γ-glutamylcysteine alleviates insulin resistance and hepatic steatosis by regulating adenylate cyclase and IGF-1R/IRS1/PI3K/Akt signaling pathways.

Type 2 diabetes mellitus (T2DM), a complex metabolism disease, which was characterized by metabolic disorders including hyperglycemia, has become a major health problem due to the increasing prevalence worldwide. γ-glutamylcysteine (γ-GC) as an immediate precursor of glutathione (GSH) was originally used for the treatment of sepsis, inflammation bowel disease, and senescence. Here, we evaluated the capacity of γ-GC on diabetes-related metabolic parameters in db/db mice and insulin resistance (IR) amelioration in cells induced by palmitic acid (PA). Our data suggested that γ-GC treatment decreased body weight, reduced adipose tissue size, ameliorated ectopic fat deposition in liver, increased the GSH content in liver, improved glucose control and other diabetes-related metabolic parameters in vivo. Moreover, in vitro experiments showed that γ-GC could maintain the balance of free fatty acids (FFAs) and glucose uptake through regulating the translocation of CD36 and GLUT4 from cytoplasm to plasma membrane. Furthermore, our finding also provided evidence that γ-GC could activate Akt not only via adenylate cyclase (AC)/cAMP/PI3K signaling pathway, but also via IGF-1R/IRS1/PI3K signaling pathway to improve IR and hepatic steatosis. Blocking either of two signaling pathways could not activate Akt activation induced by γ-GC. This unique characteristic ensures the important role of γ-GC in glucose metabolism. Collectively, these results suggested that γ-GC could serve as a candidate dipeptide for the treatment of T2DM and related chronic diabetic complications via activating AC and IGF-1R/IRS1/PI3K/Akt signaling pathways to regulate CD36 and GLUT4 trafficking.

Enhancement of Energy Storage Performance of PMMA/PVDF Composites by Changing the Crystalline Phase through Heat Treatment.

In today's contemporary civilization, there is a growing need for clean energy focused on preserving the environment; thus, dielectric capacitors are crucial equipment in energy conversion. On the other hand, the energy storage performance of commercial BOPP (Biaxially Oriented Polypropylene) dielectric capacitors is relatively poor; hence, enhancing their performance has drawn the attention of an increasing number of researchers. This study used heat treatment to boost the performance of the composite made from PMAA and PVDF, combined in various ratios with good compatibility. The impacts of varying percentages of PMMA-doped PMMA/PVDF mixes and heat treatment at varying temperatures were systematically explored for their influence on the attributes of the blends. After some time, the blended composite's breakdown strength improves from 389 kV/mm to 729.42 kV/mm at a processing temperature of 120 °C. Consequently, the energy storage density is 21.12 J/cm3, and the discharge efficiency is 64.8%. The performance has been significantly enhanced compared to PVDF in its purest state. This work offers a helpful technique for designing polymers that perform well as energy storage materials.

