM) subjects exhibited a 1.52-fold (95% CI: 1.030-2.251, P = 0.035) increased risk for GC. Stratified analyses demonstrated that the significant association of KIBRA methylation with GC risk existed in the older group (≥ 60 years; ORa  = 1.846, 95% CI: 1.037-3.287, P = 0.037) and Helicobacter pylori (H. pylori) positive subjects (ORa  = 1.933, 95% CI: 1.103-3.386, P = 0.021). Statistically significant combination effects between the environmental factors and KIBRA methylation on the GC risk were observed except for storing food under refrigeration. KIBRA methylation derived from blood cells and combinations thereof with environmental factors may be associated with the risk of GC.

Serum Helicobacter pylori KatA and AhpC antibodies as novel biomarkers for gastric cancer.

AIM: To investigate catalase (KatA) and alkyl hydroperoxide reductase (AhpC) antibodies of Helicobacter pylori as biomarkers for gastric cancer (GC). METHODS: This study included 232 cases and 264 controls. Recombinant KatA and AhpC proteins were constructed and the levels of antibodies were tested by indirect enzyme-linked immunosorbent assay (ELISA). Logistic regression was applied to analyze the relationships between KatA, AhpC and GC. The χ(2) trend test was used to evaluate the dose-response relationships between serum KatA and AhpC antibody levels and GC. Receiver operating characteristic (ROC) curve was used to evaluate the screening accuracy of KatA and AhpC as biomarkers. Combined analysis was used to observe screening accuracy of predictors for GC. RESULTS: In all subjects, the association between KatA and AhpC and GC risk was significant (P < 0.001) with odds ratio (OR) = 12.84 (95%CI: 7.79-21.15) and OR = 2.4 (95%CI: 1.55-3.73), respectively. KatA and AhpC antibody levels were strongly related to GC risk with a dose-dependent effect (P for trend < 0.001). The area under the ROC (AUC) for KatA was 0.806, providing a sensitivity of 66.81% and specificity of 86.36%; and the AUC for AhpC was 0.615, with a sensitivity of 75.65% and specificity of 45.49%. The AUC was 0.906 for KatA and flagella protein A (FlaA) combined analysis. CONCLUSION: Serum KatA and AhpC antibodies are associated with GC risk and KatA may serve as a biomarker for GC. KatA/FlaA combined analysis improved screening accuracy.

Serum Helicobacter pylori FliD antibody and the risk of gastric cancer.

FliD and CagA are important virulence factors of H. pylori. We aimed to evaluate the screening values of FliD and CagA for gastric cancer (GC). Serum samples were obtained from 232 cases and 266 controls in a case-control study. Unconditional multivariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs) was used to analyze the relationships between FliD, CagA and GC. The sensitivities, specificities and receiver operating characteristic (ROC) curves were calculated. Finally, the combined screening values of FliD, FlaA, NapA and CagA were assessed based on discriminant analysis. In all subjects, the associations of FliD and CagA with GC were evident with ORs (95% CIs) of 7.6 (4.7-12.3) and 2.5 (1.6-3.8), respectively (*p<0.001). The areas under ROC curves (AUCs) for FliD and CagA were 0.800 and 0.653, respectively. The AUC for the combination of FliD, FlaA and NapA was 0.915, which represented an increase of 0.115 over that of FliD alone (*p<0.001). These findings indicate that the FliD antibody is associated with GC and could exhibit high validity as a biomarker in screening for GC patients. The combination of FliD, FlaA and NapA improved the screening validity.

Constitutive expression of PPARγ inhibits proliferation and migration of gastric cancer cells and down-regulates Wnt/ß-Catenin signaling pathway downstream target genes TERT and ENAH.

BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the PPAR nuclear hormone receptor superfamily, which plays a crucial role in carcinogenesis. Wnt/ß-Catenin signaling pathway has been well certified to contribute to the progression of gastric malignancies. ß-Catenin mediates transcriptional regulation by forming a complex with LEF/TCF transcription factors, resulting in activation of downstream target genes such as TERT, ENAH. In this study, we aimed at detecting the effect of PPARγ on TERT, ENAH and explaining the further mechanisms of PPARγ on tumor suppression. METHODS: The pEGFP-N1-PPARγ recombinant plasmid has already been constructed by researchers in our laboratory. We stably transfected it into three gastric cancer (GC) cell lines (MKN-28, SGC-7901 and BGC-823). CCK-8 and transwell assay were employed to analyze the capability of cell proliferation and metastasis. The mRNA and protein levels were evaluated by real-time PCR and western blot analysis. RESULTS: After transfected with PPARγ overexpression plasmid, the ability of cell proliferation and migration declined significantly (p<0.05). The expression of PPARγ increased (p<0.05) and ß-Catenin was inhibited obviously (p<0.05) in the group of pEGFP-N1-PPARγ plasmid transfection. Meanwhile, the mRNA or protein levels of TERT and ENAH were suppressed (p<0.05) in pEGFP-N1-PPARγ plasmid transfection group compared with control groups. CONCLUSION: PPARγ might inhibit the proliferation and migration of GC cell lines through suppressing the expression of TERT and ENAH. PPARγ played an important role as a physiological regulator and might be a target for the treatment of GC.

PPARγ suppressed Wnt/ß-catenin signaling pathway and its downstream effector SOX9 expression in gastric cancer cells.

Wnt signaling pathway activation plays a critical role in biological processes of tumor progression. SOX9 belongs to the sry-related high-mobility group box (SOX) family and is a key transcription factor in the development and differentiation of multiple cell lineages. The purpose of this study was to investigate whether suppression of Wnt signaling pathway by PPARγ gene affects target SOX9 gene expression. The pEGFP-N1-PPARγ overexpression recombinant plasmid was structured by molecular biology technology. The overexpression plasmid and empty vector pEGFP-N1 were transfected into three types of human gastric cancer cell lines, with different levels of differentiation, MKN-28, SGC-7901 and BGC-823. The PPARγ, ß-catenin and SOX9 mRNA levels and proteins were examined by real-time PCR and Western blot analysis. The pEGFP-N1-PPARγ recombinant plasmid was constructed and transfected into MKN-28, SGC-7901 and BGC-823 successfully. High expression of PPARγ (p < 0.05) for transfection recombinant plasmid group induced obviously decreased expression of ß-catenin (p < 0.05), whereas SOX9 expression decreased significantly (p < 0.05) compared with the transfection empty vector group and normal comparison group. PPARγ can suppress ß-catenin expression in Wnt signaling pathway and its downstream effector SOX9 expression in gastric cancer cells.