Tetrastigma polysaccharide reprogramming of tumor-associated macrophages via PPARγ signaling pathway to play antitumor activity in breast cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma Hemsleyanum Diels et Gilg (SYQ) is a typical She ethnomedicine that has been used in anti-tumor treatment in Chinese folklore. The polysaccharide of SYQ (SYQ-PA) has been reported to have antioxidant and anti-inflammatory effects, but the effect and mechanism on antitumor is still unclear. AIM OF THE STUDY: To investigate the activity and mechanism of SYQ-PA against breast cancer in vitro and in vivo. MATERIALS AND METHODS: In this study, different stages of MMTV-PYMT mice, which at 4-week-old and 8-week-old representative the transition from hyperplasia to late carcinoma, were used to investigate the potential effect of SYQ-PA of breast cancer development in vivo. The mechanism was explored with IL4/13-induced peritoneal macrophages model. Flow cytometry assay was employed to analysis the change of tumor microenvironment and the macrophages typing. The inhibition of the condition medium from macrophages on breast cancer cells was detected with xCELLigence system detection. The inflammation factors were tested with cytometric bead array. Co-culture system was used to detect the cell migration and invasion. In addition, the underlying mechanism was investigated using RNAseq analysis, Q-PCR and Western blot, and the PPARγ inhibitor was used to verify the mechanism. RESULTS: SYQ-PA significantly attenuated the process of breast primary tumor growth and reduced the infiltration of TAMs accompanied promoting the polarization of M1 phenotype in MMTV-PyMT mice. Then in vitro studies showed that SYQ-PA promoted macrophages polarization form IL4/13 induced M2 toward to the anti-tumor M1 phenotypes, and the conditioned medium (CM) from the induced macrophages inhibited the proliferation of breast cancer cells. At the same time, SYQ-PA treated macrophages inhibited the migration and invasion of 4T1 in the co-culture system. Further results indicated that SYQ-PA suppressed the release of anti-inflammatory factors and promoted the production of inflammatory cytokines which may induce M1 macrophage polarization and inhibit breast cancer cell proliferation. Subsequently, the underlying mechanism analysis based on RNAseq and molecular assays indicated that SYQ-PA inhibited PPARγ expression and regulated downstream NF-κB in macrophages. After treated with PPARγ inhibitor, T0070907, the effect of SYQ-PA was decreased, or even disappeared. As the downstream, the expression of ß-catenin was also inhibited obviously, those above all contribute the process of SYQ-PA induced M1 macrophages polarization. CONCLUSIONS: Collectively, SYQ-PA was observed inhibited breast cancer, at least in part, via PPARγ activation- and ß-catenin-mediated M2 macrophages polarization. These data expound the antitumor effect and mechanism of SYQ-PA, and provide a possible that SYQ-PA can be used as an adjuvant drug for macrophage tumor immunotherapy in breast cancer.

Panax notoginseng saponins normalises tumour blood vessels by inhibiting EphA2 gene expression to modulate the tumour microenvironment of breast cancer.

BACKGROUND: Panax notoginseng saponins (PNS), the main active component of Panax notoginseng, can promote vascular microcirculation. PNS exhibits antitumor effects in various cancers. However, the molecular basis of the relationship between PNS and tumor blood vessels remains unclear. PURPOSE: To study the relationship between PNS inhibiting the growth and metastasis of breast cancer and promoting the normalization of blood vessels. METHODS: We performed laser speckle imaging of tumor microvessels and observed the effects of PNS on tumor growth and metastasis of MMTV-PyMT (FVB) spontaneous breast cancer in a transgenic mouse model. Immunohistochemical staining of Ki67 and CD31 was performed for tumors, scanning electron microscopy was used to observe tumor vascular morphology, and flow cytometry was used to detect tumor tissue immune microenvironment (TME). RNA-seq analysis was performed using the main vessels of the tumor tissues of the mice. HUVECs were cultured in tumor supernatant in vitro to simulate tumor microenvironment and verify the sequencing differential key genes. RESULTS: After treatment with PNS, we observed that tumor growth was suppressed, the blood perfusion of the systemic tumor microvessels in the mice increased, and the number of lung metastases decreased. Moreover, the vascular density of the primary tumor increased, and the vascular epidermis was smoother and flatter. Moreover, the number of tumor-associated macrophages in the tumor microenvironment was reduced, and the expression levels of IL-6, IL-10, and TNF-α were reduced in the tumor tissues. PNS downregulated the expression of multiple genes associated with tumor angiogenesis, migration, and adhesion. In vitro tubule formation experiments revealed that PNS promoted the formation and connection of tumor blood vessels and normalized the vessel morphology primarily by inhibiting EphA2 expression. In addition, PNS inhibited the expression of tumor vascular marker proteins and vascular migration adhesion-related proteins in vivo. CONCLUSION: In this study, we found that PNS promoted the generation and connection of tumor vascular endothelial cells, revealing the key role of EphA2 in endothelial cell adhesion and tumor blood vessel morphology. PNS can inhibit the proliferation and metastasis of breast cancer by inhibiting EphA2, improving the immune microenvironment of breast cancer and promoting the normalization of tumor blood vessels.

γ-Glutamylcysteine rescues mice from TNBS-driven inflammatory bowel disease through regulating macrophages polarization.

OBJECTIVE: To explore the molecular mechanism of γ-glutamylcysteine (γ-GC) in response to inflammation in vivo and in vitro on regulating the polarization of macrophages. METHODS: The expressions of gene or protein were assessed by qPCR and Western blot assays, respectively. Cell viability was investigated by CCK-8 assay. Eight-week-old male BALB/c mice were established to examine the therapeutic effects of γ-GC in vivo. The release of TNF-α and IL-4 was determined by ELISA assay. Macrophages polarization was identified by flow cytometry assay. RESULTS: Our data showed that γ-GC treatment significantly improved the survival, weight loss, and colon tissue damage of IBD mice. Furthermore, we established M1- and M2-polarized macrophages, respectively, and our findings provided evidence that γ-GC switched M1/M2-polarized macrophages through activating AMPK/SIRT1 axis and inhibiting inflammation-related signaling pathway. CONCLUSION: Collectively, both in vivo and in vitro experiments suggested that γ-GC has the potential to become a promising novel therapeutic dipeptide for the treatment of IBD, which provide new ideas for the treatment of inflammatory diseases in the future.

Pollution Characteristics and Human Health Risk Assessment of Heavy Metals in Street Dust from a Typical Industrial Zone in Wuhan City, Central China.

This study aimed to assess the pollution levels, sources, and human health risks of heavy metals in street dust from a typical industrial district in Wuhan City, Central China. In total, 47 street dust samples were collected from the major traffic arteries and streets around Wuhan Iron and Steel (Group) Company (WISC) in Qingshan District, Wuhan. The concentrations of heavy metals (Cr, Mn, Ni, Zn, Fe, Cu, and Cd) in street dust were determined by atomic absorption spectroscopy. Results indicated that the mean concentrations of Zn (249.71 mg/kg), Cu (51.15 mg/kg), and Cd (0.86 mg/kg) in street dust were higher than their corresponding soil background values in Hubei Province. Heavy metal enrichment is closely related to urban transportation and industrial production. The pollution level of heavy metals in street dust was assessed using the geo-accumulation method (Igeo) and potential ecological risk assessment (PERI). Based on the Igeo value, Cr, Mn, Fe, and Ni showed no pollution, Zn and Cu showed light to moderate contamination, and Cd showed moderate contamination. The PERI values of heavy metals in street dust ranged between 76.70 and 7027.28, which represents a medium to high potential ecological risk. Principal component analysis showed that the sources of heavy metals in street dust were mainly influenced by anthropogenic activities. Among the studied metals, Cu, Cr, Zn, Fe, and Mn mainly come from industrial processes, while Ni and Cd come from traffic exhaust. The non-carcinogenic risk indexes of heavy metals for children and adults are ranked as Cr > Cu > Ni > Cd > Zn. The health risks to children through the different exposure pathways are higher than those for adults. Hand-to-mouth intake is the riskiest exposure pathway for non-carcinogenic risk. In addition, Cr, Ni, and Cd do not pose a carcinogenic risk for the residents.

γ-Glutamylcysteine ameliorates D-gal-induced senescence in PC12 cells and mice via activating AMPK and SIRT1.

Aging is a natural process accompanied by inflammation and oxidative stress and is closely associated with age-related diseases. As a direct precursor of glutathione, γ-glutamylcysteine (γ-GC) possesses antioxidant and anti-inflammatory properties; however, whether γ-GC plays an important role in anti-aging remains unknown. Here, we investigated the protective effects and mechanisms of γ-GC in D-galactose (D-gal)-induced senescence in PC12 cells and aging mice. Our results showed that γ-GC treatment significantly reduced the percentage of senescence-associated-ß-galactosidase (SA-ß-Gal)-positive cells and inhibited D-gal-induced cell cycle arrest in PC12 cells. The results of Nissl and hematoxylin and eosin (H&E) staining in mouse brain showed that γ-GC treatment markedly reversed the damage in the hippocampus of D-gal-induced aging mice. Moreover, γ-GC increased the phosphorylation of AMP-activated protein kinase (AMPK) to promote the nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) while inhibiting the nuclear translocation of deleted in breast cancer 1 (DBC1), which leads to the activation of sirtuin 1 (SIRT1) and deacetylation of p53 in the nucleus. Therefore, γ-GC may be a potential therapeutic candidate compound for the prevention and treatment of age-related diseases.

Roles of Wnt/ß-catenin signaling pathway related microRNAs in esophageal cancer.

MicroRNAs (miRNAs) are endogenous, noncoding, single-stranded small RNAs that regulate expression of tumor suppressor genes and oncogenes and are involved in almost all tumor-related processes. MiRNA dysregulation plays an important role in the occurrence and development of esophageal cancer through specific signal pathways, including the Wnt/ß-catenin signaling pathway, and is closely related to the malignant characteristics of esophageal cancer. The interaction between miRNAs and the Wnt/ß-catenin signaling pathway, which is specifically expressed in esophageal cancer tissues, shows potential as a new biomarker and therapeutic target. This article reviews the role of miRNAs related to the Wnt pathway in the carcinogenesis of esophageal carcinoma and its role in Wnt signal transduction. The content of this review can be used as the basis for formulating or improving the treatment strategy of esophageal cancer.

L-theanine prevents progression of nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKß-AMPK signaling pathway.

BACKGROUND: L-theanine, a non-protein amino acid was found principally in the green tea, has been previously shown to exhibit potent anti-obesity property and hepatoprotective effect. Herein, we investigated the effects of L-theanine on alleviating nonalcoholic hepatic steatosis in vitro and in vivo, and explored the underlying molecular mechanism. METHODS: In vitro, HepG2 and AML12 cells were treated with 500 µM oleic acid (OA) or treated with OA accompanied by L-theanine. In vivo, C57BL/6J mice were fed with normal control diet (NCD), high-fat diet (HFD), or HFD along with L-theanine for 16 weeks. The levels of triglycerides (TG), accumulation of lipid droplets and the expression of genes related to hepatocyte lipid metabolic pathways were detected in vitro and in vivo. RESULTS: Our data indicated that, in vivo, L-theanine significantly reduced body weight, hepatic steatosis, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), TG and LDL cholesterol (LDL-C) in HFD-induced nonalcoholic fatty liver disease (NAFLD) mice. In vitro, L-theanine also significantly alleviated OA induced hepatocytes steatosis. Mechanic studies showed that L-theanine significantly inhibited the nucleus translocation of sterol regulatory element binding protein 1c (SREBP-1c) through AMPK-mTOR signaling pathway, thereby contributing to the reduction of fatty acid synthesis. We also identified that L-theanine enhanced fatty acid ß-oxidation by increasing the expression of peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase-1 A (CPT1A) through AMP-activated protein kinase (AMPK). Furthermore, our study indicated that L-theanine can active AMPK through its upstream kinase Calmodulin-dependent protein kinase kinase-ß (CaMKKß). CONCLUSIONS: Taken together, our findings suggested that L-theanine alleviates nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKß-AMPK signaling pathway.

Circ_0008035 promotes the progression of gastric cancer via the regulation of miR-1256/CEACAM6 axis.

Gastric cancer (GC) is one of the most common malignant tumors. Circular RNA (circRNA) has been shown to be involved in the progression of GC. However, the function of circ_0008035 in GC has not been studied. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_0008035, microRNA-1256 (miR-1256) and carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, and transwell assay were used to detect cell function. Western blot examined the protein levels of Ki67, Bax, MMP-2, and CEACAM6. The relationship between miR-1256 and circ_0008035 or CEACAM6 was verified by dual-luciferase reporter assays and RNA pull down. The xenotransplantation model was established in BALB/c nude mice to study the role of circ_0008035 in vivo. Circ_0008035 and CEACAM6 were significantly high-expressed in GC tissues and cells. Silencing of circ_0008035 reduced GC cell proliferation, migration, and invasion while enhancing apoptosis. MiR-1256 was a target of circ_0008035. The inhibition effect of circ_0008035 knockdown on the malignant behavior of GC cells could be reversed by miR-1256 inhibitor. In addition, CEACAM6 was a target of miR-1256. Overexpression of CEACAM6 partially restored the inhibitory effect of miR-1256 on cell progression. Animal experiments confirmed the anti-tumor effect of circ_0008035 knockdown in vivo. Collectively, circ_0008035 regulated the expression of CEACAM6 by sponging miR-1256, thereby promoting the development of GC. Our data provided a novel targeted therapy for GC.

17 ß-Estradiol alleviates oxidative damage in osteoblasts by regulating miR-320/RUNX2 signaling pathway.

The aim of this study is to investigate the effect and mechanism of 17 ß-estradiol (E2) on oxidative stress in the osteoblasts. An oxidative stress-induced damage model was established using H2O2 in MC3T3-E1 cells, and H2O2-induced cells were treated with E2. The results indicated that E2 attenuated oxidative stress in H2O2- induced MC3T3-E1 cells. In addition, H2O2 upregulated the expression of miR-320-3p and downregulated that of RUNX2, but these changes were counteracted by E2. Thereafter, we verified the interactive relationship between miR-320-3p and RUNX2. Then, H2O2-induced MC3T3-E1 cells were transfected with miR-320-3p mimics or inhibitors and treated with E2. The results indicated that miR-320-3p inhibition suppressed H2O2- induced inflammation, apoptosis, and oxidative stress and promoted the osteogenic differentiation of MC3T3- E1 cells by regulating RUNX2, ALP, and OCN, and this effect was further strengthened by E2. In conclusion, the findings suggest that E2 alleviates oxidative damage in osteoblasts by regulating the miR-320/RUNX2 signaling.

The palliative effects of folic acid on retinal microvessels in diabetic retinopathy via regulating the metabolism of DNA methylation and hydroxymethylation.

Diabetic retinopathy (DR) is one of the severe microvascular complications of diabetes. The protective effects of FA on retinal vascular endothelial cells against high glucose levels involve in multiple aspects in DR; however, the underlying mechanism is not fully elucidated. In present study, we investigated the transcriptome as well as genome-wide DNA methylation and hydroxymethylation signature in human retinal microvascular endothelial ACBRI 181 cells cultured within high glucose (HG) medium supplemented with or without FA by RNA-seq, MeDIP-seq, and hMeDIP-seq. Total 3308 differential expressed genes (DEGs) were involved in multiple biological processes and molecular functions containing angiogenesis, inflammation, S-adenosyl methionine metabolism, and hypoxia response. Moreover, the global DNA methylation and hydroxymethylation in ACBRI 181 cells with FA treatment were both compromised compared to HG. Combined with transcriptome data, four subclusters of DEGs with hyper- or hypomethylated promoters were further verified. Unexpectedly, promoters of these 487 genes all displayed a pattern of increased DNA hydroxymethylation. Furthermore, hyperglycemia rat model was established and administered with FA. The DNA methylation and hydroxymethylation changes of selected target genes COL1A1, ITGA7, MMP-14, and VEGFB confirmed by MeDIP-qPCR were consistent with the results in human ACBRI 181 cells. Finally, the presence of activated DNMT1 and TET2 induced by FA was determined in ACBRI 181 cells and hyperglycemia rat. Taken together, this research provided a resource of expression and epigenetic profiles in retinal microvascular endothelial cell, emphasizing a pharmacological mechanism of FA on DNA methylation and hydroxymethylation regulation in retinal microvessel cells of DR.

Effect of timeliness incentive nursing on postoperative rehabilitation in patients with cervical spondylotic myelopathy.

OBJECTIVE: To explore the effect of timeliness incentive nursing on postoperative rehabilitation of patients with cervical spondylotic myelopathy (CSM). METHODS: a total of 104 CSM patients treated in our hospital were recruited, who were evenly divided into two groups according to a random number table method. The control group was given routine nursing, and the research group was given timeliness incentive nursing based on routine nursing. The out-of-bed activity time after surgery, the length of hospital stay, the visual analog scale (VAS) scores before and after intervention, the Japanese Orthopedic Association (JOA) scores, the cervical spine range of motion (ROM), changes of quality of life (QOL), complications, and nursing satisfaction were compared between the two groups. RESULTS: After intervention, the out-of-bed activity time and length of hospital stay in the research group were significantly shorter than those of the control group (P<0.001). Compared with before intervention, VAS scores were significantly decreased, while JOA scores and ROM were both considerably increased after intervention in both groups (P<0.001). Of note, the improvement in the research group was more significant compared with the control group. The incidence of complications of the research group was remarkably lower than that of the control group (P<0.05). Compared with before intervention, physiological functions, physiological and emotional responsibilities, social function, mental health, energy, and overall health scores were all significantly increased after intervention in both groups, whereas the physical pain was significantly decreased (P<0.001), and these measures of the research group were higher than those of the control group. The nursing satisfaction in the research group was notably higher than that of the control group (P<0.05). CONCLUSION: Timeliness incentive nursing can effectively improve postoperative rehabilitation of patients with CSM, reduce the pain, decrease the incidence of complications, improve the QOL, and increase nursing satisfaction.

Polycyclic aromatic hydrocarbons in railway stations dust of the mega traffic hub city, central China: Human health risk and relationship with black carbon.

Twenty dust samples collected from Wuchang and Wuhan Railway Stations, the biggest transport stations in the mega traffic hub city in Central China, were analyzed for polycyclic aromatic hydrocarbons (PAHs) to investigate the concentration, sources apportionment, and relationship with black carbon (BC) and assess the health risk. The results suggested that the concentrations of PAHs, BC and TOC in Wuhan Railway Station (WHRS) (PAHs = 5940 ± 1920 ng g-1, BC = 53.2 ± 23.1 mg g-1 and TOC = 80.7 ± 44.4) were twice higher than those in Wuchang Railway Station (WCRS) (PAHs = 2580 ± 1630 ng g-1, BC = 20.4 ± 14.3 mg g-1 and TOC = 33.9 ± 20.1 mg g-1). Moreover, the 3 - and 4 - rings PAHs were major PAHs in railway station dust. The composition pattern of PAHs in these railway station dusts had a common characteristic with HMW-PAHs contribution. The results of source identification revealed that different local development features and energy consumption of trains would influence the sources of PAHs and BC. PAHs and BC were most likely related to industrial activities in WHRS. Coal and biomass combustion may influence the PAHs components and BC distribution in WCRS. Moreover, BC had played an important role in retaining PAHs in urban railway stations. Especially in WHRS, BC would more likely to absorb the high molecular weight PAHs, such as 4 -ring (p<0.05), 5 -ring (p<0.05) and 6 -ring (p<0.05) PAHs; while BC just played limited roles in the binding of volatile and semi-volatile organic pollutants, such as 2 -ring and 3 -ring PAHs. With the coexistence of BC and PAHs, passengers would face significant potential health risks by exposure to toxic dust in railway stations, especially for children. The cancer risk in WHRS was almost twice higher than that in WCRS, and it would tend to be stable by a semi-confined structure in the platform area.

Cardamonin, a natural chalcone, reduces 5-fluorouracil resistance of gastric cancer cells through targeting Wnt/ß-catenin signal pathway.

Objectives Cardamonin (CD), an active chalconoid, has been extensively studied in a wide variety of human tumors. However, the effects and underlying mechanism of cardamonin on 5-fluorouracil (5-FU)-resistant gastric cancer (GC) remain largely unclear. This study aimed to investigate the antitumor effects of cardamonin on 5-FU-resistant GC cells and explore the molecular mechanisms underlying its therapeutic potential. Methods The antitumor activities of cardamonin, 5-FU and their combination against BGC-823 and BGC-823/5-FU cells were determined using cytotoxicity assay, flow cytometry-based cell cycle analysis and Annexin V apoptosis assay. The effect of cardamonin on P-glycoprotein activity was assessed by Rh123 uptake assay. Real-time PCR, Western blotting and Co-immunoprecipitation analysis were carried out to assess the inhibition of Wnt/ß-catenin signaling pathway. A xenograft mouse model was established using BALB/c nude mice to examine the combinatorial effects of cardamonin and 5-FU on tumor growth. Results Our data provided the first demonstration that cardamonin significantly enhanced the chemosensitivity of 5-FU in GC cells via suppression of Wnt/ß-catenin signaling pathway. Additionally, the combination of cardamonin and 5-FU might result in the apoptosis and cell cycle arrest of BGC-823/5-FU cells, accompanied by the downregulated expression levels of P-glycoprotein, ß-catenin and TCF4. More importantly, our results demonstrated that cardamonin specifically disrupted the formation of ß-catenin/TCF4 complex, leading to TCF4-mediated transcriptional activation in 5-FU-resistant GC cells. Besides, through a xenograft mouse model, co-administration of cardamonin and 5-FU significantly retarded tumor growth in vivo, thus, confirming our in vitro findings. Conclusions Overall, this study revealed that cotreatment of cardamonin and 5-FU could strongly potentiate the antitumor activity of 5-FU, and put forth cardamonin as a rational therapeutic strategy for drug-resistant GC treatment.

[Effects of activation of mitochondrial aldehyde dehydrogenase 2 on inflammasome production in high glucose induced A549 cells].

OBJECTIVE: To investigate the effects of activation of mitochondrial aldehyde dehydrogenase 2(ALDH2) on high glucose-induced inflammasome production in alveolar epithelial A549 cells. METHODS: The alveolar epithelial A549 cells were cultured with 25 mmol/L high glucose complete medium and divided into 4 groups: Control group, ALDH2 agonist 20 µmol/L Alda-1 group, ALDH2 antagonist 60 µmol/L Daidzin group, 20 µmol/L Alda-1 + 60 µmol/L Daidzin group. After the cells treated for 24 h, the cell proliferation activity was measured by thiazolyl blue tetrazolium bromide(MTT) colorimetric assaymethod, and the cellular reactive oxygen species(ROS) level were detected by dihydroethidium(DHE) fluorescent staining method, the cell migration ability was performed by cell scratching experiments, the protein expressions of ALDH2 and the core components of inflammasome, nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC) and cysteinyl aspartate specific protease-1(caspase-1) were detected by western blot. RESULTS: Compared with the control group, after Alda-1 activated ALDH2 specifically, the cell proliferation activity did not change significantly, but the oxidative stress level and cell migration rate were significantly decreased(P<0.05). ALDH2 protein expression was significantly increased(P<0.05), the protein expressions of NLRP3, ASC and caspase-1 were significantly decreased(P<0.05). After Daidzin blocked ALDH2 specifically, there were no significant changes in cell proliferation, oxidative stress, cell migration rate, ALDH2 and ASC protein expressions, while NLRP3 protein expression was significantly increased(P<0.05), and caspase-1 protein expression was significantly decreased(P<0.05). Compared with Alda-1 group, there was no significant changes in cell proliferation and oxidative stress in Alda-1+Daidzin group, cell migration rate was significantly increased(P<0.05), ALDH2 protein expression was decreased(P<0.05), and the protein expressions of NLRP3, ASC and caspase-1 were significantly increased(P<0.05). CONCLUSION: Increasing ALDH2 expression in alveolar epithelial A549 cells may attenuate high glucose-induced cellular inflammatory reaction, possibly through reducing cellular ROS level and reducing inflammasome expression.

Characterization of carbonaceous fractions in PM2.5 and PM10 over a typical industrial city in central China.

Aerosol samples of PM2.5 and PM10 were collected every 6 days from March 2012 to February 2013 in Huangshi, a typical industrial city in central China, to investigate the characteristics, relationships, and sources of carbonaceous species. The PM2.5 and PM10 samples were analyzed for organic carbon (OC), elemental carbon (EC), char, and soot using the thermal/optical reflectance (TOR) method following the IMPROVE_A protocol. PM2.5 and PM10 concentrations ranged from 29.37 to 501.43 µg m-3 and from 50.42 to 330.07 µg m-3, with average levels of 104.90 and 151.23 µg m-3, respectively. The 24-h average level of PM2.5 was about three times the US EPA standard of 35 µg m-3, and significantly exceeds the Class II National Air Quality Standard of China of 75 µg m-3. The seasonal cycles of PM mass and OC concentrations were higher during winter than in summer. EC and char concentrations were generally highest during winter but lowest in spring, while higher soot concentrations occurred in summer. This seasonal variation could be attributed to different seasonal meteorological conditions and changes in source contributions. Strong correlations between OC and EC were found for both PM2.5 and PM10 in winter and fall, while char and soot showed a moderate correlation in summer and winter. The average OC/EC ratios were 5.11 and 4.46 for PM2.5 and PM10, respectively, with individual OC/EC ratios nearly always exceeding 2.0. Higher char/soot ratios during the four seasons indicated that coal combustion and biomass burning were the major sources for carbonaceous aerosol in Huangshi. Contrary to expectations, secondary organic carbon (SOC) which is estimated using the EC tracer method exhibited spring maximum and summer minimum, suggesting that photochemical activity is not a leading factor in the formation of secondary organic aerosols in the study area. The contribution of SOC to OC concentration for PM2.5 and PM10 were 47.33 and 45.38%, respectively, implying that SOC was an important component of OC mass. The serious air pollution in haze-fog episode was strongly correlated with the emissions of pollutants from biomass burning and the meteorological conditions.

Effect of phosphorus addition on the reductive transformation of pentachlorophenol (PCP) and iron reduction with microorganism involvement.

The transformation of phosphorus added to the soil environment has been proven to be influenced by the Fe biochemical process, which thereby may affect the transformation of organic chlorinated contaminants. However, the amount of related literatures regarding this topic is limited. This study aimed to determine the effects of phosphorus addition on pentachlorophenol (PCP) anaerobic transformation, iron reduction, and paddy soil microbial community structure. Results showed that the transformation of phosphorus, iron, and PCP were closely related to the microorganisms. Moreover, phosphorus addition significantly influenced PCP transformation and iron reduction, which promoted and inhibited these processes at low and high concentrations, respectively. Both the maximum reaction rate of PCP transformation and the maximum Fe(II) amount produced were obtained at 1 mmol/L phosphorus concentration. Among the various phosphorus species, dissolved P and NaOH-P considerably changed, whereas only slight changes were observed for the remaining phosphorus species. Microbial community structure analysis demonstrated that adding low concentration of phosphorus promoted the growth of Clostridium bowmanii, Clostridium hungatei, and Clostridium intestinale and Pseudomonas veronii. By contrast, high-concentration phosphorus inhibited growth of these microorganisms, similar to the curves of PCP transformation and iron reduction. These observations indicated that Clostridium and P. veronii, especially Clostridium, played a vital role in the transformation of related substances in the system. All these findings may serve as a reference for the complicated reactions among the multiple components of soils.

[Pollution Characteristics and Risk Assessment of Heavy Metals in Water and Sediment from Daye Lake].

The surface water and surface sediments were collected from Daye Lake in April 2014. The concentrations of heavy metals were determined by atomic absorption spectroscopy. The pollution potential health risk and ecological risk of heavy metals in water and sediment were assessed by the health risk assessment model and the potential ecological risk index method. The results showed that the concentrations of the heavy metals (Ni, Cd, Cu and Pb) was 49.27 µg·L-1, 2.19 µg·L-1, 12.18 µg·L-1, 12.13 µg·L-1(water) and 78.46 mg·kg-1, 77.13 mg·kg-1, 650.13 mg·kg-1 and 134.22 mg·kg-1 (sediment). Enrichment coefficient indicated that the enrichment of Cd, Cu and Pb was more serious, especially the accumulation of Cd was the most obvious. Compared to typical lakes in China, the contents of heavy metals in water and sediment were relatively high. The spatial pollutant distribution of the heavy metals in water and sediment all presented that the concentrations of the heavy metals were relatively higher in east and west of Daye Lake, relatively more uniform in the middle, and their origins were mainly from human activities. The results of environmental risk indicated that the carcinogens and chemical non-carcinogens health risk values of heavy metals by drinking water pathway were 9.77E-08~1.63E-05a-1. Therefore, the pollution of Ni and Cd should be the primary control target for environmental health risk management. The descending order of pollution degree of four metals in sediment was Cd> Cu> Pb> Ni, and Cd was the main contributor of the potential ecological risk elements.

Synergy evaluation by a pathway-pathway interaction network: a new way to predict drug combination.

Drug combinations have been widely applied to treat complex diseases, like cancer, HIV and cardiovascular diseases. One of the most important characteristics for drug combinations is the synergistic effects among different drugs, that is to say, the combination effects are larger than the sum of individual effects. Although quantitative methods can be utilized to evaluate the synergistic effects based on experimental dose-response data, it is both time and resource consuming to screen all possible combinations by experimental trials. This problem makes it a formidable challenge to recognize synergistic combinations. Various attempts have been made to predict drug synergy by network biology, however, most of them are limited to estimating target associations on the PPI network. Here, we proposed a novel "pathway-pathway interaction" network-based synergy evaluation method to predict the potential synergistic drug combinations. Comparison with previous target-based methods shows that inclusion of systematic pathway-pathway interactions makes this novel method outperform others in predicting drug synergy. Moreover, it can also help to interpret how different drugs in a combination cooperate with each other to implement synergistic therapeutic effects. In general, drugs acting on the same pathway through different targets or drugs regulating a relatively small number of highly-connected pathways are more likely to produce synergistic effects.